[go: up one dir, main page]

KR20190126812A - 질환 진단용 바이오마커 - Google Patents

질환 진단용 바이오마커 Download PDF

Info

Publication number
KR20190126812A
KR20190126812A KR1020197027295A KR20197027295A KR20190126812A KR 20190126812 A KR20190126812 A KR 20190126812A KR 1020197027295 A KR1020197027295 A KR 1020197027295A KR 20197027295 A KR20197027295 A KR 20197027295A KR 20190126812 A KR20190126812 A KR 20190126812A
Authority
KR
South Korea
Prior art keywords
hypoxia
biomarker
subject
indicator
biomarkers
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
KR1020197027295A
Other languages
English (en)
Inventor
제이슨 리.
Original Assignee
더 카운실 오브 더 퀸즐랜드 인스티튜트 오브 메디컬 리서치
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AU2017900607A external-priority patent/AU2017900607A0/en
Application filed by 더 카운실 오브 더 퀸즐랜드 인스티튜트 오브 메디컬 리서치 filed Critical 더 카운실 오브 더 퀸즐랜드 인스티튜트 오브 메디컬 리서치
Publication of KR20190126812A publication Critical patent/KR20190126812A/ko
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/70—Mechanisms involved in disease identification
    • G01N2800/7038—Hypoxia

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

저산소증-관련 유전자 서명(gene signature)의 측정에 의해 저산소증 질환을 진단하며 및/또는 모니터링하기 위한 조성물, 방법 및 장치가 개시된다. 본 발명은 저산소증 질환과 관련된 질병 또는 질환(예를 들어 저산소증 질환)을 갖는 것으로 의심되는 대상체의 조기 진단을 포함한 진단, 모니터링, 치료 결정, 또는 관리에 사용될 수 있다. 보다 특히, 본 발명은 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 특이적으로 결정하는 데 유용한 핵산 및 단백질 바이오마커를 개시한다.

Description

질환 진단용 바이오마커
본 출원은 2017년 2월 23일에 출원된 "질환 진단용 바이오마커(Biomarkers for diagnosing conditions)"라는 명칭의 오스트레일리아 가출원 2017900607에 대해 우선권을 주장하며, 이의 내용은 그 전체가 원용에 의해 본 명세서에 포함된다.
본 발명은 일반적으로, 저산소증-관련 유전자 서명(gene signature)의 측정에 의해 저산소증 질환을 진단하며 및/또는 모니터링하기 위한 조성물, 방법 및 장치에 관한 것이다. 본 발명은 저산소증 질환과 관련된 질병 또는 질환(예를 들어 저산소증 질환)을 갖는 것으로 의심되는 대상체의 조기 진단을 포함한 진단, 모니터링, 치료 결정, 또는 관리에 사용될 수 있다. 보다 특히, 본 발명은 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 특이적으로 결정하는 데 유용한 핵산 및 단백질 바이오마커에 관한 것이다.
종양 거동에 영향을 미치는 것으로 인지되는 중요한 미세환경 인자는 저산소증이다. 고형 종양에서, 저산소증은 혈관 원발성 종양(vascular primary tumor) 또는 전이에서 산소 확산이 제한된 결과 발생한다. 고형 종양에서 저산소증은 증식적 및 전이적 잠재성을 증강시킴으로써 암세포의 공격성을 증가시키는 것으로 공지되어 있다(Harris, 2002; Semenza, 2003). 지속적 저산소증은 방사선 및 화학 요법의 효능을 유의하게 감소시키고, 불량한 결과를 초래한다(Vaupel, 2004; Bache 등 2008). 이는 주로, 세포자멸사를 억제시키며(Erler 등 2004), 종양 혈관신생(Semenza, 2000) 및 상피-간엽 이행(EMT; epithelial-to-mesenchymal transition)(Hill 등 2009)을 증강시키는 생존촉진(pro-survival) 유전자의 증가로 인한 것이다. 임상 연구는 또한, 종양 저산소증이, 증강된 침범성(Pennacchietti 등 2003) 및 전이를 발달시킬 더 큰 위험성(Chang 등 2011)과 강하게 관련있으며, 이는 주로 이러한 조건 하에 세포 부착 분자(CAM; cell adhesion molecule)의 침묵화로 인한 것으로 여겨짐을 실증하였다(McGary 등 2002; Lee 등 2015; Scully 등 2012).
많은 종양 저산소증 연구는 저산소증 유도 인자(HIF; hypoxia inducible factor)의 전사 표적을 검사하는 데 중점을 두었다. HIF-α는 산소-조절 α 하위단위(HIF-1α 또는 HIF-2α)와 구성적으로 발현되는 β 하위단위(HIF-1β)로 구성된 헤테로이량체성 전사 인자이다(Ema 등 1997; Semeza and Wang, 1992). HIF-1α는 저산소증에 대한 적응을 매개하는 산소-반응성 전사 인자이다(Semenza, 2003; Dewhirst 등 2008; Poon 등 2009). 정상적인 산소 분압(oxygen tension)에서, HIF-α는 프롤릴-하이드록실라제 도메인(PHD)-함유 효소에 의해 2개의 프롤린 잔기 중 적어도 하나 상에서 하이드록실화된다(Ivan 등 2001; Jaakkola 등 2001). 그 후에, 하이드록실화된 HIF-α는 종양 억제자 폰 히펠 린다우 단백질(pVHL; von Hippel Lindau protein)에 의해 인지되고, 후속적으로 프로테아좀에 의한 분해를 위해 유비퀴틴화된다(Maxwell 등 1999; Ohh 등 2000). PHD가 이들의 효소적 활성에 산소를 필요로 하므로, 낮은 산소 농도 하에서, PHD-매개 하이드록실화는 저해되고, 그 후에 HIF-α는 핵으로 전좌하여, HIF-1β가 저산소증 반응 요소(HRE로서, 모티프 RCGTG에 의해 인지되며, 여기서 R은 A 또는 G임)에 결합하는 것을 통해 특이적인 표적 유전자 발현을 초래할 수 있다.
HIF-α는 Glut-1 및 VEGFA(refs)를 포함하는 저산소증 질환에 대한 적응을 허용하는 대사 유전자 및 혈관신생 유전자를 활성화시킨다. HIF-α는 또한, DEC1 및 DEC2와 같은 전사 억제자를 활성화시킴으로써 유전자 억제를 책임진다(Yun 등 2002; Chakrabarti 등 2004; Ivanov 등 2007). 일부 유전자가 이들 특이적인 억제자의 동원에 의해 전사적으로 하향제어되는 것으로 공지되어 있긴 하지만, 저산소증-매개 유전자 억제가 또한 이들 억제성 전사 인자와는 독립적으로 발생한다는 것이 점점 명백하다. 따라서, 모든 유전자가 HIF-α에 의해 제어되는 것은 아니며, 이는 일부 HIF-독립적 경로가 저산소증에서 유전자 발현을 조절하는 데 관여할 수 있음을 제안한다.
G9a 또는 진정염색질성(euchromatic) 히스톤-라이신 메틸트랜스퍼라제 2(EHMT2)는 히스톤 H3 라이신 9(H3K9)를 비변형된 상태로부터 디메틸화된 상태(H3K9me2)로 메틸화시킬 수 있는 더 큰 계통의 효소 중 하나이다. H3K9의 디메틸화는 유전자 억제와 연관이 있고, 후성적으로 침묵된 유전자의 마커로서 사용된다(Tachibana 등 2005). G9a는 몇 가지 종양 유형에서 빈번하게 과발현되고, 암세포에서 이의 결실(depletion)은 종양 성장 및 전이를 감소시키며, 이는 G9a가 종양원성(oncogenic) 및 전이성 잠재성에 참여함을 제안한다(Chen 등 2010; Dong 등 2012; Liu 등 2015; Zhong 등 2015; Hua 등 2014; Wozniak 등 2007). G9a 단백질 축적은 저산소증 질환에서 G9a 전사체의 수준을 변경시키지 않으면서 발생하는 것으로 제시되었다(Chen 등 2006). 그러나, G9a가 이의 환경에서 이의 활성을 발휘하는 기전은 잘 이해되지 않으며, 따라서 임상 진단에서 G9a 폴리펩타이드의 식별 및/또는 검출을 사용하는 능력은 가능하지 않았다.
본 발명은, 소정의 숙주 반응 말초 혈액 RNA 전사체(RNA 마커)가 특히 저산소증 질환에서 G9a에 의해 보편적으로, 특이적으로, 그리고 차별적으로 발현되고 제어된다는 결정으로부터 비롯된다. 이러한 RNA 전사체(바이오마커)는 질병 또는 질환의 조기 단계에서, 및 질병 또는 질환의 경로에 걸쳐 진단에 유용하다. 따라서, 이들 바이오마커는 G9a-관련 질병 또는 질환의 조기 진단, 진단, 모니터링, 예후, 및 중증도의 결정에 유용하다. 일례에서, 질병 또는 질환은 저산소증 질환과 관련있다. 특히, 저산소증에 대한 실증된 특이성을 기초로, 이러한 바이오마커는, 저산소증 질환에 의해 유발되었을 때 질병 또는 질환의 병인(etiology)을 결정하는 데 유용하다.
이러한 결정을 기초로, 본 발명자들은 차별적으로 발현된 바이오마커를 이의 비(파생된 바이오마커)를 포함하여 이용하여, G9a-관련 질병 또는 질환의 임상 징후를 제시하고 있는 대상체에서 G9a-관련 질병 또는 질환의 존재, 부재 또는 정도를 결정하는 다양한 방법, 장치, 조성물 및 키트를 개발하였다. 소정의 실시형태에서, 이들 방법, 장치, 조성물 및 키트는, 1) 일탈적인(aberrant) G9a와 관련없는 다른 질병 또는 질환(다른 암을 포함)으로부터 구별할 수 없었으며; 및/또는 2) 질병 또는 질환의 제시되는 임상 징후 및 병리에 대한 G9a 과발현(있다면)의 기여를 결정할 수 없었던 선행 기술의 과정 및 생성물을 능가하는 유의한 진전을 나타낸다.
이에, 본 발명은 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 가능성(likelihood)을 평가하는 데 사용되는 지표(indicator)를 결정하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및 (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 적어도 부분적으로 가리키는 것인 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
이들 저산소증 바이오마커에 대한 뉴클레오타이드 서열의 비제한적인 예는 서열번호 1-10에 열거되어 있다(표 5 참조). 이들 저산소증 바이오마커에 대한 아미노산 서열의 비제한적인 예는 서열번호 202-211에 열거되어 있다(표 6 참조). 예시적인 예에서, 개별적인 저산소증 바이오마커는: (a) 서열번호 1-10 중 임의의 하나에 표시된 서열, 또는 이의 보체와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 동일성을 공유하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (b) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (c) 서열번호 202-211에 표시된 서열 중 적어도 일부와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (d) 중간 또는 높은 엄격성 조건 하에, (a), (b), (c)의 서열 또는 이의 보체에 혼성화하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (e) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물; 및 (f) 서열번호 202-211 중 임의의 하나에 표시된 서열과 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물을 포함하는 군으로부터 선택된다.
본 발명의 또 다른 양태는 대상체에 존재하는 종양의 악성(malignancy)을 평가하는 데 사용되는 지표를 결정하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및 (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 종양의 악성을 적어도 부분적으로 가리키는 것인 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
이러한 방법의 하나의 이점은, 악성의 임상 징후가 관찰되기 전에 시료에서 저산소증 바이오마커가 검출될 수 있다는 점이다. 따라서, 본 발명은 종양 악성의 가능성의 조기 검출을 허용하며, 이는 일반적으로 대상체의 증가된 생존율과 연관이 있는 것으로 이해된다.
본 발명의 보다 다른 양태는 대상체에서 암 재발 가능성을 예측하는 데 사용되는 지표를 결정하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및 (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 암이 재발하는 가능성을 적어도 부분적으로 가리키는 것인 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
또 다른 양태에서, 본 발명은 대상체에서 저산소증을 감소시키는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및 (3) 지표가 대상체에서 저산소증의 존재의 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
추가의 양태에서, 본 발명은 대상체에서 저산소증 질환(예를 들어 저산소증 암)를 치료하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및 (3) 지표가 대상체에서 저산소증 질환의 존재의 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
본 발명의 보다 다른 양태는 대상체에서 저산소증 종양의 악성을 감소시키는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및 (3) 지표가, 종양이 저산소증이라는 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
또 다른 양태에서, 본 발명은 대상체에서 저산소증 종양을 치료하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및 (3) 지표가, 종양이 저산소증이라는 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
적합하게는, 시료는 생물학적 시료, 예를 들어 암 또는 종양 세포를 포함하는 생물학적 시료이다.
일부 실시형태에서, 대상체에게 보조 치료(ancillary treatment)가 투여된다. 예를 들어, 대상체에게 화학 요법 및/또는 방사선 요법 치료와 함께 G9a 길항제가 투여될 수 있다.
적어도 하나의 저산소증 바이오마커는 적합하게는, (a) 서열번호 1-10 중 임의의 하나에 표시된 서열, 또는 이의 보체와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 동일성을 공유하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (b) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (c) 서열번호 202-211에 표시된 서열 중 적어도 일부와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (d) 중간 또는 높은 엄격성 조건 하에, (a), (b), (c)의 서열 또는 이의 보체에 혼성화하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물; (e) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물; 및 (f) 서열번호 202-211 중 임의의 하나에 표시된 서열과 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물로 구성된 군으로부터 선택된다.
일부 실시형태에서, 바이오마커 값은 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커의 농도를 적어도 부분적으로 가리킨다. 동일한 실시형태 및 다른 실시형태 중 일부에서, 바이오마커 값은 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커의 유전자 발현의 수준을 적어도 부분적으로 가리킨다. 적합하게는, 바이오마커 값은 바이오마커의 풍부도(abundance)를 포함한다.
일부 실시형태에서, 적어도 하나의 저산소증 바이오마커의 수준은 정상적인(즉, 비-저산소증) 상태의 존재와 연관이 있는 바이오마커의 수준에 비해 감소되고, 이로써 지표가 저산소증을 적어도 부분적으로 가리키는 것으로 결정된다.
일부 실시형태에서, 적어도 하나의 저산소증 바이오마커의 수준은 정상적인(즉, 비-저산소증) 상태의 존재와 연관이 있는 바이오마커의 수준과 대략 동일하고, 지표가 정상산소증(normoxia)을 적어도 부분적으로 가리키는 것으로 결정된다.
일부 실시형태에서, 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 가능성을 평가하는 데 사용되는 지표를 결정하는 방법을 제공하며, 상기 방법은: (1) 대상체로부터 수득된 시료에서 적어도 하나의 그룹 1 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; (2) 그룹 2 저산소증 바이오마커에 대해 결정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 그룹 2 저산소증 바이오마커는 G9a인 단계; 및 (3) 바이오마커 값을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 적어도 부분적으로 가리키는 것인 단계를 포함한다. 적합하게는, 상기 방법은 조합 기능을 적어도 하나의 그룹 1 저산소증 바이오마커 값(들) 및 그룹 2 저산소증 바이오마커에 적용하는 단계를 추가로 포함한다.
일부 실시형태에서, 지표는 그룹 1 저산소증 바이오마커 및 그룹 2 저산소증 바이오마커 상에 기록된 바이오마커 값의 비(ratio)이다.
본원 상기 및 어디에서나 개시된 방법에서, 바이오마커 값(들)은 당업계에 공지된 임의의 적합한 기술을 사용하여 측정된다. 예를 들어, 적합한 측정은 현미경, 유세포분석, 면역검정법, 질량 분광법, 시퀀싱 플랫폼, 어레이 및 혼성화 플랫폼, 또는 이들의 조합을 사용하여 수행될 수 있다.
또 다른 양태에서, 본 발명은 저산소증 질환(예를 들어 저산소증 암)을 갖는 대상체의 가능성을 평가하는 데 사용되는 지표를 결정하기 위한 조성물을 제공한다. 이들 조성물은 일반적으로, 적어도 하나의 cDNA, 및 상기 cDNA에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하거나, 구성되거나, 본질적으로 구성되며, 여기서, 적어도 하나의 cDNA는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택된다. 적합하게는, 이러한 조성물은 세포 또는 세포 집단(population)으로부터 파생되는 mRNA에 상응하는 cDNA의 집단을 포함한다. 일부 실시형태에서, 세포는 저산소증 질환이 의심되는 세포, 적합하게는 암 또는 종양 세포이다. 일부 실시형태에서, 세포 집단은 혈액, 적합하게는 말초 혈액이다. 일부 실시형태에서, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 cDNA 중 개별적인 하나에 혼성화한다. 임의의 상기 실시형태에서, 조성물은 cDNA를 검출하기 위한 표지된 시약을 추가로 포함할 수 있다. 이러한 유형의 예시적인 예에서, 표지된 시약은 표지된 상기 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브이다. 다른 실시형태에서, 표지된 시약은 표지된 상기 cDNA이다. 적합하게는, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 고밀도 어레이 이외의 형태로 존재한다. 이들 실시형태의 비제한적인 예에서, 조성물은 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40 또는 50개 이하의 상이한 저산소증 바이오마커 cDNA를 검출하며 및/또는 정량화하기 위한 표지된 시약을 포함한다. 구체적인 실시형태에서, 조성물은 제각기의 cDNA에 대해, (1) cDNA의 반대쪽 상보 가닥에 혼성화하는 2개의 올리고뉴클레오타이드 프라이머(예를 들어 핵산 증폭 프라이머), 및 (2) cDNA에 혼성화하는 올리고뉴클레오타이드 프로브를 포함한다. 일부 실시형태에서, 올리고뉴클레오타이드 프라이머 중 하나 또는 둘 모두가 표지된다. 일부 실시형태에서, 올리고뉴클레오타이드 프로브가 표지된다. 예시적인 예에서, 올리고뉴클레오타이드 프라이머는 표지되지 않고, 올리고뉴클레오타이드 프로브는 표지된다. 적합하게는, 올리고뉴클레오타이드 프로브가 표지되는 실시형태에서, 표지된 올리고뉴클레오타이드 프로브는 형광단을 포함한다. 이러한 유형의 대표적인 예에서, 표지된 올리고뉴클레오타이드 프로브는 퀀처(quencher)를 추가로 포함한다. 소정의 실시형태에서, 상이한 표지된 올리고뉴클레오타이드 프로브는 상이한 cDNA에 혼성화하기 위한 조성물에 포함되며, 여기서, 개별적인 올리고뉴클레오타이드 프로브는 검출 가능하게 분명한 표지(예를 들어 상이한 형광단)를 포함한다.
보다 다른 양태에서, 본 발명은 적어도 하나의 cDNA, 및 상기 cDNA에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하거나, 구성되거나, 본질적으로 구성되는 복합체를 제공하며, 여기서, 적어도 하나의 cDNA는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택된다. 이들 조성물은 일반적으로, 적어도 하나의 쌍의 cDNA, 및 상기 cDNA 중 개별적인 하나에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하거나, 구성되거나, 본질적으로 구성된다. 적합하게는, 조성물은 세포 또는 세포 집단으로부터 파생되는 mRNA에 상응하는 cDNA의 집단을 포함한다. 일부 실시형태에서, 세포는 면역계의 세포, 적합하게는 백혈구이다. 일부 실시형태에서, 세포 집단은 혈액, 적합하게는 말초 혈액이다. 일부 실시형태에서, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 cDNA 중 개별적인 하나에 혼성화한다. 임의의 상기 실시형태에서, 조성물은 cDNA를 검출하기 위한 표지된 시약을 추가로 포함할 수 있다. 이러한 유형의 예시적인 예에서, 표지된 시약은 표지된 상기 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브이다. 다른 실시형태에서, 표지된 시약은 표지된 상기 cDNA이다. 적합하게는, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 고밀도 어레이 이외의 형태로 존재한다. 일부 실시형태에서, 세포는 암 또는 종양의 세포이다.
이들 실시형태 및 다른 실시형태의 다른 예에서, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 cDNA 중 개별적인 하나에 혼성화된다. 적합하게는, 조성물 또는 복합체는 cDNA를 검출하기 위한 표지된 시약을 추가로 포함한다. 예를 들어, 일부 실시형태에서, 표지된 시약은 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브이다. 일부 실시형태에서, 표지된 시약은 표지된 상기 cDNA이다. 동일한 실시형태 및 다른 실시형태 중 일부에서, 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브는 고밀도 어레이 이외의 형태로 존재한다.
보다 다른 양태에서, 본 발명은 대상체에서 저산소증의 가능성을 가리키는 지표를 결정하기 위한 키트를 제공하며, 상기 키트는 (a) 저산소증 바이오마커의 정량화를 허용하는 적어도 하나의 시약; 및 선택적으로 (b) 적어도 하나의 시약을 사용하기 위한 설명서를 포함한다.
도 1은 저산소증 질환에서 G9a 핵 축적의 사진 대표도이다. (a) 지시된 바와 같이 정상산소증 및 저산소증 질환에 노출된 MCF7 및 MDA-MB-231(MDA231) 유방암 세포로부터의 핵 추출물에서 G9a의 면역블로팅 분석이다. HIF-1a 수준을 저산소증 반응의 마커로서 사용하였고, 라민 A/C를 로딩 대조군으로서 사용하였다. (b) 정상산소증 및 저산소증 질환에 노출된 MCF7 세포로부터의 핵 추출물에서 GLP 및 Suv39h1의 면역블로팅 분석이다. (c) 지시된 바와 같이 저산소증 질환에 노출된 MCF7 세포로부터 단리된 RNA로부터 qRT-PCR에 의해 분석된 G9a 전사체 수준이다. 결과는 0시간째(정상산소증)와 비교하여 상대 mRNA 수준으로서 표현된다. (d) G9a 면역블로팅을, 20 μM 프로테아좀 저해제, MG132의 존재 또는 부재 시 9시간 동안 정상산소증 또는 저산소증 질환에 노출된 MCF7 세포로부터의 핵 추출물에 대해 수행하였다. (e 및 f) 지시된 바와 같이 정상산소증 또는 저산소증(e) 및 DMOG 처리(1 mM)(f)에 노출된 His 태깅된-유비퀴틴으로 형질감염된 MCF7 세포로부터의 단백질 추출물을 Ni2+-NTA 비드를 이용하여 풀-다운(pull-down)을 받게 하고, G9a에 대해 면역블로팅하였다. (g) G9a 면역블로팅을, 지시된 시간 동안 프롤릴 하이드록실라제 저해제(DMOG, 1 mM)로 처리한 MCF7 및 MDA231 세포로부터의 핵 추출물 상에서 수행하였다. (h) 100 μM 저산소증-모방제(mimicking agent), 데페록사민(DFA; Deferoxamine)의 존재 또는 부재 시 MCF7 및 MDA231 세포로부터의 G9a의 면역블로팅이다. 라민 A/C를 로딩 대조군으로서 사용하였다.
도 2는 저산소증 스트레스 하에 G9a 안정화의 기전의 사진 대표도이다. (a) MCF7 세포를 MG132(20 μM)의 존재 하에 지시된 발현 플라스미드를 이용하여 형질감염시키고, 항-Flag 항체를 사용하여 면역침전을 수행하고, 지시된 항체를 사용하여 면역블로팅하였다. (b) G9a 프롤린 하이드록실화를, MG132(20 μM)의 존재 하에 GFP-태깅된 PHD1, PHD2 또는 PHD3를 과발현하는 MCF7 세포에서 결정하였다. 항-하이드록시프롤린 항체를 사용하여 하이드록실화된 G9a의 면역침전을 수행하고, 뒤이어 항-Flag 항체를 이용하여 면역블로팅하였다. (c) MG132(20 μM)의 존재 하에 정상산소증or 저산소증에 노출된 Flag-태깅된 G9a를 과발현하는 MCF7 세포로부터의 항-하이드록시프롤린 항체를 이용한 프롤린 하이드록실화된 G9a의 면역침전이다. (d 및 e) G9a와 pVHL 사이의 상호작용을, 정상산소증 또는 저산소증 질환에서 지시된 발현 플라스미드를 이용하여 형질감염된 MCF7 세포로부터 결정하였고, 항-Flag 항체(d) 또는 DMOG로 처리되거나 또는 처리되지 않은 세포를 사용하여 면역침전을 수행하고, 항-HA(e)를 이용하여 면역침전시키고, 지시된 항체를 사용하여 면역블로팅시켰다. (f) RCC4 신세포암종 세포주 또는 지시된 바와 같이 정상산소증 및 저산소증 질환에 노출된 야생형 pVHL을 과발현하는 핵 추출물에서 G9a의 면역블로팅 분석이다. (g) 지시된 바와 같이 정상산소증 및 저산소증 질환에 노출된 G9a WT 및 P2A 돌연변이체를 이용하여 재구성된 G9a-/- MEF로부터의 핵 추출물에서 G9a의 면역블로팅 분석이다. (h) MG132(20 μM)의 존재 하에 정상산소증 및 저산소증에 노출된 Flag-태깅된 G9a WT 및 P2A 돌연변이체를 과발현하는 MCF7 세포로부터의 항-하이드록시프롤린 항체를 이용한 하이드록실화된 G9a의 면역침전이다.
도 3은 유방암 서브타입(subtype)에 걸쳐 저산소증 바이오마커 유전자의 발현 및 예견의 그래프 및 도식적 대표도를 보여준다. (a) shNS 및 shG9a를 발현하는 MCF7 세포로부터 저산소증-반응성 유전자의 배수 변화를 비교하는 차별적으로 발현되는 유전자의 계층적 클러스터링(hierarchical clustering)이다. 상향조절된 유전자 클러스터 및 하향조절된 유전자 클러스터를 제각기 적색 및 녹색으로 표시한다. (b) cDNA 마이크로어레이 분석 및 G9a-의존적 유전자 선택 과정의 전략을 보여주는 다이어그램이다. (c) 저산소증 바이오마커 유전자 서명; 마이크로어레이 분석으로부터 상대 발현을 표시하는 열-지도(heat-map)와 함께 도 4로부터 식별된 무재발(relapse-free) 생존율과 관련된 10개 유전자의 목록이다. (d) 10개의 G9a-억제된 유전자의 평균 발현을 유전자 서명으로서 무재발 생존율과의 관련성에 대해 분석하였다. 3개 데이터세트(KM 플로터(plotter), ROCK 및 TCGA) 각각에서 유방암 사례를 G9a-억제된 유전자 서명을 기초로 4개 사분위 중 하나에 할당하고, 이들 환자의 생존율을 비교하였다. 각각의 하위그룹에서 환자의 수를 괄호 안에 보여주고, 사분위 1 그룹(하부 25%)과 다른 그룹 사이의 생존율 비교에 대한 위험비(HR; hazard ratio) 및 로그-순위(log-rank) P 값을 또한, 각각의 패널에 보여준다. (g 및 h) 최저 발현(하부 25%, 사분위 1)을 갖는 종양과 나머지 종양 사이에서 유방암 환자의 무재발 생존율 분석을 KM 플로터 데이터베이스로부터 상이한 유방암 서브타입에서 G9a-억제된 유전자 서명을 사용하여 보여준다. ER-양성 및 ER-음성(e) 및 내강(Luminal) A, 내강 B, HER2-농화 및 기저-유사(Basal-like)(f).
도 4는 G9a-관련된 유전자의 식별의 도식적인 대표도이다. 마이크로어레이 분석으로부터의 저산소증 바이오마커 유전자 세트를 G9a 및 HIF 표적 유전자 발현과의 이의 역의 관계(inverse relationship)에 대해 여과하였다(제1 단계에서 좌측 원(circle)은 G9a에 역의 연관에 있는 유전자를 표시하고; 우측 원은 저산소증과 역의 연관에 있는 유전자를 표시함). 주목할 만하게는, 식별된 ER-양성 및 EF-음성 그룹 각각에서 44개의 유전자를 3개 데이터세트 사이에서 공통성(commonality)에 대해 분석하였다. ER-양성 및 ER-음성 그룹 각각에서 10개 유전자를 식별하였다. 조합된 20개 유전자 중에서, 14개의 별개의 유전자가 존재하였다(10개 유전자는 무재발 생존율과 관련있음).
도 5는 유전자 발현에서 G9a 저해의 분자 분석의 그래프 대표도이다. (a) UNC0642 처리 후 도 3으로부터 식별된 10개 저산소증 바이오마커 유전자의 정량적 RT-PCR 분석이다. 결과는 정상산소증(백색 박스) 또는 저산소증(검정색 박스) 조건 하에 비히클 처리와 비교하여 상대 mRNA 수준으로서 표현된다. (b) 정상산소증 또는 저산소증 질환에서 3 μM UNC0642로 처리된 MCF7 세포에서 AGTR1 및 ARNTL 프로모터 상에서 G9a, H3K9me2 및 Pol II의 ChIP 분석이다. (c) 정상산소증 및 저산소증에서 MCF7 세포에서 AGTR1 및 ARNTL 프로모터 상에서 shRNA-커플링된 ChIP 검정법이다. G9a, H3K9me2 및 RNA 중합효소 II에 의한 프로모터 점유율(occupancy)을 분석하였다. 값을 평균 ± SEM으로서 표현한다. 통계적 차이를 독립 표본 t-검정(unpaired t-test)에 의해 결정하였다(*P < 0.05, **P < 0.01), n = 3.
도 6은 G9a 및 G9a-의존적 유전자의 기능적 활성의 그래프 및 도식적 대표도를 보여준다. (a) 저산소증에서 shG9a MCF7 세포에서 변경된 상부 분자적 및 세포적 기능은 세포 발달, 성장 및 증식을 포함한다(p-값 범위: 세포-대-세포 신호전달 및 상호작용 = 8.10 x 10-3 내지 2.07 x 10-6; 세포 성장 및 증식 = 8.10 x 10-3 내지 2.70 x 10-6; 탄수화물 대사 = 8.10 x 10-3 내지 4.22 x 10-5; 세포 발달 = 8.10 x 10-3 내지 4.39 x 10-5; 세포 기능 및 유지 = 8.10 x 10-3 내지 4.91 x 10-5). (b) 인제뉴어티 경로 분석(Ingenuity Pathway Analysis)의 일부로서 기능 주석 네트워크 분석(functional annotation network analysis)은, 저산소증 바이오마커 유전자 서명에서 10개 유전자 중 7개 유전자의 하향조절이 유기체 사멸(P = 2.16 x 10-3)을 저해하는 것으로 예측됨을 드러내었다(즉, 저산소증 바이오마커 유전자 서명의 상향조절은 유기체 사멸을 촉진함). 적색 형상은 상향조절된 유전자를 표시하고, 녹색 형상은 하향조절된 유전자를 표시하고, 파선은 예측된 저해를 표시한다. (c) 제시된 바와 같은 다양한 유방 상피 세포로부터의 핵 추출물에서 G9a의 면역블로팅 분석이다. 히스톤 H3 수준을 로딩 대조군으로서 사용하였다. (d) 비히클(검정색 박스) 또는 G9a 저해제(5 μM에서 UNC0642; 투명한 박스) 처리 후, 도 6c에서 검사된 세포 상에서 MTT 검정법을 수행함으로써 세포 생존율을 분석하였다. (e) 지시된 바와 같이 다양한 농도의 UNC0642로 처리된 MCF7에 대한 IncuCyte ZOOM 타임-랩스 이미징 분석(time-lapse imaging analysis)이다. (d 및 e) 정상산소증에서 비히클 또는 G9a 저해제(UNC0642) 처리 후 MCF7 및 MDA231 세포 상에서 MTT 검정법을 수행함으로써 분석된 세포 생존율이다(투명한 원: 비히클; 회색 원: UNC0642 1 μM; 회색 삼각형: UNC0642 2 μM; 및 검정색 정사각형: UNC0642 3 μM).
도 7은 세포 운동성에 미치는 G9a의 영향의 사진 대표도이다. (a) 6시간 동안 비히클 또는 UNC0642 처리 후 MCF7 세포로부터의 핵 추출물에서 H3K9me2의 면역블로팅 분석이다. 라민 A/C 수준을 로딩 대조군으로서 사용하였다. (b) 정상산소증(21% O2) 조건과 저산소증(1% O2) 조건 둘 모두 하에, MCF7 세포에 대한 스크래치 상처 검정법(scratch wound assay)이다. 결과를 24시간마다 IncuCyte Zoom에 의해 수행된 실시간 이미징에 의해 평가하였다.
척도 막대(scale bar)는 700 μm, 10 X 배율에 상응한다. (c) G9a 저해제의 존재 또는 부재 하에 성장된 정상산소증(21% O2) 및 저산소증(1% O2) 조건에서 MDA231의 스크래치 상처 검정법이다. 척도 막대 700 μm, 10 X 배율. (d) 지시된 시간 동안 저산소증에서 shNS 또는 shG9a를 발현하는 MCF7 세포의 스크래치 상처 검정법으로부터의 현미경 사진이다. 척도 막대는 1000 μm, 4 X 배율에 상응한다.
도 8은 생체내에서 종양 성장에 미치는 G9a 저해 효과의 카툰 및 그래프 대표도이다. (a) 생체내 종양 성장 연구의 설계를 보여주는 다이어그램이다. (b) f B6 야생형(WT) 마우스(n = 6 내지 9) 그룹에게 제0일에 AT3 종양(1 x 106개 세포)을 피하 주사하였다. 종양-보유 마우스에게 2일마다 5 mg/kg UNC0642를 복강내 치료하였다. 종양 성장을 디지털 캘리퍼(digital caliper)를 사용하여 측정하고, 종양 부피를 평균 ± SEM으로서 표시한다. 비히클과 UNC0642-처리 마우스 사이에서 종양 부피에서 통계적 차이를 독립 표본 t-검정에 의해 결정하였다(* P < 0.05), n = 3. (c) 비히클 및 UNC0642-처리된 마우스에 대해 제시된 종점에서 종양 부피로서, 평균 ± SEM으로서 표시한다.
도 9는 식별된 저산소증 바이오마커를 사용하여 광범위한 저산소증 암의 진단 및 예후의 그래프 대표도이다. (a) 암 게놈 아틀라스(TCGA; The Cancer Genome Atlas)로부터의 신장 투명 세포 암종 환자를 사분위로 나누었으며, 이는 저산소증 바이오마커의 높은 발현을 갖는 환자가 더 양호한 생존율 결과와 관련있음을 보여준다. (b) 카플란 마이어(Kaplan Meyer) 플로터로부터의 폐 선암종 환자 데이터세트를 저(low) 그룹 및 고(high) 그룹으로 나누었으며, 이는 저산소증 바이오마커의 높은 발현을 갖는 환자가 더 양호한 생존율과 관련있음을 실증한다. (c) 흑색종에서 평가된 G9a의 예후값이다. 환자를 G9a 전사체의 발현을 기초로 사분위로 나누었으며(위험비 = 1.773; P = 0.0056), 이러한 사분위는 전체 생존율과 연관이 있다. (d) 환자를 G9a 전사체의 발현을 기초로 사분위로 나누었으며(위험비 = 2.532; P = 0.0106), 이러한 사분위는 전체 생존율과 연관이 있다. (e) 전이성 흑색종 환자의 결과의 G9a의 예후값이다. G9a 발현을 사용하여 계층화된 환자의 전체 생존율을 흑색종 환자와 전이 환자 사이에서 비교하였다. (g) 환자를 5-유전자 서브세트, 즉, ARNTL, CD1C, HHEX, KLRG1 및 MMP16의 평균 발현을 기초로 사분위로 나누었다. 환자의 전체 생존율은 흑색종에서 전체 생존율(OS) 및 무재발 생존율과 관련있다.
1. 정의
다르게 정의되지 않는 한, 본원에 사용되는 모든 기술적 및 과학적 용어는 본 발명이 속한 당업자에 의해 보편적으로 이해되는 것과 동일한 의미를 가진다. 본원에 기재된 것과 유사하거나 동등한 임의의 방법 및 물질이 본 발명의 실시 또는 시험에 사용될 수 있긴 하지만, 바람직한 방법 및 물질이 기재된다. 본 발명의 목적을 위해, 하기 용어가 아래에서 정의된다.
관사("a" 및 "an")는 관사의 문법적 목적어 중 1개, 또는 1개 초과(즉, 적어도 하나)를 지칭하기 위해 본원에 사용된다. 예로서, "일 요소"는 1개의 요소 또는 1개 초과의 요소를 의미한다.
본원에 사용된 바와 같이 용어 "약"은 이러한 기술 분야에서 당업자에게 쉽게 공지된 제각기의 값에 대한 통상적인 오차 범위를 지칭한다. 본원에서 "약" 값 또는 매개변수에 대한 지칭은 해당 값 또는 매개변수 자체에 관한 실시형태를 포함한다(그리고 기재함).
본원에 사용된 바와 같이, "및/또는"은 관련된 열거된 목록 중 하나 이상의 임의의 및 모든 가능한 조합, 뿐만 아니라 대안(또는)으로 해석될 때 조합의 결여를 지칭하고 포괄한다.
용어 "바이오마커"는 광범위하게는, 시료에 존재하거나 이로부터 파생된 임의의 검출 가능한 화합물, 예컨대 단백질, 펩타이드, 프로테오글리칸, 당단백질, 지질단백질, 탄수화물, 지질, 핵산(예를 들어 DNA, 예컨대 cDNA 또는 증폭된 DNA, 또는 RNA, 예컨대 mRNA), 유기 또는 무기 화학물질, 천연 또는 합성 중합체, 저분자(예를 들어 대사물), 또는 상기 중 임의의 구별 분자(discriminating molecule) 또는 구별 단편을 지칭한다. 이러한 맥락에서 사용된 바와 같이 "~로부터 파생된"은, 검출될 때 시료에 존재하고 있는 특정 분자를 가리키는 화합물을 지칭한다. 예를 들어, 특정 cDNA의 검출은 시료에서 특정 RNA 전사체의 존재를 가리킬 수 있다. 또 다른 예로서, 특정 항체의 검출 또는 특정 항체에의 결합은 시료에서 특정 항원(예를 들어 단백질)의 존재를 가리킬 수 있다. 본원에서, 구별 분자 또는 단편은, 검출되는 경우 상기-식별된 화합물의 존재 또는 풍부도를 가리키는 분자 또는 단편이다. 바이오마커는 예를 들어, 시료로부터 단리되거나, 시료에서 직접적으로 측정되거나, 시료에서 검출되거나 시료에 존재하는 것으로 결정될 수 있다. 바이오마커는 예를 들어, 기능적, 부분적으로 기능적, 또는 비-기능적일 수 있다. 구체적인 실시형태에서, "바이오마커"는 하기에서 보다 상세히 기재되는 "저산소증 바이오마커"를 포함한다.
용어 "바이오마커 값"은 대상체의 적어도 하나의 상응하는 바이오마커에 대해 측정되거나 파생된 값을 지칭하고, 전형적으로 대상체로부터 취해진 시료에서 바이오마커의 풍부도 또는 농도를 적어도 부분적으로 가리킨다. 따라서, 바이오마커 값은, 대상체에 대해 측정된 바이오마커 값인 측정된 바이오마커 값일 수 있을 것이거나, 대안적으로 예를 들어 하나 이상의 측정된 바이오마커 값에 함수를 적용함으로써 하나 이상의 측정된 바이오마커 값으로부터 파생된 값인 파생된 바이오마커 값일 수 있을 것이다. 바이오마커 값은, 이러한 값이 결정되는 방식에 따라 임의의 적절한 형태일 수 있다. 예를 들어, 바이오마커 값은 고-처리량 기술, 예컨대 질량 분광법, 시퀀싱 플랫폼, 어레이 및 혼성화 플랫폼, 면역검정법, 유세포분석, 또는 이러한 기술의 임의의 조합을 사용하여 결정될 수 있을 것이고, 하나의 바람직한 예에서, 바이오마커 값은 PCR, 시퀀싱 등과 같은 기술을 사용하여 정량화된, 발현 생성물 또는 다른 측정 가능한 분자의 활성 또는 풍부도의 수준에 관한 것이다. 이러한 경우, 바이오마커 값은 증폭 양 또는 사이클 횟수 형태로 존재할 수 있으며, 이들은 시료 내에서 바이오마커의 농도의 로드 표시(logarithmic representation)이며, 당업자에 의해 이해될 바와 같고 하기에서 보다 상세히 기재될 바와 같다.
용어 "바이오마커 프로파일"은 하나 또는 복수의 하나 이상의 유형의 바이오마커(예를 들어 mRNA 분자, cDNA 분자 및/또는 단백질 등), 또는 이의 징조(indication)를 바이오마커(들)의 특징, 예컨대 측정 가능한 양태(예를 들어 바이오마커 값)와 함께 지칭한다. 바이오마커 프로파일은 단일 바이오마커를 포함할 수 있으며, 이의 수준, 풍부도 또는 양은 질환(예를 들어 저산소증 또는 정상산소증)의 존재 또는 부재와 연관이 있다. 대안적으로, 바이오마커 프로파일은 적어도 2개의 이러한 바이오마커 또는 이들의 징조를 포함할 수 있으며, 여기서, 바이오마커는 동일하거나 상이한 부류, 예컨대 핵산 및 폴리펩타이드에 존재할 수 있다. 따라서, 바이오마커 프로파일은 적어도 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 또는 100개 이상의 바이오마커 또는 이의 징조를 포함할 수 있다. 일부 실시형태에서, 바이오마커 프로파일은 수백, 또는 심지어 수천 개의 바이오마커 또는 이의 징조를 포함한다. 바이오마커 프로파일은 하나 이상의 대조군 또는 내부 표준을 추가로 포함할 수 있다. 소정의 실시형태에서, 바이오마커 프로파일은 적어도 하나의 바이오마커 또는 이의 징조를 포함하며, 이들은 내부 표준으로서의 역할을 한다. 다른 실시형태에서, 바이오마커 프로파일은 하나 이상의 유형의 바이오마커의 징조를 포함한다. 이러한 맥락에서 본원에 사용된 바와 같이 용어 "징조"는 단순히, 바이오마커 프로파일이 바이오마커 분자 엔터티(entity) 자체보다는 바이오마커에 대한 부호, 데이터, 약어 또는 다른 유사한 표시(indicia)를 함유하는 상황을 지칭한다. 용어 "바이오마커 프로파일"은 또한 본원에서, 바이오마커 값 또는 적어도 2개의 바이오마커 값들의 조합을 지칭하는 데 사용되며, 여기서, 개별적인 바이오마커 값은 하나 이상의 대상체로부터 측정되거나 파생될 수 있는 바이오마커 값에 상응하며, 이러한 조합은 별개의 질환, 질환 단계, 질환의 서브타입, 또는 별개의 질환, 질환 단계, 질환의 서브타입에 대한 예후를 특징으로 한다. 용어 "프로파일 바이오마커"는, 예컨대 특이적인 질환, 질환의 상이한 단계 또는 중증도, 상이한 질환의 서브타입 또는 상이한 예후를 용인하거나(rule in) 또는 배제하기 위해 임상 평가를 수행하는 데 사용될 수 있는 바이오마커 프로파일에 사용하기 위해 식별되었던 바이오마커의 서브세트를 지칭하는 데 사용된다. 프로파일 바이오마커의 수는 다양할 것이지만, 전형적으로 약 10 이하이다.
용어 "상보적인" 및 "상보성"은 염기-짝짓기 규칙에 의해 관련된 폴리뉴클레오타이드(즉, 뉴클레오타이드의 서열)를 지칭한다. 예를 들어, 서열 "A-G-T"는 서열 "T-C-A"와 상보적이다. 상보성은, 핵산 염기 중 일부만 염기-짝짓기 규칙에 따라 매칭되어 "부분적"일 수 있다. 또는, 핵산 사이에 "완전한" 또는 "총" 상보성이 존재할 수 있다. 핵산 가닥 사이에서 상보성 정도는 핵산 가닥 사이에서 혼성화의 효율 및 강도에 유의한 효과를 가진다.
본 명세서 전체를 통해, 문맥상 다르게 필요하지 않는 한, 단어 "포함하다", "포함한다" 및 "포함하는"은 언급된 단계나 요소 또는 단계나 요소의 그룹의 포함을 내포하는 것으로 이해될 것이지만, 임의의 다른 단계나 요소 또는 단계나 요소의 그룹을 배제하는 것은 아니다. 따라서, 용어 "포함하는" 등의 사용은, 열거된 요소가 필요해지거나 의무적이지만, 다른 요소가 선택적이고 존재할 수 있거나 존재하지 않을 수 있음을 가리킨다. "~로 구성되는"이란, 어구 "~로 구성되는" 뒤에 무엇이 오든 간에 이를 포함하고 이로 제한됨을 의미한다. 따라서, 어구 "~로 구성되는"은, 열거된 요소가 필요해지거나 의무적이고, 다른 어떠한 요소도 존재하지 않을 수 있음을 가리킨다. "~로 본질적으로 구성되는"이란, 어구 뒤에 열거된 임의의 요소를 포함함을 의미하고, 열거된 요소에 대한 개시내용에 명시된 활성 또는 작용을 방해하거나 기여하지 않는 다른 요소로 제한된다. 따라서, 어구 "~로 본질적으로 구성되는"은, 열거된 요소가 필요해지거나 수동적이지만, 다른 요소가 선택적이고, 이들이 열거된 요소의 활성 또는 작용에 영향을 미치거나 미치지 않는가에 따라 존재할 수 있거나 존재하지 않을 수 있음을 가리킨다.
용어 "연관이 있는"은, 하나의 유형의 데이터와 또 다른 데이터 또는 상태 사이의 관계를 결정하는 것을 지칭한다.
본원에 사용된 바와 같이, 용어 "검출 가능하게 별개의" 및 "검출 가능하게 상이한"은 본원에서 상호교환적으로, 관찰에 의해 또는 계측(instrumentation)에 의해 물리적 특성에 의해 구별 가능하거나 분리 가능한 신호를 지칭하는 데 사용된다. 예를 들어 형광단은, 시료 내 또 다른 형광단으로부터, 뿐만 아니라 선택적으로 존재하는 부가적인 물질로부터 스펙트럼 특징에 의해 또는 형광 강도, 수명, 편광(polarization) 또는 광표백율(photo-bleaching rate)에 의해 쉽게 구별 가능하다. 소정의 실시형태에서, 용어 "검출 가능하게 별개의" 및 "검출 가능하게 상이한"은 동시에 검출되고 구별될 수 있는 표지(예컨대 염료, 적합하게는 유기 염료) 세트를 지칭한다.
본원에 사용된 바와 같이, 용어 "진단", "진단하는" 등은 본원에서 상호교환적으로, 대상체가 이러한 대상체에서 질환, 또는 질환의 존재나 성질을 발병시킬 가능성을 결정하는 것을 포괄하는 데 사용된다. 이들 용어는 또한, 질병의 중증도 또는 질병의 에피소드를 뿐만 아니라 논리 요법(rational therapy)의 맥락에서 결정하는 것을 포괄하며, 여기서, 진단은 요법의 초기 선택, 요법의 변형(예를 들어 용량 또는 투여량 계획의 조정) 등을 포함하여 요법을 가이드한다. "가능성"이란, 특정하게 측정되거나 파생된 바이오마커 값을 갖는 대상체가 사실상, 주어진 수학적 모델을 기초로 질환을 가질 것인지(또는 갖지 않을 것인지)의 측정을 의미한다. 예를 들어, 증가된 가능성은 상대적 또는 절대적일 수 있고, 정성적으로 또는 정량적으로 표현될 수 있다. 예를 들어, 증가된 가능성은 단순히, 적어도 2개의 저산소증 바이오마커에 대한 대상체의 측정되거나 파생된 바이오마커 값을 결정하고, 상기 대상체를 이전의 집단 연구를 기초로 "증가된 가능성" 범주에 놓음으로써 결정될 수 있다. 용어 "가능성"은 또한, 본원에서 용어 "확률"과 상호교환적으로 사용된다. 용어 "위험율"은 향후 일부 시점에서 발생하는 특정 사건의 가능성 또는 확률에 관한 것이다. "위험율 계층화"는 의사가 환자를 특정 질병 또는 질환이 발병할 낮은, 중간, 높은 또는 가장 높은 위험율로 분류할 수 있도록 공지된 임상적 위험 인자의 어레이화(arraying)를 지칭한다.
본원에 사용된 바와 같이 "형광단"은 정의된 여기 파장에서 광 에너지를 흡수하고 상이한 정의된 파장에서 광 에너지를 방출하는 모이어티를 지칭한다. 형광 표지의 예로는: Alexa Fluor 염료(Alexa Fluor 350, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660 및 Alexa Fluor 680), AMCA, AMCA-S, BODIPY 염료(BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY TR, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591, BODIPY 630/650, BODIPY 650/665), 카르복시로다민 6G, 카르복시-X-로다민(ROX), 캐스케이드 블루(Cascade Blue), 캐스케이드 옐로우(Cascade Yellow), 시아닌 염료(Cy3, Cy5, Cy3.5, Cy5.5), 단실(Dansyl), 다폭실(Dapoxyl), 디알킬아미노쿠마린, 4',5'-디클로로-2',7'-디메톡시-플루오레세인, DM-NERF, 에오신, 에리트로신, 플루오레세인, FAM, 하이드록시쿠마린, IR염료(IRD40, IRD 700, IRD 800), JOE, 리싸민(Lissamine) 로다민 B, 마리나 블루(Marina Blue), 메톡시쿠마린, 나프토플루오레세인, 오레곤 그린(Oregon Green) 488, 오레곤 그린 500, 오레곤 그린 514, 퍼시픽 블루(Pacific Blue), PyMPO, 피렌, 로다민 6G, 로다민 그린, 로다민 레드, 로돌 그린(Rhodol Green), 2',4',5',7'-테트라-브로모설폰-플루오레세인, 테트라메틸-로다민(TMR), 카르복시테트라메틸로다민(TAMRA), 텍사스 레드 및 텍사스 레드-X가 있다.
본원에 사용된 바와 같이 용어 "유전자"는 기능을 갖는 폴리펩타이드 또는 RNA 사슬을 코딩하는 핵산의 스트레치(stretch)를 지칭한다. 이것이 mRNA로 전사되는 유전자의 엑손 영역이긴 하지만, 용어 "유전자"는 또한, 엑손 영역의 발현을 지배하는 프로모터 및 인핸서와 같은 조절 영역을 포함한다.
용어 "고밀도 어레이"는 복수의 어레이 요소(예를 들어 이에 부동화된(immobilized) 특정 모이어티, 예를 들어 단백질(예를 들어 항체), 핵산(예를 들어 올리고뉴클레오타이드 프로브) 등을 갖는 별개의 영역)를 갖는 기판, 또는 기판이나 표면의 집합(collection)을 지칭하며, 여기서, 어레이 요소는 약 100 요소/cm2 이상, 약 1,000 요소/cm2 이상, 약 10,000 요소/cm2 이상, 또는 약 100,000 요소/cm2 이상의 밀도로 존재한다. 구체적인 실시형태에서, "고밀도 어레이"는, 약 100개 이상의 상이한 바이오마커, 약 1,000개 이상의 상이한 바이오마커, 약 10,000개 이상의 상이한 바이오마커, 또는 약 100,000개 이상의 상이한 바이오마커를 검출하기 위한 복수의 어레이 요소를 포함하는 것이다. 이들 실시형태의 대표적인 예에서, "고밀도 어레이"는 약 100개 이상의 상이한 유전자, 약 1,000개 이상의 상이한 유전자, 약 10,000개 이상의 상이한 유전자, 또는 약 100,000개 이상의 상이한 유전자의 바이오마커를 검출하기 위한 복수의 어레이 요소를 포함하는 것이다. 일반적으로, 고밀도 어레이의 요소는 표지되지 않는다. 용어 "저밀도 어레이"는 복수의 어레이 요소(예를 들어 이에 부동화된 특정 모이어티, 예를 들어 단백질(예를 들어 항체), 핵산(예를 들어 올리고뉴클레오타이드 프로브) 등을 갖는 별개의 영역)를 갖는 기판, 또는 기판이나 표면의 집합을 지칭하며, 여기서, 어레이 요소는 약 100 요소/cm2 이하, 약 50 요소/cm2 이하, 약 20 요소/cm2 이하, 또는 약 10 요소/cm2 이하의 밀도로 존재한다. 구체적인 실시형태에서, "저밀도 어레이"는, 약 100개 이하의 상이한 바이오마커, 약 50개 이하의 상이한 바이오마커, 약 20개 이하의 상이한 바이오마커, 또는 약 10개 이하의 상이한 바이오마커를 검출하기 위한 복수의 어레이 요소를 포함하는 것이다. 이들 실시형태의 대표적인 예에서, "저밀도 어레이"는, 약 100개 이하의 상이한 유전자, 약 50개 이하의 상이한 유전자, 약 20개 이하의 상이한 유전자, 또는 약 10개 이하의 상이한 유전자의 바이오마커를 검출하기 위한 복수의 어레이 요소를 포함하는 것이다. 일반적으로, 저밀도 어레이의 요소는 표지되지 않는다.
본원에 사용된 바와 같이, 용어 "저산소증"은, 조직 세포의 산소 분압이 정상 조직의 산소 분압과 비교하여 비정상적으로 낮은 환경을 지칭한다. 이러한 환경은 조직이 손상되거나 혈액이 유동할 때 발생할 수 있다. 저산소증은 흔히, 암, 허혈성 뇌졸중(ischemic stroke) 및 관절염을 포함하여 난치병에서 보인다. 암의 경우, 암조직이 성장함에 따라, 고형암의 내부가 혈관으로부터 산소를 받지 못하기 때문에 저산소증 환경에 맞닥뜨리게 된다. 시험관내 세포 배양 조건에서, 저산소증은 최대 약 5% O2를 갖는 환경, 바람직하게는 약 1% O2를 갖는 환경을 지칭할 수 있다. 대조적으로, 용어 "정상산소증"은 건강한 조직에 상응하는 산소 분압을 갖는 환경을 지칭한다. 시험관내 세포 배양 조건에서, 정상산소증은 약 10% 내지 약 21% 범위의 O2 농도를 갖는 조건을 지칭할 수 있다. 구체적인 실시형태에서, 정상산소증 조건의 O2 농도는 약 15%, 16%, 17%, 18%, 19%, 20% 또는 21%이다. 보다 더 구체적인 실시형태에서, O2 농도는 약 20% 내지 21%이다.
본원에 사용된 바와 같이 용어 "지표"는 당업자가, 대상체가 주어진 질병 또는 질환을 앓고 있는지 또는 아닌지의 가능성 또는 위험율을 추정하고/하거나 결정할 수 있는 임의의 정보, 수, 비, 신호, 징후, 마크 또는 기록(note)을 포함하여 결과 또는 결과의 표시를 지칭한다. 본 발명의 경우, "지표"는 선택적으로, 대상체에서 저산소증 질환 또는 G9a-관련 질병이나 질환의 진단(즉, 발생 또는 불발(nonoccurrence))에 이르는 다른 임상 특징과 함께 사용될 수 있다. 이러한 지표가 "결정된다"는 것은, 상기 지표가 100% 정확하다는 것을 내포하는 것은 아니다. 당업자는 진단에 이르는 다른 임상 표시와 함께 지표를 사용할 수 있다.
용어 "부동화된"은, 관심 분자 화학종이 고형 지지체에 적합하게는 공유 연결에 의해 고정되는 것을 의미한다. 이러한 공유 연결은 분자 화학종의 분자적 성질에 따라 상이한 수단에 의해 달성될 수 있다. 더욱이, 분자 화학종은 또한, 정전기력, 소수성 또는 친수성 상호작용, 또는 반데르발스 힘에 의해 고형 지지체 상에 고정될 수 있다. 상기 기재된 물리화학적 상호작용은 전형적으로, 분자 사이의 상호작용에서 발생한다. 특정 실시형태에서, 필요해지는 모든 것은, 분자(예를 들어 핵산 또는 폴리펩타이드)가, 지지체를 사용하고자 하는 조건 하에, 예를 들어 핵산 증폭 및/또는 시퀀싱을 필요로 하는 적용 또는 항체-결합 검정법에서 상기 지지체에 부동화되거나 부착된 채로 남아 있다는 것이다. 예를 들어, 올리고뉴클레오타이드 또는 프라이머는, 3' 말단이 효소적 연장(enzymatic extension)에 이용 가능하며 및/또는 서열 중 적어도 일부가 상보 서열에 혼성화할 수 있도록 부동화된다. 일부 실시형태에서, 부동화는 표면 부착된 프라미어로의 혼성화를 통해 발생할 수 있으며, 이러한 경우, 부동화된 프라이머 또는 올리고뉴클레오타이드는 3'-5' 배향으로 존재할 수 있다. 다른 실시형태에서, 부동화는 염기-짝짓기 혼성화 이외의 수단, 예컨대 공유 부착에 의해 발생할 수 있다.
본원에 사용된 바와 같이, 용어 "표지" 및 이의 문법적 등가물은, 검출 가능하고/하거나 정량화 가능한 신호를 제공하기 위해 사용될 수 있는 임의의 원자 또는 분자를 지칭한다. 특히, 표지는 핵산 또는 단백질에 직접적으로 또는 간접적으로 부착될 수 있다. 부착될 수 있는 적합한 표지로는, 방사성 동위원소, 형광단, 퀀처, 발색단, 매스 표지(mass label), 전자 밀집 입자(electron dense particle), 자기 입자, 스핀 표지, 화학발광을 방출하는 분자, 전기화학적 활성 분자, 효소, 공동 인자(cofactor) 및 효소 기질이 있으나, 이들로 한정되는 것은 아니다. 표지는 효소와 반응할 때 시각적으로 검출 가능한 신호를 생성시킬 수 있는 원자 또는 분자를 포함할 수 있다. 일부 실시형태에서, 표지는 보조 시약의 첨가 없이 검출 가능한 신호를 자발적으로 생성시킬 수 있고 장비의 도움 없이 시각적 수단에 의해 검출되는 "직접" 표지이다. 예를 들어, 콜로이드 금 입자(colloidal gold particle)가 표지로서 사용될 수 있다. 많은 표지가 당업자에게 잘 공지되어 있다. 구체적인 실시형태에서, 표지는 천연-발생 뉴클레오사이드 이외의 것이다. 용어 "표지"는 또한, 화학적 조작을 통해 분자에 인위적으로 첨가되거나, 연결되거나 부착된 작용제를 지칭한다.
바이오마커의 "수준" 또는 "양"은 시료에서 검출 가능한 수준 또는 양이다. 이들은 당업자에게 공지되고 본원에 또한 개시된 방법에 의해 측정될 수 있다. 이들 용어는 정량적인 양 또는 수준(예를 들어 중량 또는 몰수(mole)), 반정량적인(semi-quantitative) 양 또는 수준, 상대 양 또는 수준(예를 들어 부류 내에서 중량% 또는 몰%), 농도 등을 포괄한다. 따라서, 이들 용어는 시료에서 바이오마커의 절대 또는 상대 양, 수준 또는 농도를 포괄한다. 평가되는 바이오마커의 발현 수준 또는 양은 치료에 대한 반응을 결정하는 데 사용될 수 있다. 바이오마커의 수준이 참조 또는 대조군에 비해 "감소되는" 구체적인 실시형태에서, 감소된 수준은, 본원에 기재된 것들과 같이 당업계에 공지된 표준 방법에 의해 검출되는 바이오마커(예를 들어 단백질 또는 핵산(예를 들어 유전자 또는 mRNA))의 수준에서 참조 시료, 참조 세포, 참조 조직, 대조군 시료, 대조군 세포 또는 대조군 조직과 비교하여, 임의의 적어도 약 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% 이상의 전체 감소를 지칭할 수 있다. 소정의 실시형태에서, 감소된 수준은 시료에서 바이오마커의 수준/양에서의 저하를 지칭하며, 여기서, 저하는 참조 시료, 참조 세포, 참조 조직, 대조군 시료, 대조군 세포 또는 대조군 조직에서 제각기의 바이오마커의 임의의 적어도 약 0.9x, 0.8x, 0.7x, 0.6x, 0.5x, 0.4x, 0.3x, 0.2x, 0.1x, 0.05x 또는 0.01x의 수준/양이다. 바이오마커의 수준이 참조 또는 대조군과 "대략 동일한" 소정의 실시형태에서, 바이오마커의 수준은, 참조 시료, 참조 세포, 참조 조직, 대조군 시료, 대조군 세포 또는 대조군 조직에서 본원에 기재된 것들과 같이 당업계에 공지된 표준 방법에 의해 검출되는 바이오마커(예를 들어 단백질 또는 핵산(예를 들어 유전자 또는 mRNA))의 수준과 비교하여, 약 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1% 미만만큼, 또는 심지어 그보다 적게 달라진다.
용어 "마이크로어레이"는 기질 상에서 혼성화 가능한 어레이 요소, 예를 들어 프로브(프라이머 포함), 리간드, 바이오마커 핵산 서열 또는 단백질 서열의 배열을 지칭한다.
본원에 사용된 바와 같이 용어 "핵산" 또는 "폴리뉴클레오타이드"는 RNA, mRNA, miRNA, cRNA, cDNA mtDNA 또는 DNA를 포함한다. 상기 용어는 전형적으로, 적어도 10개 염기 길이의 뉴클레오타이드, 리보뉴클레오타이드 또는 데옥시뉴클레오타이드, 또는 둘 중 어느 유형의 뉴클레오타이드의 변형된 형태의 중합체 형태를 지칭한다. 상기 용어는 단일 및 이중 가닥 형태의 DNA 또는 RNA를 포함한다.
"수득된"이란, 보유하게 되는 것을 의미한다. 이렇게 해서 수득된 시료는 예를 들어, 특정 공급원으로부터 단리되거나 파생된 핵산 추출물 또는 폴리펩타이드 추출물을 포함한다. 예를 들어, 추출물은 대상체의 생물학적 유체 또는 조직으로부터 직접적으로 수득될 수 있다.
본원에 사용된 바와 같이, 용어 "양성 반응"은, 치료 계획의 결과가 일부 임상적으로 유의한 이득, 예컨대 질환의 예방, 중증도 또는 증상의 감소, 진행의 서행을 포함함을 의미한다. 대조적으로, 용어 "음성 반응"은, 치료 계획이 임상적으로 유의한 이득, 예컨대 질환의 예방, 또는 중증도 또는 증상의 감소를 제공하거나 질환의 진행 속도를 증가시킴을 의미한다.
"단백질", "폴리펩타이드" 및 "펩타이드"는 아미노산 잔기의 중합체 및 이의 변이체와 합성 유사체를 지칭하기 위해 본원에서 상호교환적으로 사용된다.
"프라이머"란, DNA 가닥과 짝을 지을 때, 적합한 중합제의 존재 하에 프라이머 연장 생성물의 합성을 개시할 수 있는 올리고뉴클레오타이드를 의미한다. 프라이머는 바람직하게는 증폭에서의 최대 효율을 위해 단일-가닥이지만, 대안적으로 이중-가닥일 수 있다. 프라이머는 중합제의 존재 하에 연장 생성물의 합성을 프라이밍(prime)하기에 충분할 정도로 길어야 한다. 프라이머의 길이는 적용, 이용되는 온도, 주형 반응 조건, 다른 시약, 및 프라이머의 공급원을 포함하여 많은 인자에 의존한다. 예를 들어, 표적 서열의 복잡성에 따라, 프라이머는, 핵산 사슬의 연장을 허용하기 위해 프라이머의 3' 말단에서 적어도 약 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 50, 75, 100, 150, 200, 300, 400, 500, 내지 주형 서열보다 길이가 1개 염기 더 짧을 수 있지만, 프라이머의 5' 말단은 주형 서열의 3' 말단을 지난 길이로 연장될 수 있다. 소정의 실시형태에서, 프라이머는 대형(large), 예컨대 약 35개 뉴클레오타이드 내지 수 킬로베이스(kilobase)의 폴리뉴클레오타이드일 수 있다. 프라이머는, 상기 프라이머가 혼성화하고 합성 개시 부위로서 역할을 하도록 설계된 주형 상의 서열에 "실질적으로 상보적"이도록 선택될 수 있다. "실질적으로 상보적"이란, 프라이머가 표적 폴리뉴클레오타이드와 혼성화하기에 충분히 상보적임을 의미한다. 바람직하게는, 프라이머는, 상기 프라이머가 혼성화하지만 이것이 본질적이지는 않은 주형과 어떠한 미스매치도 함유하지 않는다. 예를 들어, 비-상보적 뉴클레오타이드 잔기는 프라이머의 5' 말단에 부착될 수 있으며, 이때 프라이머 서열의 나머지는 주형에 상보적이다. 대안적으로, 비-상보적 뉴클레오타이드 또는 비-상보적 뉴클레오타이드 잔기의 스트레치는 프라이머 내로 산재될(interspersed) 수 있되, 단, 프라이머 서열은, 이것과 혼성화하고 이로써 프라이머의 연장 생성물의 합성을 위한 주형을 형성하기 위해 상기 주형의 서열과 충분한 상보성을 가진다.
본원에 사용된 바와 같이, 용어 "프로브"는 또 다른 분자의 특이적인 서열이나 하위-서열 또는 다른 모이어티에 결합하는 분자를 지칭한다. 다르게 지시되지 않는 한, 용어 "프로브"는 전형적으로, 본원에서 "표적 폴리뉴클레오타이드"로도 지칭되는 또 다른 핵산에 상보성 염기-짝짓기를 통해 결합하는 핵산 프로브를 지칭한다. 프로브는 혼성화 조건의 엄격성에 따라 상기 프로브와의 완전한 서열 상보성이 결여된 표적 폴리뉴클레오타이드에 결합할 수 있다. 프로브는 직접적으로 또는 간접적으로 표지될 수 있고, 이들의 범위 내에 프라이머를 포함한다.
본원에 사용된 바와 같이 용어 "예후"는 임상 질환 또는 질병의 가능한 경과 및 결과의 예측을 지칭한다. 예후는 보통, 질병의 선호할 만한 또는 선호할 만하지 않은 경과 또는 결과를 가리키는 질병의 인자 또는 증상을 평가함으로써 이루어진다. 당업자는, 용어 "예후"가, 소정의 경과 또는 결과가 발생할 증가된 확률을 지칭하며; 즉, 질환을 나타내지 않는 개체와 비교할 때, 주어진 질환을 나타내는 대상체에서 경과 또는 결과가 발생할 가능성이 더 크다는 것을 이해할 것이다.
본원에 사용된 바와 같이, 용어 "퀀처"는 공여자(donor) 형광단에 근접해 있는 임의의 모이어티를 포함하며, 공여자 형광단에 의해 발생되는 방출 에너지를 흡수하고, 상기 에너지를 열로서 소산시키거나 공여자 형광단의 방출 파장보다 긴 파장의 광을 방출한다. 후자의 경우, 퀀처는 수여자(acceptor) 형광단인 것으로 여겨진다. 퀀칭 모이어티는 근접(즉, 충돌(collisional)) 퀀칭을 통해, 또는 포스터(Forster) 또는 형광 공명 에너지 전달("FRET"; fluorescence resonance energy transfer)에 의해 작용할 수 있다. FRET에 의한 퀀칭은 일반적으로, TAQMAN® 프로브에서 사용되는 한편, 근접 퀀칭은 분자 비콘(molecular beacon) 및 스콜피온® 유형 프로브에서 사용된다. 적합한 퀀처는 특정 형광단의 형광 스펙트럼을 기초로 선택된다. 유용한 퀀처로는 예를 들어, BLACK HOLE™ 퀀처 BHQ-1, BHQ-2 및 BHQ-3(Biosearch Technologies, Inc.) 및 ATTO-시리즈의 퀀처(ATTO 540Q, ATTO 580Q, 및 ATTO 612Q; Atto-Tec GmbH)가 있다.
본원에 사용된 바와 같이 용어 "시료"는 대상체로부터 추출되거나, 미처리되거나, 처리되거나, 희석되거나 농축될 수 있는 임의의 생물학적 표본을 포함한다. 시료는 비제한적으로, 생물학적 유체, 예컨대 전혈, 혈청, 적혈구, 백혈구, 혈장, 침, 소변, 대변(즉, 변), 눈물, 땀, 피지, 젖꼭지 흡인물(nipple aspirate), 유관 세정물(ductal lavage), 종양 삼출물, 관절 낭액(synovial fluid), 복수(ascitic fluid), 복막액, 양수, 뇌척수액, 림프, 미세침 흡인물(fine needle aspirate), 양수, 임의의 다른 체액, 세포 용해물, 세포 분비 생성물, 염증액, 정액 및 질 분비물을 포함할 수 있다. 시료는 조직 시료 및 생검, 조직 균질물 등을 포함할 수 있다. 유리한 시료는 본원에 교시된 바와 같은 임의의 하나 이상의 바이오마커를 검출 가능한 양으로 포함하는 것을 포함할 수 있다. 적합하게는, 시료는 대상체로부터 시료의 제거 또는 단리를 허용하는 최소 침습적 방법에 의해 쉽게 수득 가능하다. 전형적으로, 시료는 혈액 세포, 예컨대 성숙, 미성숙 또는 발달중인 백혈구, 예컨대 림프구, 다형핵 백혈구, 중성구, 단핵구, 망상 적혈구, 호염기구, 체강소체(coelomocyte), 혈구(hemocyte), 호산구, 거핵구(megakaryocyte), 대식세포, 수지상 세포, 자연 살해 세포, 또는 이러한 세포의 분획(예를 들어 핵산 또는 단백질 분획)을 포함한다. 구체적인 실시형태에서, 시료는 암 또는 종양 세포를 포함한다.
본원에 사용된 바와 같이 용어 "고형 지지체"는, 분자 화학종, 예컨대 핵산 및 폴리펩타이드가 부동화될 수 있는 고형 불활성 표면 또는 본체(body)를 지칭한다. 고형 지지체의 비제한적인 예는 유리 표면, 플라스틱 표면, 라텍스, 덱스트란, 폴리스티렌 표면, 폴리프로필렌 표면, 폴리아크릴아미드 겔, 금 표면 및 실리콘 웨이퍼를 포함한다. 일부 실시형태에서, 고형 지지체는 막, 칩 또는 입자 형태로 존재한다. 예를 들어, 고형 지지체는 유리 표면(예를 들어 유동 세포 채널의 평면형(planar) 표면)일 수 있다. 일부 실시형태에서, 고형 지지체는, 예컨대 분자, 예컨대 폴리뉴클레오타이드로의 공유 부착을 허용하는 반응성 기를 포함하는 중간 물질의 층 또는 코팅을 적용함으로써 "작용화"된 불활성 기판 또는 매트릭스를 포함할 수 있다. 비제한적인 예로서, 이러한 지지체는 불활성 기판, 예컨대 유리 상에 지지된 폴리아크릴아미드 하이드로겔을 포함할 수 있다. 분자(예를 들어 폴리뉴클레오타이드)는 중간 물질(예를 들어 하이드로겔)에 직접적으로 공유 부착될 수 있으나, 중간 물질 그 자체는 기판 또는 매트릭스(예를 들어 유리 기판)에 비공유 부착될 수 있다. 지지체는, 각각이 상이한 부착된 분자 화학종을 갖는 복수의 입자 또는 비드를 포함할 수 있다.
용어 "대상체", "개체" 및 "환자"는 본원에서 동물 대상체, 특히 척추동물 대상체, 보다 더 특히 포유류 대상체를 지칭하는 데 상호교환적으로 사용된다. 본 발명의 범위에 포함되는 적합한 척추동물로는, 척색동물문, 영장류, 설치류(예를 들어 마우스, 래트, 기니피그), 토끼목(예를 들어 래빗, 토끼(hare)), 소(bovine)(예를 들어 소), 양(ovine)(예를 들어 양(sheep)), 염소(caprine)(예를 들어 염소(goat)), 돼지(porcine)(예를 들어 돼지(pig)), 말(equine)(예를 들어 말(horse)), 개(canine)(예를 들어 개(dog)), 고양이(feline)(예를 들어 고양이(cat)), 조류(예를 들어 닭, 칠면조, 닭, 거위, 반려 새(companion bird), 예컨대 카나리아, 작은 앵무새 등), 해양 동물(예를 들어 돌고래, 고래), 파충류(뱀, 개구리, 도마뱀 등), 및 어류를 포함하여 척추동물아문(subphylum vertebrata)의 임의의 구성원이 있으나, 이들로 한정되는 것은 아니다. 바람직한 대상체는 영장류(예를 들어 인간, 유인원, 원숭이, 침팬지)이다. 대상체는 적합하게는 저산소증 질환의 적어도 하나의(예를 들어 1, 2, 3, 4, 5개 이상의) 임상 징후를 가진다.
본원에 사용된 바와 같이, 용어 "치료 계획"은 문맥상 구체적으로 다르게 지시하지 않는 한, 예방적 및/또는 치료적(즉, 명시된 질환의 발병 후) 치료를 지칭한다. 용어 "치료 계획"은 천연 성분 및 약제학적 작용제(즉, "약물")뿐만 아니라 비제한적으로 식이 치료, 물리 요법 또는 운동 계획, 수술 개입 및 이들의 조합을 포함하여 임의의 다른 치료 계획을 포괄한다.
본원에 사용되는 용어 및 관련된 정의는 단지 설명을 목적으로 사용되고 제한하려는 것이 아님을 이해해야 할 것이다.
2. 저산소증 바이오마커
본 발명은 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재를 식별하거나, 저산소증 질환과 관련된 질병 또는 질환을 가진 대상체에게 예후를 제공하기 위한 방법, 장치, 조성물 및 키트에 관한 것이다. 특히, 저산소증 바이오마커는 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 가능성을 평가하기 위한 이들 양상(modality)에 사용하거나, 저산소증 질환과 관련된 질병 또는 질환을 가진 대상체에게 예후를 제공하기 위해 개시된다. 본 발명의 방법, 장치, 조성물 및 키트는 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 조기 검출에 유용하고, 따라서, 저산소증 질환과 관련된 질병 또는 질환을 가진 대상체에게 더 양호한 치료 개입을 허용한다.
본 발명자들은, 소정의 발현 생성물이 정상산소증 질환과 비교할 때 대상체에서 저산소증 질환에서 보편적으로, 특이적으로 및 차별적으로 발현된다고 결정하였다. 본원에 제시된 결과는, 독특한 생물학적으로-관련된 바이오마커 프로파일이 저산소증을 놀랄 만한 정확도로 예측한다는 명확한 증거를 제공한다. 이러한 저산소증 바이오마커 프로파일은 생체내 모델에서 입증되었다(상세한 사항에 대해서는 실시예 5를 참조). 전반적으로, 이들 확인은, 본원에 개시된 발현 생성물이 저산소증에 대한 바이오마커로서 작용할 수 있으며, 잠재적으로는 저산소증 질환, 또는 저산소증과 관련된 질병 또는 질환을 가진 대상체에 대한 치료 결정을 분류하는 데 유용한 진단약(diagnostic)로서 역할할 수 있다는 설득력 있는 증거를 제공한다. 이러한 측면에서, 이들 바이오마커를 기초로 하는 본원에 개시된 방법, 장치, 조성물 및 키트는 저산소증에 대한 신속하고 저렴한 스크리닝을 허용하는 현장 진단(point-of-care diagnostic)에서 역할을 할 수 있으며, 이는, 대상체가 저산소증 질환과 관련없는 질병 또는 질환에 대한 치료제와는 대조적으로, 저산소증 질환과 관련된 질병 또는 질환을 치료하는 데 적합한 적절한 치료제(예를 들어 G9a 길항제)에 노출될 수 있기 때문에 의료 시스템에 유의한 비용 절감을 초래할 수 있는 것으로 제안된다.
따라서, 특이적인 발현 생성물은 대상체에서 저산소증 질환의 존재 또는 부재를 식별하기 위한 수단을 제공하는 저산소증 바이오마커로서 본원에 개시된다. 대상체에서, 또는 대상체로부터 취해진 시료에서 이들 저산소증 바이오마커 수준의 분석을 통한 상기 바이오마커의 평가는, 대상체에서 저산소증 질환의 존재 또는 부재를 평가하거나 대상체에서 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 데 사용될 수 있는 지표를 결정하기 위해 측정되거나 파생된 바이오마커 값을 제공한다.
이에, 바이오마커 값은, 예를 들어 하나 이상의 측정된 바이오마커 값에 함수를 적용함으로써 하나 이상의 측정된 바이오마커 값으로부터 파생된 값인, 측정된 파생된 바이오마커 값일 수 있다. 본원에 사용된 바와 같이, 함수가 적용된 바이오마커는 "파생 마커"로 지칭된다.
바이오마커 값은 다수의 방식 중 임의의 하나의 방식에서 결정될 수 있다. 바이오마커 값을 결정하는 예시적인 방법은 WO 2015/117204에서 본 발명자들에 의해 기재되어 있으며, 상기 문헌은 그 전체가 원용에 의해 본 명세서에 포함된다. 일례에서, 바이오마커 값을 결정하는 과정은 예를 들어 대상체 상에서, 또는 대상체로부터 취해진 시료(들) 상에서 시험을 수행함으로써 바이오마커 값을 측정하는 단계를 포함할 수 있다. 그러나 보다 전형적으로, 바이오마커 값을 결정하는 단계는, 이전에 측정되거나 파생된 바이오마커 값을 받아들이거나 다르게는 수득하는 전자적 가공 장치를 갖는 것을 포함한다. 이는 예를 들어, 데이터 저장, 예컨대 원격 데이터베이스로부터 바이오마커 값을 회수하거나, 수동으로 입력된 바이오마커 값을 수득하거나, 입력 장치를 사용하는 등을 포함할 수 있을 것이다. 지표는 복수의 바이오마커 값의 조합을 사용하여 결정되며, 상기 지표는 저산소증 질환의 존재 또는 부재를 적어도 부분적으로 가리킨다. 이러한 방법의 추정은 전자적 가공 장치를 사용하여 수행되며, 지표의 징조는 선택적으로 사용자에게 디스플레이되거나 그렇지 않으면 제공된다. 이러한 측면에서, 징조는 지표 값의 그래프 표시 또는 영숫자(영숫자) 표시일 수 있을 것이다. 그러나 대안적으로, 징조는 지표 값을 예정된 역치 또는 범위와 비교한 결과일 수 있거나, 대안적으로 지표를 사용하여 파생된, 저산소증 질환의 존재 또는 부재, 또는 저산소증과 관련된 질병 또는 질환에 대한 예후의 징조일 수 있을 것이다.
일부 실시형태에서, 바이오마커 값은 예를 들어, 바이오마커 값을 더하거나, 곱하거나, 빼거나 나눔으로써 조합되어, 지표 값을 결정한다. 이 단계는, 다수의 바이오마커 값이 단일 지표 값으로 조합될 수 있도록 수행되며, 상기 단일 지표 값은, 상기 지표가 해석되고 대상체에서 저산소증 질환의 존재 또는 부재를 진단하거나 대상체에서 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 데 사용될 수 있도록 보다 유용하고 간단한 기전을 제공한다.
복수의 바이오마커 및 바이오마커 값이 사용되는 일부 실시형태에서, 효과적인 진단 또는 예후가 결정될 수 있는 것을 보장하기 위해, 적어도 2개의 바이오마커가 상호 연관 범위 내에 있는 저산소증에 관하여 상호 연관(mutual correlation)을 가지며, 상기 상호 연관 범위는 ±0.9 사이이다. 이러한 요건은, 저산소증 질환(예를 들어 저산소증 암)이 진단되는 맥락에서 고려될 때, 2개의 바이오마커가 서로에 관해 전적으로 연관되지 않음을 의미한다. 다시 말해, 조합에서 적어도 2개의 바이오마커는 질환이 변화함에 따라 상이하게 반응하며, 이는 조합될 때 대상체에서 적어도 2개의 질환을 구별하며, 저산소증 질환의 존재 또는 부재를 진단하며, 및/또는 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 이들 바이오마커의 능력에 유의하게 더해진다.
전형적으로, 바이오마커가 낮은 상호 연관을 갖는다는 요건은, 이러한 바이오마커가 상이한 생물학적 속성(attribute) 또는 도메인, 예컨대 비제한적으로 상이한 분자 기능, 상이한 생물학적 과정 및 상이한 세포 구성성분에 관한 것일 수 있다. 분자 기능의 예시적인 예는 단백질, 폴리펩타이드, 펩타이드, 핵산(예를 들어 DNA, RNA)으로의 또는 이로부터의 하기 모이어티 중 하나 이상의 첨가 또는 제거를 포함한다: 선형, 분지형, 포화된 또는 불포화된 알킬(예를 들어 C1-C24 알킬); 포스페이트; 유비퀴틴; 아실; 지방산, 지질, 인지질; 뉴클레오타이드 염기; 하이드록실 등. 분자 기능은 또한, 비제한적으로 수용체 신호전달 경로 및 핵 신호전달 경로를 포함하여 신호전달 경로를 포함한다. 분자 기능의 비제한적인 예는 또한, 하나 이상의 부위에서 핵산, 펩타이드, 폴리펩타이드 또는 단백질의 절단; 핵산, 펩타이드, 폴리펩타이드 또는 단백질의 중합; 세포막(예를 들어 외부 세포막; 핵막)을 통한 전좌; 세포 소기관(예를 들어 골지체, 리소좀, 소포체, 핵, 미토콘드리아) 안으로 또는 밖으로의 전좌; 수용체 결합, 수용체 신호전달, 막 채널 결합, 막 채널 유입 또는 유출 등을 포함한다.
생물학적 과정의 예시적인 예는: 세포 주기의 단계, 예컨대 감수분열, 체세포분열, 세포 분할, 전기(prophase), 중기, 후기, 말기 및 간기, 세포 분화의 단계; 세포자멸사; 괴사; 화학주성; 적응 및 내재 면역 반응을 포함하여 면역 반응, 전-염증성 면역 반응, 자가면역 반응, 면역관용원성 반응(tolerogenic response) 등을 포함한다. 생물학적 과정의 다른 예시적인 예는, 아데노신 트리포스페이트(ATP), 당류, 다당류, 지방산, 지질, 인지질, 스핑고지질, 당지질, 콜레스테롤, 뉴클레오타이드, 핵산, 막(예를 들어 세포 원형질 막, 핵막), 아미노산, 펩타이드, 폴리펩타이드, 단백질 등을 발생시키거나 분해하는 것을 포함한다. 세포 구성성분의 대표적인 예는 예를 들어 상기 주지된 바와 같이 소기관, 막 및 다른 것들을 포함한다.
상이한 생물학적 속성 또는 도메인을 갖는 바이오마커의 사용은, 바이오마커가 동일하거나 공통의 생물학적 속성 또는 도메인과 관련되어 있는 것보다 추가의 정보를 제공하는 것으로 이해될 것이다. 이러한 측면에서, 적어도 2개의 바이오마커가 서로 고도로 연관되어 있다면, 두 바이오마커 모두의 사용은 단일한 하나의 바이오마커의 사용과 비교하여 더 적은 진단/예후 향상을 더할 것으로 이해될 것이다. 이에, 복수의 바이오마커 및 바이오마커 값이 사용되는 본 발명의 지표-결정 방법은 바람직하게는, 서로 양호하게 연관되어 있지 않은 바이오마커를 이용하며, 이로써 상기 방법에서 각각의 바이오마커의 포함은 지표의 구별 능력에 유의하게 더해지는 것을 보장한다.
이럼에도 불구하고, 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 구별 또는 저산소증과 관련된 질병 또는 질환에 대한 예후의 제공을 수행하는 데에 이러한 지표가 정확하게 사용될 수 있도록 보장하기 위해, 상기 지표는 성능 역치 이상인 성능 값을 가진다. 성능 역치는 임의의 적합한 형태일 수 있으나, 전형적으로 적어도 0.3의 설명 분산, 또는 또 다른 성능 측정의 동등한 값을 가리킨다.
적합하게는, 바이오마커가 ±0.9 사이의 상호 연관을 가지고 조합이 적어도 0.3의 설명 분산을 제공하는 바이오마커의 조합이 이용된다. 이는 전형적으로, 필요한 바이오마커의 수를 최소화하면서도 정확한 진단 또는 예후가 수득될 수 있는 것을 보장하는 데 적합한 지표가 정의될 수 있게 한다. 전형적으로, 상호 연관 범위는 ±0.8; ±0.7; ±0.6; ±0.5; ±0.4; ±0.3; ±0.2; 및 ±0.1 중 하나이다. 전형적으로, 각각의 저산소증 바이오마커는 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재, 또는 저산소증과 관련된 질병 또는 질환에 대한 예후와 질환 연관을 가지며, 이는 질환 연관 범위 밖에 있고, 상기 질환 연관 범위는 ±0.3, 보다 전형적으로 ±0.9; ±0.8; ±0.7; ±0.6; ±0.5; 및 ±0.4 사이이다. 전형적으로, 성능 역치는 0.4; 0.5; 0.6; 0.7; 0.8; 및 0.9 중 적어도 하나의 설명 분산을 가리킨다.
이러한 맥락에서, 상기 기재된 방법 내에서 사용되는 바이오마커는, 임상적으로 적절한 진단, 예후 또는 구별을 하는 데에 바이오마커 프로파일이 사용될 수 있도록 하기 위해 충분한 성능을 유지하면서도, 최소 수의 바이오마커를 포함하는 저산소증 질환에 대한 바이오마커 프로파일을 정의할 수 있는 것으로 이해될 것이다. 사용되는 바이오마커 수의 최소화는 진단 또는 예후 시험을 수행하는 것과 관련된 비용을 최소화하고, 핵산 발현 생성물의 경우 상대적으로 간단한 기술, 예컨대 핵산 어레이 및 중합효소 연쇄 반응(PCR) 과정 등을 이용하여 시험이 수행될 수 있게 하여, 임상 환경에서 시험이 신속하게 수행될 수 있게 한다.
더욱이, 단일 지표 값의 생성은, 시험 결과가 임상의 또는 다른 의사에 의해 쉽게 해석될 수 있게 하며, 따라서 시험은 임상 환경에서 신뢰할 만한 진단에 사용될 수 있다.
적합한 바이오마커 프로파일을 발생시키는 과정은 예를 들어 WO 2015/117204에 기재되어 있으며, 이는 본원에 정의된 바와 같은 "바이오마커 프로파일" 대신에 용어 "바이오마커 서명"을 사용한다. 따라서, 용어 "바이오마커 프로파일" 및 "바이오마커 서명"은 범위 내에서 동등한 것으로 이해될 것이다. WO 2015/117204에 개시된 바이오마커 프로파일-발생 과정은, 바이오마커 프로파일을 형성하는 데 사용될 수 있는, 다시 말해 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재를 진단하는 데 또는 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 데 사용될 수 있는 바이오마커, 보다 전형적으로 파생 바이오마커의 조합을 선택하기 위한 기전을 제공한다. 이러한 측면에서, 바이오마커 프로파일은, 측정되어야 하는 바이오마커(즉, 프로파일 바이오마커), 파생 바이오마커 값이 측정된 바이오마커 값에 대해 어떻게 결정되어야 하는지, 그 후에 바이오마커 값이 후속적으로 어떻게 조합되어 지표 값을 발생시켜야 하는지 정의한다. 바이오마커 프로파일은 또한, 특정 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재를 가리키거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 정의된 지표 값 범위를 명시할 수 있다.
상기 기재된 방법을 사용하여, 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 평가하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 데 특히 유용한 많은 바이오마커가 식별되어 왔다. 이들 바이오마커는 본원에서 "저산소증 바이오마커"로서 지칭된다. 본원에 사용된 바와 같이, 용어 "저산소증 바이오마커"는, 정상 조직에 비해 저하된 농도의 산소(O2)로 인해 손상 또는 상해(insult)에 대한 반응의 일부로서, 변경되거나 발현 수준이 변경되는 숙주의 바이오마커를 지칭한다. 저산소증 바이오마커는 적합하게는, 폴리뉴클레오타이드 및 폴리펩타이드 발현 생성물을 포함하여 유전자(본원에서 상호교환적으로 "저산소증 바이오마커 유전자"로도 지칭됨)의 발현 생성물이다. 본원에 사용된 바와 같이, 저산소증 바이오마커 유전자의 폴리뉴클레오타이드 발현 생성물은 본원에서 "저산소증 바이오마커 폴리뉴클레오타이드"로 지칭된다. 저산소증 바이오마커 유전자의 폴리뉴클레오타이드 발현 생성물은 본원에서 "저산소증 바이오마커 폴리펩타이드"로 지칭된다.
저산소증 바이오마커는 적합하게는, 하기 저산소증 유전자 중 임의의 하나 이상의 발현 생성물로부터 선택된다: AGBL3, AGMO, AGTR1, ALS2CR12, ALX1, ANAPC5, ANKRD20A1, ANXA13, AP1AR, ARHGAP10, ARMCX1, ARNTL, C10orf25, C14orf169, C18orf34, C18orf62, C1QTNF9, C2orf76, C6orf165, C7orf45, C7orf62, C9orf131, C9orf85, CA10, CAPNS2, CCDC121, CCDC141, CD1C, CDH11, CEACAM7, CEP170P1, CYTIP, DBF4, DDX56, DPPA2, DPPA3P2, DTX2, EIF4G2, ELMO1, ELOVL3, ENAM, FAM172BP, FCGR1A, FFAR2, FGF12, FGFR2, FLJ42102, FLJ44838, FLJ45721, FN1, FOXP2, GATA2, GDI2, GGTLC2, GK2, GPR78, HARBI1, HEMGN, HHEX, HIST1H2AA, HMGN2, HMGN2P28, HMGN2P46, HOXC13, HPDL, HRCT1, HRH1, HS3ST3B1, HSD3B2, ICA1L, IDO2, IL10, IL17A, IL18, IL1B, KARS, KBTBD6, KCNA2, KLB, KLRG1, KMO, KRT10, KRT222, LCN1, LIG4, LINC00312, LINC00328, LINC00596, LLPH, LOC100049716, LOC100287879, LOC221442, LOC642947, LOC644714, LRRC37A5P, LRRC53, LTA, MEIG1, METTL2A, MGAT2, MGC23270, MILR1, MIR148A, MIR218-1, MIR34B, MIR494, MIR516B2, MMP16, MMP27, MPP1, MRPL30, MUTYH, MYH8, NBLA00301, NCRNA00185, ND6, NEFM, NEUROD1, NONO, NPCDR1, NPY5R, OCM, OCM2, OGN, OR10A2, OR2A12, OR2D3, OR2M3, OR2T2, OR2T35, OR4D10, OR4D2, OR5J2, OR5M10, OR8H3, OR9G1, ORM2, OTOG, PAGE2B, PLAG1, PRL, PRPF8, PSCA, PTPN20A, RBM44, RBMY1C, RBMY1F, RFK, RIMBP3, RN18S1, RN5S1, RN7SK, RN7SL1, RNF152, RNF185, RNPS1, RNU11, RNU1-4, RNU2-1, RNU4-2, RNU5F-1, RNU6-2, RNY1, RP11-165H20.1, RPL21P68, RPS27AP17, S1PR3, SART1, SDAD1, SEPP1, SETD9, SIGLEC14, SKAP1, SLC36A3, SLC8A1, SLC9B1P2, SLCO4C1, SMNDC1, SNORA1, SNORA72, SNORA75, SNORD114-2, SNORD115-10, SNORD116-19, SNORD18A, SNORD3B-1, SPOCK3, ST6GAL1, STAMBPL1, TAF1D, TAS2R14, TBCCD1, TCEB3B, TMEM100, TMIGD1, TOB2, TUBB8, UBD, UGT2B17, UQCRFS1, VNN1, ZC3HC1, ZCCHC12, ZNF222, ZNF259, ZNF439, ZNF487P, ZNF569, ZNF678, ZNF684, ZNF716, ZNF718, ZNRF3, ZSCAN29 및 CDH10. 저산소증 바이오마커에 대한 뉴클레오타이드 서열의 비제한적인 예는 서열번호 1-201에 열거되어 있다. 이들 저산소증 바이오마커에 대한 상응하는 아미노산 서열의 비제한적인 예는 서열번호 202-367에 열거되어 있다.
보다 구체적인 실시형태에서, 하나 이상의 저산소증 유전자는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택된다. 보다 구체적으로, 1, 2, 3, 4 또는 5개의 저산소증 바이오마커는 ARNTL, CEACAM7, GATA2, HHEX, KLRG1 및 OGN으로부터 선택될 수 있다.
동일한 실시형태 및 다른 실시형태 중 일부에서, 2개 이상의 저산소증 바이오마커가 표 1로부터 선택될 수 있다.
Figure pct00001
동일한 실시형태 및 다른 실시형태 중 일부에서, 2개 이상의 저산소증 바이오마커가 표 2로부터 선택될 수 있다.
Figure pct00002
Figure pct00003
동일한 실시형태 및 다른 실시형태 중 일부에서, 4개 이상의 저산소증 바이오마커가 표 3으로부터 선택될 수 있다.
Figure pct00004
Figure pct00005
Figure pct00006
Figure pct00007
동일한 실시형태 및 다른 실시형태 중 일부에서, 5개 이상의 저산소증 바이오마커가 표 4로부터 선택될 수 있다.
Figure pct00008
Figure pct00009
Figure pct00010
Figure pct00011
Figure pct00012
Figure pct00013
예시적인 예로서, 본 발명의 일부 경우에서, 적어도 6개의 저산소증 바이오마커가 측정될 수 있으며, 여기서, 적어도 6개의 저산소증 바이오마커는 ARNTL, CEACAM7, GATA2, HHEX, KLRG1 및 OGN을 포함하거나, 구성되거나, 본질적으로 구성된다.
이들 예에서, 지표-결정 방법은 적합하게는, 바이오마커 값의 쌍을 결정하는 단계를 포함하고, 여기서, 각각의 바이오마커 값은 대상체의 적어도 하나의 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 값이고, 대상체로부터 취해진 시료에서 저산소증 바이오마커의 농도를 적어도 부분적으로 가리킨다. 바이오마커 값은 전형적으로, 파생된 바이오마커 값을 바이오마커 값의 쌍을 사용하여 결정하는 데 사용되며, 여기서, 파생된 바이오마커 값은 저산소증 바이오마커의 쌍의 농도의 비를 가리킨다. 따라서, 바이오마커 값이 저산소증 바이오마커의 농도를 나타낸다면, 파생된 바이오마커 값은 바이오마커 값의 비를 기초로 할 것이다. 그러나, 바이오마커 값은 바이오마커의 농도에 관한 것이며, 예를 들어 이들이 PCR 사이클 시간을 기초로 하는 바이오마커 값으로 인해 대수적으로 관련이 있다면, 바이오마커 값은 일부 다른 방식으로, 예컨대 사이클 시간을 빼어(subtract), 저산소증 바이오마커 농도의 비를 가리키는 파생된 바이오마커 값을 결정함으로써 조합될 수 있다.
그 후에, 파생된 바이오마커 값은 하기에서 보다 상세히 기재될 바와 같이, 이러한 파생된 바이오마커 값을 지표 값으로서 사용함으로써, 또는 부가적인 가공을 수행하여, 예컨대 이러한 파생된 바이오마커 값을 참조 등과 비교함으로써 지표를 결정하는 데 사용된다.
저산소증 바이오마커 쌍이 파생된 바이오마커 값을 결정하는 데 사용되는 일부 실시형태에서, 바이오마커 쌍 중 하나의 바이오마커는 그룹 1 저산소증 바이오마커로부터 선택되고, 나머지 바이오마커는 그룹 2 저산소증 바이오마커로부터 선택되며, 여기서, 개별적인 그룹 1 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로 구성된 군으로부터 선택되는 유전자의 발현 생성물이고; 개별적인 그룹 2 저산소증 바이오마커는 G9a의 발현 생성물이다.
파생된 바이오마커 값은 조합 기능, 예컨대 첨가 모델; 선형 모델; 지지체 벡터 기계; 신경 네트워크 모델; 트리-학습 방법(tree-learning method)(예를 들어 랜덤 포레스트 모델(random forest model)); 회귀 모델; 유전 알고리즘(genetic algorithm); 어닐링 알고리즘; 가중 합계; 최근접 이웃 모델(nearest neighbor model); 앙상블 방법(ensemble method)(예컨대 배깅(bagging), 부스팅 가중 평균화(boosting weighted averaging)); 및 확률 모델(probabilistic model)을 사용하여 조합될 수 있을 것이다. 일부 실시형태에서, 바이오마커 값은 그룹 1 저산소증 바이오마커 및 그룹 2 저산소증 바이오마커에 대해 측정되거나 파생되고, 지표는 바이오마커 값을 조합함으로써 결정된다.
일부 실시형태에서, 지표는 지표 참조와 비교되며, 이때, 가능성은 비교의 결과에 따라 결정된다. 지표 참조는 참조 집단에서 많은 개체에 대해 결정된 지표로부터 파생될 수 있다. 참조 집단은 전형적으로, 상이한 특징을 갖는 개체, 예컨대 상이한 성별의 복수의 개체; 및/또는 인종을 포함하며, 이때, 상이한 그룹은 상이한 특징을 기초로 정의되며, 대상체의 지표는 유사한 특징을 갖는 개체로부터 파생된 지표 참조와 비교된다. 참조 집단은 또한, 복수의 건강한 개체, 저산소증 질환(예를 들어 저산소증 암)을 갖는 복수의 개체, 비-저산소증 G9a-관련 질병 또는 질환을 갖는 복수의 개체, 저산소증 질환의 임상 징후를 보여주는 복수의 개체, 비-저산소증 G9a-관련 질병 또는 질환의 임상 징후를 보여주는 복수의 개체를 포함할 수 있다.
지표는 또한, 제1 또는 제2 질환을 갖는 대상체의 가능성을 결정하는 데, 다시 말해, 이들 질환을 분간하는 데 사용될 수 있으며, 여기서, 제1 질환은 저산소증 질환(예를 들어 저산소증 암)이고, 제2 질환은 정상산소증 질환이다. 이러한 경우, 이는 전형적으로, 지표를 제1 및 제2 지표 참조와 비교하고, 비교 결과에 따라 가능성을 결정함으로써 달성될 수 있을 것이며, 제1 및 제2 지표 참조는 제1 및 제2 질환을 가리킨다. 특히, 이는 비교 결과를 사용하여 제1 및 제2 지표 확률을 결정하는 단계, 및 제1 및 제2 지표 확률을 예를 들어 베이스 방법(Bayes method)을 사용하여 조합하여, 하나의 질환을 갖는 대상체의 가능성에 상응하는 질환 확률을 결정하는 단계를 포함할 수 있다. 이러한 상황에서, 제1 및 제2 질환은 저산소증 암 및 또 다른 비-저산소증 암, 또는 저산소증 및 정상산소증을 포함할 수 있을 것이다. 이러한 경우, 제1 및 제2 지표 참조는 참조 집단의 제1 및 제2 그룹에 대해 결정된 지표의 분포이고, 제1 및 제2 집단은 제1 또는 제2 질환으로 제각기 진단받은 개체로 구성된다.
구체적인 실시형태에서, 본 발명의 지표-결정 방법은 적어도 하나의 전자적 가공 장치, 예컨대 적합하게는 프로그래밍된 컴퓨터 시스템 등을 사용하여 수행된다. 이러한 경우, 전자적 가공 장치는 전형적으로, 이들을 측정 또는 다른 정량화 장치로부터 수용함으로써 또는 이들을 데이터베이스 등으로부터 회수함으로써 적어도 하나의 측정된 바이오마커 값을 수득한다. 그 후에, 가공 장치는 제1 저산소증 바이오마커를 가리키는 제1 파생된 바이오마커 값, 및 선택적으로 제2 저산소증 바이오마커를 가리키는 제2 파생된 바이오마커 값을 결정한다. 동일한 실시형태 및 다른 실시형태 중 일부에서, 제1 파생된 바이오마커 값은 제1 및 제2 저산소증 바이오마커의 비를 가리키는 값이다. 1개 초과의 바이오마커 값이 파생되는 상황에서, 가공 장치는 적절하다면 제1 및 제2(및 선택적으로 제3, 제4, 제5 등) 파생된 바이오마커 값을 조합함으로써 지표를 결정할 수 있다.
그 후에, 가공 장치는 예를 들어, 지표의 영숫자 징조, 지표와 하나 이상의 지표 참조의 비교의 그래프 징조, 또는 적어도 하나의 의학 질환을 갖는 대상체의 가능성의 영숫자 징조를 발생시킴으로써 지표의 표시를 발생시킬 수 있다.
본 발명의 지표-결정 방법은 전형적으로, 대상체로부터 시료를 수득하는 단계로서, 이러한 대상체는 전형적으로 저산소증 질환(예를 들어 저산소증 암)의 적어도 하나의 임상 징후를 가지고, 여기서, 시료는 하나 이상의 저산소증 바이오마커(예를 들어 저산소증 유전자의 폴리뉴클레오타이드 또는 폴리펩타이드 발현 생성물)를 포함하는 단계, 및 시료 내에서 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커를 정량화하여, 바이오마커 값을 결정하는 단계를 포함한다. 이는 임의의 적합한 기술을 사용하여 달성될 수 있고, 저산소증 바이오마커의 성질에 따라 의존할 것이다. 적합하게는, 개별적인 측정된 또는 파생된 저산소증 바이오마커 값은 제각기의 저산소증 바이오마커의 수준, 풍부도 또는 양, 또는 해당 수준 또는 양에 적용되는 기능에 상응한다. 본원에 사용된 바와 같이 용어 "수준", "풍부도" 및 "양"은 본원에서 정량적인 양(예를 들어 중량 또는 몰수), 반정량적인 양, 상대 양(예를 들어 부류 내에서 중량% 또는 몰%), 농도 등을 지칭하는 데에 상호교환적으로 사용된다. 따라서, 이들 용어는 시료 내 저산소증 바이오마커의 절대 또는 상대 양 또는 농도를 포괄한다. 예를 들어, 복수의 저산소증 바이오마커를 사용하는 본 발명의 지표-결정 방법의 일부 실시형태에서 지표가 폴리뉴클레오타이드 발현 생성물의 농도의 비를 기초로 한다면, 이러한 과정은 전형적으로, 시료 내 적어도 일부 폴리뉴클레오타이드 발현 생성물을 증폭시킴으로써 폴리뉴클레오타이드 발현 생성물을 정량화하는 단계, 폴리뉴클레오타이드 발현 생성물의 쌍의 각각의 정의된 수준을 수득하는 데 필요한 증폭의 정도를 표시하는 증폭 양을 결정하는 단계, 및 증폭 양 사이의 차이를 결정함으로써 지표를 결정하는 단계를 포함할 것이다. 이러한 측면에서, 증폭 양은 일반적으로 사이클 시간, 사이클 횟수, 사이클 역치 및 증폭 시간이다. 예를 들어 일부 실시형태에서, 이러한 방법은 제1 폴리뉴클레오타이드 발현 생성물의 증폭 양을 결정함으로써 제1 파생된 바이오마커 값을 결정하는 단계, 제2 폴리뉴클레오타이드 발현 생성물의 증폭 양을 결정함으로써 제2 파생된 바이오마커 값을 결정하는 단계, 및 제1 및 제2 파생된 바이오마커 값을 조합함으로써 지표를 결정하는 단계를 포함한다.
일부 실시형태에서, 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재 또는 저산소증과 관련된 질병 또는 질환에 대한 예후는 2개 이상의 저산소증 바이오마커 값을 결정함으로써 구축되며, 여기서, 저산소증 바이오마커 값은 대상체에서, 또는 대상체로부터 취해진 시료에서 저산소증 바이오마커에 대해 파생된 값을 가리킨다. 이들 바이오마커는 본원에서 "시료 저산소증 바이오마커"로서 지칭된다. 본 발명에 따르면, 시료 저산소증 바이오마커는 참조 저산소증 바이오마커(본원에서 또한 "상응하는 저산소증 바이오마커"로 지칭됨)에 상응한다. "상응하는 저산소증 바이오마커"란, 예를 들어 표 5에 제시된 바와 같이 참조 저산소증 바이오마커와 구조적으로 및/또는 기능적으로 유사한 저산소증 바이오마커를 의미한다. 대표적인 상응하는 저산소증 바이오마커는 참조 저산소증 바이오마커 유전자의 대립유전자 변이체(동일한 유전자좌), 호모로그(homologue)(상이한 유전자좌) 및 오르토로그(orthologue)(상이한 유기체)의 발현 생성물을 포함한다. 참조 저산소증 바이오마커 유전자의 핵산 변이체 및 인코딩된 저산소증 바이오마커 폴리뉴클레오타이드 발현 생성물은 뉴클레오타이드 치환, 결실, 역전(inversion) 및/또는 삽입을 함유할 수 있다. 변이는 코딩 영역과 비-코딩 영역 중 어느 하나 또는 둘 모두에서 발생할 수 있다. 변이는 (인코딩된 생성물에서와 비교하여) 보존적 아미노산 치환과 비-보존적 아미노산 치환 둘 모두를 생성할 수 있다. 뉴클레오타이드 서열에 대해, 보존적 변이체는, 유전자 코드의 축퇴성(degeneracy)때문에 참조 저산소증 폴리펩타이드의 아미노산 서열을 인코딩하는 서열을 포함한다.
일반적으로, 특정 저산소증 바이오마커 유전자 또는 폴리뉴클레오타이드의 변이체는 디폴트 매개변수를 사용하는 당업자에게 공지된 서열 정렬 프로그램에 의해 결정된 바와 같이 특정 뉴클레오타이드 서열과 적어도 약 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59% 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69% 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 이상의 서열 동일성을 가질 것이다. 일부 실시형태에서, 저산소증 바이오마커 유전자 또는 폴리뉴클레오타이드는 표 5에 열거된 임의의 하나의 저산소증 바이오마커와 적어도 약 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59% 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69% 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 이상의 서열 동일성을 나타낸다.
Figure pct00014
Figure pct00015
Figure pct00016
상응하는 저산소증 바이오마커는 또한, 참조 저산소증 바이오마커 폴리펩타이드의 아미노산 서열과 실질적인 서열 유사성 또는 동일성을 나타내는 아미노산 서열을 포함한다. 일반적으로, 참조 아미노산에 상응하는 아미노산 서열은 표 6에 열거된 임의의 하나의 서열로부터 선택되는 참조 아미노산 서열과 적어도 약 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 97, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% 또는 심지어 100% 이하의 서열 유사성 또는 동일성을 나타낸다.
일부 실시형태에서, 서열 사이에서 서열 유사성 또는 서열 동일성의 계산은 하기와 같이 수행된다:
2개의 아미노산 서열 또는 2개의 핵산 서열의 동일성 퍼센트를 결정하기 위해, 서열은 최적 비교 목적을 위해 정렬된다(예를 들어 갭은 최적 정렬을 위해 제1 및 제2 아미노산 또는 핵산 서열 중 하나 또는 둘 모두에 도입될 수 있고, 비-상동성 서열은 비교 목적을 위해 묵살될 수 있음). 일부 실시형태에서, 비교 목적을 위해 정렬된 참조 서열의 길이는 참조 서열의 길이의 적어도 30%, 통상적으로 적어도 40%, 보다 통상적으로 적어도 50%, 60%, 심지어 보다 통상적으로 적어도 70%, 80%, 90%, 100%이다. 그 후에, 상응하는 아미노산 위치 또는 뉴클레오타이드 위치에서 아미노산 잔기 또는 뉴클레오타이드가 비교된다. 제1 서열에서의 위치가 제2 서열의 상응하는 위치에서의 동일한 아미노산 잔기 또는 뉴클레오타이드에 의해 점유될 때, 분자는 해당 위치에서 동일하다. 아미노산 서열 비교를 위해, 제1 서열에서의 위치가 제2 서열의 상응하는 위치에서 동일하거나 유사한 아미노산 잔기에 의해 점유될 때(즉, 보존적 치환), 분자는 해당 위치에서 유사하다.
2개의 서열 사이에서 동일성 퍼센트는, 2개의 서열의 최적 정렬을 위해 도입될 필요가 있는 갭의 수 및 각각의 갭의 길이를 고려하여 개별적인 위치에서 서열에 의해 공유되는 동일한 아미노산 잔기의 수의 함수이다. 대조적으로, 2개의 서열 사이에서 유사성 퍼센트는, 2개의 서열의 최적 정렬을 위해 도입될 필요가 있는 갭의 수 및 각각의 갭의 길이를 고려하여 개별적인 위치에서 서열에 의해 공유되는 동일한 아미노산 잔기 및 유사한 아미노산 잔기의 수의 함수이다.
Figure pct00017
Figure pct00018
Figure pct00019
서열 사이에서 서열의 비교 및 동일성 퍼센트 또는 유사성 퍼센트의 결정은 수학적 알고리즘을 사용하여 달성될 수 있다. 소정의 실시형태에서, 아미노산 서열 사이에서 동일성 또는 유사성 퍼센트는, Blossum 62 매트릭스나 PAM250 매트릭스, 및 16, 14, 12, 10, 8, 6 또는 4의 갭 중량(gap weight) 및 1, 2, 3, 4, 5 또는 6의 길이 중량(length weight)을 사용하여 또는 GCG 소프트웨어 패키지(http://www.gcg.com에서 입수 가능함)에서 GAP 프로그램 내로 통합된 Needleman 및 Wunnsch(문헌[1970, J. Mol. Biol. 48: 444-453]) 알고리즘을 사용하여 결정된다. 구체적인 실시형태에서, 뉴클레오타이드 서열 사이의 동일성 퍼센트는, NWSgapdna.CMP 매트릭스, 및 40, 50, 60, 70 또는 80의 갭 중량 및 1, 2, 3, 4, 5 또는 6의 길이 중량을 사용하여 또는 GCG 소프트웨어 패키지(http://www.gcg.com에서 입수 가능함)에서 GAP 프로그램을 사용하여 결정된다. 비제한적인 세트의 매개변수(및 다르게 명시되지 않는 한 사용되어야 하는 매개변수)는 12의 갭 페널티(gap penalty), 4의 갭 익스텐드 페널티(gap extend penalty) 및 5의 프레임시프트 갭 페널티(frameshift gap penalty)를 갖는 Blossum 62 스코어링 매트릭스를 포함한다.
일부 실시형태에서, 아미노산 또는 뉴클레오타이드 서열 사이의 동일성 또는 유사성 퍼센트는, PAM120 중량 잔기 표, 12의 갭 길이 페널티 및 4의 갭 페널티를 사용하는 ALIGN 프로그램(버전 2.0) 내로 통합된 E. Meyers 및 W. Miller의 알고리즘(문헌[1989, Cabios, 4: 11-17])을 사용하여 결정될 수 있다.
본원에 기재된 핵산 및 단백질 서열은 "쿼리(query) 서열"로서 사용되어 공개 데이터베이스에 대한 검색을 수행하여, 예를 들어 다른 계통 구성원 또는 관련된 서열을 식별할 수 있다. 이러한 검색은 Altschul 등의 NBLAST 및 XBLAST 프로그램(버전 2.0)을 사용하여 수행될 수 있다(문헌[1990, J Mol Biol., 215: 403-10]). BLAST 뉴클레오타이드 검색은 NBLAST 프로그램, 스코어 = 100, 단어길이(wordlength) = 12를 이용하여 수행되어, 본 발명의 53010개 핵산 분자에 상동성인 뉴클레오타이드 서열을 수득할 수 있다. BLAST 단백질 검색은 XBLAST 프로그램, 스코어 = 50, 단어길이 = 3을 이용하여 수행되어, 본 발명의 단백질 분자에 상동성인 아미노산 서열을 수득할 수 있다. 비교 목적을 위해 갭핑된(gapped) 정렬을 수득하기 위해, Gapped BLAST가 Altschul 등(문헌[1997, Nucleic Acids Res, 25: 3389-3402])에 기재된 바와 같이 이용될 수 있다. 제각기의 프로그램(예를 들어 XBLAST 및 NBLAST)의 BLAST 및 Gapped BLAST 프로그램을 이용할 때, 디폴트 매개변수가 사용될 수 있다.
상응하는 저산소증 바이오마커 폴리뉴클레오타이드는 또한, 하기 기재된 엄격성 조건 하에 참조 저산소증 바이오마커 폴리뉴클레오타이드 또는 이들의 보체에 혼성화하는 핵산 서열을 포함한다. 본원에 사용된 바와 같이, 용어 "낮은 엄격성, 중간 엄격성, 높은 엄격성 또는 매우 높은 엄격성 조건 하에 혼성화한다"는, 혼성화 및 세척을 위한 조건을 기재한다. "혼성화"는 본원에서, DNA-DNA 하이브리드 또는 DNA-RNA 하이브리드를 생성하기 위해 상보적 뉴클레오타이드 서열의 짝짓기를 나타내는 데 사용된다. 상보적 염기 서열은 염기-짝짓기 규칙에 의해 관련된 서열이다. DNA에서, A는 T와 짝을 짓고, C는 G와 짝을 짓는다, RNA에서, U는 A와 짝을 짓고, C는 G와 짝을 짓는다. 이러한 측면에서, 본원에 사용된 바와 같이 용어 "매치" 및 "미스매치"는 상보적 핵산 가닥에서 짝지은 뉴클레오타이드의 혼성화 잠재성을 지칭한다. 매칭된 뉴클레오타이드는 효율적으로 혼성화하며, 예컨대 상기 언급된 전형적인 A-T 및 G-C 염기쌍이다. 미스매치는 효율적으로 혼성화하지 않는 뉴클레오타이드의 다른 조합이다.
혼성화 반응을 수행하기 위한 지침은 Ausubel 등(상기 1998), 섹션 6.3.1-6.3.6에서 확인될 수 있다. 수성 및 비-수성 방법은 해당 참조에 기재되어 있고, 사용될 수 있다. 본원에서 낮은 엄격성 조건이란 지칭은, 42℃에서의 혼성화를 위해 적어도 약 1% v/v 내지 적어도 약 15% v/v 포름아미드 및 적어도 약 1 M 내지 적어도 약 2 M 염, 및 42℃에서의 세척을 위해 적어도 약 1 M 내지 적어도 약 2 M 염을 포함하고 포괄한다. 낮은 엄격성 조건은 또한, 65℃에서의 혼성화를 위한 1% 소 혈청 알부민(BSA), 1 mM EDTA, 0.5 M NaHPO4(pH 7.2), 7% SDS, 및 실온에서의 세척을 위한 (i) 2 × SSC, 0.1% SDS; 또는 (ii) 0.5% BSA, 1 mM EDTA, 40 mM NaHPO4(pH 7.2), 5% SDS를 포함한다. 낮은 엄격성 조건의 일 실시형태는 약 45℃에서 6 × 소듐 클로라이드/소듐 시트레이트(SSC)에서의 혼성화, 뒤이어 적어도 50℃에서 0.2 × SSC, 0.1% SDS에서의 2회의 세척을 포함한다(세척 온도는 낮은 엄격성 조건에 대해 55℃까지 증가될 수 있음). 중간 엄격성 조건은 42℃에서의 혼성화를 위해 적어도 약 16% v/v 내지 적어도 약 30% v/v 포름아미드 및 적어도 약 0.5 M 내지 적어도 약 0.9 M 염, 및 55℃에서의 세척을 위해 적어도 약 0.1 M 내지 적어도 약 0.2 M 염을 포함하고 포괄한다. 중간 엄격성 조건은 또한, 65℃에서의 혼성화를 위한 1% 소 혈청 알부민(BSA), 1 mM EDTA, 0.5 M NaHPO4(pH 7.2), 7% SDS, 및 60℃ 내지 65℃에서의 세척을 위한 (i) 2 × SSC, 0.1% SDS; 또는 (ii) 0.5% BSA, 1 mM EDTA, 40 mM NaHPO4(pH 7.2), 5% SDS를 포함한다. 중간 엄격성 조건의 일 실시형태는 약 45℃에서 6 × SSC에서의 혼성화, 뒤이어 60℃에서 0.2 × SSC, 0.1% SDS에서의 1회 이상의 세척을 포함한다. 높은 엄격성 조건은 42℃에서의 혼성화를 위해 적어도 약 31% v/v 내지 적어도 약 50% v/v 포름아미드 및 약 0.01 M 내지 약 0.15 M 염, 및 55℃에서의 세척을 위해 적어도 약 0.01 M 내지 적어도 약 0.02 M 염을 포함하고 포괄한다. 높은 엄격성 조건은 또한, 65℃에서의 혼성화를 위한 1% BSA, 1 mM EDTA, 0.5 M NaHPO4(pH 7.2), 7% SDS, 및 65℃ 초과의 온도에서의 세척을 위한 (i) 2 × SSC, 0.1% SDS; 또는 (ii) 0.5% BSA, 1 mM EDTA, 40 mM NaHPO4(pH 7.2), 1% SDS를 포함한다. 높은 엄격성 조건의 일 실시형태는 약 45℃에서 6 × SSC에서의 혼성화, 뒤이어 65℃에서 0.2 × SSC, 0.1% SDS에서의 1회 이상의 세척을 포함한다.
소정의 실시형태에서, 상응하는 저산소증 바이오마커 폴리뉴클레오타이드는, 매우 높은 엄격성 조건 하에 개시된 뉴클레오타이드 서열에 혼성화하는 것이다. 매우 높은 엄격성 조건의 일 실시형태는 65℃에서 0.5 M 소듐 포스페이트, 7% SDS에서의 혼성화, 뒤이어 65℃에서 0.2 × SSC, 1% SDS에서 1회 이상의 세척을 포함한다.
다른 엄격성 조건은 당업계에 잘 공지되어 있고, 당업자는 혼성화의 특이성을 최적화하기 위해 다양한 인자가 조작될 수 있음을 인지할 것이다. 최종 세척의 엄격성의 최적화는 높은 혼성화 정도를 보장하는 역할을 할 수 있다. 상세한 예에 대해서는, 문헌[상기 Ausubel 등, 페이지 2.10.1 내지 2.10.16] 및 [Sambrook 등(상기 1989) 섹션 1.101 내지 1.104]를 참조한다.
2.1 시료 제조
일반적으로, 저산소증 바이오마커 검출 또는 정량화 전에 시료를 가공한다. 예를 들어, 핵산 및/또는 단백질을 분석 전에 시료로부터 추출, 단리 및/또는 정제할 수 있다. 다양한 DNA, mRNA 및/또는 단백질 추출 기술은 당업자에게 잘 공지되어 있다. 가공은 원심분리, 초원심분리, 에탄올 침전, 여과, 분획화, 재현탁, 희석, 농축 등을 포함할 수 있다. 일부 실시형태에서, 방법 및 시스템은 제한된 가공 없이 또는 함께 원료(예를 들어 생물학적 유체, 예컨대 혈액, 혈청 등)로부터의 분석(예를 들어 RNA 또는 단백질 바이오마커의 정량화)을 제공한다.
이러한 방법은 적합한 완충제에서 시료를 균질화하고, 오염물을 제거하며 및/또는 저해제를 검정하는 단계, 표적 바이오마커와 포착 시약의 결합(예를 들어 혼성화에 의함)을 촉진하는 조건 하에 인큐베이션된 저산소증 바이오마커 포착 시약(예를 들어 표적 저산소증 핵산 바이오마커에 상보적인 올리고뉴클레오타이드가 연결되는 자기 비드)을 첨가하여 표적 바이오마커:포착(capture) 시약 복합체를 생성하는 단계, 표적 바이오마커:포착 복합체를 표적 바이오마커-방출 조건 하에 인큐베이션하는 단계를 포함할 수 있다. 일부 실시형태에서, 다수의 저산소증 바이오마커는 각각의 단리 라운드(round)에서 다수의 저산소증 바이오마커 포착 시약(예를 들어 요망되는 바이오마커에 특이적인)을 용액에 첨가함으로써 단리된다. 예를 들어, 각각이 상이한 표적 저산소증 바이오마커에 특이적인 올리고뉴클레오타이드를 포함하는 다수의 저산소증 바이오마커 포착 시약은 다수의 저산소증 바이오마커의 단리를 위해 시료에 첨가될 수 있다. 이러한 방법은 각각의 포착 단계에서 포착된 표적 저산소증 바이오마커의 수 둘 모두에서 달라지는 다수의 실험 설계를 포괄하는 것으로 고려된다. 일부 실시형태에서, 포착 시약은 단리, 정제, 검출 및/또는 정량화되고자 하는 특정 바이오마커와 우선적으로(예를 들어 특이적으로 및 선택적으로) 상호작용하는 분자, 모이어티, 성분 또는 조성물이다. 특정 저산소증 바이오마커에 대해 요망되는 결합 친화성 및/또는 특이성을 갖는 임의의 포착 시약이 본 기술에 존재할 수 있다.
예를 들어, 포착 시약은 거대분자, 예컨대 펩타이드, 단백질(예를 들어 항체 또는 수용체), 올리고뉴클레오타이드, 핵산(예를 들어 저산소증 바이오마커와 혼성화할 수 있는 핵산), 비타민, 올리고당류, 탄수화물, 지질 또는 저분자, 또는 이들의 복합체일 수 있다. 예시적이고 비제한적인 예로서, 아비딘 표적 포착 시약은 비오틴 모이어티를 포함하는 표적을 단리하고 정제하는 데 사용될 수 있으며, 항체는 적절한 항원 또는 에피토프를 포함하는 표적을 단리하고 정제하는 데 사용될 수 있고, 올리고뉴클레오타이드는 상보적 올리고뉴클레오타이드를 단리하고 정제하는 데 사용될 수 있다.
표적 저산소증 바이오마커에 결합하거나 특이적으로 결합할 수 있는 단일 가닥 및 이중 가닥 핵산을 포함하여 임의의 핵산이 포착 시약으로서 사용될 수 있다. 이러한 핵산의 예로는, DNA, RNA, 앱타머(aptamer), 펩타이드 핵산, 및 당, 포스페이트 또는 뉴클레오사이드 염기에 대한 다른 변형이 있다. 따라서, 표적을 포착하기 위한 많은 전략이 존재하고, 이에 많은 유형의 포착 시약이 당업계에 공지되어 있다.
또한, 저산소증 바이오마커 포착 시약은 포착 시약을 국소화하며, 농축시키며, 응집시키는 기능성을 포함하며, 따라서 포착 시약에 포착(예를 들어 결합, 혼성화 등)될 때(예를 들어 표적:포착 시약 복합체가 형성될 때), 표적 저산소증 바이오마커를 단리하고 정제하는 하나의 방식을 제공할 수 있다. 예를 들어 일부 실시형태에서, 저산소증 바이오마커(예를 들어 올리고뉴클레오타이드)와 상호작용하는 포착 시약의 일부는, 거시적 척도에서 사용자에 의한 조작을 허용하는 고형 지지체(예를 들어 비드, 표면, 수지, 컬럼 등)에 연결된다. 종종, 고형 지지체는 기계적 수단의 사용자가 표적:포착 시약 복합체를 불균질 용액으로부터 단리하고 정제할 수 있게 한다. 예를 들어, 비드에 연결된 경우, 분리는 비드를 예를 들어 물리적 이동에 의해 불균질 용액으로부터 제거함으로써, 달성된다. 비드가 자성(magnetic) 또는 상자성(paramagnetic)인 실시형태에서, 자기장은 불균질 용액으로부터 포착 시약(및 따라서 표적 저산소증 바이오마커)의 물리적 분리를 달성하는 데 사용된다.
저산소증 바이오마커는 임의의 적합한 기술을 사용하여 정량화되거나 검출될 수 있다. 구체적인 실시형태에서, 저산소증 바이오마커는 개별적인 저산소증 바이오마커의 수준, 풍부도 또는 양을 결정하는 시약을 사용하여 정량화된다. 이러한 유형의 비제한적인 시약은 핵산-기초 및 단백질-기초 검정법에서 사용하기 위한 시약을 포함한다.
2.2 핵산 바이오마커의 정량화 또는 검출
예시적인 핵산-기초 검정법에서, 핵산을 표준 방법에 따라 생물학적 시료에 함유된 세포로부터 단리한다(상기 Sambrook 등 1989; 및 상기 Ausubel 등 1994). 핵산은 전형적으로 분획화된 RNA(예를 들어 폴리 A+ RNA) 또는 전세포(whole cell) RNA이다. RNA가 검출의 대상물로서 사용되는 경우, RNA를 상보적 DNA로 전환시키는 것이 요망될 수 있다. 일부 실시형태에서, 핵산은 주형-의존적 핵산 증폭 기술에 의해 증폭된다. 많은 주형-의존적 과정이 주어진 주형 시료에 존재하는 저산소증 바이오마커 서열을 증폭시키는 데 이용 가능하다. 예시적인 핵산 증폭 기술은 중합효소 연쇄 반응(PCR로 지칭됨)이며, 이는 Ausubel 등(상기)의 미국 특허 4,683,195, 4,683,202 및 4,800,159 및 Innis 등(문헌["PCR Protocols", Academic Press, Inc., San Diego Calif., 1990])에 상세히 기재되어 있다. 간략하게는 PCR에서, 바이오마커 서열의 반대쪽 상보 가닥 상의 영역에 상보적인 2개의 프라이머 서열이 제조된다. 과량의 데옥시뉴레오타이드 트리포스페이트가 DNA 중합효소, 예를 들어 Taq 중합효소와 함께 반응 혼합물에 첨가된다. 동족(cognate) 저산소증 바이오마커 서열이 시료에 존재한다면, 프라이머는 바이오마커에 결합할 것이고, 중합효소는 프라이머가 뉴클레오타이드 상에 첨가함으로써 바이오마커 서열을 따라 연장되도록 유발할 것이다. 반응 혼합물의 온도를 올리고 낮춤으로써, 연장된 프라이머는 바이오마커로부터 해리되어, 반응 생성물을 형성할 것이며, 과량의 프라이머는 바이오마커 및 반응 생성물에 결합할 것이고, 이러한 과정은 반복된다. 증폭되는 mRNA 양을 정량화하기 위해 역전사효소 PCR 증폭 절차가 수행될 수 있다. RNA를 cDNA로 역전사시키는 방법은 잘 공지되어 있고, 상기 Sambrook 등 1989에 기재되어 있다. 역전사시키는 대안적인 방법은 내열성, RNA-의존적 DNA 중합효소를 이용한다. 이들 방법은 WO 90/07641에 기재되어 있다. 중합효소 연쇄 반응 방법은 당업계에 잘 공지되어 있다. 전세포 RNA가 사용되는 구체적인 실시형태에서, 전세포 RNA를 시료로서 사용하는 cDNA 합성은 전세포 cDNA를 생성한다.
소정의 유리한 실시형태에서, 주형-의존적 증폭은 실시간으로 전사체를 정량화하는 단계를 수반한다. 예를 들어, RNA 또는 DNA는 실시간 PCR 기술을 사용하여 정량화될 수 있다(문헌[Higuchi, 1992, et al., Biotechnology 10: 413-417]). 동일한 사이클 수가 고려되었으며 이들의 선형 범위에 있는 PCR 반응에서 표적 DNA의 증폭된 생성물의 농도를 결정함으로써, 원래의 DNA 혼합물에서 특이적인 표적 서열의 상대 농도를 결정하는 것이 가능하다. DNA 혼합물이 상이한 조직 또는 세포로부터 단리된 RNA로부터 합성된 cDNA인 경우, 표적 서열이 유래된 특이적인 mRNA의 상대 풍부도는 제각기의 조직 또는 세포에 대해 결정될 수 있다. PCR 생성물의 농도와 상대 mRNA 풍부도 사이의 이러한 정비례(direct proportionality)는 PCR 반응의 선형 범위에서만 참(true)이다. 곡선의 평탄부에서 표적 DNA의 최종 농도는 반응 혼합물에서 시약의 이용 가능성에 의해 결정되고, 표적 DNA의 원래 농도에 독립적이다. 구체적인 실시형태에서, 멀티플렉스(multiflexed), 탠덤(tandem) PCR(MT-PCR)이 이용되며, 이러한 MT-PCR은 예를 들어 미국 특허 출원 공개 20070190540에 기재된 바와 같이 소량의 RNA 또는 DNA로부터 유전자 발현 프로파일링을 위한 2-단계 과정을 사용한다. 제1 단계에서, RNA는 멀티플렉스 유전자 특이적 프라이머를 사용하여 cDNA로 전환되고 증폭된다. 제2 단계에서, 각각의 개별적인 유전자는 실시간 PCR에 의해 정량화된다. 실시간 PCR은 전형적으로, 당업계에서 이용 가능한 임의의 PCR 계측을 사용하여 수행된다. 전형적으로, 실시간 PCR 데이터 수합 및 분석에 사용되는 계측은 열 순환기(thermal cycler), 형광 여기 및 방출 수합을 위한 옵틱스(optics), 및 선택적으로 컴퓨터 및 데이터 획득 및 분석 소프트웨어를 포함한다.
RT-PCR 검정법의 일부 실시형태에서, TAQMAN® 프로브는 핵산을 정량화하는 데 사용된다. 이러한 검정법은 합성된 PCR 생성물을 검출하고 정량화하기 위해 에너지 전달("ET"), 예컨대 형광 공명 에너지 전달("FRET")을 사용할 수 있다. 전형적으로, TAQMAN® 프로브는 하나의 말단(예를 들어 5'-말단)에 커플링된 형광 표지(예를 들어 형광 염료)를 포함하고, 퀀처 분자는 다른 말단(예를 들어 3'-말단)에 커플링되어, 형광 표지 및 퀀처는 근접하게 존재하여, 퀀처는 FRET를 통해 염료의 형광 신호를 억제시킬 수 있다. 중합효소가, 형광 표지된 프로브가 결합된 키메라 앰플리콘 주형을 복제할 때, 상기 중합효소의 5'-뉴클레아제가 프로브를 절단하여, 형광 표지 및 퀀처를 디커플링시켜, 표지 신호(예컨대 형광)가 검출된다. 신호(예컨대 형광)는 각각의 PCR 사이클이 경과함에 따라, 절단되는 프로브의 양에 비례하여 증가한다.
TAQMAN® 프로브는 전형적으로, 저산소증 바이오마커 폴리뉴클레오타이드의 영역에 동일하게 존재하거나 이에 상보적인 서열을 갖는 인접(contiguous) 뉴클레오타이드의 영역을 포함하며, 따라서, 상기 프로브는 생성된 PCR 앰플리콘에 특이적으로 혼성화 가능하다. 일부 실시형태에서, 프로브는 표적 저산소증 바이오마커 폴리뉴클레오타이드의 영역에 완전히 상보적이거나 이에 동일하게 존재하는 서열을 갖는 적어도 6개 인접 뉴클레오타이드의 영역을 포함하며, 예컨대 검출되며 및/또는 정량화되는 표적 저산소증 바이오마커 폴리뉴클레오타이드의 영역에 상보적이거나 이에 동일하게 존재하는 서열을 갖는 적어도 8개 인접 뉴클레오타이드, 적어도 10개 인접 뉴클레오타이드, 적어도 12개 인접 뉴클레오타이드, 적어도 14개 인접 뉴클레오타이드, 또는 적어도 16개 인접 뉴클레오타이드의 영역을 포함한다.
TAQMAN® 검정법 외에도, 본원에 제시된 방법에서 PCR 생성물을 검출하는 데 유용한 다른 실시간 PCR 화학으로는, 분자 비콘, 스콜피온 프로브 및 인터칼레이팅 염료(intercalating dye), 예컨대 SYBR 그린, 에바그린(EvaGreen), 티아졸 오렌지, YO-PRO, TO-PRO 등이 있으나, 이들로 한정되는 것은 아니다. 예를 들어, TAQMAN® 프로브와 같은 분자 비콘은 FRET를 사용하여, 형광 표지(예를 들어 형광 염료) 및 프로브의 말단에 부착된 퀀처를 갖는 상기 프로브를 통해 PCR 생성물을 검출하고 정량화한다. 그러나, TAQMAN® 프로브와는 달리, 분자 비콘은 PCR 사이클 동안 온전하게 남아 있다. 분자 비콘 프로브는 용액에서 자유로울 때 스템-루프(stem-loop) 구조를 형성하며, 이로써 형광 표지 및 퀀처가 형광 퀀칭을 유발하기에 충분할 정도로 근접하게 놓일 수 있게 한다. 분자 비콘이 표적에 혼성화할 때, 스템-루프 구조는 무효화되고, 따라서, 형광 표지 및 퀀처는 공간에서 분리되게 되며, 형광 표지가 형광을 발하게 된다. 분자 비콘은 예를 들어 Gene Link™로부터 입수 가능하다(www.genelink.com/newsite/products/mbintro.asp 참조).
일부 실시형태에서, 스콜피온 프로브는 서열-특이적 프라이머와 PCR 생성물 검출 및 정량화 둘 모두로서 사용될 수 있다. 분자 비콘과 유사하게, 스콜피온 프로브는 표적 핵산에 혼성화하지 않을 때 스템-루프 구조를 형성한다. 그러나, 분자 비콘과는 달리, 스콜피온 프로브는 서열-특이적 프라이밍과 PCR 생성물 검출 둘 모두를 달성한다. 형광 표지(예를 들어 형광 염료 분자)는 스콜피온 프로브의 5'-말단에 부착되고, 퀀처는 3'-말단에 부착된다. 프로브의 3' 부위는 PCR 프라이머의 연장 생성물에 상보적이고, 이러한 상보적 부분은 비-증폭성 모이어티에 의해 프로브의 5'-말단에 연결된다. 스콜피온 프라이머가 연장된 후, 프로브의 표적-특이적 서열은 연장된 앰플리콘 내에서 이의 보체에 결합하며, 따라서, 스템-루프 구조를 개방하고, 5'-말단 상에서 형광 표지가 형광을 발하고 신호를 발생시킬 수 있게 한다. 스콜피온 프로브는 예를 들어 Premier Biosoft International사로부터 입수 가능하다(www.premierbiosoft.com/tech_notes/Scorpion.html 참조).
일부 실시형태에서, FRET 프로브 상에서 사용될 수 있는 표지는 비색 및 형광 염료, 예컨대 Alexa Fluor 염료, BODIPY 염료, 예컨대 BODIPY FL; 캐스케이드 블루; 캐스케이드 옐로우; 쿠마린 및 이의 유도체, 예컨대 7-아미노-4-메틸쿠마린, 아미노쿠마린 및 하이드록시쿠마린; 시아닌 염료, 예컨대 Cy3 및 Cy5; 에오신 및 에리트로신; 플루오레세인 및 이의 유도체, 예컨대 플루오레세인 이소티오시아네이트; 란탄족 이온의 마크로사이클릭(macrocyclic) 킬레이트, 예컨대 Quantum Dye™; 마리나 블루; 오레곤 그린; 로다민 염료, 예컨대 로다민 레드, 테트라메틸로다민 및 로다민 6G; 텍사스 레드; 형광 에너지 전달 염료, 예컨대 티아졸 오렌지-에티듐 헤테로이량체; 및 TOTAB를 포함한다.
염료의 구체적인 예로는, 상기 식별된 것 및 하기의 것이 있으나, 이들로 한정되는 것은 아니다: Alexa Fluor 350, Alexa Fluor 405, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 500. Alexa Fluor 514, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 610, Alexa Fluor 633, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700 및 Alexa Fluor 750; 아민-반응성 BODIPY 염료, 예컨대 BODIPY 493/503, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591, BODIPY 630/650, BODIPY 650/655, BODIPY FL, BODIPY R6G, BODIPY TMR 및 BODIPY-TR; Cy3, Cy5, 6-FAM, 플루오레세인 이소티오시아네이트, HEX, 6-JOE, 오레곤 그린 488, 오레곤 그린 500, 오레곤 그린 514, 퍼시픽 블루, REG, 로다민 그린, 로다민 레드, 레노그라핀(Renographin), ROX, SYPRO, TAMRA, 2',4',5',7'-테트라브로모설폰플루오레세인 및 TET.
염료/퀀처 쌍(즉, 공여자/수여자 쌍)의 예로는, 플루오레세인/테트라메틸로다민; IAEDANS/플루오레세인; EDANS/답실(dabcyl); 플루오레세인/플루오레세인; BODIPY FL/BODIPY FL; 플루오레세인/QSY 7 또는 QSY 9 염료가 있다. 공여자 및 수여자가 동일할 때, 일부 실시형태에서, FRET가 형광 탈분극에 의해 검출될 수 있다. 염료/퀀처 쌍(즉, 공여자/수여자 쌍)의 소정의 구체적인 예로는, Alexa Fluor 350/Alexa Fluor488; Alexa Fluor 488/Alexa Fluor 546; Alexa Fluor 488/Alexa Fluor 555; Alexa Fluor 488/Alexa Fluor 568; Alexa Fluor 488/Alexa Fluor 594; Alexa Fluor 488/Alexa Fluor 647; Alexa Fluor 546/Alexa Fluor 568; Alexa Fluor 546/Alexa Fluor 594; Alexa Fluor 546/Alexa Fluor 647; Alexa Fluor 555/Alexa Fluor 594; Alexa Fluor 555/Alexa Fluor 647; Alexa Fluor 568/Alexa Fluor 647; Alexa Fluor 594/Alexa Fluor 647; Alexa Fluor 350/QSY35; Alexa Fluor 350/답실; Alexa Fluor 488/QSY 35; Alexa Fluor 488/답실; Alexa Fluor 488/QSY 7 또는 QSY 9; Alexa Fluor 555/QSY 7 또는 QSY9; Alexa Fluor 568/QSY 7 또는 QSY 9; Alexa Fluor 568/QSY 21; Alexa Fluor 594/QSY 21; 및 Alexa Fluor 647/QSY 21이 있으나, 이들로 한정되는 것은 아니다. 일부 실시형태에서, 동일한 퀀처, 예를 들어, 광범위 스펙트럼 퀀처, 예컨대 Iowa Black® 퀀처(Integrated DNA Technologies, 미국 아이오와주 코랄빌 소재) 또는 Black Hole 퀀처™(BHQ™; Sigma-Aldrich, 미국 미주리주 세인트루이스 소재)가 다수의 염료에 사용될 수 있다.
일부 실시형태에서, 예를 들어 2개 이상의 모이어티(예컨대 앰플리콘)가 동시에 검출되는 멀티플렉스 반응에서, 각각의 프로브는 검출 가능하게 상이한 염료를 포함하며, 따라서 상기 염료는 동일한 반응에서 동시에 검출될 때 분간될 수 있다. 당업자는 멀티플렉스 반응에 사용하기 위한 검출 가능하게 상이한 염료 세트를 선택할 수 있다. 일부 실시형태에서, 다수의 표적 저산소증 바이오마커 폴리뉴클레오타이드는 단일 멀티플렉스 반응에서 검출되며 및/또는 정량화된다. 일부 실시형태에서, 상이한 저산소증 바이오마커 폴리뉴클레오타이드로 표적화되는 각각의 프로브는, 상기 프로브로부터 방출될 때 스펙트럼적으로 분간 가능하다. 따라서, 각각의 표적 저산소증 바이오마커 폴리뉴클레오타이드는 독특한 형광 신호에 의해 검출된다.
본원에 기재된 방법의 일부 실시형태에 사용하기 위한 실시간 PCR 프로브의 제조에 유용한 형광 표지된 리보뉴클레오타이드의 구체적인 예는 Molecular Probes(Invitrogen)사로부터 입수 가능하고, 이들은 Alexa Fluor 488-5-UTP, 플루오레세인-12-UTP, BODIPY FL-14-UTP, BODIPY TMR-14-UTP, 테트라메틸로다민-6-UTP, Alexa Fluor 546-14-UTP, 텍사스 레드-5-UTP 및 BODIPY TR-14-UTP를 포함한다. 다른 형광 리보뉴클레오타이드, 예컨대 Cy3-UTP 및 Cy5-UTP는 Amersham Biosciences(GE Healthcare)사로부터 입수 가능하다.
본원에 기재된 방법에 사용하기 위한 실시간 PCR 프로브의 제조에 유용한 형광 표지된 데옥시리보뉴클레오타이드의 예로는, 디니트로페닐(DNP)-1'-dUTP, 캐스케이드 블루-7-dUTP, Alexa Fluor 488-5-dUTP, 플루오레세인-12-dUTP, 오레곤 그린 488-5-dUTP, BODIPY FL-14-dUTP, 로다민 그린-5-dUTP, Alexa Fluor 532-5-dUTP, BODIPY TMR-14-dUTP, 테트라메틸로다민-6-dUTP, Alexa Fluor 546-14-dUTP, Alexa Fluor 568-5-dUTP, 텍사스 레드-12-dUTP, 텍사스 레드-5-dUTP, BODIPY TR-14-dUTP, Alexa Fluor 594-5-dUTP, BODIPY 630/650-14-dUTP, BODIPY 650/665-14-dUTP; Alexa Fluor 488-7-OBEA-dCTP, Alexa Fluor 546-16-OBEA-dCTP, Alexa Fluor 594-7-OBEA-dCTP, Alexa Fluor 647-12-OBEA-dCTP가 있다. 형광 표지된 뉴클레오타이드는 상업적으로 입수 가능하고, 예를 들어 Invitrogen사로부터 구매될 수 있다.
소정의 실시형태에서, 표적 핵산은 당업자에게 잘 공지된 블로팅 기술을 사용하여 정량화된다. 서던 블로팅은 DNA를 표적으로서 사용하는 것을 수반하는 반면, 노던 블로팅은 RNA를 표적으로서 사용하는 것을 수반한다. 각각은 상이한 유형의 정보를 제공하지만, cDNA 블로팅은 많은 양태에서 블로팅 또는 RNA 화학종과 유사하다. 간략하게는, 프로브는 적합한 매트릭스, 종종 니트로셀룰로스의 필터 상에서 부동화된 DNA 또는 RNA 화학종을 표적화하는 데 사용된다. 상이한 화학종은 분석을 용이하게 하기 위해 공간적으로 분리되어야 한다. 이는 종종, 핵산 화학종의 겔 전기영동, 및 뒤이어 필터 상에서 "블로팅"에 의해 달성된다. 후속적으로, 블로팅된 표적은, 변성 및 재혼성화를 촉진하는 조건 하에 프로브(통상적으로 표지됨)와 함께 인큐베이션된다. 프로브가 표적과 염기쌍을 이루도록 설계되기 때문에, 이러한 프로브는 재생 조건 하에 표적 서열의 일부에 결합할 것이다. 그 후에, 비결합된 프로브는 제거되고, 검출이 상기 기재된 바와 같이 달성된다. 검출/정량화 후, 당업자는 주어진 대상체에서 관찰된 결과를 대조군 반응 또는 통계적으로 유의한 참조군 또는 본원에 정의된 바와 같은 대조군 대상체의 집단과 비교할 수 있다. 이러한 방식으로, 검출된 저산소증 바이오마커 핵산의 양을 질병의 진행 또는 중증도와 연관시키는 것이 가능하다.
또한, 예컨대 Hacia 등(문헌[1996, Nature Genetics 14: 441-447]) 및 Shoemaker 등(문헌[1996, Nature Genetics 14: 450-456])에 기재된 것들과 같은 바이오칩-기초 기술이 고려된다. 간략하게는, 이들 기술은 다수의 유전자를 신속 정확하게 분석하기 위한 정량적인 방법을 수반한다. 유전자를 올리고뉴클레오타이드로 태깅하거나 고정된 핵산 프로브 어레이를 사용함으로써, 당업자는 바이오칩 기술을 이용하여, 표적 분자를 고밀도 어레이로서 분리하고(segregate), 이들 분자를 혼성화를 기초로 스크리닝할 수 있다. Pease 등(문헌[1994, Proc. Natl. Acad. Sci. U.S.A. 91: 5022-5026]); Fodor 등(문헌[1991, Science 251: 767-773])을 또한 참조한다. 간략하게는, 저산소증 바이오마커 폴리뉴클레오타이드에 대한 핵산 프로브가 본원에 나열된 바와 같이 스크리닝 및 진단 방법에 사용되는 바이오칩에 부착된다. 바이오칩에 부착된 핵산 프로브는 특이적인 저산소증 바이오마커 핵산, 즉, 표적 서열(예를 들어 샌드위치 검정법에서 시료의 표적 서열 또는 다른 프로브 서열)에 실질적으로 상보적이도록 설계되며, 따라서, 본 발명의 표적 서열과 프로브의 혼성화가 발생한다. 이러한 상보성은 완벽할 필요는 없으며; 임의의 수의 염기쌍 미스매치가 존재할 수 있고, 이러한 미스매치는 본 발명의 표적 서열과 핵산 프로브 사이의 혼성화를 방해할 것이다. 그러나, 미스매치의 수가 너무 커서, 심지어 최소의 엄격한 혼성화 조건 하에서도 혼성화가 발생할 수 없다면, 서열은 상보적 표적 서열이 아니다. 소정의 실시형태에서, 1개 서열 당 1개 초과의 프로브가 사용되며, 이때, 오버랩핑(overlapping) 프로브 또는 표적의 상이한 섹션에 대한 프로브가 사용된다. 즉, 2, 3, 4개 이상의 프로브가 특정 표적에 대한 중복성(redundancy)에서 구축되는 데 사용되며, 이때 3개가 바람직하다. 프로브는 오버랩핑(즉, 일부 서열을 공통적으로 가짐)이거나 별개일 수 있다.
예시적인 바이오칩 분석에서, 상기 바이오칩 상의 올리고뉴클레오타이드 프로브는 선호적인 특이적 혼성화 조건 하에 하나 이상의 저산소증 바이오마커 폴리뉴클레오타이드를 함유하는 것으로 의심되는 핵산 시료에 노출되거나 이와 접촉된다. 단일 가닥 또는 이중 가닥의 DNA 또는 RNA의 시료 추출물은 생물학적 물질의 유체 현탁액으로부터, 또는 생물학적 물질의 분쇄에 의해, 또는 비제한적으로 SDS(또는 다른 세제), 삼투성 쇼크, 구아니디늄 이소티오시아네이트 및 리소자임의 처리에 의해 수행되는 용해를 포함하는 세포 용해 단계 후에 제조될 수 있다. 본 발명의 방법에 사용될 수 있는 적합한 DNA는 cDNA를 포함한다. 이러한 DNA는 예를 들어 상기 Ausubel 등, 1994 및 상기 Sambrook 등, 1989에 기재된 바와 같이 많은 보편적으로 사용되는 프로토콜 중 임의의 하나에 의해 제조될 수 있다.
본 발명의 방법에 사용될 수 있는 적합한 RNA는 메신저 RNA, DNA로부터 전사된 상보적 RNA(cRNA) 또는 게놈 또는 서브게놈 RNA를 포함한다. 이러한 RNA는 예를 들어 상기 Ausubel 등, 1994 및 상기 Sambrook 등, 1989의 적합한 섹션에 기재된 바와 같은 표준 프로토콜을 사용하여 제조될 수 있다. cDNA는 예를 들어, 초음파처리 또는 제한 엔도뉴클레아제를 이용한 처리에 의해 단편화될 수 있다. 적합하게는, cDNA는, 생성된 DNA 단편이 부동화된 올리고뉴클레오타이드 프로브(들)의 길이보다 길지만 적합한 혼성화 조건 하에 이러한 프로브에 신속한 접근을 허용하기에 충분할 정도로 작은 길이가 되도록 단편화된다. 대안적으로, cDNA의 단편은 예를 들어 상기 기재된 바와 같이 적절한 랜덤 또는 특이적 프라이머를 수반하는 적합한 뉴클레오타이드 증폭 기술을 사용하여 선택되고 증폭될 수 있다.
통상적으로, 표적 저산소증 바이오마커 폴리뉴클레오타이드는, 개별 프로브로의 이들의 혼성화가 결정될 수 있도록 검출 가능하게 표지된다. 표적 폴리뉴클레오타이드는 전형적으로, 리포터로 검출 가능하게 표지되며, 이러한 리포터의 예시적인 예는 크로모겐(chromogen), 촉매, 효소, 형광색소, 화학발광 분자, 생물발광 분자, 란탄족 이온(예를 들어 Eu34), 방사성 동위원소 및 직접 시각적 표지(direct visual label)를 포함한다. 직접 시각적 표지의 경우, 콜로이드 금속성 또는 비금속성 입자, 염료 입자, 효소 또는 기질, 유기 중합체, 라텍스 입자, 리포좀, 또는 신호 생성 성분을 함유하는 다른 비히클 등이 사용될 수 있다. 이러한 유형의 예시적인 표지는 대형 콜로이드, 예를 들어 금속 콜로이드, 예컨대 금, 셀레늄, 은, 주석 및 티타늄 옥사이드로부터의 것을 포함한다. 효소가 직접 시각적 표지로서 사용되는 일부 실시형태에서, 비오틴화된 염기가 표적 폴리뉴클레오타이드 내로 통합된다.
하이브리드-형성 단계는 DNA 또는 RNA를 포함하는 시험 핵산에 올리고뉴클레오타이드 프로브를 혼성화하기에 적합한 조건 하에 수행될 수 있다. 이러한 측면에서, 예를 들어 문헌[NUCLEIC ACID HYBRIDIZATION, A PRACTICAL APPROACH (Homes and Higgins, eds.)(IRL press, Washington D.C., 1985)]를 참조할 수 있다. 일반적으로, 혼성화가 발생하는지의 여부는 시험 하의 올리고뉴클레오타이드 프로브 및 폴리뉴클레오타이드 서열의 길이, pH, 온도, 1가 및 2가 양이온의 농도, 하이브리드-형성 영역 내 G 및 C 뉴클레오타이드의 비율, 매질의 점도 및 변성제의 가능한 존재에 의해 영향을 받는다. 이러한 변수는 또한, 혼성하에 필요한 시간에 영향을 준다. 따라서, 바람직한 조건은 특정 적용에 의존할 것이다. 그러나, 이러한 경험적 조건은 과도한 실험 없이 일상적으로 결정될 수 있다.
하이브리드-형성 단계 후, 프로브는 세척되어, 임의의 비결합된 핵산을 혼성화 완충제와 함께 제거한다. 이러한 세척 단계는 결합된 표적 폴리뉴클레오타이드만 남긴다. 그 후에, 프로브는 검사되어, 어떤 프로브가 표적 폴리뉴클레오타이드에 혼성화되었는지 식별된다.
그 후에, 혼성화 반응은 어떤 프로브가 상응하는 표적 서열에 혼성화하였는지 결정하기 위해 검출된다. 표적 폴리뉴클레오타이드와 관련된 리포터 분자의 성질에 따라, 신호는, 형광 표지를 광으로 조사하고 형광을 형광계(fluorimeter)에서 검출함으로써; 분광광도계를 사용하여 검출될 수 있는 염료를 생성하는 효소 시스템을 제공함으로써; 또는 반사계를 사용하여 염료 입자 또는 착색된 콜로이드 금속성 또는 비금속성 입자를 검출함으로써; 방사성 표지 또는 화학발광 분자를 사용하는 경우 방사선 계수기 또는 오토라디오그래피(autoradiography)를 이용함으로써, 기계적으로 검출될 수 있다. 이에, 검출 수단은 표지와 관련된 광을 검출하거나 스캔하도록 적응될 수 있으며, 이러한 광은 형광, 발광, 집속 빔(focused beam) 또는 레이저 광을 포함할 수 있다. 이러한 경우, 전하 결합 장치(CCD; charge couple device) 또는 광전지가 사용되어, 마이크로-어레이에서 각각의 위치로부터의 프로브:표적 폴리뉴클레오타이드 하이브리드로부터 광의 방출을 스캔하고, 데이터를 디지털 컴퓨터에 직접적으로 기록할 수 있다. 일부 경우, 신호의 전자적 검출은 필요하지 않을 수 있다. 예를 들어, 핵산 어레이 포맷과 관련된 효소적으로 발생된 색상 스팟을 이용하면, 어레이의 시각적 검사는 상기 어레이 상에서 패턴의 해석을 허용할 것이다. 핵산 어레이의 경우, 검출 수단은 적합하게는, 패턴 인지 소프트웨어와 접속되어, 어레이로부터의 신호 패턴을 일반 언어 유전적 프로파일(plain language genetic profile)로 전환시킨다. 소정의 실시형태에서, 상이한 저산소증 바이오마커 폴리뉴클레오타이드에 특이적인 올리고뉴클레오타이드 프로브는 핵산 어레이 형태로 존재하고, 어레이 상에서 리포터 분자로부터 발생된 신호의 검출은 "칩 판독기"를 사용하여 수행된다. "칩 판독기"에 의해 사용될 수 있는 검출 시스템은 예를 들어 Pirrung 등(미국 특허 5,143,854)에 기재되어 있다. 상기 칩 판독기는 전형적으로, 특정 어레이 위치 또는 특징부에서의 신호가 참 양성인지 또는 아마도 불요 신호(spurious signal)인지 결정하기 위해 일부 신호 프로세싱을 또한 혼입할 것이다. 예시적인 칩 판독기는 예를 들어 Fodor 등(미국 특허 5,925,525)에 기재되어 있다. 대안적으로, 어레이가 개별적으로 주소 매김 가능한(addressable) 종류의 표지된 마이크로비드의 혼합물을 사용하여 제조되는 경우, 반응은 유세포분석을 사용하여 검출될 수 있다.
소정의 실시형태에서, 저산소증 바이오마커는 표적 RNA(예를 들어 mRNA) 또는 이러한 표적 RNA의 DNA 복사체이며, 이의 수준 또는 풍부도는 적어도 낮은, 중간 또는 높은 엄격성 조건 하에 표적 RNA 또는 DNA 복사체에 혼성화하는 적어도 하나의 핵산 프로브를 사용하여 측정되며, 여기서, 핵산 프로브는 저산소증 바이오마커 폴리뉴클레오타이드의 적어도 15(예를 들어 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30개 이상의) 인접 뉴클레오타이드를 포함한다. 일부 실시형태에서, 표적 RNA 또는 이의 DNA 복사체의 측정된 수준 또는 풍부도는 참조 RNA 또는 이러한 참조 RNA의 DNA 복사체의 수준 또는 풍부도에 대해 정규화된다. 적합하게는, 핵산 프로브는 고형 또는 반고형 지지체 상에서 부동화된다. 이러한 유형의 예시적인 예에서, 핵산 프로브는 핵산 프로브의 공간 어레이의 일부를 형성한다. 일부 실시형태에서, 표적 RNA 또는 DNA 복사체에 결합된 핵산 프로브의 수준은 혼성화(예를 들어 핵산 어레이를 사용함)에 의해 측정된다. 다른 실시형태에서, 표적 RNA 또는 DNA 복사체에 결합된 핵산 프로브의 수준은 핵산 증폭(예를 들어 중합효소 연쇄 반응(PCR)을 사용함)에 의해 측정된다. 보다 다른 실시형태에서, 표적 RNA 또는 DNA 복사체에 결합된 핵산 프로브의 수준은 뉴클레아제 보호 검정법에 의해 측정된다.
표적의 서열 증폭과 함께 또는 없이 시퀀싱 기술, 예컨대 Sanger 시퀀싱, 피로시퀀싱(pyrosequencing), 연결에 의한 시퀀싱, "차세대 시퀀싱"(NGS; Next-generation sequencing)이라고도 하는 대량 병렬 시퀀싱(massively parallel sequencing), 및 다른 고-처리량 시퀀싱 접근법이 또한 사용되어, 시료에서 저산소증 핵산 바이오마커의 존재를 검출하거나 정량화할 수 있다. 서열-기초 방법은 이전에 식별된 유전자에서 대안적 스플라이싱(alternative splicing) 및 서열 변이에 관한 추가 정보를 제공할 수 있다. 시퀀싱 기술은, 주형 제조, 시퀀싱, 검출 및 데이터 분석으로 광범위하게 나뉘는 많은 단계를 포함한다. 주형 제조를 위한 현재의 방법은 게놈 DNA를 더 작은 크기로 무작위로 절단하며, 이로부터 각각의 단편이 지지체에 부동화되는 단계를 수반한다. 공간적으로 분리된 단편의 부동화는 수천 내지 수십억 개의 시퀀싱 반응이 동시에 수행될 수 있게 한다. 시퀀싱 단계는 당업계에 보편적으로 공지된 여러 가지 방법 중 임의의 방법을 사용할 수 있다. 시퀀싱 단계의 구체적인 일례는 상보 가닥으로의 뉴클레오타이드 첨가를 사용하여, DNA 서열을 제공하는 것이다. 검출 단계는 합성된 단편의 생물발광 신호를 측정하는 것으로부터 단일 분자의 4-색 이미징까지 포함한다. NGS가 시료 내 저산소증 핵산 바이오마커의 존재를 검출하거나 정량화하는 데 사용되는 일부 실시형태에서, 이러한 방법은 적합하게는, 반도체 시퀀싱(Ion Torrent; Personal Genome Machine); 헬리코스 트루 단일 분자 시퀀싱(tSMS)(문헌[Harris et al. 2008, Science 320:106-109]); 454 시퀀싱(Roche)(문헌[Margulies et al. 2005, Nature, 437, 376-380]); SOLiD 기술(Applied Biosystems); SOLEXA 시퀀싱(Illumina); Pacific Biosciences사의 단일 분자, 실시간(SMRT™) 기술; 나노포어 시퀀싱(문헌[Soni and Meller, 2007. Clin Chem 53: 1996-2001]); DNA 나노볼 시퀀싱; Dover Systems사(Polonator)의 기술, 및 시퀀싱 전에 증폭을 필요로 하지 않거나 그렇지 않으면 네이티브(native) DNA를 변형시키는 기술을 사용하는 시퀀싱(예를 들어 Pacific Biosciences and Helicos), 예컨대 나노포어-기초 전략(예를 들어 Oxford Nanopore, Genia Technologies 및 Nabsys)으로부터 선택된다.
2.3 단백질 바이오마커의 정량화 또는 검출
다른 실시형태에서, 저산소증 바이오마커 단백질 수준은 당업계에 공지된 단백질-기초 검정법을 사용하여 검정된다. 예를 들어, 저산소증 바이오마커 단백질이 효소인 경우, 단백질은 이의 촉매 활성을 기초로 또는 시료에 함유된 단백질 분자의 수를 기초로 정량화될 수 있다. 예를 들어, 면역검정법, 예컨대 효소-연결 면역흡착 검정법(ELISA) 및 방사선면역검정법(RIA)을 포함하여 항체-기초 기술이 이용될 수 있다. 예를 들어, 항-G9A 항체 ab133482(abcam)는 그룹 2 저산소증 바이오마커 G9a를 측정하는 데 사용될 수 있을 것이다.
구체적인 실시형태에서, 많은 단백질의 동시적인 검출 및/또는 정량화를 가능하게 하는 단백질-포착 어레이가 이용된다. 예를 들어, 필터 막 상에서의 저밀도 단백질 어레이, 예컨대 유니버셜 단백질 어레이 시스템(문헌[Ge, 2000 Nucleic Acids Res. 28(2): e3])은 어레이된 항원의 이미징을 표준 ELISA 기술 및 스캐닝 전하-결합 장치(CCD) 검출기를 사용하여 허용한다. 임상 분석물의 동시적인 검출을 가능하게 하는 면역-센서 어레이가 또한 개발되었다. 현재, 건강한 대상체 또는 질병에 걸린 대상체의 체액, 예컨대 혈청, 뿐만 아니라 약물 치료-전 및 약물 치료-후 대상체에서, 단백질 어레이를 사용하여 단백질 발현을 프로파일링하는 것이 가능하다.
예시적인 단백질 포착 어레이는 보편적으로 항체 어레이로 지칭되는, 공간적으로 주소 매겨진 항원-결합 분자를 포함하는 어레이를 포함하고, 이러한 어레이는 프로테옴 또는 서브프로테옴을 정의하는 수많은 단백질의 폭넓은 병렬 분석을 용이하게 할 수 있다. 항체 어레이는 특이성 및 허용 가능한 백그라운드의 필요한 특성을 갖는 것으로 제시되었으며, 일부는 상업적으로 입수 가능하다(예를 들어 BD Biosciences, Clontech, Bio-Rad 및 Sigma). 항체 어레이를 제조하는 다양한 방법이 보고되었다(예를 들어 문헌[Lopez 등 2003 J. Chromatogram. B 787:19-27; Cahill, 2000 Trends in Biotechnology 7:47-51; 미국 특허 출원 공개 2002/0055186; 미국 특허 출원 공개 2003/0003599; PCT 공개 WO 03/062444; PCT 공개 WO 03/077851; PCT 공개 WO 02/59601; PCT 공개 WO 02/39120; PCT 공개 WO 01/79849; PCT 공개 WO 99/39210을 참조). 이러한 어레이의 항원-결합 분자는 세포 또는 세포 집단에 의해 발현되는 단백질의 적어도 서브세트를 인지할 수 있고, 이들의 예시적인 예는 성장 인자 수용체, 호르몬 수용체, 신경전달물질 수용체, 카테콜아민 수용체, 아미노산 유도체 수용체, 사이토카인 수용체, 세포외기질 수용체, 항체, 렉틴, 사이토카인, 세르핀(serpin), 프로테아제, 키나제, 포스파타제, ras-유사 GTPase, 가수분해효소, 스테로이드 호르몬 수용체, 전사 인자, 열-충격 전사 인자, DNA-결합 단백질, 징크-핑거(zinc-finger) 단백질, 류신-지퍼 단백질, 호메오도메인 단백질, 세포내 신호 전달 조정제 및 효과기, 세포자멸사-관련 인자, DNA 합성 인자, DNA 수선 인자, DNA 재조합 인자 및 세포-표면 항원을 포함한다.
공간적으로 구별되는 개별적인 단백질-포착제는 전형적으로, 지지체 표면에 부착되며, 이러한 표면은 일반적으로 평면형 또는 윤곽이 있다. 보편적인 물리적 지지체는 유리 슬라이드, 실리콘, 마이크로웰, 니트로셀룰로스 또는 PVDF 막, 및 자기 및 다른 마이크로비드를 포함한다.
현탁액 내 입자가 또한, 어레이의 기초로서 사용될 수 있되, 단, 이들 입자는 식별에 대해 코딩되며; 시스템은 마이크로비드(예를 들어 Luminex, Bio-Rad 및 Nanomics Biosystems사로부터 입수 가능함), 반도체 나노결정(예를 들어 QDOTS™, Quantum Dots사로부터 입수 가능함), 비드용 바코드(ULTRAPLEX™, Smartbeads사로부터 입수 가능함) 및 다중금속 마이크로로드(multimetal microrod)(NANOBARCODES™ 입자, Surromed사로부터 입수 가능함)를 코딩하는 색상을 포함한다. 비드는 또한, 반도체 칩(예를 들어 LEAPS technology 및 Bioarray solution사로부터 입수 가능함) 상에서 평면형 어레이로 조립될 수 있다. 입자가 사용되는 경우, 개별적인 단백질-포착제가 전형적으로 개별적인 입자에 부착되어, 어레이의 공간적 정의 또는 분리를 제공한다. 그 후에, 상기 입자는 구획화된(compartmentalized) 방식에서, 예를 들어 마이크로타이터 플레이트의 웰 내에서 또는 별도의 시험관에서 별도로 그러나 병렬로 검정될 수 있다.
작업 시, 선택적으로 단편화되어 펩타이드 단편을 형성하는 단백질 시료(예를 들어 미국 특허 출원 공개 2002/0055186 참조)는 단백질 또는 펩타이드 결합에 적합한 조건 하에 단백질-포착 어레이에 전달되고, 상기 어레이는 세척되어, 시료의 비결합된 또는 비특이적으로 결합된 구성성분을 어레이로부터 제거한다. 다음, 어레이의 각각의 특징부에 결합된 단백질 또는 펩타이드의 존재 또는 양은 적합한 검출 시스템을 사용하여 검출된다. 어레이의 특징부에 결합된 단백질의 양은 어레이의 제2 특징부에 결합된 제2 단백질의 양에 비해 결정될 수 있다. 소정의 실시형태에서, 시료 내 제2 단백질의 양은 이미 공지되어 있거나 변함없는 것으로 공지되어 있다.
구체적인 실시형태에서, 저산소증 바이오마커는 표적 폴리펩타이드이며, 이의 수준은 표적 폴리펩타이드와 면역-상호작용성인 적어도 하나의 항원-결합 분자를 사용하여 측정된다. 이들 실시형태에서, 표적 폴리펩타이드의 측정된 수준은 참조 폴리펩타이드의 수준에 대해 정규화된다. 적합하게는, 항원-결합 분자는 고형 또는 반고형 지지체 상에 부동화된다. 이러한 유형의 예시적인 예에서, 항원-결합 분자는 이러한 항원-결합 분자의 공간적 어레이의 일부를 형성한다. 일부 실시형태에서, 표적 폴리펩타이드에 결합된 항원-결합 분자의 수준은 면역검정법(예를 들어 ELISA를 사용함)에 의해 측정된다.
2.4 저산소증과 관련된 질병 및 질환
상기 및 본원 어디에서나 기재된 방법은 저산소증 환경에서 발생하는 것으로 공지된 임의의 질병 또는 질환의 가능성을 결정하기에 적합하다. 비제한적인 예로서, 적합한 질병 또는 질환은 암, 허혈성 뇌졸중, 관절염(예를 들어 류마티스 관절염), 염증, 연골 미란(cartilage erosion), 비정상적인 에너지 대사, 산화적 손상 등을 포함한다.
일부 실시형태에서, 저산소증 질환은 암 또는 종양에서 진단된다. 이러한 유형의 소정의 실시형태에서, 암은 고형 종양이다. 이러한 유형의 일부 실시형태에서, 암은 혈액 종양(즉, 고형 종양이 아님)이다. 암의 유형으로는, 하나 이상의 암 유형, 예컨대 원발성 암, 전이성 암, 유방암, 결장암, 직장암, 폐암, 구강인두암, 하인두암, 식도암, 위암, 췌장암, 간암, 담낭암, 담관암, 소장암, 요도암, 신장암, 방광암, 요로상피암, 여성 생식기 암, 자궁경부암, 자궁암, 난소암, 융모암종, 임신영양막병(gestational trophoblastic disease), 남성 생식기 암, 전립선암, 정낭암, 고환암, 생식세포 종양, 내분비선 종양, 갑상선암, 부신암, 뇌하수체암, 피부암, 혈관종, 흑색종, 골 및 연조직으로부터 기원하는 육종, 카포시 육종, 뇌암, 신경암, 안구암(ocular cancer), 뇌막암, 성상세포종, 신경교종, 교모세포종, 망막아종, 신경종, 신경아세포종, 슈반세포종, 수막종, 혈액학적 악성물로부터 기원하는 고형 종양, 백혈병, 호지킨 림프종, 비호지킨 림프종, 버킷 림프종, 전이성 흑색종, 재발성 또는 지속성 난소 상피암, 나팔관암, 원발성 복막암, 상피성 난소암, 원발성 복막 장액성 암, 비소세포 폐암, 위장관 기질 종양, 결장직장암, 소세포 폐암, 흑색종, 다형성아교모세포종, 비편평 비소세포 폐암, 악성 신경교종, 원발성 복막 장액성 암, 전이성 간암, 신경내분비 암종, 불응성 악성물, 삼중 음성 유방암, HER2 증폭 유방암, 편평세포암종, 비인두암, 구강암, 담도, 간세포암종, 두경부의 편평세포암종(SCCHN), 비-수질성 갑상선 암종(non-medullary thyroid carcinoma), 1형 신경 섬유종증, CNS 암, 지방 육종, 평활근육종, 침샘암, 점막 흑색종, 말단/흑자 흑색종(acral/lentiginous melanoma), 부신경절종(paraganglioma); 크롬친화성 세포종, 진행성 전이성 암, 고형 종양, 편평세포암종, 육종, 흑색종, 자궁내막암, 두경부암, 횡문근육종, 다수의 골수종, 위장관 기질 종양, 외투세포 림프종, 신경아교육종(gliosarcoma), 골육종, 불응성 악성물, 진행성 전이성 암, 고형 종양, 전이성 흑색종, 전립선암, 고형 종양, 재발성 또는 지속성 난소 상피암, 나팔관암, 폐암, 및 원발성 복막암이 있으나, 이들로 한정되는 것은 아니다.
2.5 일탈적인 G9a 발현과 관련된 질병 및 질환
상기 및 본원 어디에서나 개시된 바이오마커는 또한, 대상체에서 G9a-관련 질병 또는 질환의 존재 또는 부재의 가능성을 결정하기 위한 유용성을 가진다. 일탈적인 G9a 발현이 본원에서 저산소증 질환을 가리키는 것으로 보여지지만, 건강한 질환에 비해 증가된 G9a 폴리펩타이드를 갖는 정상산소증 환경에서 발생하는 다른 질환도 상기 및 본원 어디에서나 개시된 바이오마커를 이용하여 진단하기에 적합한 것으로 여겨진다.
예를 들어, 일탈적인 G9a 발현과 관련있는 질병 또는 질환은 콜린 결핍 질병 및 경계선 녹내장(borderline glaucoma)을 포함한다.
이에, 본 발명은 또한, 대상체에서 G9a-관련 질병 또는 질환의 존재 또는 부재의 가능성을 평가하는 데 사용되는 지표를 결정하는 방법을 제공하며, 상기 방법은: (1) 적어도 하나의 G9a-관련 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 G9a-관련 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 G9a-관련 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및 (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 G9a-관련 질환의 존재 또는 부재의 가능성을 적어도 부분적으로 가리키는 것인 단계를 포함하거나, 구성되거나, 본질적으로 구성된다.
2.6 키트
본 발명의 저산소증 바이오마커를 검출하고 정량화하는 데 필요한 모든 본질적인 시약은 키트에서 함께 조립될 수 있다. 일부 실시형태에서, 상기 키트는 적어도 하나의 저산소증 바이오마커의 정량화를 허용하는 시약을 포함한다. 일부 실시형태에서, 이러한 키트는: (i) 적어도 하나의 저산소증 바이오마커의 정량화(예를 들어 수준 또는 풍부도의 결정)를 허용하는 시약을 포함한다. 일부 실시형태에서, 상기 키트는 (ii) 제2 저산소증 바이오마커의 정량화(예를 들어 수준 또는 풍부도의 결정)를 허용하는 시약을 추가로 포함하며, 여기서, 상기 제2 저산소증 바이오마커는 G9a이다.
본 발명의 맥락에서, "키트"는 본 발명의 방법을 수행하는 데 필요한 상이한 시약을 함유하는 생성물이 이들의 수송 및 저장을 허용하도록 포장된 상기 생성물을 의미하는 것으로 이해된다. 키트의 구성성분을 포장하는 데 적합한 물질은 결정, 플라스틱(폴리에틸렌, 폴리프로필렌, 폴리카르보네이트 등), 병, 바이얼, 종이, 봉투(envelope) 등을 포함한다. 부가적으로, 본 발명의 키트는 상기 키트에 함유된 상이한 구성성분의 동시적인, 순차적인 또는 별도의 사용을 위한 설명서를 함유할 수 있다. 설명서는, 인쇄된 물질의 형태, 또는 이들 설명서가 대상체에 의해 판독될 수 있도록 설명서를 저장할 수 있는 전자 지지체 형태, 예컨대 전자 저장 매체(자기 디스크, 테이프 등), 광학 매체(CD-ROM, DVD) 등으로 존재할 수 있다. 대안적으로 또는 이에 더하여, 매체는 설명서를 제공하는 인터넷 주소를 함유할 수 있다.
저산소증 바이오마커의 정량화를 허용하는 시약은, 저산소증 바이오마커의 정량화를 허용하는 화합물이나 물질, 또는 이러한 화합물이나 물질의 세트를 포함한다. 구체적인 실시형태에서, 화합물, 물질, 또는 이러한 화합물이나 물질의 세트는, 비제한적으로 RNA 물질의 추출, 상응하는 RNA 등의 수준의 결정, 상응하는 cDNA의 합성을 위한 프라이머, DNA 증폭을 위한 프라이머, 및/또는 유전자에 의해 인코딩되는 RNA(또는 상응하는 cDNA)와 특이적으로 혼성화할 수 있는 프로브, TaqMan 프로브 등을 포함하여 유전자(예를 들어 저산소증 바이오마커 유전자)의 발현 수준의 결정을 가능하게 한다.
이러한 키트는 또한 선택적으로, 표지의 검출에 적절한 시약, 양성 및 음성 대조군, 세척 용액, 블로팅 막, 마이크로타이터 플레이트, 희석 완충제 등을 포함할 수 있다. 예를 들어, 핵산-기초 검출 키트는 (i) 저산소증 바이오마커 폴리뉴클레오타이드(양성 대조군으로서 사용될 수 있음); 및 (ii) 저산소증 바이오마커 폴리뉴클레오타이드에 특이적으로 혼성화하는 프라이머 또는 프로브를 포함할 수 있다. 또한, 증폭에 필요한 반응 혼합물을 제공하기 위해 다양한 중합효소(이용되는 핵산 증폭 기술에 따라 역전사효소, Taq, SEQUENASE™, DNA 연결효소 등), 데옥시뉴클레오타이드 및 완충제를 포함하여 핵산을 증폭시키는 데 적합한 효소가 포함될 수 있다. 이러한 키트는 또한 일반적으로, 적합한 수단에서, 각각의 개별적인 시약 및 효소, 뿐만 아니라 각각의 프라이머 또는 프로브에 대한 별개의 용기를 포함할 것이다. 대안적으로, 단백질-기초 검출 키트는 (i) 저산소증 바이오마커 폴리펩타이드(양성 대조군으로서 사용될 수 있음); 및 (ii) 저산소증 바이오마커 폴리펩타이드에 특이적으로 결합하는 항체를 포함할 수 있다. 상기 키트는 또한, 본원에 기재된 검정법 중 하나를 수행하기 위한 다양한 장치(예를 들어 하나 이상) 및 시약(예를 들어 하나 이상); 및/또는 저산소증 바이오마커 유전자의 발현을 정량화하기 위해 키트를 사용하기 위한 인쇄된 설명서를 특징으로 할 수 있다.
검출 가능한 표지와 선택적으로 결합될 수 있는 본원에 기재된 시약은, 실시예 또는 하기에 기재된 검정법, 예를 들어 본원에 기재된 RT-PCR 또는 Q PCR 기술을 이용하여 사용하도록 적응된 미세유체역학 카드(microfluidics card), 칩이나 챔버, 마이크로어레이 또는 키트의 포맷에서 제시될 수 있다.
이러한 시약은 또한, 본 발명의 바이오마커를 검출하고 정량화하기 위한 조성물에서 유용성을 가진다. 예를 들어, 역전사효소는 핵산 시료에서 mRNA를 포함하여 RNA 전사체를 역전사시켜, 역전사된 mRNA("cDNA"로도 지칭됨)를 포함하여 역전사된 전사체를 생성하는 데 사용될 수 있다. 구체적인 실시형태에서, 역전사된 mRNA는 전세포 역전사된 mRNA(본원에서 "전세포 cDNA"로도 지칭됨)이다. 핵산 시료는 적합하게는, 면역계의 구성성분으로부터 유래되며, 이의 대표적인 예는 예를 들어 상기에서 광범위하게 고찰된 바와 같이 내재 면역계 및 적응 면역계의 구성성분을 포함한다. 구체적인 실시형태에서, 역전사된 RNA는 유래된 혈액 세포(예를 들어 말초 혈액 세포)이다. 적합하게는, 역전사된 RNA는 유래된 백혈구이다.
시약은 적합하게는, 역전사된 전사체를 정량화하는 데 사용된다. 예를 들어, 역전사된 전사체에 혼성화하는 올리고뉴클레오타이드 프라이머는 적합한 핵산 증폭 기술, 예를 들어 본원에 기재된 RT-PCR 또는 qPCR 기술을 통해 역전사된 전사체의 적어도 일부를 증폭시키는 데 사용될 수 있다. 대안적으로, 올리고뉴클레오타이드 프로브는 예를 들어 상기 기재된 바와 같이 핵산 혼성화 분석 기술(예를 들어 마이크로어레이 분석)을 사용하여, 정량화를 위해 역전사된 전사체에 혼성화하는 데 사용될 수 있다. 따라서, 일부 실시형태에서, 제각기의 올리고뉴클레오타이드 프라이머 또는 프로브는 본 발명의 조성물에서 역전사된 전사체의 상보적 핵산 서열에 혼성화된다. 이러한 조성물은 전형적으로, 역전사된 전사체를 검출하며 및/또는 정량화하기 위한 표지된 시약을 포함한다. 이러한 유형의 대표적인 시약은, RNA 전사체 또는 역전사된 RNA에 혼성화하는 표지된 올리고뉴클레오타이드 프라이머 또는 프로브, 표지된 RNA, 표지된 역전사된 RNA, 뿐만 아니라 RNA 또는 역전사된 RNA를 표지하기 위한(예를 들어 말단 표지화, 예컨대 3' 말단 표지화) 표지된 올리고뉴클레오타이드 링커 또는 태그(예를 들어 표지된 RNA 또는 DNA 링커 또는 태그)를 포함한다. 프라이머, 프로브, RNA 또는 역전사된 RNA(즉, cDNA)(표지되거나 표지되지 않든간에)는 부동화되거나 용액 내에서 자유로울 수 있다. 이러한 유형의 대표적인 시약은, 역전사체 및 전사체에 혼성화하는 표지된 올리고뉴클레오타이드 프라이머 또는 프로브, 뿐만 아니라 표지된 역전사된 전사체를 포함한다. 표지는 당업계에서 공지된 바와 같은 임의의 리포터 분자일 수 있고, 이의 예시적인 예는 상기 및 본원 어디에서나 기재되어 있다.
본 발명은 또한, 비-역전사된 RNA 실시형태를 포괄하며, 여기서, cDNA는 제조되지 않고, RNA 전사체는 직접적으로 분석의 대상물이다. 따라서, 다른 실시형태에서, 시약은 적합하게는, RNA 전사체를 직접적으로 정량화하는 데 사용된다. 예를 들어, 올리고뉴클레오타이드 프로브는 본 발명의 저산소증 바이오마커의 정량화를 위해 예를 들어 상기 기재된 바와 같이 핵산 혼성화 분석 기술(예를 들어 마이크로어레이 분석)을 사용하여 전사체에 혼성화하는 데 사용될 수 있다. 따라서, 일부 실시형태에서, 제각기의 올리고뉴클레오타이드 프로브는 본 발명의 조성물에서 저산소증 바이오마커 전사체의 상보적 핵산 서열에 혼성화된다. 이러한 유형의 예시적인 예에서, 조성물은 전사체를 검출하며 및/또는 정량화하기 위해 전사체에 혼성화하는 표지된 시약을 포함할 수 있다. 이러한 유형의 대표적인 시약은 전사체에 혼성화하는 표지된 올리고뉴클레오타이드 프로브뿐만 아니라 표지된 전사체를 포함한다. 프라이머 또는 프로브는 부동화되거나 용액 내에서 자유로울 수 있다.
2.7 요법을 관리하는 방법
본 발명은 또한, 대상체에서 저산소증 질환의 존재에 대한 양성 진단 후, 저산소증과 관련된 질병 또는 질환(예를 들어 저산소증 암)의 관리, 또는 질병 또는 질환의 추가 진행의 예방, 또는 대상체에서 요법의 효능의 평가까지 연장된다. 일단 대상체가 저산소증 질환을 갖고 있는 것으로 양성으로 식별되면, 상기 대상체는 저산소증 질환을 치료하기 위한 치료제, 예컨대 G9a 길항제를 투여받을 수 있으며, 이의 예시적인 예는 국제 PCT 특허 공개 WO2015/200329 및 미국 특허 공개 2015/0274660에 기재되어 있으며, 이들은 그 전체가 원용에 의해 본 명세서에 포함된다.
본 발명과 함께 사용하기에 적합할 수 있는 G9a 길항제의 다른 예는 캐토신(chaetocin), BIX-01294, UNC0224, UNC0638, UNC0642, UNC0646 및 A-366을 포함한다.
전형적으로, 치료제는 약제학적(또는 수의학적) 조성물에서 약제학적으로 허용 가능한 담체와 함께, 이들의 의도된 목적을 달성하기에 효과적인 양으로 투여될 것이다. 대상체에게 투여되는 활성 화합물의 용량은 시간 경과에 따라 대상체에서 유익한 반응, 예컨대 저산소증에서의 감소 또는 이로부터의 경감을 달성하기에 충분해야 한다. 투여되는 약제학적 활성 화합물(들)의 양은 치료되는 대상체의 연령, 성별, 체중 및 일반적인 건강 상태를 포함하여 상기 대상체에 의존할 수 있다. 이러한 측면에서, 투여를 위한 활성 화합물(들)의 정확한 양은 실무자의 판단에 의존할 것이다. 저산소증 질환의 치료 또는 예방에서 투여되는 활성 화합물(들)의 유효량을 결정하는 데 있어서, 의사 또는 수의사는 저산소증의 존재와 관련된 임의의 증상 또는 임상 징후의 중증도를 평가할 수 있다. 임의의 사건에서, 당업자는 과도한 실험 없이 치료제의 적합한 투여량 및 적합한 치료 계획을 쉽게 결정할 수 있다.
치료제는 주요 기관으로의 산소 공급을 증가시키며, 주요 기관으로의 혈류를 증가시키며, 및/또는 염증 반응을 감소시키기 위해 부가(adjunctive)(완화(palliative)) 요법과 협력하여 투여될 수 있다. 이러한 부가 요법의 예시적인 예는 비스테로이드성-항염증 약물(NSAID, 정맥내 식염수 및 산소를 포함한다.
본 발명은 또한, 대상체에서 저산소증 질환(예를 들어 저산소증 암)을 치료하거나, 예방하거나 발병을 저해하는 방법에서 본원에 개시된 지표-결정 방법, 장치, 조성물 및 키트의 용도를 고려한다. 이들 방법(본원에서 "치료 방법"으로도 지칭됨)은 일반적으로: 본원에 개시된 바와 같은 지표-결정 방법으로부터 수득된 지표를 기초로, 저산소증 질환을 치료하기 위한 치료 계획에 대상체를 노출시키는 단계, 또는 저산소증과 관련 없는 질병 또는 질환을 치료하기 위한 치료 계획에 대상체를 노출시키지 않는 단계를 포함한다. 구체적인 실시형태에서, 치료 방법은: (a) 대상체의 적어도 하나의(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커에 대한 복수의 바이오마커 값을 결정하는 단계로서, 각각의 바이오마커 값은 제각기의 저산소증 바이오마커에 대해 측정되거나 파생된 값을 가리키는 것인 단계; (b) 복수의 바이오마커 값의 조합을 사용하여 지표를 결정하는 단계로서, 지표는 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재를 적어도 부분적으로 가리키는 것인 단계로서, 여기서: (i) 적어도 하나의(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커; 및 (ii) 지표는 저산소증의 존재 또는 부재를 진단하는 지표의 능력을 표시하는 성능 역치 이상인 성능 값을 갖는 것인, 단계; 및 (c) 지표가 저산소증 질환의 존재를 가리킨다는 것을 기초로, 저산소증 질환의 증상을 치료하거나 개선하거나 발병을 역전시키거나 저해하는 유효량의 작용제를 대상체에게 투여하는 단계를 포함한다.
유리한 실시형태에서, 치료 방법은: (1) 복수의 측정된 바이오마커 값을 결정하는 단계로서, 각각의 측정된 바이오마커 값은 대상체의 개별적인 저산소증 바이오마커의 측정된 값인 단계; 및 (2) 측정된 바이오마커 값 중 적어도 2개에 함수(function)를 적용하여, 적어도 하나의 파생된 바이오마커 값을 결정하는 단계로서, 적어도 하나의 파생된 바이오마커 값은 상응하는 파생된 저산소증 바이오마커 갓을 가리키는 것인 단계를 포함한다. 상기 함수는 적합하게는: (a) 2개의 바이오마커 값의 곱셈; (b) 2개의 바이오마커 값의 나눗셈; (c) 2개의 바이오마커 값의 덧셈; (d) 2개의 바이오마커 값의 뺄셈; (e) 적어도 2개의 바이오마커 값의 가중 합계(weighted sum); (f) 적어도 2개의 바이오마커 값의 로그 합계; (g) 적어도 2개의 바이오마커 값의 기하 평균; 및 (h) 적어도 2개의 바이오마커 값의 시그모이드 함수(sigmoidal function) 중 적어도 하나를 포함한다.
본 발명은 대상체에서 저산소증 질환의 존재 또는 발병을 진단하거나 모니터링하며, 및/또는 치료 효능에 대한 반응을 모니터링하는 것을 목적으로 하는 예측 의약 분야에서 실시될 수 있다. 본 발명의 바이오마커 프로파일 및 상응하는 지표는 추가로, 약물번역(pharmacotranslational) 연구에서 종점의 결정을 가능하게 한다. 예를 들어, 임상 시험은 저산소증 질환(예를 들어 저산소증 암)을 치료하거나 예방하는 데 사용되는 약제에 대한 약물학적 매개변수를 구축하기 위해 많은 개월 또는 심지어 수년이 소요될 수 있다. 그러나,이들 매개변수는 건강 상태(예를 들어 건강한 질환)의 바이오마커 프로파일 및 상응하는 지표와 관련있을 수 있다. 따라서, 임상 시험은, 요망되는 건강 상태(예를 들어 건강한 질환)와 관련된 바이오마커 프로파일을 초래하는 치료 계획(예를 들어 약제 및 약제학적 매개변수)을 선택함으로써 속행(expedite)될 수 있다. 이는 예를 들어: (1) 치료 계획을 이용한 치료 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 결정하는 단계; (2) 바이오마커 값을 사용하여 지표를 결정하는 단계; 및 (3) 지표가, 치료 계획을 이용한 치료 전 대상체에서 질환의 정도에 비해 건강한 질환(condition)의 존재 또는 더 낮은 정도(degree)의 질환의 존재를 가리킨다는 것을 기초로, 대상체의 건강 상태를 요망되는 건강 상태(예를 들어 건강한 질환)로 변화시키기에 효과적인지 결정하는 단계에 의해 결정될 수 있다. 본원에 사용된 바와 같이, 용어 "정도"는 질환의 규모(extent) 또는 단계(stage)를 지칭한다. 대안적으로, 치료 계획의 선택은: (a) 치료 계획을 이용한 치료 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커에 대한 복수의 바이오마커 값을 결정하는 단계로서, 각각의 바이오마커 값은 제각기의 저산소증 바이오마커에 대해 측정되거나 파생된 값을 가리키는 것인 단계; (b) 복수의 저산소증 바이오마커 값의 조합을 사용하여 지표를 결정하는 단계로서, 상기 지표는 저산소증 질환의 존재 또는 부재를 적어도 부분적으로 가리키는 것인 단계로서, 여기서: (i) 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커는, 상호 연관 범위 내에 있는 적어도 하나의 질환에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 지표는, 저산소증 질환의 존재 또는 부재를 진단하거나 적어도 하나의 질환에 대한 예후를 제공하는 지표의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산(explained variance)을 가리키는 것인 단계; 및 (c) 지표가, 치료 계획을 이용한 치료 전 대상체에서 저산소증의 정도에 비해 정상산소증의 존재 또는 더 낮은 정도의 저산소증의 존재를 가리킨다는 것을 기초로, 대상체의 상태를 요망되는 상태(예를 들어 정상산소증)로 변화시키기에 효과적인지 결정하는 단계에 의해 결정될 수 있다. 이에, 본 발명의 이러한 양태는 유리하게는, 이미 저산소증 질환을 진단받은 대상체에서(예를 들어 임상 시험의 맥락에서) 특정 치료 계획의 효능을 모니터링하는 방법을 제공한다. 이들 방법은 예를 들어, 치료를 받고 있는 대상체의 측정되거나 파생된 바이오마커 값이 요법의 경과 동안 또는 요법 후에 부분적으로 또는 완전히 정규화하는지(normalize) 또는 그렇지 않으면 요법에 대한 반응성과 관련된 변화를 보여주는지를 결정하기 위해 치료 효능과 연관이 있는 측정되거나 파생된 바이오마커 값을 이용한다.
이에, 본 발명은 바이오마커 프로파일을 저산소증 질환에 대한 효과적인 치료 계획과 연관시키는 방법을 제공한다. 일부 실시형태에서, 이들 방법은: (1) 저산소증을 갖고 있으며 이에 대해 효과적인 치료가 식별된 대상체의 적어도 하나의(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 정의하는(defining) 바이오마커 프로파일을 결정하는 단계; 및 (2) 이렇게 해서 결정된 바이오마커 프로파일을 저산소증 질환에 대한 효과적인 치료 계획(예를 들어 G9a 길항제)과 연관시키는 단계를 포함한다. 일부 실시형태에서, 이들 방법은: (a) 저산소증을 갖고 있으며 이에 대해 효과적인 치료가 식별된 대상체에 대해 측정되거나 파생될 수 있는 적어도 2개의 저산소증 바이오마커 값에 상응하는 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 바이오마커 값의 조합을 정의하는 바이오마커 프로파일을 결정하는 단계로서, 여기서: (i) 적어도 2개의 저산소증 바이오마커는 상호 연관 범위 내에 있는 질환에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 적어도 2개의 바이오마커 값의 조합은, 저산소증 질환의 존재 또는 부재를 진단하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 적어도 2개의 바이오마커 값의 조합의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산을 가리키는 것인 단계; 및 (b) 이렇게 해서 결정된 바이오마커 프로파일을 저산소증 질환에 대한 효과적인 치료 계획(예를 들어 G9a 길항제)과 연관시키는 단계를 포함한다. 구체적인 실시형태에서, 지표 또는 바이오마커 프로파일은 ROC 곡선을 사용하여 전반적인 확률 또는 특정 결과와 연관된다.
나아가, 본 발명은 치료 계획이 저산소증 질환(예를 들어 저산소증 암)을 갖는 대상체를 치료하는 데 효과적인지를 결정하는 방법을 제공한다. 일부 실시형태에서, 이들 방법은: (1) 치료 계획을 이용한 치료 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대한 치료-후(post-treatment) 측정되거나 파생된 바이오마커 값을 결정하는 단계; (2) 치료-후 바이오마커 값을 사용하여 치료-후 지표를 결정하는 단계로서, 여기서, 치료-후 지표는 저산소증 질환의 존재 또는 부재를 적어도 부분적으로 가리키는 것이며, 치료-후 지표는, 상기 치료-후 지표가 치료 계획을 이용한 치료 전 대상체에서 저산소증의 정도에 비해 건강한 질환의 존재 또는 더 낮은 정도의 저산소증의 존재를 가리킨다는 것을 기초로, 대상체에서 저산소증 질환을 치료하는 데 효과적인지 가리키는 단계를 포함한다. 다른 실시형태에서, 이들 방법은: (a) 복수의 치료-후 바이오마커 값을 결정하는 단계로서, 각각의 치료-후 저산소증 바이오마커 값은 치료 계획을 이용한 치료 후 대상체의 적어도 하나의(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커에 대해 측정되거나 파생된 값을 가리키는 것인 단계; (b) 복수의 치료-후 바이오마커 값의 조합을 사용하여 치료-후 지표를 결정하는 단계로서, 상기 치료-후 지표는 저산소증 질환의 존재 또는 부재를 적어도 부분적으로 가리키는 것이며, 여기서: (i) 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 저산소증 바이오마커는 상호 연관 범위 내에 있는 적어도 하나의 질환에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 치료-후 지표는, 저산소증 질환의 존재 또는 부재를 진단하는 치료-후 지표의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산을 가리키고, 여기서, 치료-후 지표는, 상기 치료-후 지표가 치료 계획을 이용한 치료 전 대상체에서 저산소증의 정도에 비해 건강한 질환(즉, 정상산소증)의 존재 또는 더 낮은 정도의 저산소증 질환의 존재를 가리킨다는 것을 기초로, 대상체에서 저산소증 질환을 치료하는 데 효과적인지 가리키는 단계를 포함한다.
본 발명은 또한, 대상체가 치료 계획에 반응하는지(즉, 양성 반응) 또는 반응하지 않는지(즉, 음성 반응) 평가하기 위해 실시될 수 있다. 본 발명의 이러한 양태는 양성 또는 음성 반응을 갖는 바이오마커 프로파일을 치료 계획과 연관시키는 방법을 제공한다. 일부 실시형태에서, 이들 방법은: (1) 치료 계획의 착수(commencement) 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 정의하는 바이오마커 프로파일을 결정하는 단계; 및 (2) 이렇게 해서 결정된 바이오마커 프로파일을 치료 계획에 대한 양성 또는 음성 반응과 연관시키는 단계를 포함한다. 다른 실시형태에서, 이들 방법은: (a) 치료 계획의 착수 후 대상체에 대해 측정되거나 파생될 수 있는 적어도 2개의 저산소증 바이오마커의 값에 상응하는 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 바이오마커 값의 조합을 정의하는 바이오마커 프로파일을 결정하는 단계로서, 여기서: (i) 적어도 2개의 저산소증 바이오마커는 상호 연관 범위 내에 있는 저산소증에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 적어도 2개의 바이오마커 값의 조합은, 저산소증 질환의 존재 또는 부재를 진단하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 적어도 2개의 바이오마커 값의 조합의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산을 가리키는 것인 단계; 및 (b) 이렇게 해서 결정된 바이오마커 프로파일을 치료 계획에 대한 양성 또는 음성 반응과 연관시키는 단계를 포함한다.
본 발명은 또한, 저산소증 질환을 갖는 대상체에 의한 치료 계획에 대한 양성 또는 음성 반응을 결정하는 방법을 포괄한다. 일부 실시형태에서, 이들 방법은: (1) 참조 바이오마커 프로파일을 치료 계획에 대한 양성 또는 음성 반응과 연관시키는 단계로서, 여기서, 바이오마커 프로파일은 대조군 대상체 또는 대조군의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 정의하는 것인 단계; (2) 치료 계획의 착수 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 정의하는 시료 바이오마커 프로파일을 결정하는 단계로서, 여기서, 시료 바이오마커 프로파일은, 참조 바이오마커 서명과 치료 계획에 대한 양성 또는 음성 반응의 연관을 기초로, 대상체가 치료 계획에 양성으로 또는 음성으로 반응하는지 가리킨다. 다른 실시형태에서, 상기 방법은: (a) 참조 바이오마커 프로파일을 치료 계획에 대한 양성 또는 음성 반응과 연관시키는 단계로서, 여기서, 바이오마커 프로파일은 대조군 대상체 또는 대조군으로부터 측정되거나 파생된 적어도 2개의 저산소증 바이오마커 값에 상응하는 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 바이오마커 값의 조합을 정의하는 것이며, 여기서: (i) 적어도 2개의 저산소증 바이오마커는 상호 연관 범위 내에 있는 저산소증에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 적어도 2개의 바이오마커 값의 조합은, 저산소증 질환의 존재 또는 부재를 진단하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 적어도 2개의 바이오마커 값의 조합의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산을 가리키는 것인 단계; (b) 치료 계획의 착수 후 대상체로부터 측정되거나 파생되는 어도 2개의 저산소증 바이오마커의 값에 상응하는 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 바이오마커 값의 조합을 정의하는 시료 바이오마커 프로파일을 결정하는 단계로서, 여기서, 시료 바이오마커 프로파일은, 참조 바이오마커 프로파일과 치료 계획에 대한 양성 또는 음성 반응의 연관을 기초로, 대상체가 치료 계획에 대해 양성으로 또는 음성으로 반응하는지 가리키는 단계를 포함한다.
관련된 실시형태에서, 나아가 본 발명은 생물학적 대상체에 의해 치료 계획에 대한 양성 또는 음성 반응을 결정하는 방법을 고려한다. 일부 실시형태에서, 이들 방법은: (1) 치료 계획의 착수 후 대상체의 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 바이오마커 값을 정의하는 시료 바이오마커 프로파일을 결정하는 단계로서, 여기서, 시료 바이오마커 프로파일은 치료 계획에 대한 양성 또는 음성 반응과 연관이 있는 단계; 및 (2) 대상체가 시료 바이오마커 프로파일을 기초로 한 치료 계획에 양성으로 또는 음성으로 반응하는지 결정하는 단계를 포함한다. 다른 실시형태에서, 이들 방법은: (a) 치료 계획의 착수 후 대상체에 대해 측정되거나 이로부터 파생된 적어도 2개의 저산소증 바이오마커의 값에 상응하는 적어도 2개의(예를 들어 2, 3, 4, 5, 6, 7, 8, 9, 10개 이상의) 바이오마커 값의 조합을 정의하는 시료 바이오마커 프로파일을 결정하는 단계로서, 여기서: (i) 적어도 2개의 저산소증 바이오마커는 상호 연관 범위 내에 있는 저산소증에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; (ii) 적어도 2개의 바이오마커 값의 조합은, 저산소증 질환의 존재 또는 부재를 진단하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 적어도 2개의 바이오마커 값의 조합의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 상기 성능 역치는 적어도 0.3의 설명 분산을 가리키고, 여기서, 시료 바이오마커 프로파일은 치료 계획에 대한 양성 또는 음성 반응과 연관있는 단계; 및 (b) 시료 바이오마커 프로파일을 기초로, 대상체가 치료 계획에 양성으로 또는 음성을 반응하는지 결정하는 단계를 포함한다.
상기 방법은 치료 과정 중 상대적으로 조기에, 즉, 효능의 임상적 표명 전에 반응자 또는 비-반응자를 식별하기 위해 실시될 수 있다. 이러한 방식에서, 치료 계획은 선택적으로 중단될 수 있으며, 상이한 치료 프로토콜이 수행될 수 있으며, 및/또는 보조 요법이 투여될 수 있다. 따라서, 일부 실시형태에서, 시료 저산소증 바이오마커 프로파일은 요법을 착수한 지 약 2시간, 4시간, 6시간, 12시간, 1일, 2일, 3일, 4일, 5일, 1주, 2주, 3주, 4주, 6주, 8주, 10주, 12주, 4개월, 6개월 또는 그 이상 이내에 수득된다.
본 발명은 또한, 본 발명의 지표-결정 방법이 하나 이상의 가공 장치를 사용하여 수행되는 방법을 고려한다. 일부 실시형태에서, 이들 방법은: (1) 바이오마커 값의 쌍을 결정하는 단계로서, 상기 바이오마커 값의 쌍은 그룹 1 저산소증 바이오마커 유전자(예를 들어 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1) 및 그룹 2 저산소증 바이오마커 유전자(예를 들어 G9a)의 폴리뉴클레오타이드 발현 생성물의 농도를 가리키는 제1 바이오마커 값으로 구성되는 단계; (2) 두 바이오마커 값 모두를 사용하여 폴리뉴클레오타이드 발현 생성물의 농도의 비를 가리키는 지표를 결정하는 단계; (3) 이전에 결정된 지표 참조를 데이터베이스로부터 회수하는(retrieve) 단계로서, 상기 지표 참조는 참조 집단으로부터 결정된 지표를 기초로 결정되고, 하나의 그룹은 저산소증 질환을 진단받은 개체로 구성되는 단계; (4) 지표를 지표 참조와 비교하는 단계; (5) 비교 결과를 사용하여, 저산소증 질환을 갖거나 갖지 않는 대상체를 가리키는 확률을 결정하는 단계; 및 (6) 확률의 표시를 발생시키는 단계로서, 상기 표시는 사용자가 저산소증 질환을 갖는 생물학적 대상체의 가능성을 평가할 수 있도록 사용자에게 디스플레이되는 단계를 포함한다.
유사한 장치는 저산소증 질환을 갖는 대상체의 가능성을 결정하는 데 제공될 수 있으며, 장치는: (A) 대상체로부터 취해진 시료를 수득하는 시료화 장치로서, 상기 시료는 폴리뉴클레오타이드 발현 생성물을 포함하는 것인, 시료화 장치; (B) 시료 내에서 폴리뉴클레오타이드 발현 생성물을 정량화하여, 3개의 바이오마커 값을 결정하는 측정 장치로서, 적어도 하나의 바이오마커 값은: (a) 그룹 1 저산소증 바이오마커 유전자(예를 들어 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1) 및 그룹 2 저산소증 바이오마커 유전자(예를 들어 G9a)의 폴리뉴클레오타이드 발현 생성물의 농도를 가리키는 바이오마커 값의 제1 쌍으로 구성된 것인, 측정 장치; (C) 적어도 하나의 가공 장치로서: (i) 측정 장치로부터 바이오마커 값의 쌍의 지표를 수용하며; (ii) 바이오마커 값을 사용하여 제1, 제2 및 제3 폴리뉴클레오타이드 발현 생성물의 농도의 비를 사용하여 지표를 결정하며; (iii) 지표를 적어도 하나의 지표 참조와 비교하며; (iv) 비교 결과를 사용하여 저산소증 질환을 갖거나 갖지 않는 대상체의 가능성을 결정하고; (v) 사용자에게 디스플레이하기 위해 지표 및 가능성의 표시를 발생시키는 가공 장치를 포함한다.
본 발명은 또한, 대상체에서 저산소증과 정상산소증을 구별하는 방법을 포괄한다. 이들 방법은 적합하게는: (a) 저산소증 질환의 임상 징후(예를 들어 저산소증 질환)를 보여주는 대상체로부터 취해진 시료를 수득하는 단계로서, 상기 시료는 폴리뉴클레오타이드 발현 생성물을 포함하는 것인 단계; (b) 측정 장치에서: (i) 시료 내 적어도 일부의 폴리뉴클레오타이드 발현 생성물을 증폭시키며; (ii) 그룹 1 저산소증 바이오마커 유전자(예를 들어 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1) 및 그룹 2 저산소증 바이오마커 유전자(예를 들어 G9a)의 폴리뉴클레오타이드 발현 생성물의 제1 쌍에 대한 증폭 양을 포함하여, 정의된 수준의 폴리뉴클레오타이드 발현 생성물을 수득하는 데 필요한 증폭 정도를 표시하는 증폭 양을 결정하는 단계; (c) 가공 시스템에서: (i) 증폭 양을 회수하는 단계; (ii) 제1 쌍에 대한 증폭 양 사이의 차이를 결정함으로써 폴리뉴클레오타이드 발현 생성물 제1 쌍의 농도의 비를 가리키는 제1 파생된 바이오마커 값을 결정함으로써 지표를 결정하는 단계; (d) 파생된 바이오마커 값을 사용하여 지표를 결정하는 단계; (e) 이전에 결정된 지표 참조를 데이터베이스로부터 회수하는 단계로서, 여기서, 지표 참조는 참조 집단의 제1 및 제2 그룹에 대해 결정된 지표의 분포이고, 상기 제1 및 제2 그룹은 저산소증 질환을 진단받은 개체 및 정상산소증 질환을 갖는 개체로 제각기 구성되는 단계; (f) 지표를 제1 및 제2 지표 참조와 비교하는 단계; (g) 비교 결과를 사용하여, 대상체가 제1 또는 제2 그룹 내에서 분류되는 확률을 결정하는 단계; (h) 지표 및 확률을 적어도 부분적으로 가리키는 표시를 발생시키는 단계; 및 (i) 사용자가 저산소증 질환 또는 정상산소증 질환을 갖는 대상체의 가능성을 평가할 수 있도록 사용자에게 표시를 제공하는 단계를 포함한다.
부가적으로, 저산소증 질환의 존재 또는 부재를 갖는 대상체의 가능성을 평가하거나, 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 데 사용되는 지표를 결정하는 방법이 제공될 수 있다. 이들 방법은 적합하게는: (1) 복수의 바이오마커 값을 결정하는 단계로서, 각각의 바이오마커 값은 대상체의 적어도 하나의 상응하는 저산소증 바이오마커에 대해 측정되거나 파생된 값을 가리키고 대상체로부터 취해진 시료에서 저산소증 바이오마커의 농도를 적어도 부분적으로 가리키는 것인 단계; (2) 복수의 바이오마커 값의 조합을 사용하여 지표를 결정하는 단계로서, 여기서: 적어도 2개의 바이오마커는 상호 연관 범위 내에 있는 저산소증 질환에 관하여 상호 연관을 가지며, 상기 상호 연관 범위는 ±0.9 사이이고; 지표는, 저산소증 질환의 존재 또는 부재를 진단하거나 저산소증과 관련된 질병 또는 질환에 대한 예후를 제공하는 지표의 능력을 표시하는 성능 역치 이상의 성능 값을 가지며, 성능 역치는 적어도 0.3의 설명 분산을 가리키는 것인 단계를 포함한다.
2.8 보조 치료
일부 실시형태에서, 상기 또는 본원 어디에나 기재된 치료 계획은 G9a 길항제를 보조 치료와 함께 투여하는 단계를 포함하는 병용 요법을 포함한다.
화학 요법 및 방사선 요법은 분열중인 세포를 신속하게 표적화하며 및/또는 세포 주기 또는 세포 분열을 교란시키는 것으로 잘 공지되어 있다. 이들 치료는 몇 가지 형태의 암 및 자가면역 질병을 치료하는 일부로서 제공되며, 치유 치료에 의해 질병의 진행을 늦추거나 그 증상을 역전시키는 것을 목적으로 한다. 따라서, 일부 실시형태에서, 대상체가 저산소증 질환(예를 들어 암 또는 종양)을 갖는 가능성을 결정하는 경우, 병용 요법은 화학치료제와 함께 투여되는 G9a 저해제를 이용할 수 있으며, 상기 화학치료제는 적합하게는 세포정지제 및 세포독성제로부터 선택된다. 세포정지제의 비제한적인 예는: (1) 미세소관-안정화 작용제, 예컨대 비제한적으로 탁산(taxane), 파클리탁셀(paclitaxel), 도세탁셀(docetaxel), 에포틸론(epothilone) 및 라울리말리드(laulimalide); (2) 키나제 저해제로서, 이의 예시적인 예로는 Iressa®, Gleevec, Tarceva™(에를로티닙(Erlotinib) HCl), BAY-43-9006을 포함하는 키나제 저해제, 스플리트(split) 키나제 도메인 수용체 티로신 키나제 서브그룹의 저해제(예를 들어 PTK787/ZK 222584 및 SU11248); (3) 수용체 키나제 표적화된 항체로서, 비제한적으로 트라스투주맙(Trastuzumab)(Herceptin®), 세툭시맙(Cetuximab)(Erbitux®), 베바시주맙(Bevacizumab)(Avastin™), 리툭시맙(Rituximab)(Ritusan®), 페르투주맙(Pertuzumab)(Omnitarg™); (4) mTOR 경로 저해제로서, 이의 예시적인 예로는 라파마이신(rapamycin) 및 CCI-778; (5) Apo2L/Trail, 항-혈관신생제, 예컨대 비제한적으로 엔도스타틴(endostatin), 콤브레스타틴(combrestatin), 안지오스타틴(angiostatin), 트롬보스폰딘(thrombospondin) 및 혈관 내피 성장 저해제(VEGI); (6) 항신생물 면역요법 백신으로서, 이의 대표적인 예로는 활성화된 T-세포, 비-특이적 면역 강화제(즉, 인터페론, 인터루킨); (7) 항생제 세포독성제, 예컨대 비제한적으로 독소루비신(독소루비신), 블레오마이신(bleomycin), 닥티노마이신(dactinomycin), 다우노루비신(daunorubicin), 에피루비신(epirubicin), 미토마이신(mitomycin) 및 미토잔트론(mitozantrone); (8) 알킬화제로서, 이의 예시적인 예로는 멜팔란(Melphalan), 카르무스틴(Carmustine), 로무스틴(Lomustine), 사이클로포스파미드, 이포스파미드(Ifosfamide), 클로람부실(Chlorambucil), 포테무스틴(Fotemustine), 부술판(Busulfan), 테모졸로마이드(Temozolomide) 및 티오테파(닐루타미드(Nilutamide)); (9) 호르몬 항신생물제, 이의 비제한적인 예로는 닐루타미드, 사이프로테론 아세테이트(Cyproterone acetate), 아나스트로졸(Anastrozole), 엑세메스탄(Exemestane), 타목시펜(Tamoxifen), 랄록시펜(Raloxifene), 비칼루타미드(Bicalutamide), 아미노글루테티미드(Aminoglutethimide), 류프로렐린 아세테이트(Leuprorelin acetate), 토레미펜 시트레이트(Toremifene citrate), 레트로졸(Letrozole), 플루타미드(Flutamide), 메게스트롤 아세테이트(Megestrol acetate) 및 고세렐린 아세테이트(Goserelin acetate); (10) 생식 호르몬(gonadal hormone), 예컨대 비제한적으로 사이프로테론 아세테이트 및 메독시프로게스테론 아세테이트(Medoxyprogesterone acetate); (11) 항대사물질로서, 이의 예시적인 예로는 시타라빈(Cytarabine), 플루오로우라실, 겜시타빈(Gemcitabine), 토포테칸(Topotecan), 하이드록시우레아, 티오구아닌, 메토트렉세이트, 콜라스파제(Colaspase), 랄티트렉세드(Raltitrexed) 및 카피시타빈(Capicitabine); (12) 동화제(anabolic agent), 예컨대 비제한적으로 난드롤론(Nandrolone); (13) 부신 스테로이드 호르몬으로서, 이의 예시적인 예로는 메틸프레드니솔론 아세테이트, 덱사메타손(Dexamethasone), 하이드로코티손(Hydrocortisone), 프레드니솔론 및 프레드니손(Prednisone); (14) 신생물제, 예컨대 비제한적으로 이리노테칸(Irinotecan), 카르보플라틴(Carboplatin), 시스플라틴, 옥살리플라틴(Oxaliplatin), 에토포시드(Etoposide) 및 다카르바진(Dacarbazine); 및 (15) 토포이소머라제 저해제로서, 이의 예시적인 예로는 토포테칸 및 이리노테칸으로부터 선택된다.
예시적인 세포독성제는 세르테네프(sertenef), 카켁틴(cachectin), 이포스파미드(Ifosfamide), 타소네르민(tasonermin), 로니다민(lonidamine), 카르보플라틴(Carboplatin), 알트레타민(altretamine), 프레드니무스틴(prednimustine), 디브로모둘시톨, 라니무스틴(ranimustine), 포테무스틴(Fotemustine), 네다플라틴(nedaplatin), 옥살리플라틴(oxaliplatin), 테모졸로마이드(Temozolomide)(TEMODAR™, Schering-Plough Corporation, 미국 뉴저지주 케닐워스 소재), 사이클로포스파미드, 헵타플라틴(heptaplatin), 에스트라무스틴(estramustine), 임프로술판 토실레이트(improsulfan tosilate), 트로포스파미드(trofosfamide), 니무스틴(nimustine), 디브로스피듐 클로라이드, 퓨미테파(pumitepa), 로바플라틴(lobaplatin), 사트라플라틴(satraplatin), 프로피로마이신(profiromycin), 시스플라틴, 독소루비신, 이로풀벤(irofulven), 덱스이포스파미드, cis-아민디클로로(2-메틸-피리딘)백금, 벤질구아닌, 글루포스파미드, GPX100, (trans, trans, trans)-비스-mu-(헥산-1,6-디아민)-mu-[디아민-백금(II)]비스[디아민(클로로)백금(II)] 테트라클로라이드, 디아리지디닐스페르민, 아르센 트리옥사이드(arsenic trioxide), 1-(11-도데실아미노-10-하이드록시운데실)-3,7-디메틸크산틴, 조루비신, 이다루비신, 다우노루비신(daunorubicin), 비산트렌(bisantrene), 미톡산트론(mitoxantrone), 피라루비신(pirarubicin), 피나피드(pinafide), 발루비신(valrubicin), 암루비신(amrubicin), 안티네오플라스톤(antineoplaston), 3'-데안시노-3'-모르폴리노-13-데옥소-10-하이드록시카르미노마이신, 안나마이신, 갈라루비신, 엘리나피드, MEN10755, 4-데메톡시-3-데아미노-3-아지리디닐-4-메틸설포닐-다우놈비신(국제 공개 WO 00/50032 참조), 메토트렉세이트, 겜시타빈 및 이들의 혼합물로부터 선택될 수 있다.
방사선 요법은 DNA 손상을 유도하는 방사선 및 파장, 예를 들어 g-조사, X-선, UV 조사, 마이크로파, 전자적 방출, 방사성 동위원소 등을 포함한다. 이러한 요법은 국소화된 종양 부위에 상기 기재된 형태의 방사선을 조사함으로써 달성될 수 있다. 이들 모든 인자가 DNA의 전구체 상에서 광범위한 손상 DNA, DNA의 복제와 수선, 및 염색체의 조립과 유지에 영향을 미칠 가능성이 크다.
X-선에 대한 선량 범위는 연장된 기간(3 내지 4주) 동안 50 내지 200 뢴트겐의 일일 선량으로부터 2000 내지 6000 뢴트겐의 단일 선량까지의 범위이다. 방사선 동위원소에 대한 선량 범위는 광범위하게 다르고, 동위원소의 반감기, 방출되는 방사선의 강도와 유형, 및 신생 세포에 의한 흡수에 의존한다.
방사산 요법의 비제한적인 예로는, 단일 샷 또는 분획화된 정위적 외부 빔 방사선 요법(4 내지 8주에 걸쳐 분획으로서 주어지는 50 내지 100 그레이(Grey)), 고선량률 근접 요법(high dose rate brachytherapy), 영구 간질 근접 요법(permanent interstitial brachytherapy), 전신 방사성 동위원소(systemic radio-isotope)(예를 들어 스트론튬 89)가 있다. 일부 실시형태에서, 방사선 요법은 방사선민감제(radiosensitizing agent)와 조합되어 투여될 수 있다. 방사선민감제의 예시적인 예로는, 에파프록시랄(efaproxiral), 에타니다졸(etanidazole), 플루오솔(fluosol), 미소니다졸(misonidazole), 니모라졸(nimorazole), 테모포르핀(temoporfin) 및 티라파자민(tirapazamine)이 있다.
화학치료제는 하기 범주 중 임의의 하나 이상으로부터 선택될 수 있다:
(i) 의학 종양학에서 사용되는 바와 같은 항증식성/항신생물 약물 및 이들의 조합, 예컨대 알킬화제(예를 들어 시스플라틴, 카르보플라틴, 사이클로포스파미드, 질소 머스타드, 멜팔란, 클로람부실, 부술판 및 니트로소우레아); 항대사물질(예를 들어 항폴레이트(antifolate), 예컨대 플루오로피리딘, 예컨대 5-플루오로우라실 및 테가푸르(tegafur), 랄티트렉세드, 메토트렉세이트, 시토신 아라비노시드 및 하이드록시우레아; 항종양 항생제(예를 들어 안트라사이클린, 예컨대 아드리아마이신(adriamycin), 블레오마이신, 독소루비신, 다우노마이신(daunomycin), 에피루비신, 이다루비신, 미토마이신-C, 닥티노마이신 및 미트라마이신(mithramycin)); 항유사분열제(antimitotic agent)(예를 들어 빈카 알칼로이드(vinca alkaloid), 예컨대 빈크리스틴(vincristine), 빈블라스틴(vinblastine), 빈데신(vindesine) 및 비노렐빈(vinorelbine) 및 탁소이드(taxoid), 예컨대 파클리탁셀 및 도세탁셀; 및 토포이소머라제 저해제(예를 들어 에피포도필로톡신(epipodophyllotoxin), 예컨대 에토포시드(etoposide) 및 테니포시드(teniposide), 암사크린(amsacrine), 토포테칸 및 캄토테신(camptothecin));
(ii) 세포정지제, 예컨대 항에스트로겐(예를 들어 타목시펜, 토레미펜(toremifene), 랄록시펜, 드롤록시펜(droloxifene) 및 이독시펜(idoxifene)), 오에스트로겐(oestrogen) 수용체 하향조절제(예를 들어 풀베스트란트(fulvestrant)), 항안드로겐(antiandrogen)(예를 들어 비칼루타미드, 플루타미드, 닐루타미드 및 사이프로테론 아세테이트), UH 길항제 또는 LHRH 효능제(예를 들어 고세렐린(goserelin), 류프로렐린(leuprorelin) 및 부세렐린(buserelin)), 프로게스토겐(progestogen)(예를 들어 메게스트롤 아세테이트), 아로마타제 저해제(예를 들어 아나스트로졸, 레트로졸, 보로졸(vorozole) 및 엑세메스탄) 및 5a-리덕타제의 저해제, 예컨대 피나스테리드(finasteride);
(iii) 암세포 침범을 저해하는 작용제(예를 들어 메탈로프로테이나제 저해제, 예컨대 마리마스타트(marimastat) 및 유로키나제 플라스미노겐 활성자 수용체 기능의 저해제);
(iv) 성장 인자 기능의 저해제로서, 예를 들어 이러한 저해제는 성장 인자 항체, 성장 인자 수용체 항체(예를 들어 항-erbb2 항체 트라스투주맙[Herceptin™] 및 항-erbb1 항체 세툭시맙[C225]), 파르네실 트랜스퍼라제 저해제, MEK 저해제, 티로신 키나제 저해제 및 세린/트레오닌 키나제 저해제, 예를 들어 표피 성장 인자 계통의 다른 저해제(예를 들어 다른 EGFR 계통 티로신 키나제 저해제, 예컨대 N-(3-클로로-4-플루오로페닐)-7-메톡시-6-(3-모르폴리노프로폭시)퀴나졸린-4-아민(게피티닙(gefitinib), AZD1839), N-(3-에티닐페닐)-6,7-비스(2-메톡시에톡시)퀴나졸린-4-아민(에를로티닙, OSI-774) 및 6-아크릴아미도-N-(3-클로로-4-플루오로페닐)-7-(3-모르폴리노프로폭시)퀴나졸리-n-4-아민(CI 1033)), 예를 들어 혈소판-유래 성장 인자 계통의 저해제, 및 예를 들어 간세포 성장 인자 계통의 저해제를 포함하는, 성장 인자 기능의 저해제;
(v) 항혈관신생제, 예컨대 혈관 내피 성장 인자의 효과를 저해하는 것들(예를 들어 항-혈관 내피 세포 성장 인자 항체 베바시주맙[Avastin™], 화합물, 예컨대 국제 특허 출원 WO 97/22596, WO 97/30035, WO 97/32856 및 WO 98/13354에 개시된 것들) 및 다른 기전에 의해 작용하는 화합물(예를 들어 리노미드(linomide), 인테그린 αvβ3 기능의 저해제 및 안지오스타틴);
(vi) 혈관 손상제, 예컨대 콤브레타스타틴(Combretastatin) A4 및 국제 특허 출원 WO 99/02166, WO00/40529, WO 00/41669, WO01/92224, WO02/04434 및 WO02/08213에 개시된 화합물;
(vii) 안티센스 요법, 예를 들어 상기 열거된 표적에 관한 것들, 예컨대 ISIS 2503, 항-ras 안티센스; 및
(viii) 유전자 요법 접근법, 예를 들어 일탈적인 유전자를 대체하는 접근법, 예컨대 일탈적인 p53 또는 일탈적인 GDEPT(유전자-지향 효소 전구약물 요법(gene-directed enzyme pro-drug therapy)) 접근법, 예컨대 시토신 데아미나제, 티미딘 키나제 또는 박테리아 니트로리덕타제 효소를 사용하는 것들, 및 화학 요법 또는 방사선 요법에 대한 환자 관용성을 증가시키기 위한 접근법, 예컨대 다약제 내성 유전자 요법(multi-drug resistance gene therapy).
면역요법 접근법은 예를 들어 환자 종양 세포의 면역원성을 증가시키기 위한 생체외 및 생체내 접근법, 예컨대 사이토카인, 예컨대 인터루킨 , 인터루킨 4 또는 과립구-대식세포 콜로니 자극 인자를 이용한 형질감염, T-세포 아네르기(anergy)를 저하시키기 위한 접근법, 형질감염된 면역 세포, 예컨대 사이토카인-형질감염된 수지상 세포를 사용한 접근법, 사이토카인-형질감염된 종양 세포주를 사용한 접근법, 및 항유전자형(anti-idiotypic) 항체를 사용한 접근법을 포함한다. 이들 접근법은 일반적으로, 암세포를 표적화하고 파괴하기 위해 면역 효과기 세포 및 분자의 사용에 의존한다. 면역 효과기는 예를 들어, 악성 세포의 표면 상에서 일부 마커에 특이적인 항체일 수 있다. 항체 단독은 요법의 효과기로서 역할을 할 수 있거나, 항체는 다른 세포를 동원하여, 세포 살해를 사실상 용이하게 할 수 있다. 항체는 또한, 약물 또는 독소(화학치료제, 방사성핵종, 리신 A 사슬, 콜라레 독소, 백일해 독소 등)에 공액되고, 단지 표적화제로서 역할을 할 수 있다. 대안적으로, 효과기는 악성 세포 표적과 직접적으로 또는 간접적으로 상호작용하는 표면 분자를 운반하는 림프구일 수 있다. 다양한 효과기 세포는 세포독성 T 세포 및 NK 세포를 포함한다.
다른 암 요법의 예는 광선 요법(phototherapy), 저온 요법(cryotherapy), 독소 요법 또는 프로-세포자멸사 요법을 포함한다. 당업자는, 이러한 목록이 암 및 다른 과다형성 병변에 이용 가능한 치료 양상의 유형을 배제하지 않음을 알 것이다.
이러한 유형의 예시적인 실시형태에서, 그룹 1 저산소증 바이오마커는 핵산 발현 생성물이고, 그룹 2 저산소증 바이오마커는 폴리펩타이드 발현 생성물이다.
본 발명이 쉽게 이해되고 실제 효과를 발휘할 수 있기 위해, 이제 특정한 바람직한 실시형태가 하기 비제한적인 예로서 기재될 것이다.
실시예
실시예 1
저산소증은 G9a 메틸트랜스퍼라제를 안정화시킨다
저산소증이 G9a 단백질의 수준을 변경시키는 기전을 결정하기 위해, MCF7 및 MDA-MB-231(MDA231) 유방암 세포를 저산소증 질환에 노출시켰다. 놀랍게도, G9a 단백질 수준에서 유의한 증가를 관찰하였다. 이러한 증가는 3시간째에 검출 가능한 한편(도 1a), H3K9을 표적화하는 2개의 다른 메틸트랜스퍼라제에서 유의한 변화가 없었다(즉, GLP 및 SUV39h1(도 1b 참조)). G9a 단백질 수준에서 이러한 증가가 G9a의 전사에서의 증가로 인한 것인지 조사하기 위해, 정량적인 PCR(qPCR)을 수행하였다. G9a 전사가 변경되지 않았음이 확인되었으며, 이는, G9a가 전사-후 조절됨을 제안한다(도 1c 참조). 사실상, 세포를 MG132(프로테아좀 저해제)와 접촉시키면, 저산소증에서가 아니라 정상산소증에서 G9a 단백질 수준에서 증가를 초래하였으며(도 1d), 이는 G9a 단백질 안정성의 저산소증-매개 조절이 프로테아좀 분해 경로의 동요(perturbation)를 수반할 수 있음을 가리킨다.
단백질 유비퀴틴화가 프로테아좀 분해와 연결되어 있으므로, 본 발명자들은 정상산소증 및 저산소증에서 G9a 유비퀴틴화의 규모를 평가하였다. 유비퀴틴화 검정법은, G9a의 폴리유비퀴틴화가 저산소증에서 유의하게 감소되었음을 드러내었다(도 1e 참조). G9a이 저산소증에서 HIF-1α 단백질과 매우 유사한 안정화 역학(stabilization dynamic)을 보여주었으므로, 본 발명자들은 G9a 단백질 안정성에 미치는 프롤릴 하이드록실라제 도메인(PHD) 효소를 저해하는 효과를 검사하였다. G9a 폴리유비퀴틴화의 수준은, DMOG 또는 데페록사민 (DFA) 중 하나로 처리된 MCF7과 MDA231 유방암 세포 둘 모두에서 G9a 단백질 수준에서의 증가(도 1g 및 1h 참조)와 일관되게 프롤릴 하이드록실라제 저해제 디메틸옥살로일글리신(DMOG)의 처리를 이용하여 뚜렷하게 감소되었다(도 1f 참조).
종합하면, 이들 데이터는, 저산소증 질환이 PHD 효소의 활성을 저해함으로써 G9a 단백질 안정화를 초래하고, 이는 HIF와는 독립적인 유전자 발현에서 변화를 용이하게 할 수 있을 것임을 강하게 제안한다.
재료 및 방법
세포 배양 및 약물 처리
유방암 세포주를 ATCC사로부터 입수하였고, ATCC 설명서에 따라 배양하였다. AT3 포유류 선암종을 이전에 기재된 바와 같이 유지시켰다(Ngiow, 2012). 모든 세포주를 미코플라즈마에 대해 정기적으로 시험하고, 쇼트 탠덤 반복 프로파일링을 사용하여 확증하였다. UNC0642를 Sigma-Aldrich사로부터 구매하고, MG132(M-1157)를 A.G. Scientific사로부터 구매하였다.
유비퀴틴화 검정법
유비퀴틴화 검정법을 이전에 기재된 바와 같이 수행하였다(문헌[Lee, Mol. Cell, 2012]). 간략하게는, 세포를 His-태깅된 유비퀴틴을 포함하는 발현 구축물로 형질감염시키고, 5 μg/ml의 MG132로 4시간 동안 처리하고, 완충제 A(6 M 구아니디늄-HCl, 100 mM 소듐 포스페이트, 10 mM Tris-HCl(pH 8.0), 5 mM 이미다졸 및 10 mM β-머캅토에탄올)에서 용해시키고, Ni2+-NTA 비드(QIAGEN)와 함께 실온에서 4시간 동안 인큐베이션하였다. 그 후에, 상기 비드를 완충제 A, 완충제 B(8 M 우레아, 100 mM 소듐 포스페이트 완충제, 10 mM Tris-HCl(pH 8.0) 및 10 mM β-머캅토에탄올) 및 완충제 C(8 M 우레아, 100 mM 소듐 포스페이트 완충제, 10 mM Tris-HCl(pH 6.3) 및 10 mM β-머캅토에탄올)로 순차적으로 세척하였다. 결합된 단백질을 완충제 D(200 mM 이미다졸, 150 mM Tris-HCl(pH 6.7), 30% 글리세롤, 0.72 M β-머캅토에탄올 및 5% SDS)를 이용하여 용출시키고, 면역블롯 분석을 받게 하였다.
실시예 2
프롤릴 하이드록실화-매개 G9a 분해
PHD 효소 활성의 저해가 G9a 단백질 안정성에서 변화를 초래하기 때문에, 본 발명자들은 공동-면역침전 검정법을 수행함으로써 G9a과 공지된 PHD 효소 사이의 상호작용을 검사하였다. 이들 실험으로부터, PHD1 및 PHD3가 G9a와 물리적으로 상호작용할 수 있었음이 분명하였다(도 2a 참조). 그러나, 항-하이드록시 프롤릴 항체를 사용하는 하이드록시프롤린 풀-다운(pull-down) 검정법은 PHD1만 G9a를 하이드록실화할 수 있었음을 드러내었다(도 2b 참조). 더욱이, G9a 하이드록실화를 정상산소증 질환에서 쉽게 검출되긴 하였지만, 이는 저산소증 질환에서는 대체로 거의 검출 불가능하였다(도 2c 참조). pVHL이 하이드록실화된 HIFα 단백질을 분해하는 데 관여하는 것으로 공지되어 있기 때문에(Ivan 등 2001; 및 Jaakkola 등 2001 참조), G9a와 pVHL 사이에서 공동-면역침전 검정법을 수행하여, G9a 분해가 또한 pVHL-의존적 방식으로 조절되었는지 결정하였다. 이러한 측면에서, G9a는 정상산소증에서 pVHL과 상호작용을 보여주었으나, 이러한 상호작용은 저산소증에서 유의하게 감소되었다(도 2d 참조). 더욱이, G9a와 pVHL 사이의 상호작용은 DMOG 처리에 의해 유의하게 저해되었으며, 이는 G9a 하이드록실화가 pVHL에 의한 G9a 인지에 필요한 본질적인 변형인 것으로 보임을 제안한다(도 2e 참조). 저산소증에서 G9a 단백질 수준을 조절하는 데 있어서 pVHL의 관여는, pVHL이 결여된 RCC4 세포주에서 추가로 확인되었다. G9a의 저산소증-의존적 안정화는 RCC4 세포에서 부재하였다. 그러나, 야생형 pVHL의 발현은 저산소증에 대한 G9a 민감성을 복구시켰다(도 2f 참조).
공지된 공통(consensus) 하이드록실화 모티프 "LXXLXP"를 기초로, 본 발명자들은 아미노산 잔기 P606 및 P1206에서 G9a 상에서 2개의 잠재적인 프롤린 하이드록실화 부위를 식별하였다. 2개의 프롤린 잔기를 부위-특이적 돌연변이유발에 의해 알라닌으로 돌연변이화시켜, G9a P2A 돌연변이체를 발생시켰다. G9a P2A 돌연변이체는 G9a-결핍 마우스 배아 섬유아세포(MEF)에서 발현된 경우 저산소증-의존적 축적을 보여주는 데 실패하였으나, 야생형 G9a와 비교하여 정상산소증에서 더 높은 수준의 단백질을 보여주는 것으로 나타났다(도 2g 참조).
그 후에, 본 발명자들은 하이드록실화 검정법을 수행하였으며, 상당한 양의 프롤린 하이드록실화가 야생형 G9a에 대해 검출된 한편, G9a P2A 돌연변이체에 대해서는 프롤린 하이드록실화가 검출 가능한 수준으로 관찰되지 않았음을 확인하였다(도 2h 참조).
이들 데이터는, PHD1 및 pVHL이 G9a 단백질 안정성을 조절하는 데 있어서 중요한 역할을 가짐을 분명하게 보여준다.
재료 및 방법
항체
하기 상업적으로 입수 가능한 항체를 사용하였다: 항-GFP(sc-8334)를 Santa Cruz Biotechnology사로부터 구매하였다. 항-HA(MMS-101P-500)를 Jomar Biosciences사로부터 구매하였다. 항-H3(ab1791), 항-H3K9me1(ab9045), 항-H3K9me2(ab1220), 항-H3K9me3(ab8898), 항-RNA 중합효소 II(ab817), 항-튜불린(ab6046), 항-폰틴(ab51500), 항-LC3(ab38394) 및 항-하이드록실 프롤린(ab37067)을 Abcam사로부터 구매하였다. 항-G9a(07-551), 항-GLP(B0422), 항-라민 A/C(05-714) 및 항-SUV39h1(S8316)을 EMD Millipore사로부터 구매하였다. 항-Flag(F3165)를 Sigma Aldrich사로부터 구매하였다. 항-HIF-1α(NB100-479), 항-PHD1(NB100-310), 항-PHD2(NBP1-30328) 및 항-PHD3(NB100-303)를 Novus Biologicals사로부터 구매하였다.
shRNA 넉다운
shRNA-매개 넉다운 세포를 이전에 기재된 바와 같이 발생시켰다(문헌[Lee, Mol. Cell, 2010]). 넉다운 세포를 발생시키기 위해, 바이러스 포장 플라스미드(pMD2.G 및 pMD-MLV)를 갖는 레트로바이러스 shRNA 구축물(shNS 및 shG9a)을 HEK293T 세포 내로 형질감염시켰다. 3일 후 표적 세포 감염에 사용하기 위해 바이러스 상층액을 수합하였다.
실시예 3
G9a 표적 유전자의 식별 및 예후 지표로서의 이의 용도
저산소증 질환에서 G9a 축적의 기능적 결과를 결정하기 위해, 본 발명자들은 정상산소증 및 저산소증 질환에 노출된 비-침묵화 대조군 shRNA(shNS) 또는 G9a shRNA(shG9a)를 발현하는 MCF7 세포로부터 단리된 RNA로부터 마이크로어레이 분석을 수행하였다. 전반적인 분석은 유전자 발현에 미치는 저산소증 및 G9a 넉다운의 일반적인 영향을 조사하였다. 가우스 곡선 접합(Gaussian curve fitting)을 사용하여, 저산소증에 반응하여 유의한 변화를 보여준 유전자를 선택하는 데 있어서 적용 가능한 컷-오프(cut-off)를 결정하였다(Hwang 등 2005에 교시된 바와 같은 방법). 저산소증-반응성 유전자는 크게는, 상향조절된 유전자 또는 하향조절된 유전자로서 범주화될 수 있었다(도 3a 참조). 유전자 침묵화에서 H3K9 메틸화에 대한 G9a 메틸트랜스퍼라제 활성 사이의 강한 연관을 고려하여(Chen 등 2010; 및 Yamamizu 등 2012), G9a를 저산소증-의존적 유전자 억제의 잠재적인 매개자로서 조사하였다(도 3b). 저산소증에 의해 하향조절된 유전자 중에서, 36%의 유전자(즉, 212개 유전자)는 이들 유전자가 G9a 넉다운 모델에서 저산소증에 의해 더 이상 하향조절되지 않았으므로 G9a-의존적인 것으로 보였다. 나머지 64%의 유전자(즉, 385개 유전자)는 G9a-독립적 유전자에서 저산소증에 의해 하향조절되었다.
종양 저산소증이 치료 내성(Vaupel, 2004) 및 암세포의 전이성 형질변환(Joyce and Pollard, 2009)와 연관있음을 고려하여, 본 발명자들은 G9a(저산소증 그 자체가 아니라)에 의해 억제되는 유전자가 환자 결과와 연관있는지 시험하였다. 유방암이 이종성이고 분자 서브타입이 양호하게 특징화되었으므로, 환자 생존율 분석을 에스트로겐 수용체-양성(ER-양성) 및 에스트로겐 수용체-음성(ER-음성) 그룹으로 나누었다. 분석을 유방암에 대한 3개의 큰 유전자 발현 데이터세트; KM 플로터, ROCK 및 TCGA에서 이들 2개 그룹 상에서 수행하였다(도 4 참조). 이전에 공개된 저산소증 마커(13개 유전자, 예를 들어 Hu 등 2009 참조)를 종양에서 저산소증에 대한 마커로서 사용하였다. 시험관내 연구의 동일한 근거를 이용하여, 본 발명자들은, 유전자의 발현이 G9a 발현과 역의 연관에 있는 유전자, 및 유전자의 발현이 저산소증(저산소증 마커에 의해 결정됨)과 역의 연관에 있는 유전자를 식별하였다. 그 후에, 이들 유전자를 도 3d에서 벤다이어그램에서 보여진 바와 같이 3개 데이터세트 사이에서의 공통성에 대해 분석하였다.
10개 유전자는, 각각의 유방암 서브타입에 대해 분석된 3개의 데이터세트 중 적어도 2개 사이에서 공통인 것으로 확인되었다(예를 들어 ER-양성에 대해 10개 유전자; 및 ER-음성에 대해 10개 유전자). 20개 유전자 중에서, 14개의 별도의 유전자가 존재하였고, 이때 6개 유전자는 오버랩핑되었다. 이들 14개 유전자 중에서, 10개 유전자만 무재발 생존율과 관련있었다(도 3c 및 도 4 참조). 이들 유전자가 예후였는지 결정하기 위해, 관련성 분석(association analysis)을 수행하여, 분석된 3개 데이터세트에서 불량한 무재발 생존율과 관련된 유전자를 확인하였다. 도 3c에서 식별된 10개 유전자(즉, ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1)를 유전자 서명으로서 무재발 생존율과 이들의 관련성에 대해 분석하였다. 10개 유전자의 평균 발현을 각각의 환자에 대한 G9a-억제된 유전자 서명으로서 사용하였다. 3개 데이터세트(KM 플로터, ROCK 및 TCGA) 각각에서 유방암 사례를 G9a-억제된 유전자 서명을 기초로 4개 사분위 중 하나에 할당하고, 무재발 생존율을 비교하였다(도 3d 내지 3f). KM 플로터 유방암 유전자 발현 데이터베이스는 분석된 최대 수의 환자를 함유하였다(n = 3524). G9a-억제된 서명의 최저 발현을 갖는 환자(1st 사분위; 검정색에서 Q1)는, 10년 후에 생존한 환자가 단지 약 50%인 더 불량한 무재발 생존율과 관련이 있는 한편, 최고 G9a-억제된 유전자 서명을 갖는 환자(사분위 4; 적색에서 Q4)는 생존한 환자가 80%에 가까운 유의하게 더 양호한 생존율과 관련이 있었다(도 3d). ROCK 및 TCGA 유전자 발현 데이터세트는 또한, G9a-억제된 유전자 서명과 무재발 생존율 사이에서 유사한 관련성을 보여주었으며, G9a-억제된 유전자 서명의 예후력(prognostic power)을 추가로 강화시켰다. ER-양성 환자 그룹에서, G9a-억제된 유전자 서명의 최저 발현을 갖는 환자 그룹(검정색에서 1st 사분위)은 그룹의 나머지(적색에서 나머지)와 비교하여 유의하게 더 불량한 생존율과 관련있었다. ER-음성 환자 그룹에서, G9a-억제된 유전자 서명을 사용한 환자 계층화는 ER-양성 그룹만큼 효율적이지는 않았다. 추가로, 유방암 환자를 4개의 조직병리학적 서브타입(내강 A, 내강 B, HER2-농화 및 기저-유사)으로 나누었다. 최저 G9a-억제된 유전자 서명을 갖는 환자의 생존율을 각각의 그룹 내에서 나머지 환자와 비교하였다(도 3f). G9a-억제된 유전자 서명은 기저-유사 그룹을 제외하고 모든 서브그룹에서 불량한 생존율과 관련된 별개의 환자 그룹(1st 사분위)을 식별할 수 있었다. 주목할 만하게는, 유전자 서명의 6개 유전자(즉, ARNTL, CEACAM7, GATA2, HHEX, KLRG1 및 OGN)는 종양 억제자 활성을 보유하는 것으로 보고되었다(Li 등 2014; Hu 등 2016; Li 등 2014; Noy 등 2010; Kershaw 등 2014; Scholzel 등 2000).
재료 및 방법
마이크로어레이 분석
간략하게는, 비-침묵화 대조군 shRNA 또는 G9a를 표적화하는 shRNA로 형질감염된 MCF7 세포를 정상산소증 또는 저산소증에 9시간 동안 노출시키고, 총 RNA를 RNAeasy Mini Kit(Qiagen)를 이용하여 단리하였으며; 500 ng의 총 RNA를 마이크로어레이 분석에 사용하였다. 마이크로어레이 분석을 Seoul National University Genome Research Facility에 의한 Affymetrix Human Gene 1.0 ST 어레이를 사용하여 수행하였다.
실시예 4
G9a 축적의 기능적 역할
환자 생존율 데이터를 사용하여 G9a-억제된 유전자 서명의 예후값을 확증할 때, 본 발명자들은 G9a-매개 억제를 반전시키는 G9a 저해제의 능력을 시험하였다. 10개의 G9a-억제된 유전자의 발현을 실시간 qPCR에 의해 분석하였다. 모든 10개 유전자의 발현은 대조군 세포에서 저산소증에 의해 유의하게 하향조절된 한편, 이러한 억제는 세포를 G9a 메틸트랜스퍼라제 활성의 저분자 저해제인 UNC0642로 처리함으로써 무효화되었다(도 4a 참조). 이는, 이들의 발현이 G9a-매개 작용을 통해 조절됨을 보여준다. G9a의 저산소증-매개 축적이 특이적 유전자의 억제를 초래하는 분자적 기전을 이해하기 위해, 염색질 면역침전(ChIP)을 10개의 G9a-억제된 유전자의 프로모터 상에서 수행하였다(도 4b 및 도 s4 참조). 저산소증은 이들 유전자의 프로모터에서 H3K9me2를 유의하게 증가시켰고, 전사 침묵화와 연관있었다(도 4b). H3K9me2에서 저산소증-매개 증가는 G9a 넉다운 또는 UNC0642 처리를 갖는 G9a-억제된 유전자의 프로모터에서 거의 완전히 무효화되었거나, 유의하게 감소되었다(도 4b 및 4c 참조). 종합하면, 이들 결과는, G9a가 H3K9me2를 증가시키는 것을 통해 특이적 유전자의 전사를 억제시키는 기전을 지지하고, H3K9me2에서 이러한 증가가 G9a의 저분자 저해제의 사용에 의해 무효화될 수 있음을 지지한다.
유방암 세포주에서 저분자 저해제를 사용한 G9a 저해의 효과
G9a의 분자 기능을 결정하기 위해, 본 발명자들은 도 3에서 획득된 유전자 발현 데이터를 이용하였으며, 인제뉴어티 경로 분석(IPA®, QIAGEN, 미국 캘리포니아주 레드우드시티 소재)의 사용을 통해 기능 주석 네트워크 분석을 수행하였다. 세포 성장 및 발달과 관련된 몇 가지 분자적 및 세포적 경로를 실시된 바와 같이 식별하였다(도 6a 참조). 또한, G9a-억제된 유전자 서명은 증가된 생존율과 관련있는 것으로 예측되었다(도 6b 참조). 웨스턴 면역블로팅 분석을 수행하여, 정상-유사(즉, MCF10A 및 Bre80 세포), 4개의 ER-양성(즉, ZR751, BT474, T47D 및 MCF7 세포) 및 8개의 ER-음성 서브타입(즉, HCC1937, HS578-T, BT549, SKBr3, MDA231, MDA157, MDA436 및 MDA468 세포)을 포함하여 14개의 상이한 유방 상피 세포에서 G9a 단백질 수준을 결정하였다. 대부분의 유방암 세포주는 정상-유사 유방 상피 세포에서 관찰된 것과 비교하여 정상산소증에서 더 높은 수준의 G9a 단백질을 발현하였다(도 6a 참조). 이들 유방암 세포주에서 G9a를 UNC0642를 사용하여 저해하는 치료적 잠재성을 평가하면, 세포 생존율은 정상-유사 Bre80 및 MCF10A 유방 상피 세포에서 영향을 받지 않은 한편, 암세포주의 생존율은 UNC0642 처리에 의해 유의하게 약화되었음이 드러났다(도 6d 참조). MCF7 및 MDA231 세포를 선택하여, UNC0642의 효과를 추가로 특징화하였다. 세포를 다양한 농도의 UNC0642의 존재 또는 부재 하에 48시간 동안 성장시켰을 때 실시간 세포 이미징을 IncuCyte Zoom을 사용하여 수행함으로써 증식을 평가하였다(도 6e 및 6a 참조). G9a의 저해는 비히클 대조군과 비교하여 증식에서 용량-의존적 감소를 초래하였다. 실험의 종료 시 UNC0642 처리된 세포(2 내지 3 μM)의 컨플루언시(confluency)는 비히클 대조군과 비교하여 2 내지 2.5배 더 적었다(도 6e 참조). 정상산소증과 저산소증 질환 둘 모두에서 세포 증식 및 생존율에 미치는 UNC0642의 저해 효과를 SRB 검정법을 수행함으로써 확인하였으며, 여기서, 48시간 처리 후 MCF7(도 6f 참조) 및 MDA231(도 6g 참조)에서 20% 미만의 세포가 존재하였다. 전반적인 H3K9me2에서 유의한 감소가 관찰되었으며(도 6h 참조), 이는 사용되는 용량이 G9a 메틸트랜스퍼라제 활성을 효과적으로 저해하고 있었음을 제안한다. 유전자 발현 분석으로부터 식별된 상당한 수의 유전자가 세포-대-세포 신호전달 및 상호작용에 관여하는 것들이었기 때문에(도 6a 참조), 본 발명자들은 정상산소증 및 저산소증 질환 하에 스크래치 상처 검정법을 수행함으로써 G9a의 약물학적 저해가 유방암 세포 운동성에 영향을 주는지 검사하였다.
스크래치 상처 검정법은, UNC0642가 비히클 대조군과 비교하여 처리된 세포에서 관찰된 더 큰 노출된 영역(denuded area)에 의해 실증된 바와 같이 세포 이동을 저해할 수 있었음을 드러내었다(도 7a 및 7b). 세포 이동에 미치는 UNC0642의 저해 효과는 또한, 세포가 심지어 72시간 후에도 상처에 근접할 수 없었던 저산소증 질환에서 명백하였다.
저산소증 질환에서 shNS 및 shG9a를 발현하는 MCF7(ER-양성) 세포를 비교하는 추가의 스크래치 상처 검정법은, G9a 넉다운이 세포의 이동 능력에서 감소를 초래함을 실증하였다(도 7c 및 7d 참조). 종합하여, 이들 결과는, 세포 증식 및 이동을 증강시키는 데 있어서 G9a의 종양원성 기능을 입증한다.
재료 및 방법
정량적인 실시간 RT-PCR 및 ChIP 검정법
정량적인 RT-PCR 및 ChIP 검정법을 이전에 기재된 바와 같이 수행하였다. 간략하게는, 총 RNA를 Trizol(Invitrogen)을 사용하여 단리시키고, Superscript III cDNA 합성 키트(Invitrogen)를 사용하여 2.5 μg의 총 RNA로부터 역전사를 수행하였다. SYBR Green Master Mix(Life Technologies)와 함께 ABI VIIA7 시스템에 의해 mRNA의 풍부도를 검출하였다. 90 내지 150 bp mRNA 특이적 단편을 증폭시키도록 프라이머 쌍을 설계하였으며, 이들 프라이머 쌍을 용융 곡선 분석에 의해 독특한 생성물로서 확인하였다. mRNA의 양을 △△Ct 방법을 사용하여 계산하고, 프라이머를 사용함으로써 정규화하여 HPRT를 검출하였다. 모든 반응을 3벌 중복으로 수행하였다.
사용된 프라이머 서열에 대해서는 표 7을 참조한다.
Figure pct00020
Figure pct00021
IncuCyte 실시간 이미징, 설포로다민 B(SRB) 및 MTT 검정법
증식 연구를 위해, 세포(5 × 103)를 96-플레이트 웰에 접종하고, 밤새 부착시켰으며, 그 후에 G9a 저해제 UNC0642(Sigma Aldrich) 또는 비히클 대조군 DMSO(Sigma Aldrich)의 존재 하에 신선한 성장 배지 내에서 인큐베이션하였다. IncuCyte Zoom(Essen BioScience)을 사용한 실시간 이미징을 통해, 또는 처리 종점 시 SRB 검정법을 수행함으로써, 증식을 평가하였다. SRB 검정법을 위해, 배지를 흡인하고, 세포를 메틸화된 스피리트(spirit)에서 고정한 후, 물로 세척하고 SRB(Sigma Aldrich) 용액(1% 아세트산 중 0.4%)으로 염색시켰다. 564 nm에서 광학 플레이트 판독기를 사용하여 염색 강도를 수득하였다. 3-(4,5-디메틸티아졸-2-일)-2,5-디페닐테트라졸륨 브로마이드(MTT) 검정법을 사용하여 세포 생존력(viability)을 결정하였다. 세포(3 × 103/웰)를 96-웰 플레이트 내로 직접적으로 접종하고, 밤새 부착시켰다. 약물 처리 후 96시간째에, 20 μL의 MTT(5 mg/mL; Sigma-Aldrich)를 첨가하였다. 플레이트를 37℃에서 3시간 동안 인큐베이션한 후, 상층액을 제거하고, 100 μL의 이소프로판올을 각각의 웰에 첨가하였다. 각각의 웰의 흡광도 값(광학 밀도)을 570 nm에서 측정하였다.
유방암 전반적인 유전자 발현의 메타-분석
마이크로어레이 분석으로부터 식별된 유전자(212개 유전자)를 유방암으로부터의 3개의 큰 유전자 발현 데이터세트; TCGA, ROCK 및 KM 플로터 데이터세트에서 조사하였다. 3개 데이터세트(TCGA, ROCK 및 KM 플로터) 각각에서 유방암 사례를 저산소증-G9a 서명을 기초로 4개 사분위 중 하나에 할당하고, 이들 환자의 생존율을 비교하였다. 본 발명자들은 또한, KM 플로터 데이터세트(버전 2014)를 사용하여, 최저 발현을 갖는 종양(하부 25%, 사분위 1)과 나머지 종양 사이에서 유방암 환자의 무재발 생존율을 비교하였다. GraphPad Prism v 6.0(GraphPad 소프트웨어, 미국 캘리포니아주 샌디에고 소재)을 사용하여 생존율 곡선을 구축하고, 로그-순위(Mantel-Cox) 검정을 생존율 곡선의 통계학적 비교에 사용하였다.
실시예 5
G9a 저해는 생체내에서 종양 성장을 감소시킨다
G9a 메틸트랜스퍼라제 활성의 저해가 종양 성장에 미치는 효과를 결정하기 위해, AT3 동계 유방 종양 세포를 C57BL/6 마우스에게 피하 주사하고, 만져질 정도의 종양이 형성되도록 한 후(2주에 걸쳐), UNC0642 G9a 저해제(도 8a)를 투여하였다. 시험관내 데이터와 일관되게, UNC0642의 투여는 종양 성장을 유의하게 감소시켰다(도 8b). 종료점에서 평균 종양 부피는 비히클 처리군과 비교하여 UNC0642 처리군에서 유의하게 더 작았으며(도 8c), 이는 종양 성장이 생체내에서 G9a 저해제의 투여에 의해 억제될 수 있음을 실증한다.
재료 및 방법
C57BL/6 마우스를 ARC Animal Resources Center로부터 구매하였다. 1개 실험 당 8 내지 10 마리의 마우스로 된 그룹을 실험 종양 검정법에 사용하여, 생물학적 차이를 검출하는 적절한 힘을 보장하였다. 모든 실험은 QIMR Berghofer Medical Research Institute Animal Ethics Committee에 의해 승인을 받았다. 총 1 x106개 AT3 종양 세포를 100 μL 부피로 마우스에게 피하 주사하고(제0일), UNC0642를 제16일 내지 제36일 사이에 2일마다 투여하였다. 종양 성장을 디지털 캘리퍼를 사용하여 측정하고, 종양 부피를 평균 ± SEM으로서 제시한다.
실시예 6
예후 지표로서의 G9a 서명
식별된 저산소증 마커가 임상 진단 및/또는 예후에 적합함을 실증하기 위해, 상기 유방암 모델에서 식별된 바이오마커를 다른 저산소증 암 유형(즉, 신장 투명 세포 암종 및 폐 선암종)에서 평가하였다. 도 9a 및 도 9b는 환자 생존율의 소급 적용(retrospective) 메타-분석에서 환자 생존율 곡선을 보여준다. 환자를 10개의 상기-식별된 저산소증 바이오마커의 이들의 평균 발현에 따라 계층하였다.
암 게놈 아틀라스(TCGA)로부터의 신장 투명 세포 암종을 갖는 환자로부터의 데이터를 사분위로 나누고(도 9a), 카플란 마이어 플로터로부터의 폐 선암종 환자 데이터세트를 이들이 "저(low)" 또는 "고(high)" 수준의 저산소증 바이오마커를 발현하는지에 따라 2개의 그룹으로 나누었다. 두 암 유형 모두에서, 고 수준의 저산소증 바이오마커를 발현하는 환자는 더 낮은 발현 수준의 저산소증 바이오마커를 갖는 환자와 비교했을 때 더 양호한 생존율 기회와 관련 있는 것으로 실증되었다.
다음, 흑색종 환자를 분석하였다. 도 9c는, G9a 발현이 또한 흑색종의 생존율 결과와 관련 있고, 구체적으로 낮은 양의 G9a 단백질을 발현하는 환자는 많은 양을 발현하는 환자보다 질병에서 생존할 가능성이 더 크다는 것을 실증한다(도 9c). 유사하게는, 도 9d는, 낮은 수준의 G9a 단백질이, 많은 양의 G9a 단백질을 갖는 환자보다 상기 환자가 무재발로 남아 있을 증가된 가능성과 연관 있음을 보여준다.
G9a 발현은 또한, 전이성 흑색종에서 생존율 결과와 특이적으로 관련있다. 예를 들어, G9a 발현을 사용하여 계층화된 환자의 전체 생존율을 모든 흑색종 환자(471명의 환자; 좌측 그래프) 및 전이성 환자(368명의 환자; 우측 그래프) 사이에서 비교하였고, 두 그룹 모두에서 전체 생존율은 낮은 수준의 G9a 단백질을 갖는 대상체에서 증가하였음을 확인하였다.
환자를 저산소증 바이오마커의 서브세트(즉, ARNTL, CD1C, HHEX, KLRG1 및 MMP16)의 평균 발현을 기초로 4개 사분위 중 하나로 할당하였다. 저산소증 바이오마커의 서브세트는 흑색종에서 전체 생존율 및 무재발 생존율과 분명하게 관련 있다. 더 높은 평균 발현을 갖는 환자(예를 들어 4th 사분위)는 더 낮은 발현을 환자(예를 들어 사분위 1)와 비교하여 더 양호한 전체 생존율(좌측 그래프) 및 무재발 생존율(우측 그래프)과 관련있었다.
본원에서 인용된 모든 특허, 특허 출원 및 공개의 개시내용은 그 전체가 원용에 의해 본 명세서에 포함된다.
본원에서 임의의 참조의 인용은 이러한 참조가 본 출원에 대한 "선행 기술"로서 이용 가능하다는 것을 용인하는 것으로 간주되어서는 안된다.
명세서 전체에서, 목적은 본 발명을 임의의 하나의 실시형태 또는 특징의 구체적인 집합으로 제한하지 않으면서 본 발명의 바람직한 실시형태를 기재하는 것이었다. 따라서, 당업자는, 본 개시내용의 측면에서, 본 발명의 범위로부터 벗어나지 않으면서 예시된 특정 실시형태에서 다양한 변형 및 변화가 이루어질 수 있음을 이해할 것이다. 이러한 모든 변형 및 변화는 첨부된 청구항의 범위 내에 포함되고자 한다.
참고문헌 (bibliography)
Harris AL (2002) Hypoxia--a key regulatory factor in tumor growth. Nat Rev Cancer 2(1): 38-47.
Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10): 721-732.
Vaupel P (2004) Tumor microenvironmental physiology and its implications for radiation oncology. Semin Radiat Oncol 14(3): 198-206.
Bache M, Kappler M, Said HM, Staab A, & Vordermark D (2008) Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies. Curr Med Chem 15(4): 322-338.
Erler JT, et al. (2004) Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol 24(7): 2875-2889.
Semenza GL (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 35(2): 71-103.
Hill RP, Marie-Egyptienne DT, & Hedley DW (2009) Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol 19(2): 106-111.
Pennacchietti S, et al. (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3(4): 347-361.
Chang Q, Jurisica I, Do T, & Hedley DW (2011) Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res 71(8): 3110-3120.
McGary EC, Lev DC, & Bar-Eli M (2002) Cellular adhesion pathways and metastatic potential of human melanoma. Cancer Bio Ther 1(5): 459-465.
Lee HK, Lee DS, & Park JC (2015) Nuclear factor I-C regulates E-cadherin via control of KLF4 in breast cancer. BMC Cancer 15: 113.
Scully OJ, Bay BH, Yip G, & Yu Y (2012) Breast cancer metastasis. Cancer Gen Prot proteomics 9(5): 311-320.
Ema M, et al. (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A 94(9): 4273-4278.
Semenza GL & Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Molecular and cellular biology 12(12): 5447-5454.
Dewhirst MW, Cao Y, & Moeller B (2008) Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8(6): 425-437.
Poon E, Harris AL, & Ashcroft M (2009) Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev Mol Med 11: e26.
Ivan M, et al. (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292(5516): 464-468.
Jaakkola P, et al. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292(5516): 468-472.
Maxwell PH, et al. (1999) The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399(6733): 271-275.
Ohh M, et al. (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2(7): 423-427.
Yun Z, Maecker HL, Johnson RS, & Giaccia AJ (2002) Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell 2(3): 331-341.
Chakrabarti J, et al. (2004) The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumor grade in human breast cancers. Br J Cancer 91(5): 954-958.
Ivanov SV, Salnikow K, Ivanova AV, Bai L, & Lerman MI (2007) Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13. Oncogene 26(6): 802-812.
Tachibana M, et al. (2005) Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 19(7): 815-826.
Chen MW, et al. (2010) H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res 70(20): 7830-7840.
Dong C, et al. (2012) G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest 122(4): 1469-1486.
Liu S, et al. (2015) G9a is essential for EMT-mediated metastasis and maintenance of cancer stem cell-like characters in head and neck squamous cell carcinoma. Oncotarget 6(9): 6887-6901.
Zhong X, et al. (2015) Overexpression of G9a and MCM7 in oesophageal squamous cell carcinoma is associated with poor prognosis. Histopathology 66(2): 192-200.
Hua KT, et al. (2014) The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. Mol Cancer 13: 189.
Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y, & Futscher BW (2007) 5-Aza-2'-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene 26(1): 77-90.
Chen H, Yan Y, Davidson TL, Shinkai Y, & Costa M (2006) Hypoxic stress induces dimethylated histone H3 lysine 9 through histone methyltransferase G9a in mammalian cells. Cancer Res 66(18): 9009-9016.
Hwang D, et al. (2005) A data integration methodology for systems biology: experimental verification. Proc Natl Acad Sci U S A 102(48): 17302-17307.
Yamamizu K, et al. (2012) Protein kinase A determines timing of early differentiation through epigenetic regulation with G9a. Cell Stem Cell 10(6): 759-770.
Joyce JA & Pollard JW (2009) Microenvironmental regulation of metastasis. Nature reviews. Cancer 9(4): 239-252.
Hu Z, et al. (2009) A compact VEGF signature associated with distant metastases and poor outcomes. BMC medicine 7: 9.
Li L, et al. (2014) Quantitative proteomics approach to screening of potential diagnostic and therapeutic targets for laryngeal carcinoma. PloS One 9(2):e90181.
Hu QP, Kuang JY, Yang QK, Bian XW, & Yu SC (2016) Beyond a tumor suppressor: Soluble E-cadherin promotes the progression of cancer. Int J Cancer 138(12): 2804-2812.
Li YW, et al. (2014) Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma. PloS One 9(1): e87505.
Noy P, Williams H, Sawasdichai A, Gaston K, & Jayaraman PS (2010) PRH/Hhex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling. Mol Cell Biol 30(9): 2120-2134.
Kershaw RM, Siddiqui YH, Roberts D, Jayaraman PS, & Gaston K (2014) PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene 33(49): 5592-5600.
Scholzel S, et al. (2000) Carcinoembryonic antigen family members CEACAM6 and CEACAM7 are differentially expressed in normal tissues and oppositely deregulated in hyperplastic colorectal polyps and early adenomas. Am J Path 156(2): 595-605.
Messick CA, et al. (2010) CEACAM-7: a predictive marker for rectal cancer recurrence. Surgery 147(5): 713-719.
Yeh CM, et al. (2014) Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncology 45(5): 2101-2107.
Tachibana M, Matsumura Y, Fukuda M, Kimura H, & Shinkai Y (2008) G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription. EMBO J 27(20): 2681-2690.
Ma DK, Chiang CH, Ponnusamy K, Ming GL, & Song H (2008) G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells. Stem Cells 26(8): 2131-2141.
Mole DR, et al. (2009) Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 284(25): 16767-16775.
Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9(6): 677-684.
Lee JS, et al. (2010) Negative regulation of hypoxic responses via induced Reptin methylation. Mol Cell 39(1): 71-85.
Lee JS, et al. (2011) Hypoxia-induced methylation of a pontin chromatin remodeling factor. Proc Natl Acad Sci U S A 108(33): 13510-13515.
Baselga J, et al. (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. New Eng J Med 366(6): 520-529.
Figueroa-Magalhaes MC, Jelovac D, Connolly RM, & Wolff AC (2014) Treatment of HER2-positive breast cancer. Breast 23(2): 128-136.
Ngiow SF, et al. (2012) Anti-TIM3 antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses established tumors. Cancer research 71(10): 3540-3551.
SEQUENCE LISTING <110> The Council of the Queensland Institute of Medical Research <120> BIOMARKERS FOR DIAGNOSING CONDITIONS <130> 35278347/VPA <140> Unassigned <141> 2018-02-23 <150> AU2017900607 <151> 2017-02-23 <160> 367 <170> PatentIn version 3.5 <210> 1 <211> 2863 <212> DNA <213> homo sapiens <400> 1 gcgattggtg ggcggggggc cgggcctggg ccggcgggga gcggattggt cggaaagtag 60 gttagtggtg cgacatttag ggaaggcaga aagtaggtca gggacggagg tgcctgttta 120 cccgcgccgg actcaccgcc gccgccgccg cgggatccga gtgcgggcgc gggcgcgggc 180 gctcccggcg agccacggtg gtgctggcta gagtgtatac gtttggaccc aagcttaact 240 tttccaatgt ggaatcctgg gccttcattg gttccgatgt cataggaatc tacgctagag 300 ggcttcctgt gtgccgggca ctgtggtttt tggaagaagc tgaccgcctg aaaagaaatt 360 ataaaacatg aaaatcgctt tgaggtgacc aagtccagag gcccctaact cctcccaagc 420 tggatctggg gtgtaagaac tgtgacttca gatcatccaa tggcagacca gagaatggac 480 atttcttcaa ccatcagtga tttcatgtcc ccgggcccca ccgacctgct ttccagctct 540 cttggtacca gtggtgtgga ttgcaaccgc aaacggaaag gcagctccac tgactaccaa 600 gaaagcatgg acacagacaa agatgaccct catggaaggt tagaatatac agaacaccaa 660 ggaaggataa aaaatgcaag ggaagctcac agtcagattg aaaagcggcg tcgggataaa 720 atgaacagtt ttatagatga attggcttct ttggtaccaa catgcaacgc aatgtccagg 780 aaattagata aacttactgt gctaaggatg gctgttcagc acatgaaaac attaagaggt 840 gccaccaatc catacacaga agcaaactac aaaccaactt ttctatcaga cgatgaattg 900 aaacacctca ttctcagggc agcagatgga tttttgtttg tcgtaggatg tgaccgaggg 960 aagatactct ttgtctcaga gtctgtcttc aagatcctca actacagcca gaatgatctg 1020 attggtcaga gtttgtttga ctacctgcat cctaaagata ttgccaaagt caaggagcag 1080 ctctcctcct ctgacaccgc accccgggag cggctcatag atgcaaaaac tggacttcca 1140 gttaaaacag atataacccc tgggccatct cgattatgtt ctggagcacg acgttctttc 1200 ttctgtagga tgaagtgtaa caggccttca gtaaaggttg aagacaagga cttcccctct 1260 acctgctcaa agaaaaaaga tcgaaaaagc ttctgcacaa tccacagcac aggctatttg 1320 aaaagctggc cacccacaaa gatggggctg gatgaagaca acgaaccaga caatgagggg 1380 tgtaacctca gctgcctcgt cgcaattgga cgactgcatt ctcatgtagt tccacaacca 1440 gtgaacgggg aaatcagggt gaaatctatg gaatatgttt ctcggcacgc gatagatgga 1500 aagtttgttt ttgtagacca gagggcaaca gctattttgg catatttacc acaagaactt 1560 ctaggcacat cgtgttatga atattttcac caagatgaca taggacatct tgcagaatgt 1620 cataggcaag ttttacagac gagagaaaaa attacaacta attgctataa atttaaaatc 1680 aaagatggtt cttttatcac actacggagt cgatggttca gtttcatgaa cccttggacc 1740 aaggaagtag aatatattgt ctcaactaac actgttgttt tagccaacgt cctggaaggc 1800 ggggacccaa ccttcccaca gctcacagca tccccccaca gcatggacag catgctgccc 1860 tctggagaag gtggcccaaa gaggacccac cccactgttc cagggattcc agggggaacc 1920 cgggctgggg caggaaaaat aggccgaatg attgctgagg aaatcatgga aatccacagg 1980 ataagagggt catcgccttc tagctgtggc tccagcccat tgaacatcac gagtacgcct 2040 ccccctgatg cctcttctcc aggaggcaag aagattttaa atggagggac tccagacatt 2100 ccttccagtg gcctactatc aggccaggct caggagaacc caggttatcc atattctgat 2160 agttcttcta ttcttggtga gaacccccac ataggtatag acatgattga caacgaccaa 2220 ggatcaagta gtcccagtaa tgatgaggca gcaatggctg tcatcatgag cctcttggaa 2280 gcagatgctg gactgggtgg ccctgttgac tttagtgact tgccatggcc gctgtaaaca 2340 ctacatgttg ctttggcaac agctatagta tcaaagtgca ttactggtgg agttttacag 2400 tctgtgaagc ttactggata aggagagaat agcttttatg tactgacttc ataaaagcca 2460 tctcagagcc attgatacaa gtcaatctta ctatatgtaa cttcagacaa agtggaacta 2520 agcctgctcc agtgtttcct catcattgat tattgggcta gctgtggata gcttgcatta 2580 attgtatatt ttggattctg tttgtgttga attttttaat cattgtgcac agaagcatca 2640 ttggtagctt ttatatgcaa atggtcattt cagatgtatg gtgtttttac actacaaaga 2700 agtcccccat gtggatattt cttatactaa ttgtatcata aagccgttta ttcttccttg 2760 taagaatcct ttactataaa tatgggttaa agtataatgt actagacagt taaatatttt 2820 taataaatgt ttcccttgtt ctataaaaaa aaaaaaaaaa aaa 2863 <210> 2 <211> 2592 <212> DNA <213> homo sapiens <400> 2 accactttgt ctaaggcagt tgaggaaggg aagtagatat aatggagctt agtggcagag 60 cagctggaat cctgagagaa gagaataact ttagttcaga gcaggtgggg aaatgagaga 120 ttgagtagga ggaccaaggt tgagggaagc agatcttctt agttgctgtc agcggctgat 180 ggggaagatt gttggtagaa ggaagtcaga atataggtac agagggataa gtttgctaag 240 aacagagatc agcaaacagc ttttctgaga gaaagaaaca tctgcaaatg acatgctgtt 300 tctgcagttt ctgctgctag ctcttcttct cccaggtggt gacaatgcag acgcatccca 360 ggaacacgtc tccttccatg tcatccagat cttctcattt gtcaaccaat cctgggcacg 420 aggtcagggc tcaggatggc tggacgagtt gcagactcat ggctgggaca gtgaatcagg 480 cacaataatt ttcctgcata actggtccaa gggcaacttc agcaatgaag agttgtcaga 540 cctagagttg ttatttcgtt tctacctctt tggattaact cgggagattc aagaccatgc 600 aagtcaagat tactcgaaat atccctttga agtacaggtg aaagcgggct gtgagctgca 660 ttctggaaag agcccagaag gcttctttca ggtagctttc aacggattag atttactgag 720 tttccagaat acaacatggg tgccatctcc aggctgtgga agtttggccc aaagtgtctg 780 tcatctactc aatcatcagt atgaaggcgt cacagaaaca gtgtataatc tcataagaag 840 cacttgcccc cgatttctct tgggtctcct ggatgcaggg aagatgtatg tacacaggca 900 agtgaggcca gaagcctggc tgtccagtcg ccccagcctt gggtctggcc agctgttgct 960 ggtttgtcat gcctccggct tctacccaaa gcctgtttgg gtgacatgga tgcggaatga 1020 acaggagcaa ctgggcacta aacatggtga tattcttcct aatgctgatg ggacatggta 1080 tcttcaggtg atcctggagg tggcatctga ggagcctgct ggcctgtctt gtcgagtgag 1140 acacagcagt ctaggaggcc aggacatcat cctctactgg ggacaccact tttccatgaa 1200 ttggattgcc ttggtagtga tagtgccctt ggtgattcta atagtccttg tgttatggtt 1260 taagaagcac tgctcatatc aggacatcct gtgagactct tccccctgac tcccccattg 1320 tgttaagaac ccagcaaccc aggagcctag tacaatatag tgatgccatc ccgtcgactc 1380 tccatttaaa ttgtttctct ttctgcataa taaacatttg ttaataaaaa ccaaattcta 1440 atttggaatg tttttcttgg aatctccact ttttatatag cactcaacct tcaaagccca 1500 tttctgatgt catttcctcc aacgatcttc cttgacccat actgaaccca gagagcccct 1560 caactgttat gtgcatgcaa cacttcctac cctgtgttgc agctacttga gtctttcatt 1620 tcacattttt aagcttttag gaggcaagga tcatgataaa tgtgcctttc ctgcatatga 1680 taggctcagt gaaacacaaa acaaaacatc atatctaagt tggattaact gtcatgttga 1740 caatttttct cattatattc cttcccaatg ttgttgtagc attggaaata ttcatgcttc 1800 tctttttgtt taaatgcttc atacctagca gataaattcc actctccttt agctccctca 1860 ttttctcctt aaacatttaa ggaaaagtgc agccttgtgc cttgatacac ttattttcta 1920 aacacagaga attacaaatg caaatagaca gagagtgtgc aagttacatg tgatgatcag 1980 tggtgcagat atgtcacaga atacttaaga aaaggaacaa gagatttggt cctcagggtt 2040 ggagtgggat caaggcaacc gttgtgctgt atatggaaga caaatttcct aaaggactgt 2100 gttatctgag atagccttgg ctaaacttta gtccctttag gtttcattca ctaattcaac 2160 taatattttt tgggtactga gttgagacag gcacatacag cttctaaact ggtggtggat 2220 aaaacaaatg agattgtgtc cactctcctg aagttgcaat gtttgcttcc tcaatctgtc 2280 catgtttctt ttctattgtt ttcatgtttt tatttatttc aaaaaatttt aaatagattt 2340 tattgatgta taatttatag taaaatttga atctttaagt gtacagttct atttattttg 2400 ataattatat aagcccatgt aaacaaaatc acaatcaaga tattaaatgt cataacccct 2460 catacctgtt tgtagtcaag cacaccaaca acctggcatt cttgcaacta ctgatatact 2520 ttatgtcact taagcttaaa cttgtatttt ctatgatttt attaagatgg aaataaacat 2580 atctacttgg ta 2592 <210> 3 <211> 1772 <212> DNA <213> homo sapiens <400> 3 ggataaatgt agcgccgcgg cgcgggccag cagctctgcg aggggccgga gcgcggcgga 60 gccatgcagt acccgcaccc cgggccggcg gcgggcgccg tgggggtgcc gctgtacgcg 120 cccacgccgc tgctgcaacc cgcacacccg acgccctttt acatcgagga catcctgggc 180 cgcgggcccg ccgcgcccac gcccgccccc acgctgccgt cccccaactc ctccttcacc 240 agcctcgtgt ccccctaccg gaccccggtg tacgagccca cgccgatcca tccagccttc 300 tcgcaccact ccgccgccgc gctggccgct gcctacggac ccggcggctt cgggggccct 360 ctgtacccct tcccgcggac ggtgaacgac tacacgcacg ccctgctccg ccacgacccc 420 ctgggcaaac ctctactctg gagccccttc ttgcagaggc ctctgcataa aaggaaaggc 480 ggccaggtga gattctccaa cgaccagacc atcgagctgg agaagaaatt cgagacgcag 540 aaatatctct ctccgcccga gaggaagcgt ctggccaaga tgctgcagct cagcgagaga 600 caggtcaaaa cctggtttca gaatcgacgc gctaaatgga ggagactaaa acaggagaac 660 cctcaaagca ataaaaaaga agaactggaa agtttggaca gttcctgtga tcagaggcaa 720 gatttgccca gtgaacagaa taaaggtgct tctttggata gctctcaatg ttcgccctcc 780 cctgcctccc aggaagacct tgaatcagag atttcagagg attctgatca ggaagtggac 840 attgagggcg ataaaagcta ttttaatgct ggatgatgac cactggcatt ggcatgttca 900 gaaaactgga tttaggaata atgttttgct acagaaaatc ttcatagaag aactggaagg 960 ctatataaga aagggaatca attctctggt attctggaaa cctaaaaata tttggtgcac 1020 tgctcaatta acaaacctac atggagacct taattttgac ttaacaaata gtttatgtac 1080 tgctcttagg ttgttttgat aaagtgacat tatagtgatt aaattcttcc ccctttaaaa 1140 aaacagttag tggttttcac tatttataaa aaattaattt tgaacttttt gttaaatttt 1200 taagttatag ctttaaaggt tttaatagga ccttcttgaa cgacttttct gtaatctgtt 1260 tatctcccac ttaatggaaa ggcaaagggg taccccaaat ccagaggtgc ctacatttca 1320 ggcagccttg gagtatttta aaaggaaaac attctttact tttatatgac attcttatac 1380 tgctgtctca aatccaaaaa catttcagag ctcttgtctc agagatgtgt gttctttttg 1440 tcagagatat ggttgatgag aatcttaaat gcttgttttg cactatcact tagtacctgt 1500 ttgaccaagg tgttaagggg atagtacctc ccaattcaag cagagaaact gacctgacta 1560 aagttaatcg cagatgaact agaagtcaca ggttaattaa atgtaagtag attgtagata 1620 ctgttttata tcaaacaatg tttataatgt gtatatagaa ttgttcactg taaaaaaaat 1680 ggccaaaatg tgtttttttt ttaataagta acttgactat aaaataaagc cgtccgtggg 1740 acgactgacc tcgttgcaaa aaaaaaaaaa aa 1772 <210> 4 <211> 1342 <212> DNA <213> homo sapiens <400> 4 cttagctgaa gatgactgac agtgttattt attccatgtt agagttgcct acggcaaccc 60 aagcccagaa tgactatgga ccacagcaaa aatcttcctc ttccaggcct tcttgttctt 120 gccttgtggc aatagctttg gggcttctga ctgcagttct tctgagtgtg ctgctatacc 180 agtggatcct gtgccagggc tccaactact ccacttgtgc cagctgtcct agctgcccag 240 accgctggat gaaatatggt aaccattgtt attatttctc agtggaggaa aaggactgga 300 attctagtct ggaattctgc ctagccagag actcacacct ccttgtgata acggacaatc 360 aggaaatgag cctgctccaa gttttcctca gtgaggcctt ttgctggatt ggtctgagga 420 acaattctgg ctggaggtgg gaagatggat cacctctaaa cttctcaagg atttcttcta 480 atagctttgt gcagacatgc ggtgccatca acaaaaatgg tcttcaagcc tcaagctgtg 540 aagttccttt acactgggtg tgtaagaagt gtccctttgc agatcaagct ttattctgaa 600 gaataaacct agctggcatg ctggtgtgta cctgtagtcc tagctatttg ggaagctgag 660 gtgggagggt cgcttgagcc caggagtttg aggctgcagt gagctatgat tgtgccactg 720 tactccagcc tgggagatag agcaagactc catctctaaa aaaaaaaaaa aatgctaatg 780 tgagaatata aattgtggga aatgagtgag ggcaaggtgg tacttcctcc ttctgagctc 840 ttcacacgta atgcaaaaac ccggtcttaa ctgattttgt tttttttctg agtatgcata 900 tatgtggttg aatgaaccaa tgtgtgattg tatcttttcc attatgtgac tgtttgacct 960 gcatattaat ttcaagatag cagtcaattc gataaggcat tttcatagag gaaagtttac 1020 agaaacagtt tatgtggttg gatcaccaaa ttatcttagg tactaaggcc tcaaaaataa 1080 gaaaaacttt attatttctc ctcagtagag tttggacata cataaggaga gaaggtacag 1140 tgatgaagga gaccataatt ctgtagtgtt gatgatcctg gattataatc tttttctctt 1200 tatctttcat agttttttta aaaacatgga ctgtatctta tctaccacta tatcccaaat 1260 acctaagata gtgcttacgt tcagtgacta ttaaataaat aaatggatga attaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aa 1342 <210> 5 <211> 6347 <212> DNA <213> homo sapiens <400> 5 tctttgagcc ggaaccgccg gtgaacttag gcgccacgtt cccggtgact gaccccggag 60 gatggtgaac aggaactact gctgaccctg tcttcgccgc tgcctctcgg gggctgccga 120 gcgcggggcc cctgtctcct ccccttgccc ggctgtgggt gaacctgcag gctccttacc 180 cacccggagg actttttttt gaaaggaaac gagggaggga gggagaggga gagagggaga 240 aaacgaaggg gagctcgtcc atccattgaa gcacagttca ctatgatctt actcacattc 300 agcactggaa gacggttgga tttcgtgcat cattcggggg tgtttttctt gcaaaccttg 360 ctttggattt tatgtgctac agtctgcgga acggagcagt atttcaatgt ggaggtttgg 420 ttacaaaagt acggctacct tccaccgact gaccccagaa tgtcagtgct gcgctctgca 480 gagaccatgc agtctgccct agctgccatg cagcagttct atggcattaa catgacagga 540 aaagtggaca gaaacacaat tgactggatg aagaagcccc gatgcggtgt acctgaccag 600 acaagaggta gctccaaatt tcatattcgt cgaaagcgat atgcattgac aggacagaaa 660 tggcagcaca agcacatcac ttacagtata aagaacgtaa ctccaaaagt aggagaccct 720 gagactcgta aagctattcg ccgtgccttt gatgtgtggc agaatgtaac tcctctgaca 780 tttgaagaag ttccctacag tgaattagaa aatggcaaac gtgatgtgga tataaccatt 840 atttttgcat ctggtttcca tggggacagc tctccctttg atggagaggg aggatttttg 900 gcacatgcct acttccctgg accaggaatt ggaggagata cccattttga ctcagatgag 960 ccatggacac taggaaatcc taatcatgat ggaaatgact tatttcttgt agcagtccat 1020 gaactgggac atgctctggg attggagcat tccaatgacc ccactgccat catggctcca 1080 ttttaccagt acatggaaac agacaacttc aaactaccta atgatgattt acagggcatc 1140 cagaagatat atggtccacc tgacaagatt cctccaccta caagacctct accgacagtg 1200 cccccacacc gctctattcc tccggctgac ccaaggaaaa atgacaggcc aaaacctcct 1260 cggcctccaa ccggcagacc ctcctatccc ggagccaaac ccaacatctg tgatgggaac 1320 tttaacactc tagctattct tcgtcgtgag atgtttgttt tcaaggacca gtggttttgg 1380 cgagtgagaa acaacagggt gatggatgga tacccaatgc aaattactta cttctggcgg 1440 ggcttgcctc ctagtatcga tgcagtttat gaaaatagcg acgggaattt tgtgttcttt 1500 aaaggtaaca aatattgggt gttcaaggat acaactcttc aacctggtta ccctcatgac 1560 ttgataaccc ttggaagtgg aattccccct catggtattg attcagccat ttggtgggag 1620 gacgtcggga aaacctattt cttcaaggga gacagatatt ggagatatag tgaagaaatg 1680 aaaacaatgg accctggcta tcccaagcca atcacagtct ggaaagggat ccctgaatct 1740 cctcagggag catttgtaca caaagaaaat ggctttacgt atttctacaa aggaaaggag 1800 tattggaaat tcaacaacca gatactcaag gtagaacctg gatatccaag atccatcctc 1860 aaggatttta tgggctgtga tggaccaaca gacagagtta aagaaggaca cagcccacca 1920 gatgatgtag acattgtcat caaactggac aacacagcca gcactgtgaa agccatagct 1980 attgtcattc cctgcatctt ggccttatgc ctccttgtat tggtttacac tgtgttccag 2040 ttcaagagga aaggaacacc ccgccacata ctgtactgta aacgctctat gcaagagtgg 2100 gtgtgatgta gggttttttc ttctttcttt cttttgcagg agtttgtggt aacttgagat 2160 tcaagacaag agctgttatg ctgtttccta gctaggagca ggcttgtggc agcctgattc 2220 ggggctgacc tttcaaaccc agagggttgc tggtcctgca catgagtgga aatacactca 2280 tggggaagct tccatgatgc acagtatctg ctgttcttca gtcctttgtc tttctttgtc 2340 attcagttct aggcctttcc tctgcacgct caatgcccag taaaatttca ggattaacta 2400 aagaagagga gaaaaagaag aaaagattct tcttaaaagt ttctaatgtt attttccttc 2460 tgaagtctga gcccatttct ggggggagaa aaaaaaagca aatcagaaaa cccacggttt 2520 ttcttttttt ctttttttct ttttttcttt ttttgcttta aaacaaaggg aaaaaagagt 2580 ttaaacaaaa aacccacaat tgaacttcca ggaaagtgtg aagacccaaa acagctttgt 2640 ctccaaagaa gatagctctc tgactgcttt ggatagtctc ctacgcacca ttttgtcagg 2700 tgggagattt ggaatacaca tgcaggacgt tagactgttg ggacagccat tttccaacaa 2760 ccaaggggcc aaaatatctg caatatagta acagccttaa taatacatcc atttttcgtt 2820 ttatacagct gttctcagct atgtcctcag tgtttcatcg catttatatt catagctatt 2880 ttcaaacacg accttttaat tgtttttgaa gtatttctaa accccttctt tccaccttac 2940 tcctccatca ttgtgataat cttcccaagt tgtattaggc cattgcccca ggccttccat 3000 gggtctgtca ggaatattcg ttacaaagca gagcaagaag cagtatgtct ctgaagtgga 3060 ttacagtggc agttatttta caaggatttg tgacactagt aacatacccg tgtaaccctt 3120 tgagaactat cagaccagct ttcagagtct taggattgtc ggtcttgcga tctgataaat 3180 tatagaactg ggcaatggta aaaacagtca caagttcaag aagttcaggt ttttaaaaca 3240 gatatcctat aatgtcatat aatttttaaa tgatttacaa gactacataa atgtgtttat 3300 aacaaacaga aatgatgtta cttgccaaaa tttttctggc aaataaaaaa ggtattttat 3360 taagattctc ataaatctga aattttattt gaaaaactga taatagccta agtcttcttt 3420 tctttttttt aggcatactg aatttctgtt ttaaaatcca ttgcatgaaa attcaatttg 3480 ccttggtata tgcagttagc attgccattt taaaaatgaa ttaaaacggt gactctgaag 3540 ttgcatgaat atcctccagt gcattaccta ttgcatgtcc accatagttc tcaaagggtt 3600 agtgtggctt ctggcattta gccgtccatt tgatcactga cagagccaag agaccaccaa 3660 agcatttcat tgttgagtgt aatttgtcct aacagcagta ttgtcatttt catgtgacct 3720 gcagagcagg tttgtatcaa tatttttttc ctagagaaaa gtcagcaact gacagacctc 3780 tttattgatt tttaggagct gcttcttgca gtgaaaggct ttacagccac tgggctgtga 3840 acttattaga gatggtcaga atgaatgcac cccatgagtc agacattggc tttgtgtgaa 3900 agccagcttt gaggggatta gcttttgaaa caatgaacag cttgccttga acttgattat 3960 tgatctattg actgtcatta acaacaactt aaacattgtc ttctgtgaaa attttccttg 4020 aagagtcctg ttctatgtct ttgccctttg acctttaact tgcaaactgg cacaaactga 4080 aggaaatctg gtgttgcttc tccattggat tagttgttct ctaaaaccta gtaagcatga 4140 gctgtttcct tagagtggag agagtggtga tggcagatct gcagatggac actttgctct 4200 ttacatgcac actctgaaaa tgccctatag gtagaagtga attttaattt cattttaata 4260 taatttcaag tctaaattca tcattttagt acaaattaca aaaactatag gaaaaaaaaa 4320 acctcaaata cttgaatggc cagtgtggct tttatataaa gcaggaattt tatactagta 4380 aaaatttctt actcatttgc taatacacat ttccagatga tttttaatga gtgtaggtat 4440 acattcttat ttggaaatgg atagtttggc tgccttgaat ttatatttat actcaacgta 4500 gcatgaaaat tagaatgcct tttggttaaa ctacatgttt atgatttggt tggggaaaat 4560 attttataat tgtgggtggc atgctgcaaa gccttgcaga ttgttatttc ttacaacctg 4620 agcgtatata gtatgagcct aagaaaaaag aagagtaaga aaagaagaat ggctttacag 4680 taaaatatca tacaatgcag acaatatttt aagaggatat tggagattat gtacgcaagg 4740 gccaagaaag caagaaatga gaaccagagt cagccctgta gctttacttc agtgcttcca 4800 ttctagatga tgctgatatt ataaagagtt agtcactgct gctaagcatg gaggactata 4860 tacataagct cgtttataca gtgtttgctt gtgggagggt ttaatccttt tagggccttg 4920 atgtcaagaa aaaaataact ggaaactata ttttgctaaa gatagaaatg aggaactgtg 4980 tcattttggg acatgtgcaa atcattgagg aactccatca ccctgcattg aaaattgatt 5040 tttttttcct ctaaaatgag aaagaaactg aataagcaat ctgttgcctc tttactcatt 5100 catcacaata tcctgattcg tcataaggct atcagtatat aagggctaga aaataatcat 5160 agcattaaga aggaaggagt ctatcattat gcttgaattc tggcaaatgt catgaataag 5220 ggttgggtca tatttacttt aatatgagac aagatttatg tgataagcaa aggcatataa 5280 ggctgctctt ttgaacagaa catttcagtt atcaggctgt actattacaa gagataagaa 5340 gacaataagg acaatgtaat cacaaacagt gggattccat ttgtttattg tacaccagct 5400 actttgtggg tatggttcct gactcctctt ctacatgagg tttgggaaaa aagtctcaaa 5460 ccaaatggaa cagtgaaagg gaaagtaatt catctagcac ataagaatag tgattcaaaa 5520 ccaatgcaga ataaatttcc atgggtcaat aacataaggt gtcagttcag tgttactaga 5580 gatatgcaag gcataaaata ttttcatcac cccatcacta ataacatgaa aagctcagac 5640 ataggatttc ccaaattgaa atgaaaacac attcatgcct gcaaaaataa ttctccttct 5700 gcttcatttc tcattacttt atctaatata aacacaaatg taaacaaggt aatggtcttc 5760 atgtaaaatg accatatagt taagaatttt agtaaaatat tgttgttctg tgtattatta 5820 aacaaatgca atgaagtatt aaaatagctg atcagtttga atttcctgta aagcagtaat 5880 tccgcatcag aattgtagat aaggttgtga atttattgac tcatttcaga acagtgtctg 5940 ttgacatggc agtcagagca ggtgaataca gatgctcttt ctgattgcaa aggttataga 6000 gctaaattag acagcattat gtgatactag caaagacaac ttctgttata aatcagaggg 6060 caaggctttt ctgaatcgat gtgataaatt actaagtaat gattaccaaa aataattact 6120 aagtaataaa agatacagac tggtttactg aaataagcaa gtgttacatt taataattac 6180 ctataatctt tttttgttaa cacataagca agtgttacct ttaataatta cctataatct 6240 ttttttgtta acacataatt tggccatttc atatactgtg tacctatttt cattccctct 6300 ctgtgggtca ttaaaaaaca caatgtggtg gataaaaaaa aaaaaaa 6347 <210> 6 <211> 4654 <212> DNA <213> homo sapiens <400> 6 ggcggcggct ggaggagagc gcggtggaga gccgagcggg cgggcggcgg gtgcggagcg 60 ggcgagggag cgcgcgcggc cgccacaaag ctcgggcgcc gcggggctgc atgcggcgta 120 cctggcccgg cgcggcgact gctctccggg ctggcggggg ccggccgcga gccccggggg 180 ccccgaggcc gcagcttgcc tgcgcgctct gagccttcgc aactcgcgag caaagtttgg 240 tggaggcaac gccaagcctg agtcctttct tcctctcgtt ccccaaatcc gagggcagcc 300 cgcgggcgtc atgcccgcgc tcctccgcag cctggggtac gcgtgaagcc cgggaggctt 360 ggcgccggcg aagacccaag gaccactctt ctgcgtttgg agttgctccc cgcaaccccg 420 ggctcgtcgc tttctccatc ccgacccacg cggggcgcgg ggacaacaca ggtcgcggag 480 gagcgttgcc attcaagtga ctgcagcagc agcggcagcg cctcggttcc tgagcccacc 540 gcaggctgaa ggcattgcgc gtagtccatg cccgtagagg aagtgtgcag atgggattaa 600 cgtccacatg gagatatgga agaggaccgg ggattggtac cgtaaccatg gtcagctggg 660 gtcgtttcat ctgcctggtc gtggtcacca tggcaacctt gtccctggcc cggccctcct 720 tcagtttagt tgaggatacc acattagagc cagaagagcc accaaccaaa taccaaatct 780 ctcaaccaga agtgtacgtg gctgcgccag gggagtcgct agaggtgcgc tgcctgttga 840 aagatgccgc cgtgatcagt tggactaagg atggggtgca cttggggccc aacaatagga 900 cagtgcttat tggggagtac ttgcagataa agggcgccac gcctagagac tccggcctct 960 atgcttgtac tgccagtagg actgtagaca gtgaaacttg gtacttcatg gtgaatgtca 1020 cagatgccat ctcatccgga gatgatgagg atgacaccga tggtgcggaa gattttgtca 1080 gtgagaacag taacaacaag agagcaccat actggaccaa cacagaaaag atggaaaagc 1140 ggctccatgc tgtgcctgcg gccaacactg tcaagtttcg ctgcccagcc ggggggaacc 1200 caatgccaac catgcggtgg ctgaaaaacg ggaaggagtt taagcaggag catcgcattg 1260 gaggctacaa ggtacgaaac cagcactgga gcctcattat ggaaagtgtg gtcccatctg 1320 acaagggaaa ttatacctgt gtagtggaga atgaatacgg gtccatcaat cacacgtacc 1380 acctggatgt tgtggagcga tcgcctcacc ggcccatcct ccaagccgga ctgccggcaa 1440 atgcctccac agtggtcgga ggagacgtag agtttgtctg caaggtttac agtgatgccc 1500 agccccacat ccagtggatc aagcacgtgg aaaagaacgg cagtaaatac gggcccgacg 1560 ggctgcccta cctcaaggtt ctcaaggccg ccggtgttaa caccacggac aaagagattg 1620 aggttctcta tattcggaat gtaacttttg aggacgctgg ggaatatacg tgcttggcgg 1680 gtaattctat tgggatatcc tttcactctg catggttgac agttctgcca gcgcctggaa 1740 gagaaaagga gattacagct tccccagact acctggagat agccatttac tgcatagggg 1800 tcttcttaat cgcctgtatg gtggtaacag tcatcctgtg ccgaatgaag aacacgacca 1860 agaagccaga cttcagcagc cagccggctg tgcacaagct gaccaaacgt atccccctgc 1920 ggagacaggt aacagtttcg gctgagtcca gctcctccat gaactccaac accccgctgg 1980 tgaggataac aacacgcctc tcttcaacgg cagacacccc catgctggca ggggtctccg 2040 agtatgaact tccagaggac ccaaaatggg agtttccaag agataagctg acactgggca 2100 agcccctggg agaaggttgc tttgggcaag tggtcatggc ggaagcagtg ggaattgaca 2160 aagacaagcc caaggaggcg gtcaccgtgg ccgtgaagat gttgaaagat gatgccacag 2220 agaaagacct ttctgatctg gtgtcagaga tggagatgat gaagatgatt gggaaacaca 2280 agaatatcat aaatcttctt ggagcctgca cacaggatgg gcctctctat gtcatagttg 2340 agtatgcctc taaaggcaac ctccgagaat acctccgagc ccggaggcca cccgggatgg 2400 agtactccta tgacattaac cgtgttcctg aggagcagat gaccttcaag gacttggtgt 2460 catgcaccta ccagctggcc agaggcatgg agtacttggc ttcccaaaaa tgtattcatc 2520 gagatttagc agccagaaat gttttggtaa cagaaaacaa tgtgatgaaa atagcagact 2580 ttggactcgc cagagatatc aacaatatag actattacaa aaagaccacc aatgggcggc 2640 ttccagtcaa gtggatggct ccagaagccc tgtttgatag agtatacact catcagagtg 2700 atgtctggtc cttcggggtg ttaatgtggg agatcttcac tttagggggc tcgccctacc 2760 cagggattcc cgtggaggaa ctttttaagc tgctgaagga aggacacaga atggataagc 2820 cagccaactg caccaacgaa ctgtacatga tgatgaggga ctgttggcat gcagtgccct 2880 cccagagacc aacgttcaag cagttggtag aagacttgga tcgaattctc actctcacaa 2940 ccaatgagga atacttggac ctcagccaac ctctcgaaca gtattcacct agttaccctg 3000 acacaagaag ttcttgttct tcaggagatg attctgtttt ttctccagac cccatgcctt 3060 acgaaccatg ccttcctcag tatccacaca taaacggcag tgttaaaaca tgaatgactg 3120 tgtctgcctg tccccaaaca ggacagcact gggaacctag ctacactgag cagggagacc 3180 atgcctccca gagcttgttg tctccacttg tatatatgga tcagaggagt aaataattgg 3240 aaaagtaatc agcatatgtg taaagattta tacagttgaa aacttgtaat cttccccagg 3300 aggagaagaa ggtttctgga gcagtggact gccacaagcc accatgtaac ccctctcacc 3360 tgccgtgcgt actggctgtg gaccagtagg actcaaggtg gacgtgcgtt ctgccttcct 3420 tgttaatttt gtaataattg gagaagattt atgtcagcac acacttacag agcacaaatg 3480 cagtatatag gtgctggatg tatgtaaata tattcaaatt atgtataaat atatattata 3540 tatttacaag gagttatttt ttgtattgat tttaaatgga tgtcccaatg cacctagaaa 3600 attggtctct ctttttttaa tagctatttg ctaaatgctg ttcttacaca taatttctta 3660 attttcaccg agcagaggtg gaaaaatact tttgctttca gggaaaatgg tataacgtta 3720 atttattaat aaattggtaa tatacaaaac aattaatcat ttatagtttt ttttgtaatt 3780 taagtggcat ttctatgcag gcagcacagc agactagtta atctattgct tggacttaac 3840 tagttatcag atcctttgaa aagagaatat ttacaatata tgactaattt ggggaaaatg 3900 aagttttgat ttatttgtgt ttaaatgctg ctgtcagacg attgttctta gacctcctaa 3960 atgccccata ttaaaagaac tcattcatag gaaggtgttt cattttggtg tgcaaccctg 4020 tcattacgtc aacgcaacgt ctaactggac ttcccaagat aaatggtacc agcgtcctct 4080 taaaagatgc cttaatccat tccttgagga cagaccttag ttgaaatgat agcagaatgt 4140 gcttctctct ggcagctggc cttctgcttc tgagttgcac attaatcaga ttagcctgta 4200 ttctcttcag tgaattttga taatggcttc cagactcttt ggcgttggag acgcctgtta 4260 ggatcttcaa gtcccatcat agaaaattga aacacagagt tgttctgctg atagttttgg 4320 ggatacgtcc atctttttaa gggattgctt tcatctaatt ctggcaggac ctcaccaaaa 4380 gatccagcct catacctaca tcagacaaaa tatcgccgtt gttccttctg tactaaagta 4440 ttgtgttttg ctttggaaac acccactcac tttgcaatag ccgtgcaaga tgaatgcaga 4500 ttacactgat cttatgtgtt acaaaattgg agaaagtatt taataaaacc tgttaatttt 4560 tatactgaca ataaaaatgt ttctacagat attaatgtta acaagacaaa ataaatgtca 4620 cgcaacttat ttttttaata aaaaaaaaaa aaaa 4654 <210> 7 <211> 3484 <212> DNA <213> homo sapiens <400> 7 actgggtcaa gcacagccct gagcggccgc gtgtccgagg cccaggtgcc ctctagagcc 60 ctgtagttcc tgcccctctc tgcccctctc ggctcctgct gttccgccgc tgtcgtccga 120 accatcccaa cccccagtcc acccagacag cgcccgagct aggggaggga acggtctggg 180 agtcggcagc tggcgccagg gcggccggag gatgccgagg ggccggagcc gggagggccc 240 gaggccgagg cgcactctac ccccagctcc taccctgtaa gccccgccag cctccggacg 300 tgctgtccct gggcccgtcg ccctcggggc tcccgccgga actccttcac tctcagaggc 360 cgagtccctc ccctccccac ggctgcgtgt ggccgttgcc gtctgcaccc agaccctgag 420 ccgccgccgc cggccatgga ggtggcgccc gagcagccgc gctggatggc gcacccggcc 480 gtgctgaatg cgcagcaccc cgactcacac cacccgggcc tggcgcacaa ctacatggaa 540 cccgcgcagc tgctgcctcc agacgaggtg gacgtcttct tcaatcacct cgactcgcag 600 ggcaacccct actatgccaa ccccgctcac gcgcgggcgc gcgtctccta cagccccgcg 660 cacgcccgcc tgaccggagg ccagatgtgc cgcccacact tgttgcacag cccgggtttg 720 ccctggctgg acgggggcaa agcagccctc tctgccgctg cggcccacca ccacaacccc 780 tggaccgtga gccccttctc caagacgcca ctgcacccct cagctgctgg aggccctgga 840 ggcccactct ctgtgtaccc aggggctggg ggtgggagcg ggggaggcag cgggagctca 900 gtggcctccc tcacccctac agcagcccac tctggctccc accttttcgg cttcccaccc 960 acgccaccca aagaagtgtc tcctgaccct agcaccacgg gggctgcgtc tccagcctca 1020 tcttccgcgg ggggtagtgc agcccgagga gaggacaagg acggcgtcaa gtaccaggtg 1080 tcactgacgg agagcatgaa gatggaaagt ggcagtcccc tgcgcccagg cctagctact 1140 atgggcaccc agcctgctac acaccacccc atccccacct acccctccta tgtgccggcg 1200 gctgcccacg actacagcag cggactcttc caccccggag gcttcctggg gggaccggcc 1260 tccagcttca cccctaagca gcgcagcaag gctcgttcct gttcagaagg ccgggagtgt 1320 gtcaactgtg gggccacagc cacccctctc tggcggcggg acggcaccgg ccactacctg 1380 tgcaatgcct gtggcctcta ccacaagatg aatgggcaga accgaccact catcaagccc 1440 aagcgaagac tgtcggccgc cagaagagcc ggcacctgtt gtgcaaattg tcagacgaca 1500 accaccacct tatggcgccg aaacgccaac ggggaccctg tctgcaacgc ctgtggcctc 1560 tactacaagc tgcacaatgt taacaggcca ctgaccatga agaaggaagg gatccagact 1620 cggaaccgga agatgtccaa caagtccaag aagagcaaga aaggggcgga gtgcttcgag 1680 gagctgtcaa agtgcatgca ggagaagtca tcccccttca gtgcagctgc cctggctgga 1740 cacatggcac ctgtgggcca cctcccgccc ttcagccact ccggacacat cctgcccact 1800 ccgacgccca tccacccctc ctccagcctc tccttcggcc acccccaccc gtccagcatg 1860 gtgaccgcca tgggctaggg aacagatgga cgtcgaggac cgggcactcc cgggatgggt 1920 ggaccaaacc cttagcagcc cagcatttcc cgaaggccga caccactcct gccagcccgg 1980 ctcggcccag caccccctct cctggagggc gcccagcagc ctgccagcag ttactgtgaa 2040 tgttccccac cgctgagagg ctgcctccgc acctgaccgc tgcccaggtg gggtttcctg 2100 catggacagt tgtttggaga acaacaagga caactttatg tagagaaaag gaggggacgg 2160 gacagacgaa ggcaaccatt tttagaagga aaaaggatta ggcaaaaata atttattttg 2220 ctcttgtttc taacaaggac ttggagactt ggtggtctga gctgtcccaa gtcctccggt 2280 tcttcctcgg gattggcggg tccacttgcc agggctctgg gggcagattt gtggggacct 2340 cagcctgcac cctcttctcc tctggcttcc ctctctgaaa tagccgaact ccaggctggg 2400 ctgagccaaa gccagagtgg ccacggccca gggagggtga gctggtgcct gctttgacgg 2460 gccaggccct ggagggcaga gacaatcacg ggcggtcctg cacagattcc caggccaggg 2520 ctgggtcaca ggaaggaaac aacattttct tgaaagggga aacgtctccc agatcgctcc 2580 cttggctttg aggccgaagc tgctgtgact gtgtcccctt actgagcgca agccacagcc 2640 tgtcttgtca ggtggaccct gtaaatacat cctttttctg ctaacccttc aaccccctcg 2700 cctcctactc tgagacaaaa gaaaaaatat taaaaaaatg cataggctta actcgctgat 2760 gagttaattg ttttattttt aaactctttt tgggtccagt tgattgtacg tagccacagg 2820 agccctgcta tgaaaggaat aaaacctaca cacaaggttg gagctttgca attctttttg 2880 gaaaagagct gggatcccac agccctagta tgaaagctgg gggtggggag gggcctttgc 2940 tgcccttggt ttctgggggc tggttggcat ttgctggcct ggcagggggt gaaggcagga 3000 gttgggggca ggtcaggacc aggacccagg gagaggctgt gtccctgctg gggtctcagg 3060 tccagcttta ctgtggctgt ctggatcctt cccaaggtac agctgtatat aaacgtgtcc 3120 cgagcttaga ttctgtatgc ggtgacggcg gggtgtggtg gcctgtgagg ggcccctggc 3180 ccaggaggag gattgtgctg atgtagtgac caagtgcaat atgggcgggc agtcgctgca 3240 gggagcacca cggccagaag taacttattt tgtactagtg tccgcataag aaaaagaatc 3300 ggcagtattt tctgttttta tgttttattt ggcttgtttt attttggatt agtgaactaa 3360 gttattgtta attatgtaca acatttatat attgtctgta aaaaatgtat gctatcctct 3420 tattccttta aagtgagtac tgttaagaat aataaaatac tttttgtgaa tgcccaaaaa 3480 aaaa 3484 <210> 8 <211> 2399 <212> DNA <213> homo sapiens <400> 8 gctcagcaca gaggtaggaa ggacagcaga gctgacagtc acagcagccc tgacaagaga 60 gttcctggag cccaagctct tctccacaga ggacaagcag gcagcagaga ccatggggtc 120 cccttcagcc tgtccataca gagtgtgcat tccctggcag gggctcctgc tcacagcctc 180 gcttttaacc ttctggaacc tgccaaacag tgcccagacc aatattgatg tcgtgccgtt 240 caatgtcgca gaagggaagg aggtccttct agtagtccat aatgagtccc agaatcttta 300 tggctacaac tggtacaaag gggaaagggt gcatgccaac tatcgaatta taggatatgt 360 aaaaaatata agtcaagaaa atgccccagg gcccgcacac aacggtcgag agacaatata 420 ccccaatgga accctgctga tccagaacgt cacccacaat gacgcaggaa tctataccct 480 acacgttata aaagaaaatc ttgtgaatga agaagtaacc agacaattct acgtattctc 540 ggagccaccc aagccctcca tcaccagcaa caacttcaat ccggtggaga acaaagatat 600 tgtggtttta acctgtcaac ctgagactca gaacacaacc tacctgtggt gggtaaacaa 660 tcagagcctc ctggtcagtc ccaggctgct gctctccact gacaacagga ccctcgttct 720 actcagcgcc acaaagaatg acataggacc ctatgaatgt gaaatacaga acccagtggg 780 tgccagccgc agtgacccag tcaccctgaa tgtccgctat gagtcagtac aagcaagttc 840 acctgacctc tcagctggga ccgctgtcag catcatgatt ggagtactgg ctgggatggc 900 tctgatatag cagccttggt gtagtttctg catttcggga agagtgtttt tattatccac 960 ctgcagactg gactggattc ttctagctcc ttcaatccca ttttctcctg tggcatcact 1020 aagtataaga cctgctctct tcctgaagac ctataagctg gaggtggaca actcaatgta 1080 aatttcaagg aaaaaccctc atgcctgaga tgtgggccac tcagagctaa ccaaaatgtt 1140 caacaccata actagagaca ctcaaattgc caaccaggac aagaagttga tgacttcatg 1200 ctgtggacag tttttcccaa gatgtcccaa gcctcatcgt gacgaggctc ttatcccact 1260 ccatttttcc ctgctcatgc ctgcctcttt aatttggtaa gataatgctg taactagaat 1320 ttcacaatca gcgccttgtg caggtaattt gacagagtgt tggatgtgtc atgtcatcat 1380 gtcaaaccca aatatttgac ctaagggatc ctttattctg cccagtggct aactttaaca 1440 acatccctaa tacaactgtt tattcaaatg cacggtggtc cctgttagag ttagacctct 1500 agactcacct gttctcacgc cctgttttaa tttaacccag ctatgggatg ccagataaca 1560 gaattgctgc ctactagctg aacagggagg agtttgtgca gttgctgaca cttcttgttg 1620 cacataaata aatacagtgg gtactataga gactcagttg caaaaattaa caaatatgct 1680 gcttgattaa aatgggtagg cttctcatgt ggctcattct ttaatctatt ctcttttatt 1740 tggtttggtt catggggtct ctgcctatgg atcatacttc aaactcttgg tgtgatcctc 1800 ctgattgtca caatattagt taccctggtg tgctgtattc tctaaaacct ttaaatgttt 1860 gcatgcagcc attcgtcaaa tgtcaaatat tctctctttg gctggaatga caaaaactca 1920 aataaatgta tgattaggag gacatcataa cctatgaatg atggaagtcc aaaatgatgg 1980 taactgacag tagtgttaat gccttatgtt tagtcaaact ctcatttagg tgacagcctg 2040 gtgactccag aatggagcca gtcatgctaa atgccatata ctcacactga aacatgagga 2100 agcaggtaga tcccagaaca gacaaaattt tcctaaaaac atgagagtcc aggctgtctg 2160 agtcagcaca gtaagaaagt cctttctgct ttaactctta gaaaaaagta atatgaagta 2220 ttctgaaatt aaccaatcag tttatttaaa tcaatttatt tatattcttc tgttcctgga 2280 ttcccatttt acaaaaccca ctgttctact gttgtattgc ccagtaggag ctatcactat 2340 attttgcaga atggaaactg ccctgactca tgaatcacaa ataaaagcca attgtatct 2399 <210> 9 <211> 3536 <212> DNA <213> homo sapiens <400> 9 actgcatttc accctagaga aagaatgctg gcaaagatct ctaccacatg gaaactgttc 60 ttaaagctgc tgggccctga aattttactc agcagtttga aatcaagaca tagcttttct 120 cattcaccct cccacttggg gctaatgcac agacatgaac atctattgag gaaaaccaca 180 aaaaacttca aaacagctac aacgggaaaa agagagtttt gtcccacagt cagcaggcca 240 ctagtttatt aacttccagt caccttgatt tttgctaaaa tgaagactct gcagtctaca 300 cttctcctgt tactgcttgt gcctctgata aagccagcac caccaaccca gcaggactca 360 cgcattatct atgattatgg aacagataat tttgaagaat ccatatttag ccaagattat 420 gaggataaat acctggatgg aaaaaatatt aaggaaaaag aaactgtgat aatacccaat 480 gagaaaagtc ttcaattaca aaaagatgag gcaataacac cattacctcc caagaaagaa 540 aatgatgaaa tgcccacgtg tctgctgtgt gtttgtttaa gtggctctgt atactgtgaa 600 gaagttgaca ttgatgctgt accaccctta ccaaaggaat cagcctatct ttacgcacga 660 ttcaacaaaa ttaaaaagct gactgccaaa gattttgcag acatacctaa cttaagaaga 720 ctcgatttta caggaaattt gatagaagat atagaagatg gtactttttc aaaactttct 780 ctgttagaag aactttcact tgctgaaaat caactactaa aacttccagt tcttcctccc 840 aagctcactt tatttaatgc aaaatacaac aaaatcaaga gtaggggaat caaagcaaat 900 gcattcaaaa aactgaataa cctcaccttc ctctacttgg accataatgc cctggaatcc 960 gtgcctctta atttaccaga aagtctacgt gtaattcatc ttcagttcaa caacatagct 1020 tcaattacag atgacacatt ctgcaaggct aatgacacca gttacatccg ggaccgcatt 1080 gaagagatac gcctggaggg caatccaatc gtcctgggaa agcatccaaa cagttttatt 1140 tgcttaaaaa gattaccgat agggtcatac ttttaacctc tattggtaca acatataaat 1200 gaaagtacac ctacactaat agtctgtctc aacaatgagt aaaggaactt aagtattggt 1260 ttaatattaa ccttgtatct cattttgaag gaatttaata ttttaagcaa ggatgttcaa 1320 aatcttacat ataataagta aaaagtaaga ctgaatgtct acgttcgaaa caaagtaata 1380 tgaaaatatt taaacagcat tacaaaatcc tagtttatac tagactacca tttaaaaatc 1440 atgtttttat ataaatgccc aaatttgaga tgcattattc ctattactaa tgatgtaagt 1500 acgaggataa atccaagaaa ctttcaactc tttgcctttc ctggccttta ctggatccca 1560 aaagcattta aggtacatgt tccaaaaact ttgaaaagct aaatgtttcc catgatcgct 1620 cattcttctt ttatgattca tacgttattc cttataaagt aagaactttg ttttcctcct 1680 atcaaggcag ctattttatt aaatttttca cttagtctga gaaatagcag atagtctcat 1740 atttaggaaa actttccaaa taaaataaat gttattctct gataaagagc taatacagaa 1800 atgttcaagt tattttactt tctggtaatg tcttcagtaa aatattttct ttatctaaat 1860 attaacattc taagtctacc aaaaaaagtt ttaaactcaa gcaggccaaa accaatatgc 1920 ttataagaaa taatgaaaag ttcatccatt tctgataaag ttctctatgg caaagtcttt 1980 caaatacgag ataactgcaa aatattttcc ttttatacta cagaaatgag aatctcatca 2040 ataaattagt tcaagcataa gatgaaaaca gaatattctg tggtgccagt gcacactacc 2100 ttcccaccca tacacatcca tgttcactgt aacaaactga atattcacaa taaagcttct 2160 gagtaacact ttctgattac tcatgataaa ctgacatggc taactgcaag aattaaatct 2220 tctatctgag agtaataatt tatgatgact cagtggtgcc agagtaaagt ttctaaaata 2280 acattcctct cacttgtacc ccactaaaag tattagacta cacattacat tgaagttaaa 2340 cacaaaatta tcagtgtttt agaaacatga gtccggactg tgtaagtaaa agtacaaaca 2400 ttatttccac cataaagtat gtattgaaat caagttgtct ctgtgtacag aatacatact 2460 tattcccatt tttaagcatt tgcttctgtt ttccctacct agaatgtcag atgtttttca 2520 gttatctccc catttgtcaa agttgacctc aagataacat ttttcattaa agcatctgag 2580 atctaagaac acaattatta ttctaacaat gattattagc tcattcactt attttgataa 2640 ctaatgatca cagctattat actactttct cgttattttg tgtgcatgcc tcatttccct 2700 gacttaaacc tcactgagag cgcaaaatgc agctttatac tttttacttt caattgccta 2760 gcacaatagt gagtacattt gaattgaata tataataaat attgcaaaat aaaatccatc 2820 taaatagaag ggttctgttt tatttggaaa aattgaatct ttaaactatc ataatcttga 2880 atgactgtca tctttctagt tttcagaaaa ataatgtatt cctatattat ttttatgata 2940 aaacttatgg agcaaaacac catcaaataa ctctcaaatt aagaaaaaat tcaaaagtca 3000 gtagttttag ataagataat gataagggag aaagaacatt ggtaaaaggt atgaattcca 3060 gaattaaaga aataatttgg ggatttctag ataagaggat atatatgaac atgcatacct 3120 tacaccttca tatacacaac cttaaatcac aaataaaaca aaataaacaa tacaaattat 3180 accaccaaga ttcagaagat atcagacgaa ataattagag aaagtaaaaa tatgctgtct 3240 ccattatatt cataatgttt cattcttgac actaataatt agaggcttta aatttttaaa 3300 tgatttactt tttactaaca ttgctgaaaa aaactaaaga catacataaa tggaaagatg 3360 tcttgtgttt atggatggta agatttaatg ttgttaagac aacaatacta tccaatatga 3420 tatgcagact gaacacagtt gccatcaaaa tctcaatgat gctttcacac aaataaaatg 3480 gaacttcaag agacccccaa ataaagagaa gaatcttgaa aataaaaaaa aaaaaa 3536 <210> 10 <211> 2362 <212> DNA <213> homo sapiens <400> 10 actataaatt cggagctgcc tcctcgccaa tgattccagc gcctgacagc caggacccca 60 ggcagcagcg agtgacagga cgtctggacc ggcgcgccgc tagcagctct gccgggccgc 120 ggcggtgatc gatggggagc ggctggagcg gacccagcga gtgagggcgc acagccggga 180 cgccgaggcg gcgggcggga gacccgcacc agcgcagccg gccctcggcg ggacgtgacg 240 cagcgcccgg ggcgcgggtt tgatatttga caaattgatc taaaatggct gggtttttat 300 ctgaataact cactgatgcc atcccagaaa gtcggcacca ggtgtatttg atatagtgtt 360 tgcaacaaat tcgacccagg tgatcaaaat gattctcaac tcttctactg aagatggtat 420 taaaagaatc caagatgatt gtcccaaagc tggaaggcat aattacatat ttgtcatgat 480 tcctacttta tacagtatca tctttgtggt gggaatattt ggaaacagct tggtggtgat 540 agtcatttac ttttatatga agctgaagac tgtggccagt gtttttcttt tgaatttagc 600 actggctgac ttatgctttt tactgacttt gccactatgg gctgtctaca cagctatgga 660 ataccgctgg ccctttggca attacctatg taagattgct tcagccagcg tcagtttcaa 720 cctgtacgct agtgtgtttc tactcacgtg tctcagcatt gatcgatacc tggctattgt 780 tcacccaatg aagtcccgcc ttcgacgcac aatgcttgta gccaaagtca cctgcatcat 840 catttggctg ctggcaggct tggccagttt gccagctata atccatcgaa atgtattttt 900 cattgagaac accaatatta cagtttgtgc tttccattat gagtcccaaa attcaaccct 960 cccgataggg ctgggcctga ccaaaaatat actgggtttc ctgtttcctt ttctgatcat 1020 tcttacaagt tatactctta tttggaaggc cctaaagaag gcttatgaaa ttcagaagaa 1080 caaaccaaga aatgatgata tttttaagat aattatggca attgtgcttt tctttttctt 1140 ttcctggatt ccccaccaaa tattcacttt tctggatgta ttgattcaac taggcatcat 1200 acgtgactgt agaattgcag atattgtgga cacggccatg cctatcacca tttgtatagc 1260 ttattttaac aattgcctga atcctctttt ttatggcttt ctggggaaaa aatttaaaag 1320 atattttctc cagcttctaa aatatattcc cccaaaagcc aaatcccact caaacctttc 1380 aacaaaaatg agcacgcttt cctaccgccc ctcagataat gtaagctcat ccaccaagaa 1440 gcctgcacca tgttttgagg ttgagtgaca tgttcgaaac ctgtccataa agtaattttg 1500 tgaaagaagg agcaagagaa cattcctctg cagcacttca ctaccaaatg agcattagct 1560 acttttcaga attgaaggag aaaatgcatt atgtggactg aaccgacttt tctaaagctc 1620 tgaacaaaag cttttctttc cttttgcaac aagacaaagc aaagccacat tttgcattag 1680 acagatgacg gctgctcgaa gaacaatgtc agaaactcga tgaatgtgtt gatttgagaa 1740 attttactga cagaaatgca atctccctag cctgcttttg tcctgttatt ttttatttcc 1800 acataaaggt atttagaata tattaaatcg ttagaggagc aacaggagat gagagttcca 1860 gattgttctg tccagtttcc aaagggcagt aaagttttcg tgccggtttt cagctattag 1920 caactgtgct acacttgcac ctggtactgc acattttgta caaagatatg ctaagcagta 1980 gtcgtcaagt tgcagatctt tttgtgaaat tcaacctgtg tcttataggt ttacactgcc 2040 aaaacaatgc ccgtaagatg gcttatttgt ataatggtgt tactaaagtc acatataaaa 2100 gttaaactac ttgtaaaggt gctgcactgg tcccaagtag tagtgtcttc ctagtatatt 2160 agtttgattt aatatctgag aagtgtatat agtttgtggt aaaaagatta tatatcataa 2220 agtatgcctt cctgtttaaa aaaagtatat attctacaca tatatgtata tgtatatcta 2280 tatctctaaa ctgctgttaa ttgattaaaa tctggcaaag ttatatttac tttaaaataa 2340 aataatttta ttgcaaaaaa aa 2362 <210> 11 <211> 2141 <212> DNA <213> homo sapiens <400> 11 gccgacgcgt gcagacgtcc ttctaatcct agtcttcgtt tggtccggtt gcactcttcc 60 tatagcccag agggcgagag ggcctgtggc ctgggggaag gaggacgagg ttctgcctgg 120 atcccagcag taggacgctg tgccatttgg gaacaaagga atagtctgcc tggaatccct 180 gcagatcttg gggccggagg ccagtccaac ccttggagca ggaagaaacg caaagttgtc 240 aagaaccaag tcgagctgcc tcagagccgg cccgcagtag ctgcagactc cgcccgcgac 300 gtgtgcgcgc ttctctgggc cagagcgagc ctgttttgtg ctcgggttaa gagatttgtc 360 ccagctatac catgggccgc actcgggaag ctggctgcgt ggccgctggt gtggttatcg 420 gggctggtgc ctgctactgt gtatacagac tggcttgggg aagagacgag aacgagaaaa 480 tctgggacga agacgaggag tctacggaca cctcagagat tggggttgag actgtgaaag 540 gagctaaaac taacgctggg gcagggtctg gggccaaact tcagggtgat tcagaggtca 600 agcctgaggt gagtttggga ctcgaggatt gtccgggtgt aaaagagaag gcccattcag 660 gatcccacag cggaggtggc ctagaggcca aggccaaggc ccttttcaac acgctgaagg 720 aacaggcaag tgcaaaggca ggcaaagggg ctagggtggg taccatctct gggaacagga 780 cccttgcacc gagtttaccc tgcccaggag gcaggggtgg aggctgccac cccaccagga 840 gtggatctag ggccgggggc agggcaagtg gaaaatccaa gggaaaggcc cgaagtaaga 900 gcaccagggc tccagctaca acatggcctg tccggagagg caagttcaac tttccttata 960 aaattgatga tattctgagt gctcccgacc tccaaaaggt cctcaacatc ctggagcgaa 1020 caaatgatcc ttttattcaa gaagtagcct tggtcactct gggtaacaat gcagcatatt 1080 catttaacca gaatgccata cgtgaattgg gtggtgtccc aattattgca aaactgataa 1140 aaacaaaaga ccccataatt agggaaaaga cttacaatgc ccttaataac ttgagtgtga 1200 acgcagaaaa tcagggcaag attaagacgt acatcagtca agtgtgtgat gacaccatgg 1260 tctgtcgctt ggactcagct gtgcagatgg ctgggctaag actgttaacc aacatgactg 1320 tgactaatca ttaccaacat ttgctttcct attcttttcc agactttttt gctttgttat 1380 tcctgggaaa tcacttcacc aagatacaga ttatgaaact aattataaac tttactgaaa 1440 atccagccat gacaagagag ctggtcagtt gtaaagtacc atcagaattg atttccctct 1500 ttaataaaga atgggataga gagattcttc ttaatatcct taccctattt gagaatataa 1560 atgacaacat aaaaaatgaa gggctcgcat catccaggaa agaattcagc agaagttcac 1620 tttttttctt attcaaagag tctggagttt gtgttaagaa aatcaaagca ctagcaaatc 1680 acaatgatct ggtggtgaaa gtaaaagtcc tgaaagtatt aaccaaactc taatttggag 1740 tctgtcccaa acaatattga gatatttgca gttggtacga tgtgatttgt aaattctttg 1800 tttttcattg tgcgtatatg gtaaagagat cttttcagct gctattttgg aataatgact 1860 atcatatatc ataacagtga ctgatgttgg ttgtaatggt tgggtttagg atgaaccatt 1920 ttaaggatgc caaatgaaat attagtattt gtacacagaa agaatttatt gatttgatct 1980 tattacctag attgagattt tttaatcttt cctctaccta aactgacaat gaattggtta 2040 tacatcatgc ataagctaca cttttatatt agtttatatt tgttattcta agacttgtgt 2100 ttcatcaata aagttgtgtt ttaagcagca gaaaaaaaaa a 2141 <210> 12 <211> 3100 <212> DNA <213> homo sapiens <400> 12 gcgctctggc gccgccgcgg tcgctctagg aaagtggcgg agcgaccctc tatggtcccg 60 ggcccacccg aaagcgttgt tcgtttcttc ctgtggtttt gttttctcct ccccccaact 120 cggaaggcgt cctgtgaccc ccgggacctc aagagctgta accgcccctg tgtgtggtcg 180 aggcttttga aaccaaactc tagcctctcc aacctagaaa ctgcatactt tccacaaatt 240 ttgagatttt tgagaccctg gtacttttca cgaagtcacc ttaattatca ccaaaaagct 300 cctgcaagat gggagtggtt atactccatt tacaggaaag gaaccaaggc tcagagaaga 360 aatgtgctcc gttcaccgtg tgctcctcct cagccatcct ggccgtgctc agtcatctga 420 ccagctgacc tccgtgttcc cccactccct ggggagctcc tccgcctttt ggcttccaat 480 gctattgctg catgctgaag actcccgcat tggtaactcc agtctgactg tgggacataa 540 atgttattga actttagact tgtatatcga actgattact caagagctgc atttgcatgt 600 gtaatggaca tcccaaacct aacatacccc ccaaatgaat tcctgatatc tacctaacct 660 gttcttgcaa cagtcttctt cccagggatg ggtgaagatc ccatcatctt tccagttgct 720 caagccaaaa accttgatgt cactgttgtc tcttcttttt ttcatccaaa attcacctgt 780 gatttatcca caaattctgt cggcttcatc gttaaaatat attcattatc aagccacttt 840 caacacttcc actgctataa ccaccaagcc accttcatcc accttctgga ttattatatt 900 ggcttccaga cgggttgccc tacagtctat tcacggcccc agagtaatcc tcttaaacct 960 aagttagatc atgtcattca tttgttcaaa accttcaaag gcttcccaac ttattagagc 1020 aaagccaagg acctcgcagt ggcacccgat gcctctcatg atctgtctct ttagttcttt 1080 attgtgtctg cagtgctgaa aacagtgctc agcagggaac agacactcag taaatagctg 1140 ttgaatgaat gaatttataa gatgccttat tgtttacaaa gtacttttac atcttatctt 1200 ctggttattc atcttcacca tagtctcatg aagcacagat tatcatatct gtcttgcaaa 1260 tcagtaaact gaagcaagag aggctgacct gcctgaagta atacagtggt ttgttggtgg 1320 aggctaaact aagtcatagg ttcattctct taagttgggg ctttctgctc tgtagggagc 1380 tgtctctgca tatggcaaag cacaaagctg aatgaggtct ggacaaagaa gctccactcg 1440 caatctagag agtatctgga ctattgcagt gattaaatga ggtaatgtaa ggcacttagc 1500 acaatgtata acacagaaga aatgagagtc gttgttactt ttattattaa attgttataa 1560 gttggttgat gctggtggtt ggagagtttg gggtaaaggg caatggccag agatctagaa 1620 atggtttagg aaaagcgtca ggagcaaaca tgacccgttg ggactgtctg ctctatgtac 1680 actaaaataa aaagataatt tttaaaaagc cattttgtta gtaaggtagt tactaattaa 1740 aactaactcc tttaatgtct acataaagat ggattatccc tttttcctat acctgaaaac 1800 aactgggcca gccatagaag ggccagaggt atgtcaacta aagcattggg taaacgagga 1860 tggatttttt aaaaagagag agacgaaagt caggaaataa aggggtgtgt gtccctaagt 1920 gtggacagag tcctgggcag taaggatgga gaggagggag agccagaaaa atatatgaag 1980 gagaggaggg taaaggagaa tgggaaaaag acagggagag aaagcaggta gggttttatg 2040 ccttcagcct agctgttagt ataataatag ttaacactta ttgagtgctt attgtgtgcc 2100 aggcactgtt tgcagcattt gaggatctca cgtgagattc ctgaggcatg attattcctg 2160 agggtttgct ccaccttctc tggttttggt ccctgcactt tgtggtgtga ctccggtgcc 2220 tcctggtgaa ccacatgcct gtcccactga tgttgacttg accactgatt tgaattggct 2280 gaccgcatgt gactggatgc aaggggtaca tcacatccca gaagaaactt caagtcattg 2340 tgtttctgcc aggactctgc tctttccctc tgccttgaga atagcatgtc ccaagtaggg 2400 gctgcccctt tagtctagga accaggatga taagacacat ggagcagagc cacagaagct 2460 cacatgtaac cacaacggtc ccacgtaatg ttagagaaac aaatgctctt gtaacactga 2520 gattcttggt ggtattattg cattaaagtt gactaatgta cctcccacca accgtaagag 2580 ataggaattg ttattatcct gtgatattgt gaaatacata gttgatcttc tccccgtttc 2640 ctgacataca acttctaaaa tccttagaat ctccaaagtg atgtcttttt atatgctgat 2700 gagttgactg atgcctggca gcccctgggt agcttcagga tggggctggt cactggaaag 2760 accacagcag gattagaagg atggcaattt cagctccacc ccatcaacat ctggggagga 2820 gggcaactga aggtgaagtg gatcaccaat ggctgatgga ttaatcaatc atgcctgtgt 2880 tacaaagtct ccataaaagc tcccaaagga ctgggttcag agagcttctg gatacctgaa 2940 cacatggatg ttactggagg gtgccacctg gggtcggggg gtgcaaaggg gaaggagtat 3000 ggaagctccg caccctttcc ttcatacctc actatatgca tttctttttc tatatccttt 3060 ggaatatcat ttgtaataaa ccaggaaatg tgtttcgctg 3100 <210> 13 <211> 2502 <212> DNA <213> homo sapiens <400> 13 gagtgcaccg cagccgctgc attcaggaac cgctttagct tcgcccccgg ccggccgggc 60 ggggaagact ggtgtggtct ggccatggat gggctccagg ccagtgcagg gccgttgagg 120 cgcgggcggc cgaagcgccg gcgcaagccc cagccacaca gcgggtcggt cctggccctg 180 cccttgaggt ccaggaagat acgaaagcag ctgcgaagtg ttgtatcccg catggcagcg 240 ctgaggacgc agacgctgcc tagcgagaac tcggaggaat cgagggtgga gtcgacggcc 300 gacgacctgg gggacgcgct acccggtggg gcggcggtgg cggccgtccc ggacgcagcc 360 cggcgagagc catacggcca cctggggccc gcagagctgc tggaggcctc gcccgccgcg 420 cgctccctgc agaccccgtc ggcgcgcctg gtgcccgctt ccgcgccgcc cgcgcgcctg 480 gtggaggtgc ccgccgcgcc ggtccgggtg gtggagacct cggccctgct gtgcaccgcg 540 caacacttag cggccgtcca gtcgtccggg gcccctgcga cggcgtcggg gccgcaggtg 600 gataacacgg gtggggagcc ggcctgggac tccccgctgc ggcgcgtctt ggccgagctg 660 aaccgcatcc ccagcagccg gcggcgagcg gcccgcctct ttgagtggct catcgcgccc 720 atgccgccag atcactttta ccggcgccta tgggagcgcg aggcggtgct ggtgcggcgg 780 caggaccaca cctactacca gggacttttc tctaccgctg acctggattc gatgctgcgc 840 aacgaggagg tgcagttcgg ccagcatttg gacgccgctc gctacatcaa cggacgacgc 900 gagaccctga acccacccgg ccgcgcgctg cccgccgccg cgtggtccct gtaccaggcc 960 ggctgctccc tgcgtctcct ctgtccgcag gctttctcta ctactgtgtg gcagtttttg 1020 gctgtgcttc aagagcagtt tggaagcatg gcaggctcca acgtttacct cacgccccct 1080 aactcgcagg gctttgcccc ccactacgac gacatcgagg ccttcgtgct gcagctggaa 1140 ggtaggaaac tctggcgtgt ataccgaccc cgagtcccaa ccgaggaact ggctctgaca 1200 tccagcccca acttcagtca ggacgacctc ggtgagccgg tgctgcagac cgtgctggaa 1260 cctggagatt tgctgtattt tcctcggggc ttcattcacc aagctgaatg ccaggatgga 1320 gtccactctc tgcacctcac cttgtccacg taccagcgca atacctgggg tgacttctta 1380 gaggccatac tgcctctggc agtgcaggct gcaatggaag aaaatgtgga gtttcggagg 1440 ggtctgcccc gagacttcat ggattacatg ggggcccagc attcagattc taaggatccg 1500 cgaagaaccg ctttcatgga gaaggtgcgg gtcttggttg cccgcctggg acactttgct 1560 cctgttgatg ctgtggccga ccagcgagcc aaagacttca ttcacgattc tctgccccct 1620 gttttgactg atagggagag ggcactaagt gtttacgggc ttccaattcg ctgggaggct 1680 ggagaacctg taaacgtggg ggcccagttg acaacagaaa cagaagtcca tatgcttcag 1740 gatgggatag ctcggctggt gggtgagggg ggccatttgt ttctctatta cacagtggaa 1800 aactcccgtg tgtatcatct ggaagaaccc aagtgcttgg aaatataccc ccagcaagct 1860 gatgccatgg aactgttgct tggttcttat ccagagtttg tgagagtggg ggacctgccc 1920 tgtgacagtg tggaggacca gctgtccttg gcaaccacgt tgtatgataa ggggctgctg 1980 ctcactaaga tgcctctagc cctaaattag tttcttgttg attgctggaa acaaggcagt 2040 agtgattctc cgctgccact gctacctttt tttttttttt ttccttaaac tcacgttctt 2100 accttgataa gcatcagtgt gctcacattt acctttatca ctgcttcagt gtcacaaacc 2160 tcggaaggtc ttctaggaag aaccatctca tctaggtaca aaaggaaaag gagaagttgg 2220 aggtggaaaa aaaacccttg atccgtgatc atttcagagc accaacttca tcaccttcag 2280 gcttcagtgt actgggtaac actgaccatg tcgttctgct tgagacagat attagatttt 2340 ttttggaatt tggatctttc atctgagttc tttttcatgg gcgggtcggg gtcagtatcc 2400 tgtttgttat tgttaaattt gtatgaacct tagaaaagtt attaaagtgc caaagaatgt 2460 ttccctttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 2502 <210> 14 <211> 3398 <212> DNA <213> homo sapiens <400> 14 tgtctgctca atcaagtcaa atactgaaca acttcctggc ggagaggctg agaattttat 60 acttgcttgc tcgaaagcac cccaaataag atgatccacg ccaacacctc ccctttacag 120 gttttaaaat attcttataa ctatgactga aaacaagaca gtttcctctt cttccactag 180 agatgatcaa accaatatag gtttaacatg tcaggaagta aaggctctca gagagaaggc 240 atggtcaagg acaaatgaag gcaatgccat gtctcaaagt ttggttctat atggagcctc 300 taaggagaac agtgaaggtt ttcatgaaag taaaatgaca aatactgaag gggtgaataa 360 aggcatttac tttagctacc catgtcgacg tcacagctgt gccgtagtaa atattccagc 420 accttgtgtc aacaaaatga tttcacacat ccaagatgtg gagtccaaaa tacaggagca 480 tttgaaaagg tttgaaactt cttttgaaga atggagcaga acttcttcca caaaagacct 540 gaaagaagat tggagtgtaa ctacaccagt gaaagaggtc aaaccaggag aaaagagaga 600 tgaaaagtgt ccagagttaa agcaggaaat ggaaacattg ctctcagagg ccattcgtct 660 cattaaaagt ctagaaactg accgggcaga cgctgaagaa gctttaaaac aacagagatc 720 aagaaagaat atgattaaca tgaaaattga ctcttggtca gtctggaaac ttcaagaact 780 cccattggct gtgcagaaag aacatgaggc ctatttgagt gatgttatag aattacaatg 840 gcatcttgaa gataaagcta atcaactaca acattttgaa aaacaaaaga cagagttaga 900 agaagcaaat gcaaagattc aagcagacat agactacatg aatgaacatg gccctctact 960 ggactctaag cagaatcagg aacttcaaga tctgaagaac cattataaaa aaaaaatgga 1020 ggtaatggac ctacacagaa aagttaatga agaacttgaa gaagctttag aagcctgtga 1080 aaatgccaga ttgaaggctc agcaaattaa agaagagatt gataaggata tttaccagga 1140 tgaaaaaacc atagaggcct acaagagaga gatatatcaa cttaacagtc tatttgatca 1200 ttactcttca tcagtgataa atgttaatac taatattgag gagaaggaag aggaagtgac 1260 tgaagcaata agggaaacaa agtcatcaaa aaatgaatta cattctctat caaaaatgct 1320 ggaagatttg agaagagttt atgaccaact aacctggaag caaaaaagtc atgaaaatca 1380 gtatctggaa gcagttaatg atttttatgc tgcaaaaaaa acatgggata ttgagctttc 1440 tgatgttgca aaagattttt cagctatttc tttggcatgt acaaaactga cggaagacaa 1500 taaaaaactt gagattgata ttaacaaaat aacagtaaaa accaatgaaa gcatacggaa 1560 aaaatcaaaa tacgaatctg aaataaaata tttgacaata atgaagttaa agaatgataa 1620 acatctcaag aacatctata aggaggctta tcgcattggt actcttttcc acctaaccaa 1680 acacaagaca gatgaaatgg aagataaaat agcagaagtg agaagaaagt tcaagggtag 1740 agaagaattc ctgaaaaaac tcactcaagg tgaagtggct gctggaatgg tgcttcagaa 1800 aaaactatat tccatttacg aagtccaggc acttgagcgg aaagagctta taaaaaatag 1860 agcaatatgt gccatgtcac tggcagaact acaggaacct ctgcttcaac tagaagatga 1920 agctgaaaga atcagaagtc tcgacaaaga acattctgtt atgcttaata atataattga 1980 tcagaaagat cttattagaa gaaaggtggg aaaagtaaag aaaaaattac gaaaaaaggg 2040 gaagaaaacc cttgatgcat taatagaaac tgagagtaaa cgctcagcaa tttttaaaga 2100 cctagaagca actaaaagta agacaatgat tttttatgca aaaataaatg aattgaatga 2160 ggaattaaaa gcaaaagaag aagaaaagaa aagttttgat cagacacttg aaatattaaa 2220 gaacaaattt ataactatga gatttaaaag ggaacatgca caaactgtgt ttgatcatta 2280 tatgcaagag aaaaaagact gtgaagagag aatctttgag gaagatcaga gatttagagt 2340 gctccttgct gtaagacaaa aaactcttca agatacccaa aaaataatag ctgattcact 2400 tgaagaaaat ctgcgtttag ctcaagagta tcaacagcta cagattacat tcttaaaaga 2460 aaaggacaat tatttcaata tatatgataa acagctatca cttgatactt caattagaga 2520 taagaaacag ctctgtcagc tgcagagaag gatgcacaca ctgtggcagg agcacttcaa 2580 actggtggtc ctcttcagcc agatgaggct ggccaacttc cagacagact ctcaggagag 2640 tattcagaaa atattagctg tgcaggagga atcttcaaat ttaatgcaac acatcttagg 2700 tttcttccag actttgacag atggcacatg cgaaaacgat ggttaagcaa acaaccaatg 2760 tatcttggat gctgaaataa aagacaagaa aagtcacaca gttcagataa cagtgtaatt 2820 ggacattcac ctgtttgcca tttcacactt ccatgaacga aaaactcact cacctcccag 2880 catgctttgc cactctttta ctcacagcaa atccataaca atgaaacagg tgactttcat 2940 gctgctgtca ggaacgatct aatttcagct ctgggtgact gattgcaatt ggctttgcct 3000 catctgataa ttaatctatg tcaccattaa ttggaagaga gaataattac tggcggtgtt 3060 gacagtgact gttcgcttcc ccagatttcc ctatcgtctt ggcccaaata aaggctttgc 3120 cattcagtac ttaaagtttg tgtaaactgt aacaatatct atgcccatgt gacactttga 3180 gacactctgt ctaatgtact tttgtttttg tgtttaccag tcttttttag ctcactgaga 3240 gctgtctctc tcaatcactc ctcaatgttc tatcttaatt ttgtggaagt ttaaagtttt 3300 caatgagctg gagatgaatg attaatgaat aaatttaaat gcttcatttt gtccaaaaaa 3360 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 3398 <210> 15 <211> 1834 <212> DNA <213> homo sapiens <400> 15 aatacccaga tcttcaaggt tggcaaagaa gagaaaagct ccttgggaac ttagttacca 60 ggtcttatag caccagctct gtgtcctcag agtcgctgtc atcaaggaga cctctcactg 120 gtcaccgccg cagcccccac atggaccagt atgtgtccac agctcctccc cgattcccta 180 tagcacagct gggaacattt aaacaagact ctgcaggaat gggacggata ttcaagggga 240 atttgctgca gaagaaagca cttaccacat ttgaaaatga acaccatatt cgtttcttca 300 cattgttggt tcttttccat gtgatggtgt tgctgaggaa tcatagcagg atacaagggg 360 tttctgaaga ctggaaaagg gccaacagca tatttcgaaa ctttctacgt ttgaagtcat 420 ccaggaacac agcagaagca gaataaatga cactacgttt ctctctcatg gccttcatac 480 catggatttc ccctgctcaa gatgaaaaga aattaagagg aaatcagatt gcttagagat 540 agcagattat tgctcacttt ttaaaaggag ctccacagag agaatgaaga acgtgtaact 600 ttttgcaatg ataatgtctg ctttgttctt gaggggcact cttccttttt ctgttcagga 660 atattccgga ggagagctgc agatgccacc caaccctgcg aaatctgccc tgcgtgtcga 720 aacagatcca gcagtgcaaa gaacttcttc attaggacat caagcctgta gtcatatttt 780 caattgctgc tgtaactttt tccttgcaag tgctttcact tatttcggga ccacctaagg 840 ctctgtgtgg tatacagcaa cacagtttga gatatttctg tgatgttctg tatatcatat 900 agttgctaac aacctgtcaa agtcatcctg acaccaaact gagaagctga tggtttgggt 960 aacatattag aggagatgaa aaaaccgaca gtcctcatta ctgtaataaa accagcagag 1020 acacactgag aatcaattac tgattgtgac ctaatgaact aaccctcagt caagtagaaa 1080 actgcaccaa gcctcttaca ttatcaaatg atttaggatg gagcactgtc tgaagacggg 1140 caacaagtcg aggcagatga gttttcttat attgtggctg acttaattac cttgttcctg 1200 agtgcagaga tcaaattgag caacttaagg tgctaaagct ctgtgccagc tggaaatgaa 1260 aaggaaataa ttaacaccaa caagagctac gtctaaggtt gtggcacctc ctgacagaag 1320 caaggagact caaagttaag gcggctgcaa agtccttgac gaggtgagcc ctgctctatc 1380 cgcctggctg gattcgtcca ggttgcctgt ggcagctgtg cactgaagag tccggctggg 1440 gagccaggga ttcagaactc acagtgcagc ctgacgacca aagggcaaat ccacctgagg 1500 acctgagtgc agatggctgg gctccccgga acaaagtgga ggaatgacag aggtgtaact 1560 cttacaccac agcctccatc tgtgtgtcgc agagaaaaat actataatgg agactattct 1620 tacacacata cacacacaca cacacacaca gagttcttgt caccgatgga acagtctgtc 1680 tttgtctttc atctcccaca ttcatgtcca gatcccattg cgctgcatca cacgtgaacc 1740 cagtgaggtc aacaatgaat ggatggtgtt cacaaagaaa ccagcttatg gaaggggacc 1800 tgttacaatt ctttgaatta agttcttgga agcc 1834 <210> 16 <211> 1933 <212> DNA <213> homo sapiens <400> 16 gcacagtatc tgggtccagc ctgcagccct agggtccagg tgatgtttcc gtgtgtgtgg 60 cccttcttca cagtggcctc ctagaaaaac aagaccctga ctcaaagaac acctctcact 120 acattcagag tctgtcatct gaaccatgag gatctggtgg cttctgcttg ccattgaaat 180 ctgcacaggg aacataaact cacaggacac ctgcaggcaa gggcaccctg gaatccctgg 240 gaaccccggt cacaatggtc tgcctggaag agatggacga gacggagcga agggtgacaa 300 aggcgatgca ggagaaccag gacgtcctgg cagcccgggg aaggatggga cgagtggaga 360 gaagggagaa cgaggagcag atggaaaagt tgaagcaaaa ggcatcaaag gtgatcaagg 420 ctcaagagga tccccaggaa aacatggccc caaggggctt gcagggccca tgggagagaa 480 gggcctccga ggagagactg ggcctcaggg gcagaagggg aataagggtg acgtgggtcc 540 cactggtcct gaggggccaa ggggcaacat tgggcctttg ggcccaactg gtttaccggg 600 ccccatgggc cctattggaa agcctggtcc caaaggagaa gctggaccca cggggcccca 660 gggtgagcca ggagtccggg gaataagagg ctggaaagga gatcgaggag agaaagggaa 720 aatcggtgag actctagtct tgccaaaaag tgctttcact gtggggctca cggtgctgag 780 caagtttcct tcttcagata tgcccattaa atttgataag atcctgtata acgaattcaa 840 ccattatgat acagcagcgg ggaaattcac gtgccacatt gctggggtct attacttcac 900 ctaccacatc actgttttct ccagaaatgt tcaggtgtct ttggtcaaaa atggagtaaa 960 aatactgcac accaaagatg cttacatgag ctctgaggac caggcctctg gcggcattgt 1020 cctgcagctg aagctcgggg atgaggtgtg gctgcaggtg acaggaggag agaggttcaa 1080 tggcttgttt gctgatgagg acgatgacac aactttcaca gggttccttc tgttcagcag 1140 cccgtgacag aggagagttt aaaaatccgc cacaccatcc atcagaatca gcttgggatg 1200 aacttattca gatggtttta ctttattaat tcctccaatt attacaataa tcataaaaag 1260 gtgaaaatgg aaaagttatt cccaaaactg attctgtgta acttactatt tttccaggag 1320 taaatattta aaatagctgc atggtttatt ctaatttatt tcacatttct tattcctatt 1380 atctgaagaa tccctcgtct gtgcgtttct tgtgggaaga gtgttttaat atcattttag 1440 tgctctgagg agtcatatga agatgtatcc ctcatctgtg tttctgagga cattaagggg 1500 aaattagagg gaaatgttta ttcaatttag tactagcaac agctttaagc tggtgatgct 1560 gtcatactcc agaaagctgt agacactgct cattttgtct tttaaaaaaa ttttatttta 1620 ttttaagttc tgggatacat atgcaaaaca tgcatgtttg ttacataggt aaacatgtgc 1680 tgtggtggtt tgctgtatct atcaacccat cacctaggta ttaagccctg catgcattag 1740 ctatttgtcc tggtgctctc cctcccactt tgctcatttt ctaacctagg ttttaatcac 1800 cattttaccc aacaaatcat tgttcgatca ttatttgcca gacttgaatc tctatgtgtt 1860 ttctaggact gctctaataa agtacacaaa ctgggagtct ttaaacaaca aaaaaaaaaa 1920 aaaaaaaaaa aaa 1933 <210> 17 <211> 1252 <212> DNA <213> homo sapiens <400> 17 tcgagagttg ggttcagtcc tggcccgttg tggggacggc acgcggggga aggggagggg 60 acggagaccg aagaacggag gtccttatgt ttcttttctt tccttaaatc ttgcccggcc 120 tgaagaggcc ggaagttgca tctctggaca agtaaactct gagacctggg aatggcgggc 180 gggacccgct cctcccttgg ggtctagagg agacccccgg agatggtccc tgatgagcag 240 cgtgatggtg gaaagctgga ctggtctccc gaaaggcgaa gccgaggctt cttcctctga 300 acttttggca cgttctttga cttgcttgtg gccgtagtgt caggcctgta ttgcacattt 360 atgtctgtgg tgcatttctc catctgggcc agctgagggg cccacggaca tagggcaccc 420 acaataggcg tgtgtctgct gtgtgtttgt gttcggccgt cctgcttctc tgtttccaca 480 cgtacacatg cccctgtgtt actttggttc atcttctgta ctctgtcagt tttctgctgg 540 tcagaacatc tgtgactgtg acagagctgt ccaggattgc agtggatagg aatttcttca 600 catggctcct ggagaagtga ccatcacagt tcgcctcatc cgttcctttg aacatcgcaa 660 tttcaaacct gtagtgtatc acggagtgaa tttggaccaa actgtaaagg aatttatcgt 720 atttctaaag caagatatcc ctttaaggac caacctgcca ccaccattca gaaattataa 780 atatgatgca ctaaagatta ttcatcaagc acataaatca aagacaaatg aacttgtgtt 840 gagtttggaa gatgacgaaa gactcctgct gaaagaagac agcactctga aagcagctgg 900 aatcgccagt gaaactgaaa ttgcattctt ctgtgaagaa gattataaga actacaaagc 960 taatcccatt tcatcctggt gaaaacatct cgagggcttc ctttttgcat acctgtatta 1020 agctctttat tccactgctg aatttttgaa attgacaaac aaatcttaaa aaattaatcc 1080 caggctatac tctttgagct aaaatctggt tatttctttc tcttcaggtc tttccttctc 1140 tctttctttt tctttgttgt tgtaaaataa tatattatga gaaaaacatt tgatcttttt 1200 aaagggaaat aaattgttat taaaaattat tgtggaaaaa aaaaaaaaaa aa 1252 <210> 18 <211> 2215 <212> DNA <213> homo sapiens <400> 18 cttccatctc catggttacg cggcggtggc tgcgagcgcc caactgctcc gactgtcgcg 60 gtgagggccc caggacagaa gcagacagac acggctcctg ctgtcgattc cgatccagcc 120 agaatgcctc caactcaggc cgaaagtgtt ataaggagta ttatacgaga aataggacaa 180 gaatgtgcag cccatggaga gattgtttct gaaactctga ttgcttttat ggtgaaagct 240 gttgtcctgg atccaagtaa tggctttaac atggatagaa ccctcatgaa aagtgatgtg 300 cagaatcttg ttaagctttg tatgactcgg ctattggata ctaaaaatcc atccctggac 360 actattaaga tgcaagtcta cttcgatatg aattatacga atcgagtgga atttctcgaa 420 gaacatcacc gggtcctaga gtctagatta ggctctgtta cccgagaaat tacagataac 480 agagcatgtg ctaaagaaga attggaaagc ctctaccgga agattatcag ctatgtgtta 540 ctccgctctg gccttggatc ccctacagac atcaagactg tcagagaggt aacagctgct 600 ctacagagtg tttttcctca ggcagagctt gggacatttc taactctttc taagaaggac 660 aaagaacgcc agctgaaaga actcaccatg attgttactg gaattcgttt atttaacaga 720 gactgtggaa aaggaggaga aggcattgat gatttgccag ctgttctcca tgtagcaatc 780 ccagccacca tgcagcatat tgattaccag cttgagactg cccggagcca ggtataccgc 840 tacacagcca tccttgagaa ggcagccaac gacccactca tgagggctga acttcagcca 900 tatatgttaa aagaagcgct atataatata cgacaatatg aggtcttcct tcagatcatt 960 ttgtcagata taattactgg tgctcaagaa gtggaaatga tgacaaaaca gttaggagcc 1020 catctggaac aactaaaaat gaccataaaa tcaaagatag cggtcccaac atcacaagtc 1080 tttcctatct tcattgcact ttctactctg tggaccagct tgcaagacga aactattgtg 1140 gttggtgtcc tcagtaattt attcactcac attcagccat tcttgggtgc tcacgaacta 1200 tactttcctg agagagtgat gcaatgtcat cttaatggag cgactgtgaa aactgatgtg 1260 tgtagaatga aagaacacat ggaagataga gtaaatgtgg cagatttcag aaaactagaa 1320 tggcttttcc cagaaacaac agcaaatttt gataaactgt taattcaata tcggggattt 1380 tgtgcttaca cgtttgctgc aacagatggt cttctccttc caggaaatcc agcaattgga 1440 attttaaaat ataaagaaaa atattacaca ttcaatagta aagatgctgc atattcattt 1500 gcagaaaatc ctgaacatta tattgacata gttagagaaa aggccaaaaa aaatacagag 1560 ttaattcaac tattggaact tcatcaacag tttgaaacat ttattccata ttctcagatg 1620 agagatgctg acaaacatta tataaaacca attacaaaat gtgaaagtag cacacagacg 1680 aatacacaca tactgccacc aacgattgtg agatcatatg agtggaatga atgggaatta 1740 agaagaaaag ctataaaatt ggctaatttg cgccagaaag ttactcactc agtacaaact 1800 gatcttagtc acttgagaag agaaaattgt tcccaagtgt accctccaaa ggacactagc 1860 acccagtcca tgagggaaga cagcactggg gtgcccaggc ctcagattta cttggctggt 1920 cttcgtggag gaaagagcga aatcaccgat gaggtcaagg tgaacttaac tagagatgtg 1980 gatgaaacct aattacagac aacgttttaa aatagatgct actcaattat gaacaatagc 2040 aagtacttaa aggtatatta acatctatac aaattaattt tgtaggggtg gcacattcat 2100 tggttgtgtg actgtttatt gggttcccat attttatcaa actgttttct gtaacacatt 2160 tttcattctg ttgaaattga aaaataaaac tgtccattta tcttttattt gttag 2215 <210> 19 <211> 1171 <212> DNA <213> homo sapiens <400> 19 atctttatcc ctttaagcat ggtttatttt ctgagcaagg agtcatcatg ggagaccttt 60 tttccttatt ttgggaggta gatcctcccc caatacctgt aaattgtgcc attccaaatc 120 aggattatga atgctggaag gatgactctt gtggaaccat agggagcttc ctgctttggt 180 attttgttat cgtatttgtc ctgatgttct tctctagggc ttctgtctgg atgtctgagg 240 ataaaaagga tgaaggcagt gggacaagta cttcagtaag gaaagcaagc aaagagactt 300 cctgtaagcg gcaaagcaaa gacagtgcct gggatccctc acaaacaatg aagaaaccaa 360 agcagaacca acttacccct gtaaccaact cagaagtggc tttggtcaat gcctatcctg 420 aacaaagacg agccaggcgc cagtctcagt tcaatgaggt gaaccagaac caacatgaca 480 gtgatactac ggagtatggc agtgaagagt ctaactcaga agcctcctcg tggaaggaga 540 gtgaaagtga acaccaccca tcaccagaca gtattaagag gagaaaaatg gctcagaggc 600 aaaggaatct gggaagttac caaatgagcg aaaggcactg cctccactgc aaagccttga 660 gaaccaacga atggttggcg caccattccc gacagaagcc ttcagtaaca ccgccaatga 720 aaagagacag tcaagaggaa agttccatat ctgacattaa caagaaattt agtaaatttt 780 gaattttatc acgttcttcc ttcacttgaa gccaaatgaa agagatgaat aaaacatgaa 840 aaatcaccag agctataggt gaggagactt ttacaacaaa gtctctctac caacaaacaa 900 aaacatactt ggaacccaag aggtaaaatc tcacacaatt cttcgttcaa aaaaaaaaag 960 gccatcacgt gtttatggca ccattggaac accaaagatc tatatctgct atgatttttt 1020 tatttgaaat agcacaagac agatattttg tgccttgagt gtatatattt tgtgccttga 1080 gtgtatgtat tttgtttatg tctgtaatat gaataagaaa gctctttgaa aatgtattat 1140 ttatgttgag aaaccaaaaa aaaaaaaaaa a 1171 <210> 20 <211> 1038 <212> DNA <213> homo sapiens <400> 20 agttgggagc ctgatggagg acaagtaggg cctcgaggac aggtgcgtga cagaagcaca 60 ggaaaaaaaa gaaaaatgaa gaaataaaaa cacgagttca tcagtaaaga ggtaccctgg 120 cagcataaat attatgataa gctaaaagct ggaatcatct ggaaaaataa ataagactcc 180 tcatgtcctt ttcggtccat aaccagaagg gcagcaaaag gcctttgcca ctggaacctc 240 ttctttttct ccaagtccca cgtagcaatt acctgcactt tcaagaagag aaacaacgac 300 tacacctaaa gaaattcctt cttgatagga tgtttctagt ggccaagata caagcaaatg 360 tagaaagaaa agatgttgct gactactatg aacaaatgtt tcagtcagtt ttgaaacatc 420 acctaggaga agcagtgaca ggattgctgc tcatctatcc cacttccatt ctgcatatcc 480 tcgagtcctc cagcgacact ctctacaaag ttcttttaga ttatattggc catgtcaaag 540 atgaaacagt attttttatt caacaaatga aaattatagt catttctcat aacattccaa 600 tgaggctttt tatgcaatgg catgtttcag tgataaaagt tccagttatg tatctcgacg 660 atgtgacaca gtcacagtcc ctaaaggagg tcatcacaga ttttctcaca caaactcata 720 aactgtcact ctacctttgc cagactatga aagtaggcac taaaggacca ggcgataact 780 tacaccaagt tgcacctgac ctactcctcc cagaacaaat cataaagtac ttgtgcaaat 840 ccgaagaatt catggacccg gcaacattta taaacatgta taatagaccc atacacatca 900 ctctggattc tgaggtggta tggcctgctc cttcacgttt ctaggattga gagggataat 960 gtgcccatgt ctcttaagga gtttgtgcta cttaaataaa aaaaacattt ttaaagttaa 1020 aaaaaaaaaa aaaaaaaa 1038 <210> 21 <211> 3424 <212> DNA <213> homo sapiens <400> 21 gtgatgcaat gatgacctca gggtaaactg ccagaaggct aagggaaatg gaatggctgc 60 tggaggacct gcttggggct aagggggata tggggcttct ctggggccaa ctgacccatg 120 ccctagcctg cagacactgc ggcagcagct gcttccagag tccaggaaat ctggtgacac 180 tattcttatt cgtggtttgg cagattcaga gatggtggca gcttgggagg ttgcgacagc 240 ttcatccctg gtgctctggg aatatggtgc aaggcaagga actaccactt ctgcaccgtg 300 tggccttcct tgatcacctg tgtaagcaga aatcagaagt ggaggaagaa ggggaagaag 360 aggaagaggg ggaagacgag gcatctctgg atccactgaa gccatgttct cctaccaaag 420 aagctcccac tggagagcaa gccactccag ccccacccca gccatcctgt ggttctgagg 480 gcctcctcaa ggctataggg ataccagagc aaacagtcat gcagcccgtg agcccttcca 540 gatccttccc catcttccag attctgacca gctttcctgt gaggcacaag atagcatcag 600 ggaaccgcca gcagcagaga aaaagccagc tcttctgggg tctcccctct ctgcacagcg 660 agtccttgga ggccatcttc ctgagctcag gtggcccctc tcctctgaag tggtctgttt 720 gttcttctgt cttcttcaac aagcttgcct tcctacctag gtccaacctg ttgcttcccc 780 agtatcactc ctcagcccag ttttctaccc atggggccca tactatggaa gatctagaag 840 ggatggcccc cgatcctcag ctgcttccac ctccatcttc tccttctgtc tcatcactac 900 tcctccatct gaggcccttc cctgtggacc acaagggagt tttatctggc gctgaggcac 960 ccacacagtc ccctggaact agccccctgg aagttctccc tggatatgag actcatttgg 1020 aaaccacagg acacaaaaag atgccccaag cttttgagcc tccgatgcca cccccctgcc 1080 aatccccagc ttctctgtca gaacccagaa aagttagccc tgaaggagga cttgctatat 1140 ctaaggactt ctggggaacc gtgggataca gagagaaacc tcaggcctct gagtcttcaa 1200 tgccagtccc ttgccctccc ctagactccc tgccagaact ccagagagag agttccctgg 1260 aagatccatc cagatataag ccccagtggg aatgcagaga aaactcagga aacctctggg 1320 cttttgagtc tccagtcttg gacctcaacc cagagctctc tggaaccagc cctgaatgtg 1380 tcccaccagc atctgagaca ccatggaagg gcatgcaaag tagagaaaat atttgggtcc 1440 ctgcagaccc agtttcacct cccagccttc cctcagtccc tctcctggag tctctagtaa 1500 tgggccccca gggagtcctg tctgaatcca aagctttgtg ggagaccatg gggcagaaag 1560 agaacctctg ggcatctgat tccccagacc ctgttcatag cacacctcca accaccctta 1620 tggaaccaca cagaatcaat cctggggaat gcctcgctac atcagaagct acatggaagg 1680 atactgagca ttccaggaat tcctcggctt ctaggtctcc atctctggcc ctcagcccac 1740 ccccagctct tgcaccggag ctgctcagag ttagatccat gggggtcctg tctgattctg 1800 aagctagatg tggggacata caaaagacaa aaaactcctg ggcctctaag cacccagctt 1860 gtaacttacc ccaagacctg catggagcca gccctctggg agtcttgtct gattctcagt 1920 ctattgtagg ggaaatggag caaaaagaaa actgtgttcc tgtgttccca ggtaggggct 1980 ccagcccatc ctcaaactct gtttcaaagt cccacgtaag tgagcctatc gcagaccaaa 2040 gcaactataa gcctgacggg gaggcagtgg agcaaagaaa gaaccactgg gccactgagc 2100 tcccagcccc cagctcactc tctactcctc taccagagcc acacattgac cttgaacttg 2160 tgtggagaaa tgtgcaacaa agagaagttc cccaaggccc cagccctctg gcagtggatc 2220 ccctacaccc agtaccccag cctcccaccc tagctgaagc tgtgaagatt gaacgcactc 2280 atcctggtct acccaaggga gtaacgtgcc caggggttaa ggcagaggcc ccactctccc 2340 agagatggac tgtcccagag ttgctcaccc atcctgggat ccatgcctgg cagtggagta 2400 gagagctgaa actcaggctg aagaaactgc ggcagagccc tgcctccaga gcccctggcc 2460 caagtcaatc attttgcagc tcccctattc tgagctccac aattccagac ttctggggac 2520 tcccttcctg cccaccacag cagatttatc cccccaatcc atgcccccac tcttcaagtt 2580 gtcatcctca agaagttcag cgcacagtac ctcagcctgt ccagtcctcc cactgtcatc 2640 acttccaatc ctcttcccag cttcagccac aggagtctgg cagggcggaa caagggtctc 2700 agagagggga gaaaatgaag gggaagatgg tgagccaggt cccatcccaa gggccatgtg 2760 tacacatgga ggctggtgtg gactatctat ctccaggccc aggagaaccc tcaaactcta 2820 aggttctggt ctcaggcaag agaaaggaca aggcttcagc ctcatcctca gccaaaaaga 2880 gagagcaccc taggaaaccc aaagcaggag accatagaag agggactgca aggttggggt 2940 tatccacagt cacagggaag aaccaccctg cccaggccag aagcctagta gaggcccctg 3000 taagcacatt tccccaaagg tctcaacaca ggggccagag ctctcaacac actgctcttc 3060 cccagctgct tctccccaaa gcttcgggtc cccaggatca gccagaggca gggcgaagag 3120 caagtgacat cctgacccct cgccactgta agcactgtcc ttgggcccac atggagaagt 3180 atctctcctt ccctaccctc aaggcttccc ttaccagggg tttgcaaaag gtgttagcca 3240 aatgcctgga taaccatcga cccctaccca ccaaatctag tcagtagaga aaaggctggt 3300 aatactagca cttggtatgc caagacctga agccaaacca gggggaaggt ggggatgtgg 3360 agacaagaaa tggaaattct aataaactag ctgaattaga taaatcccaa aaaaaaaaaa 3420 aaaa 3424 <210> 22 <211> 1328 <212> DNA <213> homo sapiens <400> 22 cgaggctgcg ccgcgtggag tggcttggct taacagcagg gagggcagag cgatgctctt 60 tgacctccca gaagagtcac gtgggctgac ccagagccgg ggcggaaagg ctgcgttagt 120 ttcttccggg tcattgacag aagcgtcaat tcctgggagt agttcgttgg ttttctttcc 180 cctcatcctt ttgcctgctc ccggcgaggg gtggctttga tttcggcgat gagctcccag 240 aaaggcaacg tggctcgttc cagacctcag aagcaccaga atacgtttag cttcaaaaat 300 gacaagttcg ataaaagtgt gcagaccaag aaaattaatg caaaacttca tgatggagta 360 tgtcagcgct gtaaagaagt tcttgagtgg cgtgtaaaat acagcaaata caaaccatta 420 tcaaaaccta aaaagtgtgt taaatgttta caaaagacag tgaaggattc ttatcacata 480 atgtgcaggc catgtgcctg tgaacttgaa gtttgcgcaa aatgtggaaa gaaagaagac 540 attgttattc cgttgaataa agaaacagaa aaaatagaac atactgaaaa taatctaagt 600 tccaaccata gaagaagctg cagaagaaat gaagaaagtg atgatgattt agattttgat 660 attgatttag aagacacagg aggagaccat caaatgaatt aatatcactg tattaaaagt 720 ctgccgggca cagtggctca cgcctgtaat cccaacactt tgggaggcca aggagggtgg 780 atcacctgag gtcaggagtt cgagaccagc ctggccaaca tggcggaacc ccatctccac 840 taaaagtaca aaaaattagc tgggcgtggt ggctcatgcc tgtaatccca gctactcagg 900 aggctgaggc aggaggattg cttgaaccct ggaggcggag attgaagtga gctgagttcg 960 tgccattaca ctccagcctg ggtgacagag tgagactctg tctcaaaaaa aataaaataa 1020 aaagtcaatt tagaatgtga aattctgacc accttttggc tttgagtatt ttccaaaaga 1080 tatttgaaat cctaatgagg aaatcagaaa aagctatgga aaaatagaca aatttcatac 1140 atgaacaata taaattgtgt atattactta acatcaaact aaacaagatt cagaattgat 1200 ggttgtataa gaactagctc atgtaaaaat aaaataacat tattacattg cctcaaaaat 1260 tggtcctcgg taagtgcctt ttgataaatg atctcaaata aatgactcat agcaaaaaaa 1320 aaaaaaaa 1328 <210> 23 <211> 3386 <212> DNA <213> homo sapiens <400> 23 ttcaattccc ctgcatccac actgcaaccg ggtgcaagtc tttcctaggt tatagacagc 60 ccgcctcccc acgagacctt ctgcggactg gctgcccctg gcctcggcct gggtgggtgg 120 gtggtgctcg cgccgcccct actttcccct ggggccctgg agagccgcgc gctgggtgtg 180 tgtgtgtgtg cgcgcgcggg tttggtgggg aaatctcctt cagtggaagc tgctgagtgt 240 cgttggcgga aagtatcctg gagcccagca aaagcctcca aagcactaga gcttccctaa 300 agaaaagcag aataaaagaa agacaagaag ggaagcccgt tcctctaaag cccgggtttc 360 caatagtccc ggatcctcct ggagttgggc gaaggcgcag ttggcagcag ccgctgctgg 420 cacccggact tggaaaggcg gtgttccccc ttttcgggag gagggaggca gggacttgca 480 ggcaagagtt gcacctggtc taggaacctg cagagaaaag aactctgggg agaagaactg 540 ccccggagcg cagcagccac cctccgacca tgccccggtg aggggggcgg acttcgaggg 600 caacttgccg cggactgcct gggcttagcc agcgagctac gcgctcccgg gagcccggaa 660 ttgcacggcg cagcccggcg gggggctatc gtctatgtct tcttggggcg ccagacgaat 720 cggggtctcg tttttgctgg aagagcccag tgttggtggc ttcaggtggc tgctgccgcc 780 gccgccgccg ccgccgctgc tagtgcggtt tccgccgctg gtgcgaagag aagagacacg 840 cgagcgggga gacctccaag gcagcgaggc atcggacatg tgtcagcaca tctggggcgc 900 acatccgtcg agcccgaggg gagatttgcc ggaacaattc aaactgcgat attgatcttg 960 ggggtgactg tccctggccg gctgtcgggt gggagtgcga gtgtgcactc gctcggaagt 1020 gtgtgcgagt gtgtatgtgt gtgtgccgtg tcgggctccc cccttccccc cgttttcccg 1080 tcgagtgatg cacttggaat gagaatcaga ggatggaaat agtctgggag gtgctttttc 1140 ttcttcaagc caatttcatc gtctgcatat cagctcaaca gaattcacca aaaatccatg 1200 aaggctggtg ggcatacaag gaggtggtcc agggaagctt tgttccagtt ccttctttct 1260 ggggattggt gaactcagct tggaatcttt gctctgtggg gaaacggcag tcgccagtca 1320 acatagagac cagtcacatg atcttcgacc cctttctgac acctcttcgc atcaacacgg 1380 ggggcaggaa ggtcagtggg accatgtaca acactggaag acacgtatcc cttcgcctgg 1440 acaaggagca cttggtcaac atatctggag ggcccatgac atacagccac cggctggagg 1500 agatccgact acactttggg agtgaggaca gccaagggtc ggagcacctc ctcaatggac 1560 aggccttctc tggggaggtg cagctcatcc actataacca tgagctatat acgaatgtca 1620 cagaagctgc aaagagtcca aatggattgg tggtagtttc tatatttata aaagtttctg 1680 attcatcaaa cccatttctt aatcgaatgc tcaacagaga tactatcaca agaataacat 1740 ataaaaatga tgcatattta ctacaggggc ttaatataga ggaactatat ccagagacct 1800 ctagtttcat cacttacgat gggtcgatga ctatcccacc ctgctatgag acagcaagtt 1860 ggatcataat gaacaaacct gtctatataa ccaggatgca gatgcattcc ttgcgcctgc 1920 tcagccagaa ccagccatct cagatctttc tgagcatgag tgacaacttc aggcctgtcc 1980 agccactcaa caaccgctgc atccgcacca atatcaactt cagtttacag gggaaggact 2040 gtccaaacaa ccgagcccag aagcttcagt atagagtaaa tgaatggctc ctcaagtagg 2100 gaacaaagcc aagaagaatc ccacctcagt gaaatgctac aactgtgaat tgacgtaacc 2160 tagaatgtcc cccttcttgc ttctctctcc ttctttcccc caagcctcat tcattcttgg 2220 gattggccct ttcttcatga aaagtgtctg caaaaccatg gcagaggaat acatctctca 2280 cacatactca caaacacaca cacaagcact tgcacataca tacaaacaca tgcaaacata 2340 cctacacaca cacacactct tacaacctcc atcatgggaa gtcaagtttc agaaacaaaa 2400 gtctcattca taagaggtct tagaagaaaa taaccagtta acctgatttc aattttgata 2460 ccgttttcct gaactaataa atctacccaa tgagactttt cagcctttgt acatacaaaa 2520 ttcttccaaa agagagagga gaaaatacag ctctgatggc atcaaacgga ctttgcatca 2580 agtaatttca gatagtgtcc taggatcctt tgagggtgct ggtagcaggt gagcaggaca 2640 aagttgacca aggacactta tttctagatt atgattcttc tgtttactca acaatttaca 2700 aagaaaaaaa ggacagacat tgaagagcta cacattgtat atatatcacc acagactata 2760 aggaaatgga attatttccc tctttgtcac atatctgtag taggatttgc caagatcaga 2820 aatgatccat ttgctgtttc ttgttttcca aaggtcatac attgtgtttg gttattgtta 2880 ccagctcaat aaatgtgttt aacgagttaa tttcattttt ctggctttgg tctgttctcc 2940 ttccttacag gctaagccct ggctccatgc aactgcattc tttgatttca cttgttcctt 3000 catctacatg ttttgttcat ttgcagccag tttttactga gtttgtggca atcaggaatg 3060 catttgctaa gcaagtatga ctttaattcc actccatggc tcaatcattc acatgaggtg 3120 agcttcagcc tgagatagca ggcgacagac ttcttgcgtt tcaaaactgc catgcccccc 3180 tgtgatgctc ccgtgaagga atgcactttg ccttgtaagt tcctgggaaa ggggtatgtt 3240 ttctctccag gtgcagccag atctcacaaa gtacaaaacg aatgcctttc ttttcttgtt 3300 tataatggtc actcactgtg tttggttact gtcaagaaat caataaatgt gtttaacaag 3360 ttacccagta aaaaaaaaaa aaaaaa 3386 <210> 24 <211> 1040 <212> DNA <213> homo sapiens <400> 24 cacatgtaaa ctacttgaac tccatttcat cttttttcat accatctcta agattgctgc 60 cgcatttgct tgttaaactg aaagcatgtt tcttgcaaag gctctattgg aaggagcaga 120 tcgaggtctt ggagaagctc ttggaggcct ctttggagga ggtggtcaga gaagagaagg 180 aggaggaaga aatattggag ggatagttgg aggaattgtg aattttatca gtgaggctgc 240 agcagctcag tatactccag aaccgcctcc cactcagcag catttcacca gtgtggaggc 300 ctcagaaagt gaggaagtta ggcgatttcg gcaacaattt acacagctgg ctggaccaga 360 catggaggtg ggtgccactg atctgatgaa tattctcaac aaagtccttt ctaagcacaa 420 agatcttaag actgacggtt ttagtcttga cacctgccgg agcattgtgt ctgtcatgga 480 cagtgacacg actggtaagc tgggctttga agaatttaag tatctgtgga acaacatcaa 540 gaaatggcag tgtgtttata agcagtatga cagggaccat tctgggtctc tgggaagttc 600 tcagctgcgg ggagctctgc aggccgcagg cttccagcta aatgaacaac tttaccaaat 660 gattgtccgc cggtatgcta atgaagatgg agatatggat tttaacaatt tcatcagctg 720 cttggtccgc ctggatgcca tgtttcgtgc cttcaagtct ctggatagag atagagatgg 780 cctgattcaa gtgtctatca aagaatggct gcagttgacc atgtattcct gaagtgggaa 840 ctgagaagtc aagatcctcc ctggaggaca ggactgaaaa ccttgccaag ctgtacacag 900 ttgctgatac cctgtgcaac agctctcatt tcctggcaag ctctttcaca accctacata 960 tttctgatca tgtgctgcct tttactgctg aattaaaaca gatatttcat aaaaaaaaaa 1020 aaaaaaaaaa aaaaaaaaaa 1040 <210> 25 <211> 2762 <212> DNA <213> homo sapiens <400> 25 ggcgaggaag tgggggcgct gagcaagcga gaggaaggct gaagggagct aggaaaaggg 60 cgctgatctc tgcagcctgg gagggctttt gtctcccgga ggaaggccag aagagatggg 120 gtcccgaggg cagggctcac acagcaagaa aacgaggagc atgcctgtca ttttgagccc 180 acagagaacg gggagcggag ccactggagg accggctgct cgggcttatt cggtagccga 240 ggcggttaaa cagttcaggg ctggaccagc cgggactgga gcagggtgca gtctccaggg 300 ttgctgggca gcaccgagac cctttgagca ccgaacgaat aaactacggg agctttccac 360 acttgcacat tgttcccgcg agttgcagac gcaggttcct gatgctagcg ctcattcctt 420 ggcagtcacc ctcagtgaac tacacagttg ccgtgacctt caggatgaat gcttggattc 480 caggtttgct gagggcccca gaaggctcct tccaccgtat catagtctaa taaataattt 540 tgtcaagcca gagaagctaa caaaggtaga gacaaggctt aaagaaaaga tagtggcgga 600 aatgacggat ctgaacaagc atataaaaca agctcaaacc cagcggaaac agctactgga 660 ggaatccagg gagctacacc gagaaaagtt acttgtccag gctgaaaaca gattctttct 720 ggaatacctg actaacaaaa ctgaagagta cacagagcaa cctgagaagg tatggaacag 780 ctatttacaa aaaagtggag agattgaacg aagaagacaa gaatcagcct ccagatatgc 840 agaacaaatt tcagtgctta aaacagcgct cttgcaaaag gaaaatatcc aatccagttt 900 gaagcggaag ttgcaggcaa tgagggacat tgctatatta aaggaaaagc aggagaaaga 960 aatacagaca ttacaggagg agacaaagaa agtccaagct gagacagctt caaagacacg 1020 ggaagtacag gcccagctcc tccaggagaa aagattactg gagaaacaac tgagcgagcc 1080 agacaggagg ctactgggaa agagaaaaag aagagagctt aatatgaagg cccaggcctt 1140 gaagttggca gcaaagcggt ttatttttga atactcctgt ggcatcaaca gagagaacca 1200 gcagttcaag aaggaattac tgcagctaat tgagcaagcc cagaaactaa cggctactca 1260 aagccactta gaaaacagga agcagcagct gcagcaggaa cagtggtatc tggagtcctt 1320 aatccaggcg aggcagagac tgcaaggaag tcataatcag tgcctaaata gacaggatgt 1380 tccaaagacc acacccagtc ttccccaagg caccaaatca aggattaatc caaagtaact 1440 tctaaaataa cactgattaa ataagaactg gagcaagtac tcttaagtgc tacattaacc 1500 tggttagaaa ggctgttgga ttccagattg ctattgtaaa atctccatca tgatgtgttg 1560 gagtgaagga ttagatggtt ttatccaaca gtcctactag atatttggta accagcttcc 1620 cttaactagc tttttcttta aatactcgtt aataagctat tccacaaacc tccagttaac 1680 ctaacacatg accctaacct agccatttac catacatcaa actagctaaa ggaaaccaac 1740 ctaaggaagt gaaaacagtt gtgatttatt tcatctagct aaattgtatt tctttataga 1800 gaaagtacct ttaaggatag cattccaaat agactttgaa tagcgttctg ccagtttatc 1860 ctcattcctt ttgaccaact tagcagacaa aagcagtttt tacaagctct ttgtgagttt 1920 gtgccagtga ccaggtagct ccttctagtt ttctcatgag tgaaaaagca ttctgataac 1980 agcaagtcca gtaagtgcta ggcagagtga cctttcatct gatgctaagc ccctacaagt 2040 ttgagaaggt aagaaaagat gaaggagaca tatattaggt cagctcttac ttttgaaaat 2100 gttttatttg aagaaacacc tgtagcattg aggtgactga atgcctccac ttatttcagg 2160 aaaacgtatc caaaaaaagt tgaaatattt ggacaacttt ttttttaagt gccatcgatt 2220 tccctagcag cattctaaaa gatagcaagt aaaatgatgt ttgttatcct aaatgcttta 2280 gttttaggtc atttattaat tttcttacag gtgcactttc tagtacatga agtatccttt 2340 gtaattaatg tgtgccatat gtttattccc atttagtata actataaatt atattttaaa 2400 ttatatattt ttaggatagt tatatttttt ttgggttcta cgacattgaa gttggactag 2460 tgatttattt gaatgctgaa tcctagtata ggggaatata atcttatatt ttaacagggg 2520 tcctctatgg gaaaatagga tgaactttgt ttcccagaaa ttgttaagtg atgaaaaact 2580 tcaaaataat tttcctgcat tttctgcttt atttacatgt aaagtgaatt ccctgaaaat 2640 tggatttaaa aagcattctc cttcaatgtg cctttacctt gtagctttaa caacttttct 2700 gttaaatatg tagtttttta ttaaacaatg ttattaaata aaaacattta tccactgatt 2760 tt 2762 <210> 26 <211> 9127 <212> DNA <213> homo sapiens <400> 26 agtgtgagct gagctctttc cctgaatgaa tccaagtaac cctggccttc tgaaatgacc 60 agcagacaca caactgtcca gaggctgccc aaagtataaa ctctggttct aaagtaccat 120 gtccagccaa ggaagtccta gtgttgcgct ttctacgacg acagtcagtt cagttgctgt 180 gcaggctggg gactccaaaa tcgttatagc tgtcataaag tgtggcaaat gggtacaact 240 tcaactggct gaatcacagc ccaatcttct agaaattggc agcagtcaag atgaaaccaa 300 aaaacttctt catgatcatg aacttctttt ggccaagctc aaggctttgg aagatcgggt 360 atgggaactc ttgcaggaag cagacaagac agctgaagag aacaaggatc agagtcaggt 420 ctatgatgcc atggccgaga ctctgggtga agcatgggca gctctggtgt ccatgcttga 480 aagaagaaca gagctcctta ggttgacttc tgaatttttt gaaaatgcct tagagtttgc 540 tattaaaata gaccaagctg aagatttcct ccagaatact catgagtttg agagtgctga 600 gtccttaaaa tcacttcttc agcttcatga acatcatact aaagaactct tggaacggtc 660 tttagccctt ttaaacaaaa gtcaacaact cactgacttc atagaaaaat tcaagtgtga 720 aggacctaat gtgaatcctg agttgactca gggagctcat agcagctgtc tgaaggttga 780 ccgccttctt gaacttctac aagacaggag aagacaacta gacaagtact tgaagcaaca 840 gtggcaagaa ttgagtcaag ttctgcagat atgtcagtgg gaccaacaag aaaaccaggt 900 tacttgttgg tttcagaaaa ctataagaaa tttacaggaa caaagtctag gttcatcact 960 ttcagacaat gaggatcgaa ttcataagca agaggaactg ataataaaag caaaggaatg 1020 gaattctgct gttgagaagc tgaagagtga ggcactgaga attctgctgt caaaggacta 1080 cgtggagaaa gaacacctcc agctctctca ccagaaactc agtcagcttc aagaagaatt 1140 tggtcaactc atggtggaaa ggaatacctg gttaaagaag gcgaatgaat tttttaacag 1200 tgctaacaag gcatttgatg tacttggaag agttgaagct taccttaagc tccttaaatc 1260 agagggttta agtctggctg ttttggcagt gaggcatgag gaattacaca gaaaaattaa 1320 agactgcaca actgatgctt tgcaaaaggg acaaacctta atcagccaag tagactcctg 1380 cagctctcag gtgtccggca tccatgagat gatggggtgc attaagagac gagtggatca 1440 tctgaccgaa cagtgttcag cgcacaagga atatgctctt aagaaacaac aactaacagc 1500 ctcagtggag ggttacctac ggaaggtgga aatgtcaatt cagaaaatca gtccagtact 1560 ttctaatgca atggatgttg gttctacccg ttctgaatca gagaagattt tgaataaata 1620 tctggaacta gatatccaag ctaaggagac atcacatgaa ttagaagcag ctgcaaaaac 1680 catgatggag aaaaatgaat ttgtatctga tgaaatggta tcactttcct ctaaagctag 1740 atggctagca gaagaattaa acctatttgg ccaaagcatt gactatagat cgcaagtcct 1800 gcaaacttac gtggcatttc tgaagtcatc agaggaggta gagatgcagt ttcagagctt 1860 aaaagaattt tatgaaaccg aaatccctca gaaggagcag gatgatgcta aagccaagca 1920 ttgttctgac tcggctgaga agcagtggca gctattttta aagaagagtt ttataacaca 1980 agatctaggg cttgagttcc ttaatttaat aaatatggca aaagagaacg agatattaga 2040 tgtgaaaaat gaagtgtacc tcatgaagaa caccatggaa aaccagaaag cagaacggga 2100 agaacttagc ctccttcggc tggcatggca gcttaaagcc acggaaagca agcctggaaa 2160 acagcagtgg gcggcattca aagagcaact taaaaagact tctcacaact taaaacttct 2220 tcaggaagca cttatgcctg tgtctgcact tgacctcgga gggagcctcc agttcatttt 2280 agatctacga caaaaatgga atgacatgaa gcctcagttc cagcaattga atgatgaggt 2340 tcagtacatt atgaaagaat cagaggagtt aactggcaga ggagcccctg taaaagaaaa 2400 gtctcaacaa ctgaaggacc ttattcactt ccatcaaaaa cagaaagaga gaatccagga 2460 ttacgaggat atcctgtaca aggtggtcca gttccatcaa gtcaaggaag agctgggacg 2520 tctcatcaaa tcaagagagc tggagtttgt agagcagccg aaggaactgg gtgatgccca 2580 tgatgtgcag attcacctcc ggtgctctca ggaaaagcaa gcccgtgtag accatctcca 2640 cagactggcc ctttccttag gagtcgacat catctcatca gtgcagcggc ctcactgctc 2700 taatgtttct gcaaagaacc tacagcagca gctggagctc cttgaggagg acagcatgaa 2760 gtggcgtgcc aaagctgagg agtatggacg gaccctgtcc cgtagtgtgg agtactgcgc 2820 catgagagac gagataaatg agctcaaaga ctcattcaaa gatatcaaaa agaaattcaa 2880 taatttgaag tttaattaca ctaagaaaaa tgaaaaatct cggaatctga aggcgcttaa 2940 atatcaaatt cagcaagttg atatgtatgc tgaaaaaatg caggctttga aaaggaaaat 3000 ggaaaaagtt agtaataaaa cctctgattc tttcttaaat tatccaagtg ataaagttaa 3060 tgtccttttg gaagtcatga aggatttgca aaaacatgtg gatgactttg acaaagttgt 3120 gacagattac aagaagaatt tggacctgac tgagcatttc caggaggtga tagaagagtg 3180 tcatttttgg tacgaagatg caagtgccac agttgtaaga gttggaaaat attccacaga 3240 gtgcaagaca aaggaagctg tgaaaattct ccaccagcag tttaataagt ttattgcacc 3300 ctcagtgccg cagcaagaag aaaggattca ggaggccact gaccttgctc agcacttata 3360 tggtttggaa gaaggacaga aatatattga gaaaatagtg acaaaacaca aagaggttct 3420 tgaatctgtg actgaattat gtgagtccct cacagagctc gaagaaaaac tgaagcaggg 3480 agatgtttta aagatgaatc cgaatttgga agacttccat tatgattaca ttgacttgct 3540 aaaggaacca gcaaaaaata agcagacaat attcaatgaa gaaaggaata aggggcaggt 3600 gcaggtggca gatcttttgg gcatcaatgg aacaggggaa gagcgactac cacaagacct 3660 gaaggtgtcc actgacaagg agggtggcgt ccaggacctg ctcctgcctg aagacatgct 3720 ctcaggggaa gaatatgagt gtgtctcacc tgatgacatc tccttgcctc ctctcccagg 3780 aagccctgag tcccctcttg caccatctga catggaggtg gaagagcctg tcagctcctc 3840 cctcagcctt cacataagca gctatggggt gcaggctggg accagcagcc caggggatgc 3900 ccaggaatct gttcttccac cacctgttgc ctttgcggat gcatgcaatg ataagagaga 3960 aacattttca agtcattttg agaggcctta cctccagttc aaagctgagc ccccactaac 4020 ctccagagga ttcgtggaaa agagtactgc cttacacaga atcagtgctg aacatccaga 4080 gagcatgatg agtgaagtgc atgagagagc tttacagcag caccctcagg ctcagggtgg 4140 tttgctagaa acacgggaga aaatgcatgc tgataataac ttcactaaaa cccaagatag 4200 gctgcatgct tcctctgatg cattctcggg cctcaggttt caatcaggca ccagcagggg 4260 ctatcagagg caaatggttc ctcgagaaga gattaaaagc acatcagcaa agagcagcgt 4320 ggtcagccta gctgaccagg cacctaattt ctccaggctc ctgtctaatg taactgtcat 4380 ggaaggttct ccagtgactt tggaagttga agtaacagga tttccagagc ctacactgac 4440 atggtacaag aagggccaga aattgtctgc agatgggcac ttacaggttt tacacaagga 4500 gacaaggcat tcggtgttca ttccaaaggt atgcaaggca gacgcaggcc tctatgtggc 4560 tcgggcccaa aactctagcg gcgctctctc ttccaatgtc atcctccacg tgacaggtaa 4620 ctgcaggctg ccaatcacaa gagtaaactg gataaccctg tgtgtcgtct atgttagtgt 4680 gtccctaatg tactggctcc tcacacaata actgtggtgt tggcaccaat ggacatcatt 4740 ctcatgtgcc taaagaaaag tgccgccgtt tatcttcctg cacctcctgc aaagcatctc 4800 ccaccaagtg tatctccagt ctgatcacca tacttgtttg gctaatacca ctgctaggtg 4860 aaataatcaa attttctgga gcgtttaata tatttgagaa gcttggtaaa ttatctgtag 4920 tggataagaa cagatttttg tactctagaa acagatgttt tcaacataat atgcagcaaa 4980 attattctat gcctattccc tcctaattta agggcgtgca gatgaaggct gacatcggca 5040 tagaaatgtg ctaaatttca aatatggttg ttcaataata tatttttaat tgtattttaa 5100 aacatccctt tgtagggaat atcagtagaa ctattgaatt gatgttgtat ttttgcatta 5160 gctgtccttt aattttgctt tccatgtctt gatcttgtta ccgaaatgca ttctgtgtaa 5220 tttcaacgta gactacgttc ctgagtctga tgatgtcatt gtaaataatc attcctcatg 5280 ttgctctcac gggtttgaca ttggaggata gatgtgccat caactttaaa tagagtttcc 5340 atcttttgtc agctctgcat gtcatacagc aagatggaac acaggttgca agaaagaacc 5400 aacgttattc ctgacattct attgatgtgt tttgagcagc aatgtgtaac caggtgtttc 5460 tgcttctaat cttgattctg ctgatgacca tttttatact ttatggcaaa gcctcattgc 5520 ctcagtttcc tgtctggaaa atgagttcat catctacctc ttgggcaatt gagagttttc 5580 attttgtgtc ttttaaacat ctggaaaatg gaaaacactg agggctaagg ataatgatat 5640 tgtttaatgt aatttgtcat cagaccggcc tcctgctcac tatttctttt tttttagatg 5700 ctgttttttt agaatattaa attaaaggag tgctgttaat atgtaatctt caactagttc 5760 catggaggaa agtgatgttt tatgaattag agcttaaatt cctatctaat ttctgaagac 5820 tgcattcttt tcaaagactt gaaattaaac tcaggaggat acattttgtt tgttctaggg 5880 ggaaacgtaa tagaatggta tgagatgaat tctatccttt tacaataatt attactataa 5940 tattgaagta ttctatgcct ttctgaaaca ctttattcag aaaagatcat tttttggctt 6000 ccttttaaaa ataagcttga agtagggaag catttgcttc ttagatttta aatgtagtct 6060 tattatgctg aggaaaatct ttagttgaaa gaataattca ttacagattt ttgatgaagg 6120 gaagaaatta attatgttgc tggaagactg tctacaaata atcaaaatat ttaaatgtaa 6180 tgtattcaag ttgttattaa aaagttactg aatgttatct gaagatgtga aatgtgtagt 6240 caagtaaaaa gttggcgtat actttcttgg gctgcatatc caatttaatt aaaaaattaa 6300 atctcagttt ccttctaaat tttgatagaa ctatattaaa agcttgtata cacagcattc 6360 taggaaattt ctcttaacta tctttttttt gttttttttg tttttttttt ttttttttga 6420 gaaagagtct tgctctcttg cccagtgcag tggtgccatc ttggctcact gcaacctcca 6480 cctccgggtt caagcaattc tcctgcttca gcctcctgag tagctaggat tacaggcatg 6540 cctacctaat atttacattt ttagtagaaa ccaggtttca ccatgttggc caggctgggc 6600 ctcagcctcc caaagtgcca ggattacagg tatgagccac catagccggc ctcttgtatc 6660 ctttttgtcc aatttcaaat aatgtgtgaa tcttgcctaa ctgctgttgc ccacgttgaa 6720 gctaaagagt aaaaacctat tcatgaacaa agaaggcagg tgagacccgg taacaaactg 6780 tctctcttcc cactttctct ttcttattaa tttggcagga tctcccttcc cattttgtca 6840 acatggttga atttgtgtgt tggggttgtt agggcatggg aattcctggt ttgctttctc 6900 tattgcatgc ttgttcatgt taactctttg gggagcagaa tgagatacat atgcatccat 6960 ggttatgatg gaaaaaagca tgcaaaatcc atttttagag agagagagaa agagaaaggt 7020 gggggtgggg gagcacaaag atcagaagag tactatgctg atattcaaga tatagtacag 7080 atagctttct gtgtacctat ccatctacct attcatctgg gctattgatt gactcccaca 7140 gcagtaaaga ataattacgc agttattctt ctggttatgt tttaatttca aaaagttaag 7200 tgtgattttc ctttttgctg ggatttctgt cttgagcaaa taattattct tatgaaagta 7260 tcaattgcag ttactggtta aaaatgtaag acctaggaaa tttaagtgtt gtttctattt 7320 taaggtatat acataattta taaccattta cttctagaga aaatcctgaa tggttagtaa 7380 tatcaaaaca ttttcaacaa gaaaactaaa atgaaaagaa agtttaaaaa ttacatgtgt 7440 tacagctctt ttagaatttg tctagcaggt tttctggtga aaattaaact caagattttc 7500 accagaaaac gttttaaaac ttctaaactc ttaaacaaat tataaatact tgatactttg 7560 aagaactgca aaacaaaatg tttttaagtt ttcataaggc aaaatcattg agttttccag 7620 ctttgatttt ccaataaaag gatgtataaa tatttggtgg tagtttttca cactcaattc 7680 caagagaaat ttactgtagg aatctgtaca tttgaatctc tgaatattct atgatattta 7740 aaatatttga acaagatgca gaaaattttt tagctatatt aatcaataat ggtaacctct 7800 atcactcata atcaagacac atacttaaaa tagatgacta caagaccctt ctaactgctt 7860 tgctcaaatt taaatttcct caagtagttc atagaccctt tacaacctgg cctcccctct 7920 ctggcctcgg tttgatcccc tcctattacc cccaacccct agtaaagtga catttaactt 7980 cagggtttta acatatcatg ctcttctctc cagccctttc ttcctataac tctcttacta 8040 tcttcaccac cctatcttca tgtgacttaa ctcttgctta tgttccagtt ctgctgagac 8100 acaacttccc ctgggaagcc tcctgaccca tcaagtccag agtagatggt cctgccatgt 8160 gcactgtcag cacctgcact gcccagccac gcccctgaat atacacaaag gaatcgcagg 8220 tttgagcatc agtctcctct ggctaggctg taagaacctt atcagcagga ttcatgacag 8280 ccctgttgtc attgtattgc cagtacctaa gacacagtca cactcagtaa actcttttga 8340 attgaattgt tgccaaaggt aaacaaagat aaacctagct tgtttttctc ccctttttag 8400 agggaggaga ggggaaatgt aaaaagacaa agatgattct cccttcttat agacaggagt 8460 caatccgaat caggccctaa caatgaagca ctcatgaaaa tctctcacct catctgcaaa 8520 acttgtgtga gaaccctcca gaccctctgg gctagaccct gattgaaaat ttgaatttaa 8580 aaatagatgc tggctccacg gactaaaata atagtaagga ggaaagagga aaggtccagg 8640 attgttgttc ctggatcaat attgttccaa cattttaaag tgttccaaca ttttaaaaca 8700 tatgtactta ggcataaatc atcatccggt atgaggaact ggatgcctcc actctctatg 8760 actaaatcca aactgtcaaa accagaattt atgtacttct ttagaacact acgtaaatga 8820 tcaatattta attgtagctg gggctcagta gtctgggctg tgaacagatc ttatttgaaa 8880 ccagtatttc atacaaactt gtaaatataa agaaagccaa atccaagaac ttaagagtat 8940 ttgaattcca aatgaagaaa ggaaagaata tcttattttg ttctgcttta tgtttgtctt 9000 tattcatgac catttcttac taaaaatcac catctgaagc ttttgaaact cctgttgtat 9060 gcacagcatt ttaagtgcag ccatgaaata agttagttga aacaaaataa aatatctcct 9120 tccagta 9127 <210> 27 <211> 3455 <212> DNA <213> homo sapiens <400> 27 acttgcaaat cgctgtgtgc tcgcagaagc cagcacttcc acagtctcta accttcccat 60 ggcgagtgct gcagctctat cagcagaacc tttctctccg tgtgaggaag agcttttttc 120 ccccctttcc tttttttttt ttttcctttc cccttaatca gaagcactga atgaaagcca 180 atcagagaga gctcgccccc gttttcttcg gttccctgct gtccagagtt aaaagtgatg 240 ctgagaaaga gcttgagtta gattgaagta gaatcagtga tagaaaataa cagccgaaaa 300 caaacaaaaa ggggacatag tgacaatttc tcctgggtta ttttggctgg aaccaacttc 360 cattatccag aagctgataa aaaagctttg ggaaacatga acaaaacatt gatgaaatgt 420 tggaaaccag ttgaaacaca gtaaaaccaa ctgggtaaaa taggaccact tctcttcatc 480 tacactggga tttgtcaaga agtgaactat gacaatacat caatttttgc tactgtttct 540 attctgggta tgcctgccac atttctgctc tccagaaata atgttcagaa ggacgcctgt 600 gccacagcaa agaattttaa gttcacgtgt accaaggagt gatggcaaaa ttctccatcg 660 tcaaaaacgt ggttggatgt ggaatcaatt tttcttactt gaagaatata caggatctga 720 ttatcagtac gtaggcaagc tacattcaga ccaagataaa ggagatggat cactcaaata 780 tatcttatct ggagatggag ctggtactct ttttattatt gatgaaaaaa caggtgatat 840 tcatgccaca aggcgaattg atagggagga aaaggccttt tatactctac gcgcacaagc 900 tattaacaga agaactctga ggccagtaga gccagagtca gagtttgtga tcaaaattca 960 tgatatcaat gacaatgagc caacgttccc agaagaaatc tatacagcta gtgttcccga 1020 aatgtctgtt gtaggtactt ctgtggtgca agtcacagct acagatgccg atgacccttc 1080 atatgggaac agcgccagag tcatttacag catacttcaa gggcagccct atttctctgt 1140 ggagcctgaa acaggtatca tcaggactgc tttaccgaac atgaacagag aaaacagaga 1200 gcaataccaa gtggtcatcc aggccaaaga catgggcggc cagatgggag gcttatcggg 1260 gacaaccact gtgaacatca cgctgacaga tgtcaatgac aacccaccac gtttccccca 1320 gaacactatt catcttcgag ttcttgaatc ctccccagtt ggcacagcca ttggaagtgt 1380 caaagcaact gatgctgaca ctgggaaaaa tgctgaagta gaataccgaa ttattgatgg 1440 tgacggtact gatatgtttg acatcgtgac tgagaaggac acacaggaag gcatcatcac 1500 tgtgaaaaag ccactcgact atgagagccg aagactttat actctgaaag tcgaagcaga 1560 aaacacccat gtagatcccc gtttttatta cctaggacca tttaaagata ctaccatagt 1620 gaaaatctct atagaagatg tggatgaacc tcctgttttt agtaggtcct cctatctgtt 1680 tgaagttcat gaagatattg aagtgggcac aatcattggt actgtaatgg caagggaccc 1740 agattctatt tccagcccca ttagattttc cttggatcgc catactgacc ttgacagaat 1800 ctttaacatt cattcaggaa atggatctct ttatacatca aaacctcttg accgtgaact 1860 atctcagtgg cataatctta ctgttattgc tgctgaaatc aacaatccca aagagacaac 1920 acgcgtggct gtttttgtga gaattttgga tgttaatgac aatgccccac agtttgctgt 1980 gttctatgac acttttgtat gtgaaaatgc cagaccaggg cagctaatac agactataag 2040 tgcagtagac aaagatgacc ctttaggtgg acagaaattt tttttcagtt tagctgctgt 2100 caatccaaac ttcacagtac aggataatga agataatact gccagaatct taaccagaaa 2160 aaatggattc aatagacatg aaatcagtac ctatctcttg cctgtggtga tatcagacaa 2220 tgattaccca attcagagca gcacaggcac actgaccatt cgagtgtgtg cttgtgacag 2280 ccaaggcaac atgcaatcct gcagtgctga agccctgctc ctccctgccg gcctcagcac 2340 tggggccttg atcgccatcc tcctctgcat catcattcta ctggttatag tagtactgtt 2400 tgcagctctg aaaagacagc gaaaaaaaga gcctctgatc ttgtcaaaag aagatatcag 2460 agacaacatt gtgagctata acgatgaggg tggtggagag gaggacaccc aggcctttga 2520 tatcggcacc ctgaggaatc ctgcagccat tgaggaaaaa aagctccggc gagatattat 2580 tccagaaacg ttatttattc ctcggaggac tcctacagct ccagataaca cggacgtccg 2640 ggatttcatt aatgaaaggc taaaagagca tgatcttgac cccaccgcac ccccctacga 2700 ctcacttgca acctatgcct atgaaggaaa tgattccatt gctgaatctc tgagttcatt 2760 agaatcaggt actactgaag gagaccaaaa ctacgattac ctccgagaat ggggccctcg 2820 gtttaataag ctagcagaaa tgtatggtgg tggggaaagt gacaaagact cttaacgtag 2880 gatatatgtt ctgttcaaac aagagaaagt aactctaccc atgctgtctc cacttcacaa 2940 tatttgatat tcaggagcat tttcctgcca gtcagcacaa ttttttttct catttacttc 3000 ttaatttgtt cattaattac attaattctt tcctgtagga tgtctcatgg aatatatatg 3060 acattttatt taatcacttc caagagccaa agctatggaa atacagtgtt gtccatctta 3120 gtaaataaaa gataatttca gaaacatgaa caggatagtt ctcccttaag caacctcaca 3180 aacaagccgc ttctgttagg tacatgtcct gcccttgcaa atgaagcttt taaaaaggtg 3240 aagaaaaatt ttacagtata tcctgttctg tacattaaat taaaaaaaca aaaatgtaca 3300 tgtgatgtta gtaggtgtga tatgcaacct ggtatacaga catttgtgca atttcatttc 3360 atcaaattct atctgctaat gttttatatt tatatttttg tatttatttt taaaaaaata 3420 aaccagtttt tacaactaaa aaaaaaaaaa aaaaa 3455 <210> 28 <211> 6810 <212> DNA <213> homo sapiens <400> 28 cgccccgcac ccgcctgccc gcccgccacc tccccccggt ttctcattcc tgccactagc 60 gcgctcggcg gctcattccg cggccgccgc cagctgaggg gagcgtcgcg ggccgaggag 120 cagatgccgc gggggccgct cgcagccgcc gctgacttgt gaatgggacc gggactgggg 180 ccgggactga caccgcagcg cttgccctgc gccagggact ggcggctcgg aggttgcgtc 240 caccctcaag ggccccagaa atcactgtgt tttcagctca gcggccctgt gacattcctt 300 cgtgttgtca tttgttgagt gaccaatcag atgggtggag tgtgttacag aaattggcag 360 caagtatcca atgggtgaag aagaagctaa ctggggacgt gggcagccct gacgtgatga 420 gctcaaccag cagagacatt ccatcccaag agaggtctgc gtgacgcgtc cgggaggcca 480 ccctcagcaa gaccaccgta cagttggtgg aaggggtgac agctgcattc tcctgtgcct 540 accacgtaac caaaaatgaa ggagaactac tgtttacaag ccgccctggt gtgcctgggc 600 atgctgtgcc acagccatgc ctttgcccca gagcggcggg ggcacctgcg gccctccttc 660 catgggcacc atgagaaggg caaggagggg caggtgctac agcgctccaa gcgtggctgg 720 gtctggaacc agttcttcgt gatagaggag tacaccgggc ctgaccccgt gcttgtgggc 780 aggcttcatt cagatattga ctctggtgat gggaacatta aatacattct ctcaggggaa 840 ggagctggaa ccatttttgt gattgatgac aaatcaggga acattcatgc caccaagacg 900 ttggatcgag aagagagagc ccagtacacg ttgatggctc aggcggtgga cagggacacc 960 aatcggccac tggagccacc gtcggaattc attgtcaagg tccaggacat taatgacaac 1020 cctccggagt tcctgcacga gacctatcat gccaacgtgc ctgagaggtc caatgtggga 1080 acgtcagtaa tccaggtgac agcttcagat gcagatgacc ccacttatgg aaatagcgcc 1140 aagttagtgt acagtatcct cgaaggacaa ccctattttt cggtggaagc acagacaggt 1200 atcatcagaa cagccctacc caacatggac agggaggcca aggaggagta ccacgtggtg 1260 atccaggcca aggacatggg tggacatatg ggcggactct cagggacaac caaagtgacg 1320 atcacactga ccgatgtcaa tgacaaccca ccaaagtttc cgcagagcgt ataccagatg 1380 tctgtgtcag aagcagccgt ccctggggag gaagtaggaa gagtgaaagc taaagatcca 1440 gacattggag aaaatggctt agtcacatac aatattgttg atggagatgg tatggaatcg 1500 tttgaaatca caacggacta tgaaacacag gagggggtga taaagctgaa aaagcctgta 1560 gattttgaaa ccaaaagagc ctatagcttg aaggtagagg cagccaacgt gcacatcgac 1620 ccgaagttta tcagcaatgg ccctttcaag gacactgtga ccgtcaagat ctcagtagaa 1680 gatgctgatg agccccctat gttcttggcc ccaagttaca tccacgaagt ccaagaaaat 1740 gcagctgctg gcaccgtggt tgggagagtg catgccaaag accctgatgc tgccaacagc 1800 ccgataaggt attccatcga tcgtcacact gacctcgaca gatttttcac tattaatcca 1860 gaggatggtt ttattaaaac tacaaaacct ctggatagag aggaaacagc ctggctcaac 1920 atcactgtct ttgcagcaga aatccacaat cggcatcagg aagccaaagt cccagtggcc 1980 attagggtcc ttgatgtcaa cgataatgct cccaagtttg ctgcccctta tgaaggtttc 2040 atctgtgaga gtgatcagac caagccactt tccaaccagc caattgttac aattagtgca 2100 gatgacaagg atgacacggc caatggacca agatttatct tcagcctacc ccctgaaatc 2160 attcacaatc caaatttcac agtcagagac aaccgagata acacagcagg cgtgtacgcc 2220 cggcgtggag ggttcagtcg gcagaagcag gacttgtacc ttctgcccat agtgatcagc 2280 gatggcggca tcccgcccat gagtagcacc aacaccctca ccatcaaagt ctgcgggtgc 2340 gacgtgaacg gggcactgct ctcctgcaac gcagaggcct acattctgaa cgccggcctg 2400 agcacaggcg ccctgatcgc catcctcgcc tgcatcgtca ttctcctggt cattgtagta 2460 ttgtttgtga ccctgagaag gcaaaagaaa gaaccactca ttgtctttga ggaagaagat 2520 gtccgtgaga acatcattac ttatgatgat gaagggggtg gggaagaaga cacagaagcc 2580 tttgatattg ccaccctcca gaatcctgat ggtatcaatg gatttatccc ccgcaaagac 2640 atcaaacctg agtatcagta catgcctaga cctgggctcc ggccagcgcc caacagcgtg 2700 gatgtcgatg acttcatcaa cacgagaata caggaggcag acaatgaccc cacggctcct 2760 ccttatgact ccattcaaat ctacggttat gaaggcaggg gctcagtggc cgggtccctg 2820 agctccctag agtcggccac cacagattca gacttggact atgattatct acagaactgg 2880 ggacctcgtt ttaagaaact agcagatttg tatggttcca aagacacttt tgatgacgat 2940 tcttaacaat aacgatacaa atttggcctt aagaactgtg tctggcgttc tcaagaatct 3000 agaagatgtg taaacaggta tttttttaaa tcaaggaaag gctcatttaa aacaggcaaa 3060 gttttacaga gaggatacat ttaataaaac tgcgaggaca tcaaagtggt aaatactgtg 3120 aaataccttt tctcacaaaa aggcaaatat tgaagttgtt tatcaacttc gctagaaaaa 3180 aaaaacactt ggcatacaaa atatttaagt gaaggagaag tctaacgctg aactgacaat 3240 gaagggaaat tgtttatgtg ttatgaacat ccaagtcttt cttctttttt aagttgtcaa 3300 agaagcttcc acaaaattag aaaggacaac agttctgagc tgtaatttcg ccttaaactc 3360 tggacactct atatgtagtg catttttaaa cttgaaatat ataatattca gccagcttaa 3420 acccatacaa tgtatgtaca atacaatgta caattatgtc tcttgagcat caatcttgtt 3480 actgctgatt cttgtaaatc tttttgcttc tactttcatc ttaaactaat acgtgccaga 3540 tataactgtc ttgtttcagt gagagacgcc ctatttctat gtcattttta atgtatctat 3600 ttgtacaatt ttaaagttct tattttagta tacgtataaa tatcagtatt ctgacatgta 3660 agaaaatgtt acggcatcac acttatattt tatgaacatt gtactgttgc tttaatatga 3720 gcttcaatat aagaagcaat ctttgaaata aaaaaagatt tttttttaat tctgggtttg 3780 attcttaaca ttgaaacaaa cgttaagtat ttctaatgat ccatttatat ttctaattta 3840 attgtgatct tttaataacc ctatttatga tctgttgttg tctgtctgct gcttttattg 3900 tttatttaaa atcaaatatg ttttacaaat gttttttcag acaagattct gtaacatcat 3960 gtaaagcttt tttgtacatt cttggtgtta acctcctggc ttctcttcac acacatcttc 4020 taaaaaagaa ggatgtgaaa gaactaggtc agtctatgac tttgcaatat gtgttatata 4080 gtatgcattt atcttgtata tcagtaattt gatggttatg agagatgaat ccatgaggga 4140 atggagctat cagaactcta atgttccagg tatacattct atgccccaca ctgagcactg 4200 gggaactggg ggactagagt caaaaatata aatttgccca gactctaatg ttattctatt 4260 ttttcttctg ttgaacttac caggctattg taagactctt gatagttgaa actgcttatt 4320 tttcctcctg taattttaac taattgtaaa atgatgtggc attttatgtt ttaatgagaa 4380 tgggcgattc atttaaaaaa gctttgttta gaatatgctt ggggccgtaa gctcagaatg 4440 agggcaggga ccattttgga ttctgagagt cgatgccatt tggtccagga gtgtgtctac 4500 agtcccctgc attccagcta gtttcttggg gattgaaact tatgtgaagg gcatttcacc 4560 tgttcagttg ggccaaaggt caaaacgtag caatacttgg ggaaagacca cataaagtca 4620 cactgcaagt gctttccctc tttcccccta cacacagggc acgtgctttt tcttggattg 4680 cagacaattt ttacagtttt tttctgactt tattgtgaaa gtttgtttca agcatttctt 4740 gatatcatgt tatgtactat ttttatgatt tagtcaacat gcatacaaag aaatgttttt 4800 tatgaagtgc tcacttccat tttactttgc attgaaatca aattgggctg aacacttcaa 4860 tggaatacat tttgtggaca atgtcacttt agaatctttc atctcagtga aggattacac 4920 attctcaata cttccataat tgcaggttgt gttcattttt ttatatagtt tttgtaatcc 4980 aaagaatatt ttgctagatt tgcacagatc tccaattgaa tttgcaatga agaaataact 5040 caaaaggaat atgaatagca tttaaataag tatacagctg taagtaaccc tgtcaccatg 5100 gatgatcctt ttctctagga atgtatttgg attagagatg acaactacat tttcgcattt 5160 ttatgttgaa gtctttttta aaaaggctgt ttacttttca gtagttaaga atacttgttt 5220 ttctttttct tttttttttt tttttttacc ttttattttt tcgttaagcc tctattgttt 5280 gtagaacact cttagaaact tggaaataaa atgtctttcc caactagtgg agtccttttt 5340 catttggagc acattgcctt aaaagaagtc ttaatttaaa cggtccttcc ttattctaaa 5400 gtaatcactg ttttatacca tctatgcagc taaaagaagg aacatgcttc tgttcttttc 5460 ctcaagtaat ggttattgtt tctagtcatc attcattcat tgattcattc attaattcat 5520 caaaatctta ttttataaac cctgttccac ttactggagg attcagaatg aatcttacta 5580 ccttttctga catcttttga taattcagcc ctgtaccaaa gtatccacct tgttgtctta 5640 taatcaccta tttacctatt tgccctccta gaaaatgcaa gaagatattt tctctccttc 5700 caaattgaag gaagaacata aaagatataa caggaaggag atggtgagat atagagtgtg 5760 agcggaaatt aggccagctg tggcaattct ggacagatct tgggtttagc taagttattt 5820 cttttaggcc tgggtttctg ggggtgacag ggaagataaa agagtagttt atttgcacct 5880 cttggagaat tgcttaaaaa tatagagatc atggctctgt atgtcaggtg gaaccaggtc 5940 aggagtattt gaaactgctc ctgggtcatt gtgacatatc cttcacatct ttttgagaaa 6000 ctttataaga caatgggggt gaatgggggc tgggcagttg gagtctctga gcagaagagg 6060 ggcaaaattt atttggcagg cagtgtggag gacagattag gagcatataa acccagaggt 6120 gtgccccagg agggcttttg caaaggtcaa tatgagatag aatgagggcc tgaaataatt 6180 cagtaatttg gagatggaga agaggaaaga cttctctgct cttgcactgc catcagcctg 6240 gtctgggcca tggtcatctc tgacccggaa gactgacccc acctcttggc tcaccctctg 6300 cctcccaacc tcctcttcac aaagaagcca gagggatact tttaacacac aacccagatc 6360 acatgacttc gtaacttaaa cctcttcact ggcttcccaa agacttaaaa tgaattctga 6420 tgcctttatt ttattgcttt acatgaacag ggccctgcga acctctccag tgtcattcca 6480 ctccatcctc ctttcagtgc acgatgctcc agccacactg gccatctttc ggttcctgat 6540 acaaaaaaaa acacgttcct tttccatgga aagcaggtca cccttgttat tttgtatcga 6600 tgacaactct ttaaacttat tttgcttttt ggctttatgt atgtgtgtgg gtgggtggga 6660 ctgactgccc cactagaatg taagctccat gagggcaggg aatcttgctt tcttgtttac 6720 cattgtatac tcagttcttt acacagtgcc tgaaacataa caggtacaca ataaatatct 6780 attgaatgaa agcaaaaaaa aaaaaaaaaa 6810 <210> 29 <211> 1091 <212> DNA <213> homo sapiens <400> 29 aactgacttg aagatgtgtg attattttca gtaggcagac atctaaccct gaaaaccact 60 cgcttgcaga gcgctggatc agcaatgcct actagttctt cattcaaaca ccggattaaa 120 gagcaggaag actacatccg agattggact gctcatcgag aagagatagc caggatcagc 180 caagatcttg ctctcattgc tcgggagatc aacgatgtag caggagagat agattcagtg 240 acttcatcag gcactgcccc tagtaccaca ttggttgatc gtgtttttga tgaaagcctc 300 aacttccaaa agattcctcc attagttcat tccaaaacac cagaaggaaa caacggtcga 360 tctggtgatc caagacctca agcagcagag cctcccgatc acttaacaat tacaaggcgg 420 agaacctgga gcagggatga agtcatggga gataatctgc tgctgtcatc cgtctttcag 480 ttctctaaga agataagaca atctatagat aagacagctg gaaagatcag aatattattt 540 aaagacaaag atcggaattg ggatgacata gaaagcaaat taagagccga aagtgaagtc 600 cctattgtga aaacctcgag catggagatt tcttctatct tacaggaact gaaaagagta 660 gaaaagcagc tacaagcaat caatgctatg attgatcctg atggaacttt ggaggctctg 720 aacaacatgg gatttcccag tgctatgttg ccatctccac cgaaacagaa gtccagccct 780 gtgaataacc accacagccc gggtcagaca ccaacacttg gccaaccaga agctagggct 840 cttcatcctg ctgctgtttc agccgcagct gaatttgaga atgctgaatc tgaggctgat 900 ttcagtatac atttcaatag agtcaaccct gatggggaag aggaagatgt tacagtacat 960 aaatgacttt ctcttgattg ttgaaaaatc attacctgtg gaatgactag gaatattgga 1020 agcagcatag tgttgacgta cgcaaaacaa gacagcttgg tcagctacaa aaaacaaaaa 1080 aaaaaaaaaa a 1091 <210> 30 <211> 2282 <212> DNA <213> homo sapiens <400> 30 gttgtacttt tagcttcccc catcctgcaa ggccactcaa ccatgtgcta gctggagtga 60 tctttattca caatgtcttt acaaaggctc ctgcaacaca gcagcaatgg caatttggcg 120 gacttctgcg ctgggccagc gtatagctct tactccacac tcaccggcag ccttacgatg 180 gacgataata gaaggattca aatgctagca gacacggtgg ctactctgcc tcggggacga 240 aagcagcttg ctttgaccag atcaagttct ttaagtgact tttcctggtc tcaaagaaag 300 cttgttactg tggagaagca ggataatgaa acatttggat ttgaaattca gtcttacagg 360 ccccagaatc agaatgcctg ctcctcggaa atgttcactt tgatatgcaa aatacaggag 420 gacagcccag ctcactgtgc tggcctgcaa gctggtgatg tccttgcaaa tatcaatggt 480 gtgagcacag aaggttttac ctacaaacaa gtcgttgacc tgatcagatc gtccggaaac 540 ctgctaacga tagagactct taatggaaca atgattctga aaagaacgga gcttgaagca 600 aagctgcagg ttttaaagca aactttgaaa caaaaatggg tggagtacag atctctgcag 660 ttacaggaac atcgtctgct tcatggtgat gcagctaatt gccccagttt ggaaaacatg 720 gacttggatg aattgtcttt gtttggaccc ctgcctgggc caggcccagc ccttgtggac 780 cggaatcgat tatccagtga gagcagctgt aagagctggc tgagctccat gacgatggac 840 agtgaagatg gctaccagac gtgtgtgtct gaggactcca gcaggggtgc cttcagtcgg 900 cagacgagta cagatgatga gtgctttatc cccaaggagg gggatgattt tctgaggagg 960 tcatcttcaa ggaggaaccg gagcatcagt aacaccagca gcggatccat gtctcccttg 1020 tgggagggca acttatcaag catgtttggg accctgcccc ggaagagcag aaagggaagt 1080 gtccgaaagc aactcttgaa atttatccct ggccttcatc gtgctgtgga agaggaagaa 1140 agtcgctttt gacggattgt ggtgtccttt caaattagct tatttcacaa atatctctag 1200 actcacccag atcccagctt ggtgggaaag tgcagaagaa ttgcaaaact gacatcccat 1260 ttcacagcaa tagtgacctt tatttaaatt gttgtgttat agtttatgct tcttaaatca 1320 tttttcaacc taaacagcca atttctaagc agacaggaaa actaaataat aagttaatta 1380 atataacaaa gatgcaggtt cctgctcatt ccagtaatgt ctttgaaagc aaaactaata 1440 tttattttct agattatccc tgtgaataat tgagaacttt ttggagtcaa gtatgaataa 1500 aggtgtggca gaatataata atctggacta ttttctatag gataattgct gggttataaa 1560 atcttaggtt tgcttatgcc cagtagctcc tgcggaggct taataatagg caattttgaa 1620 tttgttcaaa cctgtaatgg cttgtaaaca aagatgacca tcagctgttt ctcacatcta 1680 tagtgacaat aaagcgggaa gtataagatt taataggagg ggttaaggtt catgagaacc 1740 atggaaagat gtggtctgag atgggtgctg caaagatcat aataaagtca tttttataga 1800 cagtctaaac aaaatgggtg gggatgtcgt gttttttgcc caattcagct tttgttctgc 1860 ctgaacatta atggcaagtc tagaactctc cgaatcctac agctttgtaa ttttttttct 1920 acaaatgtct aacatccaaa actgagggtt gggaaaagga cttccctcct gtagtttttt 1980 tcatattact tctcacttta tatcttatat tctaaatagc tatcacctca gcagtctttt 2040 gcctattggt tatgttagta tcacattact tctagccttt caattactcc atgttttatt 2100 taatatccat tgaagtctat gaattctctg ttctggtggc acagctattc ataacctata 2160 ttctagagta gacaatctgg actatgtaat aaatagtctg ctgattttaa aaaaaaaaaa 2220 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2280 aa 2282 <210> 31 <211> 2115 <212> DNA <213> homo sapiens <400> 31 atggtttctc caacgaaaat gataataagg tctccgttaa aggaaacaga taccaacttg 60 aaacataata atggaattgc cgcatcaaca acagcagcgg gccacttgaa tgtgttttct 120 aacgacaata attgcaacaa taacaatacc actgaatcct ttccgaagaa aagatctctt 180 gagcgcctcg agctccaaca gcagcagcat ttgcatgaaa agaaaagggc cagaatagaa 240 agggccaggt ctattgaagg cgctgtccaa gtcagcaaag gtacgggtct gaaaaatgtc 300 gagccaaggg ttacgcctaa ggaattgctg gaatggcaaa caaattggaa aaagataatg 360 aaaagagatt ctcgcattta ctttgacatt actgatgatg tagagatgaa tacatataat 420 aagtccaaga tggacaaacg cagagattta ttgaaaagag ggtttcttac attgggtgcg 480 caaataactc aattttttga cactactgtc acaatagtta tcacaagaag gtctgttgag 540 aacatatatt tactaaaaga taccgacatt ttatcgagag ctaaaaaaaa ctacatgaaa 600 gtttggagtt acgaaaaggc tgccagattt ctgaaaaatc ttgatgttga tttggatcat 660 ttgagcaaga ctaaatctgc ttctttagct gcgcccacat tgtccaatct tctacacaat 720 gaaaaattat atggaccaac ggatagagac cccagaacta aaagagacga tattcactac 780 tttaaatatc ctcatgtata cctttatgac ctatggcaaa cttgggcccc cataataact 840 ttggaatgga aacctcaaga actaacaaac ttagacgaac taccttaccc aatattgaaa 900 ataggttcat tcggaagatg cccttttata ggggatagga attatgacga aagttcttat 960 aagcgcgtag taaagagata ctcgagagac aaagcaaaca aaaaatatgc actgcaactt 1020 cgtgctctat ttcaatatca tgccgacacc ttactgaata cgtcatcagt taatgatcaa 1080 acgaaaaacc taatattcat acctcacaca tgcaacgatt ctaccaagag cttcaaaaaa 1140 tggatgcaag aaaaggcaaa aaattttgag aagaccgagt taaagaagac ggatgatagc 1200 gcagttcaag atgttcgtaa tgaacatgct gaccaaaccg atgaaaaaaa tagtatatta 1260 ttaaatgaaa ctgaaaccaa agagcctccg ttgaaagaag aaaaagaaaa taaacaatct 1320 atagcagaag aatcgaataa gtacccacag cgaaaagagc tggctgccac accaaaacta 1380 aaccatccag tattagctac ttttgcaagg caagaaactg aagaagtgcc ggatgatttg 1440 tgcactttga aaacaaagtc acgtcaggca tttgaaatca aagcaagtgg tgcacatcaa 1500 tctaatgatg tggcaacctc ttttggcaat ggtttgggcc caacaagagc aagcgtcatg 1560 agtaagaaca tgaagtcatt aagtagacta atggttgata gaaagctggg agtaaagcag 1620 acaaatggaa ataacaaaaa ttatacagcc actatagcaa ctactgctga aacatcaaag 1680 gaaaatagac acagattaga ttttaatgct ttgaaaaaag acgaagcccc ttcgaaagag 1740 acgggcaaag atagtgctgt acacttagaa actaatagaa agccccagaa tttccctaag 1800 gtagctacca aatcagtctc cgcagactcc aaagttcata atgacatcaa gataacaacc 1860 acagaatctc caacagcatc gaagaaatca acttccacaa acgtcacctt acattttaac 1920 gcacagacag cacagacagc acagccggtg aagaaagaaa cggtaaaaaa ttccggatac 1980 tgtgaaaatt gtcgtgtaaa atacgaatct ttagaacaac acatagtttc tgagaagcat 2040 ttgtctttcg ctgaaaacga tttaaatttt gaggctattg actcgttaat tgaaaatctc 2100 agatttcaaa tatag 2115 <210> 32 <211> 2889 <212> DNA <213> homo sapiens <400> 32 taccacaaat ttactggctt aaaacgacgc aagtctgtag gtcagaagtc tgacacgggt 60 cttaactggt gacccgagtc agatttggga cacaaagaac agaaaccaag ctgtgcaggt 120 ttctgacagg cagtccggtt agggagccct acagcaaccc gccggtcctc tctctcaggc 180 agttgctgcc atggctcatt attccaaccg gttctcctca gcccagtcta tctcagtggc 240 tccattcata gggtgatgtg cccggcggga cactaaccct aaccaagcag agagacggtc 300 atgcccgtca cgacctcggc cctcgccccg gccgaggctt ctcctgcagg tcgcgagaat 360 caggtgcgtc agcggcgtcc gggaacgccg gaagagccag tggagcggct ctgtagtcca 420 aagtaccccg tcgaccccag cacggccgct ccaccgcctc ctactagacc cagtcctagg 480 gactgcgcag tcgcagagct ccgtccgagt accggaagcc taggccgcca gcacttccgg 540 gaagtgactt cgtctccgaa gccgattggt tgttgctttg ctcccgctcg cgtcggtggc 600 gtttttcctg cagcgcgtgc gtgctgcgct actgagcagc gccatggagg actctgaagc 660 actgggcttc gaacacatgg gcctcgatcc ccggctcctt caggctgtca ccgatctggg 720 ctggtcgcga cctacgctga tccaggagaa ggccatccca ctggccctag aagggaagga 780 cctcctggct cgggcccgca cgggctccgg gaagacggcc gcttatgcta ttccgatgct 840 gcagctgttg ctccatagga aggcgacagg tccggtggta gaacaggcag tgagaggcct 900 tgttcttgtt cctaccaagg agctggcacg gcaagcacag tccatgattc agcagctggc 960 tacctactgt gctcgggatg tccgagtggc caatgtctca gctgctgaag actcagtctc 1020 tcagagagct gtgctgatgg agaagccaga tgtggtagta gggaccccat ctcgcatatt 1080 aagccacttg cagcaagaca gcctgaaact tcgtgactcc ctggagcttt tggtggtgga 1140 cgaagctgac cttctttttt cctttggctt tgaagaagag ctcaagagtc tcctctgtca 1200 cttgccccgg atttaccagg cttttctcat gtcagctact tttaacgagg acgtacaagc 1260 actcaaggag ctgatattac ataacccggt tacccttaag ttacaggagt cccagctgcc 1320 tgggccagac cagttacagc agtttcaggt ggtctgtgag actgaggaag acaaattcct 1380 cctgctgtat gccctgctca agctgtcatt gattcggggc aagtctctgc tctttgtcaa 1440 cactctagaa cggagttacc ggctacgcct gttcttggaa cagttcagca tccccacctg 1500 tgtgctcaat ggagagcttc cactgcgctc caggtgccac atcatctcac agttcaacca 1560 aggcttctac gactgtgtca tagcaactga tgctgaagtc ctgggggccc cagtcaaggg 1620 caagcgtcgg ggccgagggc ccaaagggga caaggcctct gatccggaag caggtgtggc 1680 ccggggcata gacttccacc atgtgtctgc tgtgctcaac tttgatcttc ccccaacccc 1740 tgaggcctac atccatcgag ctggcaggac agcacgcgct aacaacccag gcatagtctt 1800 aacctttgtg cttcccacgg agcagttcca cttaggcaag attgaggagc ttctcagtgg 1860 agagaacagg ggccccattc tgctccccta ccagttccgg atggaggaga tcgagggctt 1920 ccgctatcgc tgcagggatg ccatgcgctc agtgactaag caggccattc gggaggcaag 1980 attgaaggag atcaaggaag agcttctgca ttctgagaag cttaagacat actttgaaga 2040 caaccctagg gacctccagc tgctgcggca tgacctacct ttgcaccccg cagtggtgaa 2100 gccccacctg ggccatgttc ctgactacct ggttcctcct gctctccgtg gcctggtgcg 2160 ccctcacaag aagcggaaga agctgtcttc ctcttgtagg aaggccaaga gagcaaagtc 2220 ccagaaccca ctgcgcagct tcaagcacaa aggaaagaaa ttcagaccca cagccaagcc 2280 ctcctgaggt tgttgggcct ctctggagct gagcacattg tggagcacag gcttacaccc 2340 ttcgtggaca ggcgaggctc tggtgcttac tgcacagcct gaacagacag ttctggggcc 2400 ggcagtgctg ggccctttag ctccttggca cttccaagct ggcatcttgc cccttgacaa 2460 cagaataaaa attttagctg ccccagtttg tgcctccagc atatgaaaag gactatttga 2520 atccccaaaa catcaggagt cgggaaactt cggaagacag ctgtgcctgg ctctgtggct 2580 gcatgcagtg cttcacttgg ccagcagagg tcagctgtgc cgagctgccc cagccatgag 2640 aagagaagcc tgcccttgct ggcaggtggc tatggccggc ccagagcctt cctgcccagc 2700 tcctgcagcc ctgctgcctg ggatcaggct gggagatggg ccttcctgac cgccagcctt 2760 cctctccccg agcacacgca catgtagatt cggggggaag ctgcctgctc ttccttagag 2820 gagccggggc agctatctgc tggtcccttt ctgaacaact gttgatgtgt gaaaaaaaaa 2880 aaaaaaaaa 2889 <210> 33 <211> 1393 <212> DNA <213> homo sapiens <400> 33 agccctttgt ttatggcctg atctagctaa ggcttctaga cttcaggagc ttaagaatcg 60 tccggagggc tgggcgtggc ggtgcaggcc tgtagtccca cccactccga aggctgcgga 120 gggaggatca acttgagtct gggaactcag ccaggaattc aagaccagcc tgggcaacac 180 agtgaggccc cctacccaca tcctctccgt ccccgcaatc tccttccatc ccagggtgtt 240 gctgaaaatg tcagatgcaa atttggatag cagcaagaag aatttcttgg agggggaagt 300 agatgatgag gaaagtgtga ttttgacact ggtgccagtt aaagatgacg caaatatgga 360 acaaatggaa ccaagcgttt cttcaacttc tgatgtcaaa ctggagaagc ctaagaaata 420 caatccaggt catctacttc aaacaaatga gcaatttaca gctccacaaa aagctagatg 480 caaaatacca gcccttccct tgccgaccat tttgcctccc attaataagg tgtgtcggga 540 cactttgcgg gactggtgtc aacaactcgg tttgagtact aatggcaaga aaatcgaagt 600 ttatctgagg cttcataggc atgcttaccc tgaacaacgg caagatatgc ctgaaatgtc 660 acaagagacc agattacagc gatgttcgag gaaacgcaag gcagtgacca agagagcaag 720 gcttcagaga agttatgaga tgaatgagag agcagaagag accaatacag ttgaagtgat 780 aacttcagca ccgggagcca tgttggcatc atgggcaaga attgctgcaa gagctgttca 840 gcctaaggct ttgaattcat gttccattcc tgtttctgtt gaggcctttt tgatgcaagc 900 ctctggcgtc aggtggtgtg tggtccatgg cagacttctc tcggcagaca caaagggttg 960 ggtacgcctg cagtttcatg caggtcaggc ctgggtgcct accactcaca ggaggatgat 1020 ttctctcttc ttgttacctg cctgcatttt cccatcccca ggcatagaag ataatatgtt 1080 atgccccgac tgtgctaaga ggaataagaa gatgatgaaa agattaatga cagtagagaa 1140 gtagcagcaa cctgtttgaa tacaatgtac taaaggaggg atgtactttc agatcatgta 1200 acctattacg aaggagtgga agaggagaca atttgaatga atcctcatga tctacaaaac 1260 aaaatcatag tgactaggac tccacagtga agatggttga ctagtgacac agccccatct 1320 aaagaatccc tttctgtatg tctgaaaacc cattaaaata aagtcactgc aattggcctt 1380 gtaaaaaaaa aaa 1393 <210> 34 <211> 1052 <212> DNA <213> homo sapiens <400> 34 ctttccgggc taccttgtag caatttgagg ctctgtcatc agtttctgct acgtttcaaa 60 gatccaggag aagcttagtg ttgtgtcaag acgccgatgg acccatcaca gtttaatcca 120 acctacaacc cagggtctcc acaaatgctc accgaagaaa attcccggga cgattcaggg 180 gcctctcaaa tctcctccga gacgttgata aagaacctta gtaacttgac tatcaacgct 240 agtagcgaat ctgtttcccc tctattggaa gctttactcc gtcgagagtc tgtgggggca 300 gcagtcctca gggaaatcga agatgagtgg ctttacagca ggagaggagt aagaacactg 360 ctgtctgtgc agagagaaaa gatggcaaga ttgagataca tgttactggg cggagttcgt 420 acgcatgaaa gaagaccaac aaacaaggag cctaagggag ttaagaagga atcaagacca 480 ttcaaatgtc cctgcagttt ctgcgtgtct aatggatggg atccttctga gaatgctaga 540 atagagaatc aagacaccaa gccacttcag ccataaatct tattcttgca cctttttttc 600 ttgctagtaa ttttatatag caggttgaga aagctactct atgctagtat agactataca 660 ccaataattt tgataatgag ttctaggatg tatttttctt gtatcttttt cttcctacta 720 tgatactagt aattcataag ggatctgtgt aatctgaatg tatttcaata actttagctc 780 tactgtttga tttgacccaa agaagccaag acgatataag tattcccatg tgtcttagaa 840 gcccaaagtc agtgagatga aacccaacat caagaaattg aagcaaagtt acttgtggat 900 aaagaaagca ttaggtagtt tggctatagc ataattagat tttctggctt tcaaaaattt 960 ggattgcaat cacagcaaac tttgttattt ttacagtttt cagtacaaaa gtgtttatat 1020 agaaacaata aagttgacat ttgagtacct tt 1052 <210> 35 <211> 2835 <212> DNA <213> homo sapiens <400> 35 agaaggccgc acgccccggg catgcgcagc ggctcgctcg gaagctgcga cgccgagttt 60 cactctggct gccttctcct gagagtcgga gccacagcca gagccctgcc caggccgagc 120 cggagctgca gcccgagcgc ggtggtgccc tcagccccgt cctcttgtcc tcctcagcct 180 cggtgccttg gaatttgtgt cgctgagtca gcaagccttt cagatttgcc cggtttttgt 240 tgtttgtggt ttgtatcaag atgggaactc aaacaagtca ttcctcctaa ggagctggtg 300 tcttcatcca gaagggacag tttgtgccag ctctccagag agaaaaggat ctggtactgt 360 tctggagtgg cctgtagcag acactgaacc accagccagc tgcatttgtt gtcctggaag 420 tcattgccaa ctctgccagt cacactgggg tccccagaga agtcaagatc tgccggaggc 480 gctgggcaat gaccccggga ctccaggcca gaggggtctg aagctgtttg ggaaagcagc 540 gggactcctt gggaagatgg ccatggcccc aagcccttcc ctggtgcagg tgtacaccag 600 ccccgcggct gtggccgtgt gggaatggca ggacgggctg ggcacctggc acccctacag 660 tgccaccgtc tgcagcttca tcgagcagca gtttgtccag cagaagggcc aacgttttgg 720 gcttgggagc ctggcccaca gcatcccctt gggccaggca gacccctcgc tggcccctta 780 cattattgac ctccccagct ggacccagtt ccgccaggac accggcacca tgcgggctgt 840 gcggagacac ctgttccccc agcactcagc ccctggccga ggtgtcgtct gggagtggct 900 gagcgacgat ggctcctgga ctgcctatga agccagcgtc tgtgactatc tggagcagca 960 ggtggccagg ggcaaccagc tcgtggactt ggcccccctg gggtacaact acactgtcaa 1020 ctacaccacc cacacgcaga ccaacaagac ttccagcttc tgccgcagcg tgcggcgcca 1080 agcagggccg ccttacccgg tgaccaccat catcgctccg ccgggccaca caggcgtcgc 1140 ctgctcttgc caccagtgcc tcagtggcag cagaactggc cccgtgtcag gccgctaccg 1200 ccactccatg accaacctcc ctgcataccc cgtcccccag caccccccac acaggaccgc 1260 ttctgtgttt gggacccacc aggcctttgc accgtacaac aaaccctcac tctccggggc 1320 ccggtctgcg cccaggctga acaccaccaa cgcctggggc gcagctcctc cttccctggg 1380 gagccagccc ctctaccgct ccagcctctc ccacctggga ccgcagcacc tgcccccagg 1440 atcctccacc tccggtgcag tcagtgcctc cctccccagc ggtccctcaa gcagcccagg 1500 gagcgtccct gccactgtgc ccatgcagat gccaaagccc agcagagtcc agcaggcgct 1560 cgcaggcatg acgagtgttc tgatgtcagc cattggactc cctgtgtgtc ttagccgcgc 1620 accccagccc accagccctc ccgcctcccg tctggcttcc aaaagtcacg gctcagttaa 1680 gagattgagg aaaatgtccg tgaaaggagc gaccccgaag ccagagccag agccagagca 1740 ggtcataaaa aactacacgg aagagctgaa agtgccccca gatgaggact gcatcatctg 1800 catggagaag ctgtccacag cgtctggata cagcgatgtg actgacagca aggcaatcgg 1860 gtccctagct gtgggccacc tcaccaagtg cagccatgcc ttccacctgc tgtgcctcct 1920 ggccatgtac tgcaacggca ataaggatgg aagtctgcag tgtccctcct gcaaaaccat 1980 ctatggagag aagacgggga cccagcccca gggaaagatg gaggtattac ggttccagat 2040 gtcgctcccc ggccacgagg actgcgggac catcctcata gtttacagca ttccccatgg 2100 tatccagggc cctgagcacc ccaatcccgg aaagccgttc actgccagag ggtttccccg 2160 ccagtgctac cttccagaca acgcccaggg ccgcaaggtc ctagagctcc tgaaggtggc 2220 ctggaagagg cggctcatct tcacagtggg cacgtccagc accacgggtg agacggacac 2280 cgtggtatgg aacgagatcc accacaagac agagatggac cgcaacatta cgggccacgg 2340 ctatcccgac cccaactacc tgcagaacgt gctggctgag ctggctgccc agggggtgac 2400 cgaggactgc ctggagcagc agtgacctcg caccccagca cgcccgcctc tggtggccac 2460 cccgctgccc catggctggc tgggtggcca ggcaggaagt gcccagcccg agaggctggg 2520 aggtttgttg agggtgtggg gtgtgcccca cctgaagccg gggctccccc tgcctgcctc 2580 tctctcctcc tcccctctgg gaattgggca gccctgggca gttgtactca tgggggctta 2640 ggatgcagct acctcagtgc gcagggcccg tctgtcctct gggggctgct tcgggcccgc 2700 ggtgctcggg gcctggtgtg gggcgagtag agacttcccc agcctggacg ggcgtgggtt 2760 ctgggtcagc ttcttttacc tcaattttgt ttgcaataaa tgctctatag ccaaagccaa 2820 aaaaaaaaaa aaaaa 2835 <210> 36 <211> 3911 <212> DNA <213> homo sapiens <400> 36 gcagacggca accgggccgc tgattgggcg gcgaaggagc cattcgggga gactctggtg 60 ggttcggctg ccccaagagt gataagttcg gcttcagaca cgccttagcg ccagcagtga 120 gtcggagctc tatggaggtg gcagcgggta ccgagtggcg gctgcagcag cgactcctct 180 gagctgagtt tgaggccgtc cccgactcct tcctccccct tccctccccc ttttttttgt 240 tttccgttcc cctttcccct cccttcccta tccccgacga ccggatcctg aggaggcagc 300 tgcggtggca gctgctgagt tctcggtgaa ggtatttcat ttctcctgtc ccctcccctc 360 cccaccccat ctattaatat tattcttttg aagattcttc gttgtcaagc cgccaaagtg 420 gagagtgcga ttgcagaagg gggtgcttct cgtttcagtg cttcttcggg cggaggagga 480 agtaggggtg cacctcagca ctatcccaag actgctggca acagcgagtt cctggggaaa 540 accccagggc aaaacgctca gaaatggatt cctgcacgaa gcactagacg agatgacaac 600 tccgcagcaa acaactccgc aaacgaaaaa gaacgacatg atgcaatctt caggaaagta 660 agaggcatac taaataagct tactcctgaa aagtttgaca agctatgcct tgagctcctc 720 aatgtgggtg tagagtctaa actcatcctt aaaggggtca tactgctgat tgtggacaaa 780 gccctagaag agccaaagta tagctcactg tatgctcagc tatgtctgcg attggcagaa 840 gatgcaccaa actttgatgg cccagcagca gagggtcaac caggacagaa gcaaagcacc 900 acattcagac gcctcctaat ttccaaatta caagatgaat ttgaaaaccg aactagaaat 960 gttgatgtct atgataagcg tgaaaatccc ctcctccccg aggaggagga acagagagcc 1020 attgctaaga tcaagatgtt gggaaacatc aaattcattg gagagcttgg caagcttgat 1080 cttattcacg aatctatcct tcataagtgc atcaaaacac ttttggaaaa gaagaagaga 1140 gtccaactca aagatatggg agaggatttg gagtgcctct gtcagataat gaggacagtg 1200 ggacctagat tagaccatga acgagccaag tccttaatgg atcagtactt tgcccgaatg 1260 tgctccttga tgttaagtaa ggaattgcca gcaaggattc gtttcctgct gcaggatacc 1320 gtagagttgc gagaacacca ttgggttcct cgcaaggctt ttcttgacaa tggaccaaag 1380 acgatcaatc aaattcgtca agatgcagta aaagatctag gggtgtttat tcctgctcct 1440 atggctcaag ggatgagaag tgacttcttt ctggagggac cgttcatgcc acccaggatg 1500 aaaatggata gggacccact tggaggactt gctgatatgt ttggacaaat gccaggtagc 1560 ggaattggta ctggtccagg agttatccag gatagatttt cacccaccat gggacgtcat 1620 cgttcaaatc aactcttcaa tggccatggg ggacacatca tgcctcccac acaatcgcag 1680 tttggagaga tgggaggcaa gtttatgaaa agccaggggc taagccagct ctaccataac 1740 cagagtcagg gactcttatc ccagctgcaa ggacagtcga aggatatgcc acctcggttt 1800 tctaagaaag gacagcttaa tgcagatgag attagcctga ggcctgctca gtcgttccta 1860 atgaataaaa atcaagtgcc aaagcttcag ccccagataa ctatgattcc tcctagtgca 1920 caaccaccac gcactcaaac accacctctg ggacagacac ctcagcttgg tctcaaaact 1980 aatccaccgc ttatccagga aaagcctgcc aagaccagca aaaagccacc accgtcaaag 2040 gaagaactcc ttaaactaac tgaaactgtt gtgactgaat atctaaatag tggaaatgca 2100 aatgaggctg tcaatggtgt aagagaaatg agggctccta aacactttct tcctgagatg 2160 ttaagcaaag taatcatcct gtcactagat agaagcgatg aagataaaga aaaagcaagt 2220 tctttgatca gtttactcaa acaggaaggg atagccacaa gtgacaactt catgcaggct 2280 ttcctgaatg tattggacca gtgtcccaaa ctggaggttg acatcccttt ggtgaaatcc 2340 tatttagcac agtttgcagc tcgtgccatc atttcagagc tggtgagcat ttcagaacta 2400 gctcaaccac tagaaagtgg cacccatttt cctctcttcc tactttgtct tcagcagtta 2460 gctaaattac aagatcgaga atggttaaca gaactttttc aacaaagcaa ggtcaatatg 2520 cagaaaatgc tcccagaaat tgatcagaat aaggaccgca tgttggagat tttggaagga 2580 aagggactga gtttcttatt cccactcctc aaattggaga aggaactgtt gaagcaaata 2640 aagttggatc catcccctca aaccatatat aaatggatta aagataacat ctctcccaaa 2700 cttcatgtag ataaaggatt tgtgaacatc ttaatgacta gcttcttaca gtacatttct 2760 agtgaagtaa acccccccag cgatgaaaca gattcatcct ctgctccttc caaagaacag 2820 ttagagcagg aaaaacaact actactatct ttcaagccag taatgcagaa atttcttcat 2880 gatcacgttg atctacaagt cagtgccctg tatgctctcc aggtgcactg ctataacagc 2940 aacttcccaa aaggcatgtt acttcgcttt tttgtgcact tctatgacat ggaaattatt 3000 gaagaagaag ctttcttggc ttggaaagaa gatataaccc aagagtttcc gggaaaaggc 3060 aaggctttgt tccaggtgaa tcagtggcta acctggttag aaactgctga agaagaagaa 3120 tcagaggaag aagctgacta aagaaccagc caaagcctta aattgtgcaa aacatactgt 3180 tgctatgatg taactgcatt tgacctaacc actgcgaaaa ttcattccgc tgtaatgttt 3240 tcacaatatt taaagcagaa gcacgtcagt taggatttcc ttctgcataa ggtttttttg 3300 tagtgtaatg tcttaatcat agtctaccat caaatatttt aggagtatct ttaatgttta 3360 gatagtatat tagcagcatg caataattac atcataagtt ctcaagcaga ggcagtctat 3420 tgcaaggacc ttctttgctg ccagttatca taggctgttt taagttagaa aactgaatag 3480 caacactgaa tactgtagaa atgcactttg ctcagtaata cttgagttgt tgcaatattt 3540 gattatccat ttggttgtta cagaaaaatt cttaactgta attgatggtt gttgccgtaa 3600 tagtatattg cctgtatttc tacctctagt aatgggcttt atgtgctaga ttttaatatc 3660 cttgagcctg ggcaagtgca caagtctttt taaaagaaac atggtttact tgcacaaaac 3720 tgatcagttt tgagagatcg ttaatgccct tgaagtggtt tttgtgggtg tgaaacaaat 3780 ggtgagaatt tgaattggtc cctcctatta tagtattgaa attaagtcta cttaatttat 3840 caagtcatgt tcatgccctg attttatata cttgtatcta tcaataaaca ttgtgatact 3900 tgatgtagtg a 3911 <210> 37 <211> 5180 <212> DNA <213> homo sapiens <400> 37 gcagatgcaa aatgtgtctc tggccagcag gaggaaggaa gaggaagtga gagcagcggc 60 agccggcggt gcagcagccg gccgacccag agtgtaagtg cgtgtgctgg ggcgagcggg 120 agcgggcgag gatgggcaca ggatagaggc agagccaccc acgccgccgc ggccccacgc 180 tgggcgacag agcctccagt tccccttcaa tggtggcggg tcgccggagc tctgatcgcc 240 gggaaccctt gccgctgctg tcctgcgacc ccaagcaggt atagacacgt gtggccgttt 300 acgctgtagg atcctcattc ccactggctt tgaacatttt ggggacttac aatgccgcca 360 cccgcggaca tcgtcaaggt ggccatagaa tggccgggcg cctaccccaa actcatggaa 420 attgatcaga aaaaaccact gtctgcaata ataaaggaag tctgtgatgg gtggtctctt 480 gccaaccatg aatattttgc actccagcat gccgatagtt caaacttcta tatcacagaa 540 aagaaccgca atgagataaa aaatggcact atccttcgat taaccacatc tccagctcag 600 aacgcccagc agctccatga acgaatccag tcctcgagta tggatgccaa gctggaagcc 660 ctgaaggact tggccagcct ctcccgggat gtcacgtttg cccaggagtt tataaacctg 720 gacggtatct ctctcctcac gcagatggtg gagagcggca ctgagcgata ccagaaattg 780 cagaagatca tgaagccttg ctttggagac atgctgtcct tcaccctgac ggccttcgtt 840 gagctgatgg accatggcat agtgtcctgg gatacatttt cggtggcgtt cattaagaag 900 atagcaagtt ttgtgaacaa gtcagccata gacatctcga tcctgcagcg gtccttggcc 960 attttggagt cgatggtgct caatagccat gacctctacc agaaagtggc gcaggagatc 1020 accatcggcc agctcattcc acacctgcaa gggtcagatc aagaaatcca aacctatact 1080 attgcagtga ttaatgcgct tttcctgaag gctcctgatg agaggaggca ggagatggcg 1140 aatattttgg ctcagaagca actgcgttcc atcattttaa cacatgtcat ccgagcccag 1200 cgggccatca acaatgagat ggcgcaccag ctgtatgttc tacaagtgct cacctttaac 1260 ctcctggaag acaggatgat gaccaaaatg gacccccagg accaggctca gagggacatc 1320 atatttgaac ttcgaagaat tgcttttgat gctgagtctg aacctaacaa cagcagtggc 1380 agcatggaga aacgcaagtc catgtacacg cgagattata agaagcttgg gttcattaat 1440 catgtcaacc ctgccatgga cttcacgcag actccacctg ggatgttggc tctggacaac 1500 atgctgtact ttgccaagca ccaccaagat gcctacatcc ggattgtgct tgagaacagt 1560 agtcgagaag acaagcatga atgtcccttt ggccgcagta gtatagagct gaccaagatg 1620 ctatgtgaga tcttgaaagt gggcgagttg cctagtgaga cctgcaacga cttccacccg 1680 atgttcttca cccacgacag atcctttgag gagtttttct gcatctgtat ccagctcctg 1740 aacaagacat ggaaggaaat gagggcaact tctgaagact tcaacaaggt aatgcaggtg 1800 gtgaaggagc aggttatgag agcacttaca accaagccta gctccctgga ccagttcaag 1860 agcaaactgc agaacctgag ctacactgag atcctgaaaa tccgccagtc cgagaggatg 1920 aaccaggaag atttccagtc ccgcccgatt ttggaactaa aggagaagat tcagccagaa 1980 atcttagagc tgatcaaaca gcaacgcctg aaccgccttg tggaagggac ctgctttagg 2040 aaactcaatg cccggcggag gcaagacaag ttttggtatt gtcggctttc gccaaatcac 2100 aaagtcctgc attacggaga cttagaagag agtcctcagg gagaagtgcc ccacgattcc 2160 ttgcaggaca aactgccggt ggcagatatc aaagccgtgg tgacgggaaa ggactgccct 2220 catatgaaag agaaaggtgc ccttaaacaa aacaaggagg tgcttgaact cgctttctcc 2280 atcttgtatg actcaaactg ccaactgaac ttcatcgctc ctgacaagca tgagtactgt 2340 atctggacgg atggactgaa tgcgctactc gggaaggaca tgatgagcga cctgacgcgg 2400 aatgacctgg acaccctgct cagcatggaa atcaagctcc gcctcctgga cctggaaaac 2460 atccagatcc ctgacgcacc tccgccgatt cccaaggagc ccagcaacta tgacttcgtc 2520 tatgactgta actgaagtgg ccgggcccag acatgcccct tccaaaactg gaacacctag 2580 ctaacaggag agaggaatga aaacacaccc acgccttgga accgtccttt ggtaaaggga 2640 agctgtgggt ccacattccc ttcagcatca cctctagccc tggcaacttt cagcccctag 2700 ctggcatctt gctcaccgcc ctgattctgt tcctcggctc cactgcttca ggtcacttcc 2760 catggctgca gtccactggt gggacaagag caaagcccac tgccagtaag aaggccaaag 2820 ggcccttcca tcctagccct ctgcaggcat gcccttcctt cccttgggca ggaaagccag 2880 cagccccaga ctgcccaaaa acttgcccac cagaccaagg gcagtgcccc aaggcccctg 2940 tctggaggaa atggcctagc tatttgatga gaagaccaaa ccccacatcc tcctttcccc 3000 tctctctaga atcatctcgc accaccagtt acacttgaat taagatctgc gctcaaatct 3060 cctcccacct ctctccctgc ttttgccttg ctctgttcct ctttggtccc aagagcagca 3120 gccgcagcct cctcgtgatc ctccctagca taaatttccc aaacagtcca caggtcccat 3180 gcccactttg cgtctgcact gtgatcgtga caaatcttcc ctcctcacca gctagtctgg 3240 ggtttcctct ccctgcccca ggccagaact gccttcttca tttccaccca cgctcccagc 3300 ctcttagctg aaagcacaaa tggtgaaatc agtagtctcg ctccatctct aatagactaa 3360 acctaaatgc ctctaggacg gactgttgct atccaagcgt ttggtgttac cttctcctgg 3420 gaggtcctgc tgcaactcaa gttccacagg atggtcaagc tgtcagacat ccaagtttac 3480 atcattgtaa ttattactgg tatttacaat ttgcaagagt tttgggttag tttttttttt 3540 tttttttgct ttgtttttgt acaaaagagt ctaacatttt ttgccaaaca gatatatatt 3600 taatgaaaag aagagataca taaatgtgtg aatttccagt ttttttttaa ttattttaat 3660 cccaaacatc ttcctgaaaa taacattccc ttaaacatgc tgtggaataa aatggattgt 3720 gatgatttgg ggagctggtg ttttgattta gtaacttagg ttcttgctac tcagtcatca 3780 gcatcacctg ggagcttgtt ggagatgcca gctcttcagc tccaccctag acctgctgaa 3840 ttgggtgatg tttatgtaca ttggtttgaa aaacactgct gtgggaaacc ctccaccatt 3900 gctaggtcac cataggctct gagcatcagt ggagaatgtt acttctaaga agaccatctc 3960 gactcactga gaaaatcaga cccactgtat gaaaatatct attcctttta cattgctgtc 4020 tcttgaccat gactttctct tttttctttc ttaccatgat ataatttata gaatgggtct 4080 aattaaagac atcacaactt tgagggagca catttagcaa tgaaaagaat gcatacccac 4140 agacctgaaa taagccagaa ctaaataaat ctaaccgtgg gttaataaat tataggtcag 4200 agcccagcga aggatgtttc ttaagtcatt tgcactggag gcattatcag gattgtaaac 4260 tcccagcact gggagggatg tcagaagggt ccaagcatgc agtattaagc gtggcacagc 4320 accagccact ctggcctcac agcacaagct gtggaagcat ccaggtcatt tctctttacc 4380 gtcatcagga tgtgcaatta cagattgacc tgggttgaga tgatatggtc cagagcactg 4440 catgcattgc aggaaaaaag tcctttgcat tcacaggggt tccttcttcc catcagagca 4500 ctcacacctg tgtcaagctg ttaattcctt gatcattaag cttcgatgtt attaacatgt 4560 acttgctatc aggagcagtt attaatctac ccatcatcat gataaaacag taagtgttag 4620 gtcaaaggca gcaaacaaag tcatattatt tttttcttat gggttacaag atccaatcca 4680 tgaaaaaggg aactttctgg accaggatct ctgaggtcct gagacactgg gtttaagaaa 4740 tgtatctgtc ctgtgacctt ggttggggag atccagcccc tctctcttct ggcactccag 4800 ctttggtgca tttaatagaa agaaaccttt tcaggactat gaaaggcagc attctccagc 4860 tcctccctag accctccttt ggacctgtga gatctgaaga gtatgccatc tgtttccatt 4920 cattttgtga ccatgtgggg aaggattgtt gcccatattt ggccacctca ccttctctct 4980 ccaggctgcc caaggctttt tttcccatgc aatgagccta ccacctccaa ctcatctcct 5040 gttgcctgca gtttcctaag cctgggcaac tcagccaaat ccaaggcaga agtaaagtag 5100 gaagactgat gttgtcgtga agtccaagtt gcattctgct attcatatta ctcaaaataa 5160 aactgattac ttaatttgaa 5180 <210> 38 <211> 1455 <212> DNA <213> homo sapiens <400> 38 gagattggat agcggcgggg cgcaggaaag aggtcgcgcc agcccgggca ggcagctttg 60 caagtccgcg ttatatatcg cagtggctgc gcccgggata gctggctgcg ccgccgcgca 120 catgcctagg ttcgacgccc tcctcccttt gcccaggagt tccttctgtc ccggctctgt 180 tccgtctcgc cccgaggttc acgccatcct cggagcccca gcctttcacc cagcgcctcc 240 aagctttgga ccttgacttc tgcaaaacta gatggtcaca gccatgaatg tctcacatga 300 agtaaatcag ctgttccagc cctataactt cgagctgtcc aaggacatga ggcccttttt 360 cgaggagtat tgggcaacct cattccccat agccctgatc tacctggttc tcatcgctgt 420 ggggcagaac tacatgaagg aacgcaaggg cttcaacctg caagggcctc tcatcctctg 480 gtccttctgc cttgcaatct tcagtatcct gggggcagtg aggatgtggg gcattatggg 540 gactgtgcta cttaccgggg gcctaaagca aaccgtgtgc ttcatcaact tcatcgataa 600 ttccacagtc aaattctggt cctgggtctt tcttctcagc aaggtcatag aactcggaga 660 cacagccttc atcatcctgc gtaagcggcc actcatcttt attcactggt accaccacag 720 cacagtgctc gtgtacacaa gctttggata caagaacaaa gtgcctgcag gaggctggtt 780 cgtcaccatg aactttggtg ttcatgccat catgtacacc tactacactc tgaaggctgc 840 caacgtgaag ccccccaaga tgctgcccat gctcatcacc agcctgcaga tcttgcagat 900 gtttgtagga gccatcgtca gcatcctcac gtacatctgg aggcaggatc agggatgcca 960 caccacgatg gaacacttat tctggtcctt catcttgtat atgacctatt tcatcctctt 1020 tgcccacttc ttctgccaga cctacatcag gcccaaggtc aaagccaaga ccaagagcca 1080 gtgaaggttt ggagagaaca atgaagctcc aggctctctc ttctccaggg caccaagagg 1140 ctgggcttag ttttgggaga atgattaggt tgccttacct gcatggtttc cccagaggat 1200 gtgtgcccca aggtggctgg aatttttgac agacaagaag ggtgaccttg ggatgggggt 1260 gtggtctgtt actttaatgt ttctgttttt aatgtgaagg ccaagcaggc cctgggatgg 1320 gagtggggcg gaggagggtc ctaagagctg attatttaat ttctatccag aaatctttct 1380 tcttcttgct ctgttttttt aaattaaaga tttcaacaaa aaaaaaaaaa aaaaaaaaaa 1440 aaaaaaaaaa aaaaa 1455 <210> 39 <211> 5674 <212> DNA <213> homo sapiens <400> 39 ctttttattt tgagcctttt tgatactgaa catgatatct gagtgaagaa tttttgtttt 60 attattaaga aataaatgta tcttgcttct tgagatctcc ctggcttcag caatttgtag 120 ttatttccac tatagaccat taagaatata tttcaaaggc aagctaacaa agttcaagta 180 aaaattattt tttatatatt acagcttcta attggcattg gtttcttctc aggttaaagc 240 tgtatttttc ttaaaggctt ataaaaattt tgctgaaaaa aatgttggtg cttcggtgca 300 ggcttggaac ctcttttcct aaactagata acttggtacc aaaaggcaaa atgaagattc 360 tcctggtctt tctagggctt cttggtaatt ctgttgctat gccaatgcac atgccccgaa 420 tgcctggatt tagcagtaaa agtgaggaga tgatgcggta taatcaattc aactttatga 480 acggcccaca tatggcacac ctggggccct tctttggaaa cggtctccct cagcaatttc 540 cacagtacca gatgcccatg tggcctcagc caccacccaa cacatggcat ccacggaaat 600 cctcagcacc caaacgtcat aacaagactg atcagaccca agaaacccag aaacccaacc 660 agactcagtc aaaaaagcca ccacaaaagc ggcctttgaa gcagccatca cataatcaac 720 ctcagcccga agaggaagct caaccccctc aggcattccc accatttgga aatgggctat 780 tcccctatca acaaccacca tggcaaattc cacagaggtt accaccacca ggttatggac 840 gcccaccaat cagcaatgaa gaagggggga atccttactt tggatatttt ggatatcatg 900 gctttggggg tcgccctcct tattattcag aagaaatgtt tgaacaagat tttgaaaaac 960 ccaaagaaga agatcctcct aaagcagaaa gtccaggcac agaacccaca gctaattcaa 1020 cagtcactga gacgaattct acccaaccaa atcctaaagg gagtcaggga ggaaatgaca 1080 ccagccccac aggaaacagt accccaggac taaacactgg gaacaaccct ccagctcaaa 1140 atgggattgg cccactccct gcagtcaacg cttcaggcca gggagggcca ggaagtcaaa 1200 tcccatggag accaagtcag ccaaatattc gtgaaaatca tccatatcct aatataagaa 1260 attttccttc aggaagacag tggtatttca ctggtactgt catggggcac agacagaata 1320 ggccttttta cagaaatcaa caagttcaaa ggggtcctcg gtggaacttc tttgcttggg 1380 aacgtaaaca agtagctcgt ccaggaaatc cagtttatca caaagcttac cctcctactt 1440 caagaggcaa ttatcccaat tatgcaggaa atccagcaaa tctcagaaga aagcctcagg 1500 ggccaaataa acaccctgta ggaactactg ttgccccact gggtcccaaa cctggccctg 1560 ttgttcgcaa tgaaaaaatc caaaatccaa aggagaagcc cctgggtcca aaagaacaaa 1620 taatagttcc tacaaagaat ccaaccagcc cctggagaaa ctctcaacag tatgaagtta 1680 ataaatcaaa ttataaactg cctcactctg agggttatat gccagtccca aattttaatt 1740 ctgttgatca acatgaaaac tcctattacc caagaggaga ttccagaaaa gtcccaaatt 1800 ctgatggaca aacccaaagc cagaatttgc ccaaagggat tgttttaggg tcaagaagga 1860 tgccatatga atcagaaact aatcagtcag aattaaagca cagctcatat cagcctgctg 1920 tataccctga ggaaatccct tctcctgcaa aagaacattt tcctgctgga agaaatactt 1980 gggaccacca agaaatctct ccacctttta aggaagatcc agggaggcaa gaagaacatt 2040 taccccatcc ttcccatggt tctagaggaa gtgttttcta ccctgaatat aacccatatg 2100 atcccaggga aaactcacca taccttagag gcaatacatg ggatgagaga gatgattctc 2160 ccaatactat ggggcaaaaa gaaagtccac tctaccccat aaatacccca gaccagaagg 2220 agatagtccc ttataatgaa gaggacccag ttgatccaac tggagatgaa gtctttcctg 2280 gacaaaatag atggggtgaa gagttgagct tcaaaggagg cccaacagtt aggcactatg 2340 aaggtgaaca atatacctca aatcagccaa aggaatatct tccctattct ttagataatc 2400 catcaaaacc aagggaggat ttttattaca gtgaatttta cccatggagc ccggatgaga 2460 attttccatc atataataca gcttctacta tgccaccacc tatagagagc aggggctact 2520 acgttaataa tgccgctgga ccagaagaaa gcactctatt tccttcacgg aattcctggg 2580 accacaggat acaagcccaa gggcagagag aaagaaggcc gtattttaac agaaatatct 2640 gggatcaggc aacacattta caaaaagccc cagctaggcc accagaccag aaaggtaacc 2700 agccctatta cagtaacacc ccagctgggc ttcagaaaaa tccaatatgg catgaaggtg 2760 agaatttgaa ctatggcatg caaataacta ggatgaattc tccagagaga gaacattcat 2820 ctttccctaa cttcatccca ccaagttacc catcaggtca aaaagaagca catttatttc 2880 acctaagcca gagaggctct tgctgtgctg gtagctccac agggcccaag gacaatccac 2940 tagctctaca agactacact ccatcctatg gtcttgcacc tggggagaac caagacacca 3000 gtcctctgta tacagacggt agtcatacca agcagacaag agatatcatc tccccaacaa 3060 gcatcctacc aggccaaaga aacagctcag agaagaggga aagccaaaac ccttttagag 3120 atgatgtgtc cacgctgagg aggaacacac catgttctat aaagaatcaa ctgggccaaa 3180 aggaaattat gccctttcct gaagccagtt cccttcaatc aaagaataca ccttgtctca 3240 aaaatgatct tggaggagat gggaacaaca ttctggaaca agtttttgaa gacaaccagc 3300 tcaatgaaag aactgttgac cttactcctg agcagcttgt tattggtaca cctgatgaag 3360 gctccaatcc agaaggcatc caaagtcaag tccaagaaaa tgagagtgag aggcaacagc 3420 aaagaccatc taacattctg catttgccat gctttggctc caaattagca aagcatcact 3480 cttccaccac cggaactcca tctagcgatg gaaggcaaag cccatttgat ggggattcaa 3540 ttacgcctac tgaaaatcct aacacattgg ttgagttagc tactgaggaa caatttaaga 3600 gtataaatgt agacccactt gatgcagatg aacacagtcc atttgaattc cttcaaagag 3660 ggaccaatgt acaggaccag gtacaagact gcttactact tcaggcctag gggttatcca 3720 accaagcatt cttggggaaa gagaaatcac tgacattcta taccaatggt tcccaaaatt 3780 ttttccccaa gacttaatta agtgtctgac tgtcttggtg atccttaagt tttctcccct 3840 ctcagcaata ggagtagcga cccaggtgga gctgagatta ggcctctggg gatcaccaga 3900 tctagcactt tcacagatta gtgcagacct taaaaaagca agaaggccat gaccatccct 3960 gcctcgaaac ttgcaagtca cttgtctgag ttagtttcct tttgcttgat gacttctttt 4020 gctctcaaag ttccatactt gcaaaattgg tttttcaaga ctgaaaggca gattaacttt 4080 ccattctact tatggagatc cacacatcag tatagtcctg atgcactgta cgttttttgc 4140 ttgtgttgat cttgtcaggt ttttttccta ctcaatattc tcttcaagca ttttttttct 4200 tccactgcca ctctctttac ctttatcatt tctttttctt agctttcttc cttcttttct 4260 ctctccctca accattctgt atttagcttt ctaatcctca tctttttctc tctgtatatc 4320 acttcttaca tattaaatta gctattttaa ccatttctag tctcttcttt atgtctacct 4380 cctccattat gtcttcgtct cttccaacct atctgttctg tctcccaatg taccacttat 4440 caactaatcc ctctcctctc tgattccttt cttcccttca atttatcttt ttccctgtta 4500 caccattttc atcttaagac tgcatgtcac tctcttcctt tttgtatcca ctctccaaat 4560 cgtaccctaa atttttcttg acccagctta accatcatta cagaatatat tttggaaatg 4620 gtagacactg atagctactt tgtttttagt tatcttaggg tctctaccaa gtagacacag 4680 ttcagttaga gagacgtatt taaggagaag ggaaggcagg atacccagaa ctagcagcct 4740 agggaaaagg cttaggaaga tggagaatga ggaactgaag aaactgccgc tctgagactg 4800 cacatccagg aaaaaagact aggacttgcc acacactgcc aattcataat ccgcaggatc 4860 tgtagaagac attttgggaa acactgtctt aaataaaaac tcaatgttta gttgtttttt 4920 ttttttttta ctagttcagc ataagggatt ctaccagtat gtgctactac taacattctt 4980 catgtccatg cagaattact tacagacact ctttcttggt atcttgaata aattgtgtaa 5040 attattttga aaagtggata tttctatatg ccttgcttat aatacatcag ggattattat 5100 tcttattaat aacatgttgg cctattatct ggatgtccct tgcctagagc aggaaaaaag 5160 tctcagaatt acctaaaaac atactttata actttaagag atttcttagg atacatcttc 5220 aggggcagat ttcataacaa catctcaaaa atttggggaa acacaacgtt gaaaacttcc 5280 taagaaaagg aatcttgccc ttgaatcttc tgaagtacct agcacagtgt cttcaacata 5340 gaaggtaccc aataaatata tatcaattca ttttttaatg actttcaaca ctcccatgaa 5400 aacaccgtag tctgcttttc ctgaaaggtg actgtctagg atgctgaatg agccaccact 5460 ccgtagcttt atatattcag caacatttcc atcatagaat ttcagcgtta gaagggatct 5520 tagaggtaga ttatccaggc catcccctac tgcttacatt cccctccccc tggccagttt 5580 tatattttaa tcacacattg aaaaattcat taacttattc tgtataaaac tgtcttttaa 5640 gaattatcct ttcaaaataa aaatgttatt gttt 5674 <210> 40 <211> 2295 <212> DNA <213> homo sapiens <400> 40 aaaaccccag caggttagct tctcattaaa tagcttctcc tgagggcaga ccttgttaag 60 aagaacaaaa tgctctggcg tatttcaaaa tggctccttt tccccaccca ctaccagagg 120 catggataat caccctgagg acctgtgaga gatccaggag cttaaaaaaa attggggagc 180 ggggaagagg gaatggctag gtccctctga cttgtccaca ctgatccttc aggtttacct 240 atcctggtac ttgttccatt ggaggcttca gcggctagtt tctgctctgt ggttaccaat 300 gacacaggag ctgagcttcc aaaaatttat tgaacaatct gacttactag gagaacttaa 360 atatgacttc aatgaaaaag atgaattcag acatactgag acacaaaggc cttttgtctt 420 taactattat gaaaatgtcc ttgagaaaaa tagcaagcgc taccaggccc ttggccattt 480 gcttgaacaa tacatttatg agcttttgga gaaagtgtgc aaattagaaa aagtatatat 540 cccacctgag gctgataaag aagaaccaag aagcttcttt ttcatgagcg agaaagcatt 600 aacaaatcac cattctgctc ttcttatcct tcttcaagac catggggtct ttcgagctgg 660 tcagtggagt caacaggcaa taatacatca tggtctccaa catggaagtc agataccatg 720 tattcaaatg gcattgcagg cacactatga tgtaattgtg ctaaacccca atgataattt 780 tgtggaacca aaggtggaaa aagagtggaa aggcctttta acacaaaata ttgagtcatc 840 ttctctaaaa atggttcaag gtgggagctt tttctctctc cagcatcctc ccaaatgcat 900 tccaaaaaga tgcagcaaca cccccgaaga acacacggct tacatatggg attacttcat 960 ttcaaagact gaaggcaagg atattgcctt cattgtacat ggttatggag gcttggtttt 1020 tatggacttg cttgttcgta gaaggtggga agtgatgagc aaagtatatg ctgttgcact 1080 tatcgactct gaacatcacg taggacacca gctgggaagt gatgtacaat tattagcatg 1140 gataaagcac cactgccgtg aatgggtgac aagtcctaag cctttggata aacctgcagc 1200 tactgttttc aaaaaggaat ttcctatggt ttctgctggc acagaaaagt acatcttagc 1260 cccttcctct agccttcagt caatttttaa gtactttaaa aaagctttaa aagccagaac 1320 aaccattaat ttctctcgaa tgccaatagt gactagaagc tccacaaaaa gaaagcaaag 1380 tgcttaaact acttttgtca tctaagattt ttttgtcctt ctgcaacttt gctaatacag 1440 attctggaag aaaaaagaac actttcaact cacacacaat atgatgttct ggcttgaggt 1500 ttgatttgtt actttttatt atttggtttt tatgaggcag ggtctgactt tgctgcccag 1560 ggtggtatgg aaatctggcc tcaagcgaac ctcccacctc agcctcccaa agtgctgaga 1620 ttataggcat tagccactgc acatggccat ggccaggttt gttgcttttt tttttttgga 1680 ggaggaggag gaggagtctc tgtcacccag gttggagtgc agtggcacca tctcagctca 1740 ctgcaacctc cacctcctgg tttcaagcag ttctcctgcc tcagcctccc aagtagctgg 1800 gactacaggc acatgccacc acgcccagct aatttttgta tttttactag agacgggctg 1860 ttcgccaggc tggtctagga ctcttgacct caggtgatcc acccaccttg gcctcccaaa 1920 gtgctgggct tacaggcata agccactgca cctggccatt ttgttgcttt tttgaaaagt 1980 gaacatattc tctcttttgt agcctgttga tgaactggga attcagtgtc atcattaata 2040 ttttacagtg ttagttaagt gtgaagatct ttcttttaaa aagctgtggt ttgatataat 2100 gacaacaaaa tggcaattga taaaaattag atattgaatc aatctttgat ttctataata 2160 ataccatagt aaaattaaaa gtgaacataa aaattaaaca tcataagcaa actgcattct 2220 ttgtgtgttt atgttttttg ttaaaatttg ttgtactccc tgttcaccag gtctgaagaa 2280 aaataaattt taaat 2295 <210> 41 <211> 2268 <212> DNA <213> homo sapiens <400> 41 aatatcttgc atgttacaga tttcactgct cccaccagct tggagacaac atgtggttct 60 tgacaactct gctcctttgg gttccagttg atgggcaagt ggacaccaca aaggcagtga 120 tcactttgca gcctccatgg gtcagcgtgt tccaagagga aaccgtaacc ttgcactgtg 180 aggtgctcca tctgcctggg agcagctcta cacagtggtt tctcaatggc acagccactc 240 agacctcgac ccccagctac agaatcacct ctgccagtgt caatgacagt ggtgaataca 300 ggtgccagag aggtctctca gggcgaagtg accccataca gctggaaatc cacagaggct 360 ggctactact gcaggtctcc agcagagtct tcacggaagg agaacctctg gccttgaggt 420 gtcatgcgtg gaaggataag ctggtgtaca atgtgcttta ctatcgaaat ggcaaagcct 480 ttaagttttt ccactggaat tctaacctca ccattctgaa aaccaacata agtcacaatg 540 gcacctacca ttgctcaggc atgggaaagc atcgctacac atcagcagga atatctgtca 600 ctgtgaaaga gctatttcca gctccagtgc tgaatgcatc tgtgacatcc ccactcctgg 660 aggggaatct ggtcaccctg agctgtgaaa caaagttgct cttgcagagg cctggtttgc 720 agctttactt ctccttctac atgggcagca agaccctgcg aggcaggaac acatcctctg 780 aataccaaat actaactgct agaagagaag actctgggtt atactggtgc gaggctgcca 840 cagaggatgg aaatgtcctt aagcgcagcc ctgagttgga gcttcaagtg cttggcctcc 900 agttaccaac tcctgtctgg tttcatgtcc ttttctatct ggcagtggga ataatgtttt 960 tagtgaacac tgttctctgg gtgacaatac gtaaagaact gaaaagaaag aaaaagtggg 1020 atttagaaat ctctttggat tctggtcatg agaagaaggt aatttccagc cttcaagaag 1080 acagacattt agaagaagag ctgaaatgtc aggaacaaaa agaagaacag ctgcaggaag 1140 gggtgcaccg gaaggagccc cagggggcca cgtagcagcg gctcagtggg tggccatcga 1200 tctggaccgt cccctgccca cttgctcccc gtgagcactg cgtacaaaca tccaaaagtt 1260 caacaacacc agaactgtgt gtctcatggt atgtaactct taaagcaaat aaatgaactg 1320 acttcaactg ggatacattt ggaaatgtgg tcatcaaaga tgacttgaaa tgaggcctac 1380 tctaaagaat tcttgaaaaa cttacaagtc aagcctagcc tgataatcct attacatagt 1440 ttgaaaaata gtattttatt tctcagaaca aggtaaaaag gtgagtgggt gcatatgtac 1500 agaagattaa gacagagaaa cagacagaaa gagacacaca cacagccagg agtgggtaga 1560 tttcagggag acaagaggga atagtataga caataaggaa ggaaatagta cttacaaatg 1620 actcctaagg gactgtgaga ctgagagggc tcacgcctct gtgttcagga tacttagttc 1680 atggcttttc tctttgactt tactaaaaga gaatgtctcc atacgcgttc taggcataca 1740 agggggtaac tcatgatgag aaatggatgt gttattcttg ccctctcttt tgaggctctc 1800 tcataacccc tctatttcta gagacaacaa aaatgctgcc agtcctaggc ccctgccctg 1860 taggaaggca gaatgtaact gttctgtttg tttaacgatt aagtccaaat ctccaagtgc 1920 ggcactgcaa agagacgctt caagtgggga gaagcggcga taccatagag tccagatctt 1980 gcctccagag atttgcttta ccttcctgat tttctggtta ctaattagct tcaggatacg 2040 ctgctctcat acttgggctg tagtttggag acaaaatatt ttcctgccac tgtgtaacat 2100 agctgaggta aaaactgaac tatgtaaatg actctactaa aagtttaggg aaaaaaaaca 2160 ggaggagtat gacacaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2220 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 2268 <210> 42 <211> 2069 <212> DNA <213> homo sapiens <400> 42 atgctgccgg actggaagag ctccttgatc ctcatggctt acatcatcat cttcctcact 60 ggcctccctg ccaacctcct ggccctgcgg gcctttgtgg ggcggatccg ccagccccag 120 cctgcacctg tgcacatcct cctgctgagc ctgacgctgg ccgacctcct cctgctgctg 180 ctgctgccct tcaagatcat cgaggctgcg tcgaacttcc gctggtacct gcccaaggtc 240 gtctgcgccc tcacgagttt tggcttctac agcagcatct actgcagcac gtggctcctg 300 gcgggcatca gcatcgagcg ctacctggga gtggctttcc ccgtgcagta caagctctcc 360 cgccggcctc tgtatggagt gattgcagct ctggtggcct gggttatgtc ctttggtcac 420 tgcaccatcg tgatcatcgt tcaatacttg aacacgactg agcaggtcag aagtggcaat 480 gaaattacct gctacgagaa cttcaccgat aaccagttgg acgtggtgct gcccgtgcgg 540 ctggagctgt gcctggtgct cttcttcatc cccatggcag tcaccatctt ctgctactgg 600 cgttttgtgt ggatcatgct ctcccagccc cttgtggggg cccagaggcg gcgccgagcc 660 gtggggctgg ctgtggtgac gctgctcaat ttcctggtgt gcttcggacc ttacaacgtg 720 tcccacctgg tggggtatca ccagagaaaa agcccctggt ggcggtcaat agccgtggtg 780 ttcagttcac tcaacgccag tctggacccc ctgctcttct atttctcttc ttcagtggtg 840 cgcagggcat ttgggagagg gctgcaggtg ctgcggaatc agggctcctc cctgttggga 900 cgcagaggca aagacacagc agaggggaca aatgaggaca ggggtgtggg tcaaggagaa 960 gggatgccaa gttcggactt cactacagag tagcagtttc cctggacctt cagaggtcgc 1020 ctgggttaca caggagctgg gaagcctggg agaggcggag caggaaggct cccatccaga 1080 ttcagaaatc cttagaccca gcccaggact gcgactttga aaaaaatgcc tttcaccagc 1140 ttggtatccc ttcctgactg aattgtccta ctcaaaggag cataagtcag agatgcacga 1200 agaagtagtt aggtatagaa gcacctgccg ggtgtggtgg ctcatgccta taatcccaga 1260 actttgggag gctgaggcag gtggatcact tgaggtcggg agattgagaa catcctggtc 1320 aacatgggaa aaccccgtct ctactaaaaa tacaaaaaaa ttagctgggc atggtggcac 1380 atgcctataa tcccagctac tctggaggct gaggcaggag aatccttgaa cccgggagtt 1440 ggaggttgca gtgagctgag atcacgccac tgcactccag cctagcgaca gagcaagact 1500 ccatttaaaa aaaaaaaaaa aaaaaaaaag aagcaccttc aggctggaga agcagcgtag 1560 ctaacacaag tccagtcctt gtgatgtggc tggtagttgg ggatggccag gctgaagcag 1620 agagtcctag agaaatctcg atacaagctt caaagcaaca cctagacact gctctagcgg 1680 ttgatcctgg agataaacca acaagagaga gatggaagag aaatactaaa tgaggtcaaa 1740 gaagactcag aaaggttctg agcctggaga tgagcaggga ggcctcaggg cttagacctt 1800 taatgatagg ggtttccctg cattggtttg acctgttgcc tttttgatgt gctctgtttg 1860 ttttcatgtg ttgtcttgtc tcccctgcta aactgggagc tgccaggggt ctgggtctta 1920 tctccttcct ccatggtacc ccacacaggc caggatgtgg tttggtaccc agcaatcaga 1980 gattggcact ccctcataca ggggaaagca acctggtcta gcaaattgaa aataaagatg 2040 ataaaactct gaaaaaaaaa aaaaaaaaa 2069 <210> 43 <211> 6174 <212> DNA <213> homo sapiens <400> 43 agtgctgctg gccgggagtt gctctcaccg cagctggaaa cagctgcccc cgccccgcgc 60 ccctacccag actccgggta accgctccca cttcgcgcct ctcggaattc cagaactcgg 120 gtggccggcc cctggaaagc cgcagccggc gcgatgcatt ctgtagacct caccctgctg 180 ggacggacct cctaatcttc agaaccgcgg gccgcaggga gttaaattgc tgccttcctc 240 tccttctctc gtgcggttgg tggcttgttt tctaaaggaa cgttttattc actttttagt 300 attttctacc gggggcgcgc tacccgcctg ggtccagact ctgctttgta aacgggtttt 360 ctatgtatgt atgtgtaggt atactttgga caccttacaa cgcttgcgcc tctccaacag 420 aggcacgtct tgttattttg ggcatcgttc ttccccttcc acttggtacc ccgaacgcag 480 tgtgactaaa ctccccactg ccccttggac gccgatcgcc ttggggtgca agtttggggt 540 gcaaacgtct acttcgcaag agggcctggg accgccccgc cccgcccccc ggccgccaga 600 ggttggggaa gtttacatct ggattttcac acattttgtc gccactgccc agactttgac 660 taaccttgtg agcgccgggt tttcgatact gcagcctcct caaattttag cactgcctcc 720 ccgcgactgc cctttccctg gccgcccagg tcctgccctc gccccggcgg agcgcaagcc 780 ggagggcgca gtagaggctg gggcctgagg ccctcgctga gcagctatgg ctgcggcgat 840 agccagctcc ttgatccggc agaagcggca ggcgagggag tccaacagcg accgagtgtc 900 ggcctccaag cgccgctcca gccccagcaa agacgggcgc tccctgtgcg agaggcacgt 960 cctcggggtg ttcagcaaag tgcgcttctg cagcggccgc aagaggccgg tgaggcggag 1020 accagaaccc cagctcaaag ggattgtgac aaggttattc agccagcagg gatacttcct 1080 gcagatgcac ccagatggta ccattgatgg gaccaaggac gaaaacagcg actacactct 1140 cttcaatcta attcccgtgg gcctgcgtgt agtggccatc caaggagtga aggctagcct 1200 ctatgtggcc atgaatggtg aaggctatct ctacagttca gatgttttca ctccagaatg 1260 caaattcaag gaatctgtgt ttgaaaacta ctatgtgatc tattcttcca cactgtaccg 1320 ccagcaagaa tcaggccgag cttggtttct gggactcaat aaagaaggtc aaattatgaa 1380 ggggaacaga gtgaagaaaa ccaagccctc atcacatttt gtaccgaaac ctattgaagt 1440 gtgtatgtac agagaaccat cgctacatga aattggagaa aaacaagggc gttcaaggaa 1500 aagttctgga acaccaacca tgaatggagg caaagttgtg aatcaagatt caacatagct 1560 gagaactctc cccttcttcc ctctctcatc ccttcccctt cccttccttc ccatttaccc 1620 atttccttcc agtaaatcca cccaaggaga ggaaaataaa atgacaacgc aagacctagt 1680 ggctaagatt ctgcactcaa aatcttcctt tgtgtaggac aagaaaattg aaccaaagct 1740 tgcttgttgc aatgtggtag aaaattcacg tgcacaaaga ttagcacact taaaagcaaa 1800 ggaaaaaata aatcagaact ccataaatat taaattaaac tgtattgtta ttagtagaag 1860 gctaattgta atgaagacat taataaagat gaaataaact tattacttta aaggaaagga 1920 tttggagaat tgaactcaca aactgatgtt atatactcaa tagcttaaac tcatgataat 1980 gctgcgatgt gtggttttgc ttgattttgt attttatttg ggcatctgga attgacacac 2040 cattacattc tgtttgcagg attttttttg taaccatgaa attgaacatt tccaaattat 2100 aaactatgtt aatacctata aaatatatag ccaggaacca tttatcatca agaaaagtgt 2160 aagaaattat ttttgagatg taatttaaga ttgttttatg taaaaggaaa atcttgtatg 2220 gcatcgaata gccttaatga gtttaattct ttcacaaaaa tgatttcaaa ttatcctaga 2280 gtataacatt tttatcaaag atattatttc cggagttctt ctttctttct tttttttttt 2340 tttttagtaa tttagcaaaa acattactgt tctaatgctg aagtgacttt tgccagtgcc 2400 atgtccaggt ggtgaggtat aagttacttg ctcttagcat ttggtctgat ttttttgctt 2460 tgtggacacc tttgagagta tccacaaagc aatgtctcag gtgtggacac ctgagagcat 2520 gttttagaaa gctttgtacc ctgtcttgtg gcaggaaaga aagaacaggg gttttacata 2580 aggaaataag tcctaggaaa ttagtcaacg caaattgcat ttgcgtttgt accttaccac 2640 agtcttatat tgttttttaa actctgccat gaaatttgga gacatgactg tgaaattcct 2700 aacttactat cttacaaagc cagtagctaa tttgttgctc tatgtatgat cctgttacaa 2760 gtccagtttg caattcattt gtttcctaga acacagaagg gtaccagtaa tacactaaat 2820 tttcaaggtg tgtagagaaa taatatggaa ttagcagcta tgactccaac agacaggatt 2880 gtgtgagcag ctgaaaggag caaaaaagaa ctcagtgtaa gagaaggcac atacatagtt 2940 aagaatacta aagtattttt aaaaatcaag gaagaaataa atgttacaca atttgcattg 3000 gaataaatag atctatttag tcctacaaat caggagtggt gtagagacat ccaaatttaa 3060 agaaaaaaaa acacaaaaca gaatgttaaa aaatgtatgc agatttatgg atattatcaa 3120 tgagaagaca tagcatgtaa cttctcctat atctctactg tccagcatgt attgttccaa 3180 atatgactcc ctaaaatata tacactttgc agaagctcta ggccctcacc tcaaaccttg 3240 ccattggttg ccgtatttca aggtcaatat agtttccctc actttacaca atcattattc 3300 ttcaatagtg gaccatatcc ttcaccaggt atcctatttc tgttatctag aggttagcag 3360 aaaatgaaat gaaggaattt ccctaagcag ttgggaagaa caaattgtat gcatgtaggc 3420 aaagattttg aagatacatt tgcaagagat atttgtttaa ccaaaatatt tggaaagtaa 3480 caaataaaga catttaaatt ttctaaaaat ggacttgctc ttctaggaaa agaatacccc 3540 tggggcaaaa atataactct agctgtattt cttcttgtca ctcttgattc aacttgatta 3600 taaatacacc tgtcactacc agaaccaaaa aaaaaaagaa aaaaatccca agcacaaagc 3660 ttattttatt tgaaaaaaat aaaaaagaaa cttcaacact atgggacact ggctctttta 3720 gcatgaaatg acttgagctt ttgtagtgat gatacacata cacactcatc agtaaaacga 3780 tggtttcata aataacacaa ttgatgcaaa tcataaaaat caattacaat tatgatttca 3840 tgacaaaata tatttaatta agtttgttat gaaaaaaata gagatatgaa tcactaacaa 3900 aattcctcca ttttcagtgg ctattcatca tttatcatct agactcacat ttgtctcctt 3960 cctgatagca gttaagaaaa aattctaacc acacaatttg tatattgttt ttctccgtat 4020 tatgttaagc aaatgttcac tgcagtaaaa tgttttggaa attagctttg tcttatttcc 4080 agtttagttc agagaattaa ttggaaacct gatttctttt acacataaac ctgacaaaaa 4140 atgtagctta gagcaaaggg tgaatgtttg cttaactcct gcttacttct caagtacatg 4200 aaaactttaa tagaatatgc cagtattcac tgagttttta aaaatattac catgtgtaaa 4260 catataatat ccaacttcat ccaaaaatat ggttgagttt aagtactttg tttttcaggc 4320 ttatttcaag tataataatt ctttgatttt cattgttctg atttctgggt cttcaattca 4380 ttcgtcactt ttccttttta agtaaaataa gctttttttt tttttttttt ttttttttgg 4440 agttgcattg ggatttttcc caggaaaaaa tatggctttt agtaatgctt tgcaattggc 4500 tacgcagata taaattaaga tatgtttatt ctgagttctt attggaataa gtttcaaaat 4560 caacgagctt aagaatgaaa acaaaacttt tgagagtctc acaaaatagc tttctggtca 4620 atacacctta cttgattttt aagctcgcag aataaagtat agaaacaaat ggagctgaag 4680 ttccatttgc taattcagag acttttgtgc ttccgcaaat tggagggcag caagccatcc 4740 tattctcata gtaatcgttt tggctttgaa atttacatac aatttaatag cacattttta 4800 gccattatgg attggcgcaa taaagagata tcaatgtaat gcaatgtgat gctttatggg 4860 cctcattcta attcagaaag cttgtttaaa agaactaaga ctcttctgtt taataaaata 4920 gcaacaatct aatatctaga ttggtagtcc tgcggtgcca ctagtgggag atgagagtat 4980 taagacaaga gtaaggacaa ggaaagactt aaaggttgca tattgaaaag tttggaattc 5040 ctaatttggg agcactgatt tcttggtgaa gaagtaagta tgactacgtt gccagtaatt 5100 ttttaaaaac atagacccag aaatagcaaa tcgatttcac cctcatacct tagtctacaa 5160 ggccttgctc ttgagaaggt tttccatgat attgcttaat ttcatctgca caagatgaga 5220 cacaaacata aaaattccct gctcatttta ataccataaa aggctgaggt tatttctctg 5280 tcataaaatt gtaaatagca ttttttaagt caaaattaca tttaaaacag tggattgttc 5340 tacaaatata tatgtgtata tatacatatg cttctgaaat aaggatatat tatatgagtt 5400 tttatttgat ttgtggtctt tagtcatagg taatcaaaaa taaagagatt tgaatgcaaa 5460 actttataca ttaatgtaca tttctaatga tggtacaaat tgccacttta taataaaaaa 5520 gaaacaggtg ggaataataa tcaaagcacg tgttccttca gtactttggt gatttttaat 5580 cccccttgtg atgcacagga aattattttt tagttacaaa aagttatctt agaaatctat 5640 acttcccaat acagatttca tgttaagtca tatcaaattg agaatttgtg gtgaaagaat 5700 aggaaaagga tgctagatgc tgatctttct ttttcaggat ttttcctgga gcccaagtta 5760 aaaattcaat acttaaatct aagttaagtg aaaattaata atgttcagaa tgatgtattg 5820 agctttagta acagacggaa gcaaaaaaaa ataagaatat ttaacattat gataatagcc 5880 ttaaaataat gtaataaaaa ttgcatcatt aaatgttcta ttagttggaa agaatgagct 5940 gatgtttctt tgtctttgct ccaagtacaa tttaaagaca gtgacattca ttttacttaa 6000 aattgttcaa aaagtccaaa acatactccc atggctagaa ttggtattag ctccaataca 6060 aggttaaatg ttacaatctt aagaaattat tgacactgaa atgtttagta aacatgttgt 6120 atgagaaact aaacaaatta atgtttcatt tttccattaa agcacagatt attc 6174 <210> 44 <211> 2162 <212> DNA <213> homo sapiens <400> 44 cttcacctgg ggattgcaaa ggaagtgaga acatccccga gcaagaccaa aaattgctga 60 ataaacacaa acccccttga gaatcacgcc aagaggtgct gcctcttcac ctggggattg 120 caaagcctca ccgccatgga cagcgtgccc ctcatctgtg actacggctc tggcttcagc 180 aaggtgggat ttgcaggaat ggaaagccca atgggcatgt tccccactgt cctcgggaaa 240 cttcggcacg atgtgagtga tgtcggggtc tcttccctgt ggggtgctgc tcatccagag 300 gtggcctgct ggcccggtca accccatccc ctctgccaca gggcggccaa ggcaatctgc 360 tgagcggggc gtggtgggtg cgaacttgcc tccacaaatc caagtcggga gcacctggct 420 tgataacata cagatggccg ggccacctag agtctctgcc tcagctggtc gggggtggga 480 gatggggtgg gcaaggcctt gcccctctca ccactcccag catgcggccc actctgagag 540 ccgcaggctt agagagagca gcgatgtgta aatcagtaaa gtggatgcat tgtgaaaaat 600 cagtcttact gcccgtctcc catctctggc tcttctcaca ttcagagagg tatggacaca 660 gagaaggagc aatttgcctt tagggtaaac gggagtccat tagggtgagt ggcaatggac 720 actcagcctc cgtgatagga aggcagtagg agggcaggtg gggaccggga cacaggccct 780 ccaagaggcc catctctgac atgccagcaa gtggatccca catcgccaga tcttcctgtg 840 tttcaaggga atttagaaac acaggtgttt ctattgtggt aaagtataca cagtgtaaag 900 ctgtgttaac tgcacagttc agtggcatca agaacattca ccaccatcta tctccagaac 960 gttctcatcc tcccaaacgg aagctctggc cccattaaaa accaactgct catccccctc 1020 ccccggacaa cacagtcgcg tcataactga aactgggcga gtgggtctga gcctggctgc 1080 atgccaggta gggacagaga tgcctcttct cccggaagag gaaccacctg ctccgagagg 1140 tgacttctcg aatccacatg gtgacaaagt ggtgggggca agacccccca gtgcaactgc 1200 gttcccagct catgctctgg atcatggagc tcatcctctg gaagttccaa tcgtccgtgg 1260 tagggagcag cgtcgtgacg tggaagatct cagatgtcgc aggacctcat ggcgatcact 1320 cttgctcttt gcagcacttg gagcaaatta ttggcagtgt ttctaattat ccaagataca 1380 ctggctcccg gagctgtgac agaggagaaa atcccgtctc cctctctaag aggataaaat 1440 gcacatggat gctgggagcc agtggatttc ctcctcgttg tccaagtggc agggatcata 1500 gcagggacca ccctggcaaa tcgcaggtgc ctgcactcga gctagccaac cagcttgctg 1560 cttggggatt atggagctca gtggttaaga gctggggctt cagggccggg gagactgagg 1620 ctccaatctc agccctgtcc tcagcacatg catgactcag cgcaagggtg ctgctgtggc 1680 agaggcatct cttttgcata atgtgattgt ccaaagtatg tatctcagag attcggcctg 1740 aaggttaaat gagatgagtg aatgtatgtt tggtgcagtt tctggaccat agggagtgtt 1800 tagcaatgat gacgatagca gtgatgataa caatgactag tatattcgtg tattcgctta 1860 gaacaacaga aatgtggcca tgtgcggtgg gtcacgcctg taatcccagc actttgggag 1920 gccgaggtgg gtggatcacc tgaggtcagg agtttgagac cagcctggcc aacatggcaa 1980 aaccccgtct ctactaaaaa tacaaaaatt agctgggcgt ggtggcacac gcctgtaatt 2040 ccagctactc tggaggctga ggcaggagaa tcgcttgaac ccgggaggca gagggtgcag 2100 tgagctgaga tcgcgccact gcactccacc tgggcgacag agtgagactt catctcaaaa 2160 ac 2162 <210> 45 <211> 3007 <212> DNA <213> homo sapiens <400> 45 gatacagcag cagctggtgc tcctggccag gctgtgcgtg ctctctctgc ctctctctct 60 cggactctct gctctctctc tctgactctc tcctctctct ctgttggcct ggtgaaatgt 120 tcttggctgt aggcacacag agccttggac tcaaggctgt tggagtcgag gacaccttga 180 cttcggtcct ggaggttgaa attctgcctc tgagaagcta acagtcttcc tgtggtcgcc 240 actcctcccc agcagccccc tccttgccaa ggacggtcca gaaggagccc cactggggcc 300 tccccgctca gcaaagcaga cctcacctcc cactaccagc ttgaagtcac agcagccaga 360 ggaaattctg ccaccatttt cccaggtctg cagcccctcc agctgggaac ctgctcctgg 420 agccatccct ctgcaaacag agagcccaga gtgcctcggg gaaaattggc tgaataaaag 480 agcgatcagg acgccacggc tccgcctgaa gcgatggccc agccctaccc ccccgcccag 540 tacccccctc cgccacagaa cggcatccct gccgagtacg ccccgccccc accgcacccc 600 acgcaggact actccggcca gaccccggtc cccacagagc atggcatgac cctgtacaca 660 ccagcacaga cccaccccga gcagccaggc tccgaggcca gcacacagcc catcgccggg 720 acccagacag tgccgcagac agacgaggcg gcacagacgg acagccagcc gctccacccc 780 tccgacccta cagagaagca gcagcccaag cggctacacg tctccaacat ccccttccgg 840 ttcagggacc ccgacttgcg gcaaatgttc gggcaattcg gaaaaatttt agacgtggag 900 atcattttta acgagcgggg ctccaagggt tttgggtttg taacttttga aactagctca 960 gatgctgacc gagcccggga gaagctgaat gggacgatcg tagagggacg gaaaattgag 1020 gtcaataatg ccacggcccg agtgatgacc aacaagaaga cggggaaccc ctacaccaac 1080 ggctggaagc taaatccagt ggtcggcgca gtctacgggc ctgaattcta tgcagtgacg 1140 gggttcccct accccaccac cggcacagcc gttgcctacc ggggcgcaca tcttcggggc 1200 cggggccggg ccgtgtataa tacatttcgg gctgcgccac ccccaccccc catcccgact 1260 tacggagcgg tcgtgtatca ggatggattt tatggtgctg agatttatgg aggctacgca 1320 gcctacagat acgctcagcc cgctgcagcg gcggcagcct acagcgacag ttacggcaga 1380 gtctacgcag ctgccgaccc gtaccatcac accatcgggc ccgcggcgac ctacagcatt 1440 ggaaccatgt gaaaccttcc accgtttcct tctcggacca tgaagggcaa aaacaaaaaa 1500 acaaaaaaaa tcacaaaaca aaaaaaacaa aaaaagatgt taagatccaa gcaacaaaaa 1560 aaaaaccaac caaaccaaga ggcatccaac caagtccaag tcccgcgtcc tggccacacg 1620 cccgcaccga gggagcacgc cggcaggggc gccgaggagc ggccccagga caggacggcc 1680 ccaccgcgtc ctggctggca gcacagtggg aacacgcccc tccgtctcag gcagtggggg 1740 agttggaggg gaaggggcct cccttgtggg acccgtgggg ggctctgttt tccatccagt 1800 cttcctttcc cagcccccaa ctcccaagac agacagtgtg gagcccagcg gcggcggagc 1860 aggcccgggc ctgagcaggc aggcgctgct agcaagactt gatctttgtg gccagctgtg 1920 ccagggggcc ggcggggctg aggggtgcgg gcagctttca tcccaggggc tccactgggc 1980 cccgtcaccc tcctgtcgcg tcccctgcgt cccacctccc tcctgcccgg cagtcccgcc 2040 cgtgccccca gcctggcgag gaagccgtcc aacagtagcc ccggggccag ctcccaacag 2100 aaagggctga cgtggctcca ggactcaggg gcgctccatg ggaggacgaa ggaagcccag 2160 ccagccagga gccactcctc acacctccaa gtgtggccaa gtgggccctg aggccaagga 2220 cttacttgct cttcctggcc atctctccct ttctggagga ggcccggggc ctgtgtacac 2280 caaggctgac ctcgtgctgc ctgctgggac ccagccctcc ctgccgctcc cctgtgagcc 2340 cagtccaccg tgggcgccca gggccaggga cgggccagcg cccggctgca tcgcgaggtt 2400 gggagtcaca gtggctgtgg gcctggacgg gcacagccag agcaggggcc catgggaagg 2460 gcaagggatg gggaagcctg ggccggcccc ttccctgctc ccaaggcagg tgtccaggtg 2520 gcgggagcag caccaaggac agccaggctt acccggtggg aggagcagga gcagagcagg 2580 tggcagggag gaacccctgg cgaggcaggg agcactgaag tagggaagca gcaaaaaata 2640 caggctccca acgtggctcc actgtctcat gaagtgtcaa aaatttaaaa atacacctca 2700 ctttctattc agcatcagct attgaaatgg aattctcctt ttctattccc gttgtacata 2760 gccccacgcc ctgcctccgg ctttgtcctc tgtacagagc cccctgtccc ctctgctgtt 2820 ccggaccctt ttcttgcagc agctcaaccc cccgactcac tcagatcccc aggactgcag 2880 ccgagccccg ggcttccttt cttaccattc tgtatgcttc caaggtgtga ccattcaaac 2940 taacagtatt attaagatta ttaataaaga tttctttctt caaaccagga aaaaaaaaaa 3000 aaaaaaa 3007 <210> 46 <211> 2509 <212> DNA <213> homo sapiens <400> 46 cattgaggca atttcttccc taatctattc ctttgtgctg aactttttta agtttgacac 60 tctagatatc cgtctgcctc aagcaaaaca gttgacagaa acccatgaac ccatcatgcc 120 ctgattcata ggaagtaatt actaataatc ctaattctgg ttcatagttt gcttgtcagt 180 aattacagct gcagttgaat gctttcagca ttaaccatca acccagagtt gcagatccct 240 cctcatctca gggaaatgga acttctcaca tatcacagac aacttggagg aagctcagct 300 ggaccagaag agccagaaat cgggagcatg caatggcaga tcatcagggc aaggccactc 360 accagcaggg aggcccagtg aatgcagagc aggtggcaac aggaaagact ggaggccagt 420 ctgataggaa ggcaaacacc agcaagaggc aattccggga tcatttatgg gaaaccgagg 480 catggtctgc agaggcaacc gcccccccca ccgtcacttc cagagagatg aacggaaacc 540 tgatctctga gaacccaatc ttctcaacaa gttgtcaaca tgctaataag catagtgtct 600 tactctgtag caggtacttt tactttatgt gttattaact ctccatcttc tcaacaatca 660 tatcaagcaa gtgctacttc tatccccgat gtatgtataa atttgtccaa ccatgtagct 720 cataagtaaa ttaactgtaa tttccaaacc tagatacacc gaccctagaa actacactct 780 cactactttc ctacccacca acacctctta aagttgaggt gagaactaag taacaagcac 840 ttatgagctg caaatttcag tggaaagcac tagtccaagc atttgtttga aaccccccac 900 acaatttgta caacaaccct atgagatagt gtgtccgtca gcatttggtc acaaaaacaa 960 aaggtatttt gcatgttcta agtatccaca gttctaatgc aggaaattag aggtttgcag 1020 tcttttggaa agacttagca atgaattcag ggaagccacc aggacctttc tgcctgctgc 1080 tgtatctatg caagtgggag tcgacactca cccagaggcc actgaacacc ttaagggcct 1140 ctgggagggt ctctctggct tctcagccag cattcctgag ataggtgatt cttaggctta 1200 cctgaaagcc attataaatc tgttatctac ctgcccacac acttgcctgc aaccaactcc 1260 cttaaaacat aatggctgct acttctctca ttttaggaaa atctcaccca agtccctctc 1320 cttggcagac tctacacaaa gccatacaca aaaagatgtt ctaagaacca tagttattgg 1380 cttctccaca gtacagggga gacttagaag gcagtaaaga tgcatcaagt tgagaacaaa 1440 tgatctggta gaattaggta gaattcatat acccatttta cagttgatga aactgaggca 1500 gaggcacaaa gcagttaatc aatttacgcc taatcacata actttagtaa atgataaagc 1560 catgattcaa atgtagaggg actggctcca taatctatgc tcttgccatt gcatgagatt 1620 gttttcatgg aagacttaac tcagcacagt ttggcacacc cgttagtgct acactcattg 1680 tggtggctgg gttttattct tattgataca tttcttgtgt tactatattt gtttttctca 1740 taattagcac aactgggatt gctcagccaa tacccatgga atgttgaata cccccaccca 1800 cagtctgccc catatctcaa ggcaacctag acaggttttc ttcctctaat gaattatcat 1860 tatgacttag tccaagattt ctaaataatt accagttcca aaaaaccagc atcctgagta 1920 tccacagata tgtgcatgaa tacaagcata catgcacaca catatgcacg cacacacaca 1980 cactcagtct ttatgagcag caacgtaact gtatttcaat ggatgcgatt gatgagggca 2040 agttccagga gcttcaccca ggcaatcccg gctggccaat tattgcagac agcctgctcc 2100 cacctattca ccacacagaa cacatgtcaa aatgcactcg gaaacaacac taggctgcag 2160 cacactgaga aggtgaggct gagcatcgga cttgctgact ttgggctgcc cggcattgcc 2220 cggaacacgt ttgtggtccc tgattccatc tctagatact gcagggaagg ctctgtaatt 2280 ggaaaatgct gcccaagcag aaagtctgcc ttgcttaata aacagggctc tctgaagaag 2340 ttcaaaatta ccagaggaga aacacagcct agtgttacca tcagtgttct agaactggct 2400 gaaattgatc aaaggtttta gctgcgatct ttctcctaca gctcatttaa ccatgcaatt 2460 aggcagttaa gtagatgcaa aatatttaaa attaaagatg cttctcatc 2509 <210> 47 <211> 8742 <212> DNA <213> homo sapiens <400> 47 acgcccgcgc cggctgtgct gcacaggggg aggagaggga accccaggcg cgagcgggaa 60 gaggggacct gcagccacaa cttctctggt cctctgcatc ccttctgtcc ctccacccgt 120 ccccttcccc accctctggc ccccaccttc ttggaggcga caacccccgg gaggcattag 180 aagggatttt tcccgcaggt tgcgaaggga agcaaacttg gtggcaactt gcctcccggt 240 gcgggcgtct ctcccccacc gtctcaacat gcttaggggt ccggggcccg ggctgctgct 300 gctggccgtc cagtgcctgg ggacagcggt gccctccacg ggagcctcga agagcaagag 360 gcaggctcag caaatggttc agccccagtc cccggtggct gtcagtcaaa gcaagcccgg 420 ttgttatgac aatggaaaac actatcagat aaatcaacag tgggagcgga cctacctagg 480 caatgcgttg gtttgtactt gttatggagg aagccgaggt tttaactgcg agagtaaacc 540 tgaagctgaa gagacttgct ttgacaagta cactgggaac acttaccgag tgggtgacac 600 ttatgagcgt cctaaagact ccatgatctg ggactgtacc tgcatcgggg ctgggcgagg 660 gagaataagc tgtaccatcg caaaccgctg ccatgaaggg ggtcagtcct acaagattgg 720 tgacacctgg aggagaccac atgagactgg tggttacatg ttagagtgtg tgtgtcttgg 780 taatggaaaa ggagaatgga cctgcaagcc catagctgag aagtgttttg atcatgctgc 840 tgggacttcc tatgtggtcg gagaaacgtg ggagaagccc taccaaggct ggatgatggt 900 agattgtact tgcctgggag aaggcagcgg acgcatcact tgcacttcta gaaatagatg 960 caacgatcag gacacaagga catcctatag aattggagac acctggagca agaaggataa 1020 tcgaggaaac ctgctccagt gcatctgcac aggcaacggc cgaggagagt ggaagtgtga 1080 gaggcacacc tctgtgcaga ccacatcgag cggatctggc cccttcaccg atgttcgtgc 1140 agctgtttac caaccgcagc ctcaccccca gcctcctccc tatggccact gtgtcacaga 1200 cagtggtgtg gtctactctg tggggatgca gtggctgaag acacaaggaa ataagcaaat 1260 gctttgcacg tgcctgggca acggagtcag ctgccaagag acagctgtaa cccagactta 1320 cggtggcaac tcaaatggag agccatgtgt cttaccattc acctacaatg gcaggacgtt 1380 ctactcctgc accacagaag ggcgacagga cggacatctt tggtgcagca caacttcgaa 1440 ttatgagcag gaccagaaat actctttctg cacagaccac actgttttgg ttcagactcg 1500 aggaggaaat tccaatggtg ccttgtgcca cttccccttc ctatacaaca accacaatta 1560 cactgattgc acttctgagg gcagaagaga caacatgaag tggtgtggga ccacacagaa 1620 ctatgatgcc gaccagaagt ttgggttctg ccccatggct gcccacgagg aaatctgcac 1680 aaccaatgaa ggggtcatgt accgcattgg agatcagtgg gataagcagc atgacatggg 1740 tcacatgatg aggtgcacgt gtgttgggaa tggtcgtggg gaatggacat gcattgccta 1800 ctcgcagctt cgagatcagt gcattgttga tgacatcact tacaatgtga acgacacatt 1860 ccacaagcgt catgaagagg ggcacatgct gaactgtaca tgcttcggtc agggtcgggg 1920 caggtggaag tgtgatcccg tcgaccaatg ccaggattca gagactggga cgttttatca 1980 aattggagat tcatgggaga agtatgtgca tggtgtcaga taccagtgct actgctatgg 2040 ccgtggcatt ggggagtggc attgccaacc tttacagacc tatccaagct caagtggtcc 2100 tgtcgaagta tttatcactg agactccgag tcagcccaac tcccacccca tccagtggaa 2160 tgcaccacag ccatctcaca tttccaagta cattctcagg tggagaccta aaaattctgt 2220 aggccgttgg aaggaagcta ccataccagg ccacttaaac tcctacacca tcaaaggcct 2280 gaagcctggt gtggtatacg agggccagct catcagcatc cagcagtacg gccaccaaga 2340 agtgactcgc tttgacttca ccaccaccag caccagcaca cctgtgacca gcaacaccgt 2400 gacaggagag acgactccct tttctcctct tgtggccact tctgaatctg tgaccgaaat 2460 cacagccagt agctttgtgg tctcctgggt ctcagcttcc gacaccgtgt cgggattccg 2520 ggtggaatat gagctgagtg aggagggaga tgagccacag tacctggatc ttccaagcac 2580 agccacttct gtgaacatcc ctgacctgct tcctggccga aaatacattg taaatgtcta 2640 tcagatatct gaggatgggg agcagagttt gatcctgtct acttcacaaa caacagcgcc 2700 tgatgcccct cctgacccga ctgtggacca agttgatgac acctcaattg ttgttcgctg 2760 gagcagaccc caggctccca tcacagggta cagaatagtc tattcgccat cagtagaagg 2820 tagcagcaca gaactcaacc ttcctgaaac tgcaaactcc gtcaccctca gtgacttgca 2880 acctggtgtt cagtataaca tcactatcta tgctgtggaa gaaaatcaag aaagtacacc 2940 tgttgtcatt caacaagaaa ccactggcac cccacgctca gatacagtgc cctctcccag 3000 ggacctgcag tttgtggaag tgacagacgt gaaggtcacc atcatgtgga caccgcctga 3060 gagtgcagtg accggctacc gtgtggatgt gatccccgtc aacctgcctg gcgagcacgg 3120 gcagaggctg cccatcagca ggaacacctt tgcagaagtc accgggctgt cccctggggt 3180 cacctattac ttcaaagtct ttgcagtgag ccatgggagg gagagcaagc ctctgactgc 3240 tcaacagaca accaaactgg atgctcccac taacctccag tttgtcaatg aaactgattc 3300 tactgtcctg gtgagatgga ctccacctcg ggcccagata acaggatacc gactgaccgt 3360 gggccttacc cgaagaggac agcccaggca gtacaatgtg ggtccctctg tctccaagta 3420 cccactgagg aatctgcagc ctgcatctga gtacaccgta tccctcgtgg ccataaaggg 3480 caaccaagag agccccaaag ccactggagt ctttaccaca ctgcagcctg ggagctctat 3540 tccaccttac aacaccgagg tgactgagac caccattgtg atcacatgga cgcctgctcc 3600 aagaattggt tttaagctgg gtgtacgacc aagccaggga ggagaggcac cacgagaagt 3660 gacttcagac tcaggaagca tcgttgtgtc cggcttgact ccaggagtag aatacgtcta 3720 caccatccaa gtcctgagag atggacagga aagagatgcg ccaattgtaa acaaagtggt 3780 gacaccattg tctccaccaa caaacttgca tctggaggca aaccctgaca ctggagtgct 3840 cacagtctcc tgggagagga gcaccacccc agacattact ggttatagaa ttaccacaac 3900 ccctacaaac ggccagcagg gaaattcttt ggaagaagtg gtccatgctg atcagagctc 3960 ctgcactttt gataacctga gtcccggcct ggagtacaat gtcagtgttt acactgtcaa 4020 ggatgacaag gaaagtgtcc ctatctctga taccatcatc ccagaggtgc cccaactcac 4080 tgacctaagc tttgttgata taaccgattc aagcatcggc ctgaggtgga ccccgctaaa 4140 ctcttccacc attattgggt accgcatcac agtagttgcg gcaggagaag gtatccctat 4200 ttttgaagat tttgtggact cctcagtagg atactacaca gtcacagggc tggagccggg 4260 cattgactat gatatcagcg ttatcactct cattaatggc ggcgagagtg cccctactac 4320 actgacacaa caaacggctg ttcctcctcc cactgacctg cgattcacca acattggtcc 4380 agacaccatg cgtgtcacct gggctccacc cccatccatt gatttaacca acttcctggt 4440 gcgttactca cctgtgaaaa atgaggaaga tgttgcagag ttgtcaattt ctccttcaga 4500 caatgcagtg gtcttaacaa atctcctgcc tggtacagaa tatgtagtga gtgtctccag 4560 tgtctacgaa caacatgaga gcacacctct tagaggaaga cagaaaacag gtcttgattc 4620 cccaactggc attgactttt ctgatattac tgccaactct tttactgtgc actggattgc 4680 tcctcgagcc accatcactg gctacaggat ccgccatcat cccgagcact tcagtgggag 4740 acctcgagaa gatcgggtgc cccactctcg gaattccatc accctcacca acctcactcc 4800 aggcacagag tatgtggtca gcatcgttgc tcttaatggc agagaggaaa gtcccttatt 4860 gattggccaa caatcaacag tttctgatgt tccgagggac ctggaagttg ttgctgcgac 4920 ccccaccagc ctactgatca gctgggatgc tcctgctgtc acagtgagat attacaggat 4980 cacttacgga gagacaggag gaaatagccc tgtccaggag ttcactgtgc ctgggagcaa 5040 gtctacagct accatcagcg gccttaaacc tggagttgat tataccatca ctgtgtatgc 5100 tgtcactggc cgtggagaca gccccgcaag cagcaagcca atttccatta attaccgaac 5160 agaaattgac aaaccatccc agatgcaagt gaccgatgtt caggacaaca gcattagtgt 5220 caagtggctg ccttcaagtt cccctgttac tggttacaga gtaaccacca ctcccaaaaa 5280 tggaccagga ccaacaaaaa ctaaaactgc aggtccagat caaacagaaa tgactattga 5340 aggcttgcag cccacagtgg agtatgtggt tagtgtctat gctcagaatc caagcggaga 5400 gagtcagcct ctggttcaga ctgcagtaac caacattgat cgccctaaag gactggcatt 5460 cactgatgtg gatgtcgatt ccatcaaaat tgcttgggaa agcccacagg ggcaagtttc 5520 caggtacagg gtgacctact cgagccctga ggatggaatc catgagctat tccctgcacc 5580 tgatggtgaa gaagacactg cagagctgca aggcctcaga ccgggttctg agtacacagt 5640 cagtgtggtt gccttgcacg atgatatgga gagccagccc ctgattggaa cccagtccac 5700 agctattcct gcaccaactg acctgaagtt cactcaggtc acacccacaa gcctgagcgc 5760 ccagtggaca ccacccaatg ttcagctcac tggatatcga gtgcgggtga cccccaagga 5820 gaagaccgga ccaatgaaag aaatcaacct tgctcctgac agctcatccg tggttgtatc 5880 aggacttatg gtggccacca aatatgaagt gagtgtctat gctcttaagg acactttgac 5940 aagcagacca gctcagggag ttgtcaccac tctggagaat gtcagcccac caagaagggc 6000 tcgtgtgaca gatgctactg agaccaccat caccattagc tggagaacca agactgagac 6060 gatcactggc ttccaagttg atgccgttcc agccaatggc cagactccaa tccagagaac 6120 catcaagcca gatgtcagaa gctacaccat cacaggttta caaccaggca ctgactacaa 6180 gatctacctg tacaccttga atgacaatgc tcggagctcc cctgtggtca tcgacgcctc 6240 cactgccatt gatgcaccat ccaacctgcg tttcctggcc accacaccca attccttgct 6300 ggtatcatgg cagccgccac gtgccaggat taccggctac atcatcaagt atgagaagcc 6360 tgggtctcct cccagagaag tggtccctcg gccccgccct ggtgtcacag aggctactat 6420 tactggcctg gaaccgggaa ccgaatatac aatttatgtc attgccctga agaataatca 6480 gaagagcgag cccctgattg gaaggaaaaa gacagacgag cttccccaac tggtaaccct 6540 tccacacccc aatcttcatg gaccagagat cttggatgtt ccttccacag ttcaaaagac 6600 ccctttcgtc acccaccctg ggtatgacac tggaaatggt attcagcttc ctggcacttc 6660 tggtcagcaa cccagtgttg ggcaacaaat gatctttgag gaacatggtt ttaggcggac 6720 cacaccgccc acaacggcca cccccataag gcataggcca agaccatacc cgccgaatgt 6780 aggacaagaa gctctctctc agacaaccat ctcatgggcc ccattccagg acacttctga 6840 gtacatcatt tcatgtcatc ctgttggcac tgatgaagaa cccttacagt tcagggttcc 6900 tggaacttct accagtgcca ctctgacagg cctcaccaga ggtgccacct acaacatcat 6960 agtggaggca ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg 7020 caactctgtc aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac 7080 agtttcccat tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact 7140 gttgtgccag tgcttaggct ttggaagtgg tcatttcaga tgtgattcat ctagatggtg 7200 ccatgacaat ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg 7260 ccagatgatg agctgcacat gtcttgggaa cggaaaagga gaattcaagt gtgaccctca 7320 tgaggcaacg tgttatgatg atgggaagac ataccacgta ggagaacagt ggcagaagga 7380 atatctcggt gccatttgct cctgcacatg ctttggaggc cagcggggct ggcgctgtga 7440 caactgccgc agacctgggg gtgaacccag tcccgaaggc actactggcc agtcctacaa 7500 ccagtattct cagagatacc atcagagaac aaacactaat gttaattgcc caattgagtg 7560 cttcatgcct ttagatgtac aggctgacag agaagattcc cgagagtaaa tcatctttcc 7620 aatccagagg aacaagcatg tctctctgcc aagatccatc taaactggag tgatgttagc 7680 agacccagct tagagttctt ctttctttct taagcccttt gctctggagg aagttctcca 7740 gcttcagctc aactcacagc ttctccaagc atcaccctgg gagtttcctg agggttttct 7800 cataaatgag ggctgcacat tgcctgttct gcttcgaagt attcaatacc gctcagtatt 7860 ttaaatgaag tgattctaag atttggtttg ggatcaatag gaaagcatat gcagccaacc 7920 aagatgcaaa tgttttgaaa tgatatgacc aaaattttaa gtaggaaagt cacccaaaca 7980 cttctgcttt cacttaagtg tctggcccgc aatactgtag gaacaagcat gatcttgtta 8040 ctgtgatatt ttaaatatcc acagtactca ctttttccaa atgatcctag taattgccta 8100 gaaatatctt tctcttacct gttatttatc aatttttccc agtattttta tacggaaaaa 8160 attgtattga aaacacttag tatgcagttg ataagaggaa tttggtataa ttatggtggg 8220 tgattatttt ttatactgta tgtgccaaag ctttactact gtggaaagac aactgtttta 8280 ataaaagatt tacattccac aacttgaagt tcatctattt gatataagac accttcgggg 8340 gaaataattc ctgtgaatat tctttttcaa ttcagcaaac atttgaaaat ctatgatgtg 8400 caagtctaat tgttgatttc agtacaagat tttctaaatc agttgctaca aaaactgatt 8460 ggtttttgtc acttcatctc ttcactaatg gagatagctt tacactttct gctttaatag 8520 atttaagtgg accccaatat ttattaaaat tgctagttta ccgttcagaa gtataataga 8580 aataatcttt agttgctctt ttctaaccat tgtaattctt cccttcttcc ctccaccttt 8640 ccttcattga ataaacctct gttcaaagag attgcctgca agggaaataa aaatgactaa 8700 gatattaaaa gtatttgaat agtaaaaaaa aaaaaaaaaa aa 8742 <210> 48 <211> 6373 <212> DNA <213> homo sapiens <400> 48 cttgaacctt tgtcacccct cacgttgcac accaaagaca taccctagtg attaaatgct 60 gattttgtgt acgattgtcc acggacgcca aaacaatcac agagctgctt gatttgtttt 120 aattaccagc acaaaatgcc atcagtctgg gacgtgatcg ggcagaggtg tactcacagt 180 agtgtaaata ctgctgtaaa tagttgtctg atggtggctt tgacagtgag ctagcttctg 240 agttttccct tctttttata ctgttttctg tgctggcttt tttgaatctt cctaattttt 300 catctcttta acaaactcct atgaagttga aaccgggaag tttgctctaa catttccaga 360 gaaggtatta agtcatgatg caggaatctg cgacagagac aataagcaac agttcaatga 420 atcaaaatgg aatgagcact ctaagcagcc aattagatgc tggcagcaga gatggaagat 480 caagtggtga caccagctct gaagtaagca cagtagaact gctgcatctg caacaacagc 540 aggctctcca ggcagcaaga caacttcttt tacagcagca aacaagtgga ttgaaatctc 600 ctaagagcag tgataaacag agaccactgc aggtgcctgt gtcagtggcc atgatgactc 660 cccaggtgat cacccctcag caaatgcagc agatccttca gcaacaagtc ctgtctcctc 720 agcagctaca agcccttctc caacaacagc aggctgtcat gctgcagcag caacaactac 780 aagagtttta caagaaacag caagagcagt tacatcttca gcttttgcag cagcagcagc 840 aacagcagca gcagcaacaa cagcagcaac aacagcagca gcaacaacaa caacaacagc 900 agcaacaaca gcagcagcag cagcaacagc agcagcagca gcaacagcat cctggaaagc 960 aagcgaaaga gcagcagcag cagcagcagc agcaacagca attggcagcc cagcagcttg 1020 tcttccagca gcagcttctc cagatgcaac aactccagca gcagcagcat ctgctcagcc 1080 ttcagcgtca gggactcatc tccattccac ctggccaggc agcacttcct gtccaatcgc 1140 tgcctcaagc tggcttaagt cctgctgaga ttcagcagtt atggaaagaa gtgactggag 1200 ttcacagtat ggaagacaat ggcattaaac atggagggct agacctcact actaacaatt 1260 cctcctcgac tacctcctcc aacacttcca aagcatcacc accaataact catcattcca 1320 tagtgaatgg acagtcttca gttctaagtg caagacgaga cagctcgtca catgaggaga 1380 ctggggcctc tcacactctc tatggccatg gagtttgcaa atggccaggc tgtgaaagca 1440 tttgtgaaga ttttggacag tttttaaagc accttaacaa tgaacacgca ttggatgacc 1500 gaagcactgc tcagtgtcga gtgcaaatgc aggtggtgca acagttagaa atacagcttt 1560 ctaaagaacg cgaacgtctt caagcaatga tgacccactt gcacatgcga ccctcagagc 1620 ccaaaccatc tcccaaacct ctaaatctgg tgtctagtgt caccatgtcg aagaatatgt 1680 tggagacatc cccacagagc ttacctcaaa cccctaccac accaacggcc ccagtcaccc 1740 cgattaccca gggaccctca gtaatcaccc cagccagtgt gcccaatgtg ggagccatac 1800 gaaggcgaca ttcagacaaa tacaacattc ccatgtcatc agaaattgcc ccaaactatg 1860 aattttataa aaatgcagat gtcagacctc catttactta tgcaactctc ataaggcagg 1920 ctatcatgga gtcatctgac aggcagttaa cacttaatga aatttacagc tggtttacac 1980 ggacatttgc ttacttcagg cgtaatgcag caacttggaa gaatgcagta cgtcataatc 2040 ttagcctgca caagtgtttt gttcgagtag aaaatgttaa aggagcagta tggactgtgg 2100 atgaagtaga ataccagaag cgaaggtcac aaaagataac aggaagtcca accttagtaa 2160 aaaatatacc taccagttta ggctatggag cagctcttaa tgccagtttg caggctgcct 2220 tggcagagag cagtttacct ttgctaagta atcctggact gataaataat gcatccagtg 2280 gcctactgca ggccgtccac gaagacctca atggttctct ggatcacatt gacagcaatg 2340 gaaacagtag tccgggctgc tcacctcagc cgcacataca ttcaatccac gtcaaggaag 2400 agccagtgat tgcagaggat gaagactgcc caatgtcctt agtgacaaca gctaatcaca 2460 gtccagaatt agaagacgac agagagattg aagaagagcc tttatctgaa gatctggaat 2520 gagaactgac ttgtgaaacc tcagcgtgaa gggacatatc actgaccttc ataaccactc 2580 cacaaccatg aatatttgac aaatttttac tgtgactatt tattaagcat ggataaagga 2640 gacagcccta aaggaactta ctaagccagc cctttgggat tcagtaccaa caggcaaatt 2700 gcttgttttc ttcttcttct tcttcttttt tttttttttt ttagaaaaaa agacaaaaac 2760 tgattttctt gaaaaaaaaa aatgaactgt tctttctata atggctttgc ccatttaaaa 2820 aatgtggctc ttaagggttc atgaaatgac tgaatatgag gatacatgtc ctgtagaaag 2880 caaatgcgcc tcatatactg ccaaaaatag tgttagtttc attaatgtga attttccagc 2940 attcagtagt tgtaatgtta gaaacaattg ctggtcaagt tcaacttgtt gctattgttt 3000 ttaatttgca caggagtagt atcagaaatt agtgtcactg cttgtatcta gctgaatttt 3060 aaacaacaga acattagttt tttatgttgg tgccaccaac tgtaaatgac ataagttagt 3120 tattacaaaa cacagtaatt agactgttgc aaccatctaa aaccttaggc ttccagtctg 3180 tgctgttagt gttaagatgt aaagtgcaat cctaagctaa cattatctgt gcaagcacca 3240 tagaaacatt tgcatatctg catagatctt acaactgtac tctttacctc cttgtgataa 3300 agctttgtct acctgcaaac acagtcaaag gctacagctg caaaccaaag ccaactctaa 3360 ccatggccaa gagctcaagg acagaagcag ccacatgctt tggtcagcct tctgtaactt 3420 caattagtac aaaggaacct tttccatgaa ctacctgctg ttttctgatg acctctggga 3480 tcttttcatt tagccctaaa caaagaaaca aatatgacaa aaaccacaac taaaaaatgt 3540 taattcagtc acagagtaat cttctgaggc caaaagtcca tctaaatgca atgaagattt 3600 gctttcatta aagacagagg tgaggacaaa atccgcagtg gaagttatga tatgctagaa 3660 agcaacaaat gtggatcact gaccaaaacg attatgtact tgatgcaaat gcagattgca 3720 tattgttata tatatagtac tttgtgtttt tgttttccct cattcagtca gttattttca 3780 gtggtgaata catgttgtta gaagatgtct tgtatggtct taatctttgt tgtgtactat 3840 ttttttatag tcttaagtta taatgaaaaa acaaaaagta ggaaccaaac ataaaaggtc 3900 tagtaaagcc aaaaattaat ttcatattga ttttaaagtg atctagctga gtttttacac 3960 tgaaagcaaa gattatagca attgtagtcc atggtattta ttttcagtca aaccaaagtt 4020 acatataatt ctgcctctgc ttatacggga tattaacact aacaatacac tcccttcaaa 4080 gacttgcaca ggccaaattg ttggaatgct ggttttcttg acaattccaa accccaaaac 4140 tatgataatg agttatgatg tagttgaaaa tagcatagtc agatgtttgc ttaaaaccta 4200 gaaacttaac atgttgcttt tcatgtgctg tgccaagtct tgataatact ttttccccca 4260 accaagggac ctcataacct gattatggtt attgctttac aaacagtttt gacagaaggt 4320 ggctgctaga gcttaacata cgttcccgtt ccatgtgatg gaaccggttc ttgcaaacta 4380 agctcatcat tgattctttg ctgaagtcag caaatagagt tagagagata cccagtcatc 4440 tatcacacca aataaaagga cataacggct ttcaaaaggg ttttcccact tacccaaaag 4500 gctttctgaa agcttctacc tctgcaaaaa aaaaaaaaga aaaaaaaaaa aagaaaaaca 4560 ttagaacaat tatggcagat tgcatgaaac gtgagaacgt cacagtaact gctacttttc 4620 attatgtttg tctttgggtc atgatcaacg aaccggaagt ttacaatatg gtattaaaag 4680 aaagatgggt atggtgaaag atggttttca gtcatctagg atcctactgt aaggattatc 4740 tgaaaggaaa aatgggtctt tcaggtgcat gttcaaaagg ctttgaggga ctggaagtaa 4800 ctgcgagagt tgtaccatca gaagggtggc ctaagactac aatgctaaag tatgcatacc 4860 tcagttagaa aacttttgaa aggaagtctc agccacagaa tgcatatacc tgtagagttt 4920 tgcatgggtt ttatatgaat acaattttaa aaaatagctg cttgcacatt ataccagaaa 4980 aacctccaaa actgcaattg ctttgaaaat agattttagg ttttttggag tttcctgaaa 5040 tgcttggtct gtattttgat aattgtgcat attatgtaaa aatgttggtg gacccataaa 5100 tgaccagact ttttctaaga aaaatgttgc tttaatgcat ttcatgaatt tttactctta 5160 tatcattgct tgctagtaat agcaaatctg cttttctgca tctgctttgc gtagctattg 5220 taaggctttg aactaatgta tgtatttatt gcttgaactt ctgtgcatac cttataaagc 5280 ataatgtctg acaatttaaa tggctcatgt attcttgctt ctatcataag ctgattatgg 5340 ggactatgat cttttgtata cagcaaattt taaactgtag cacaaacatc tgtttatgta 5400 ttggtggaat atacctgttt tatttatctt ttttgaggta aactaatttt tgatactttt 5460 cattactgtg tactatgttc atactttgaa ttctctgacg ttagaagtca tggttgagaa 5520 ttgtaacagc tgttattcgt tctgtattca tggctttcac tgctgaataa aataaaggac 5580 caaacctagg atttgaaaga aaactgtcta cctctaacac cagggagtta tcagatttta 5640 ttttacatag ttttagtcta caaagacaca attgcttaaa cctagtgggc ttaaggctta 5700 tattctatgt ggttggattc gtggcacagt tgtactattt gaaaatcaat taaaatttta 5760 tgtgaatgtt acaagtattt ggtagaatta ccactaactg ggttttcttt agataactca 5820 gatatggaga aaatgtcatc agcattctgt gtctacagct gcttaacttc ataagaatgc 5880 atttctttgt gattagggaa tcgaagaata gtcagctagg aatagagcta cagaagtaca 5940 cttacataaa ccatcctgga ctttaatgtc cctgggcaga ttcagtcgca aaatccaata 6000 tgatattttg taaagttttc aagttggaca tttacatttt tgagaatttt gagacttcat 6060 cttacacatg ccagtattaa cacacatttg gacaatagct ttattaagtc tataaagcta 6120 ttgaaaggaa catggcttac ccttgttatt tcactagttc aggttgcaac gaaaggtttt 6180 tttgtccatg aacacttggc atatcttact tagcaaaaaa gaaggatgta cattttacta 6240 tagaattaat gtatgaacag tgtgtcactg ctgttggatg taaaaatgta tatgaaacca 6300 tttcattcac ttgattacat ttctgaagta taaataaaaa aatctaattc tttttgaccc 6360 atttataaaa aaa 6373 <210> 49 <211> 2441 <212> DNA <213> homo sapiens <400> 49 agagtgccgg gagcgcctga ttggcggccc tcccggcgcc tgcaggcccc gccccggctg 60 cggaggctca gtcacagccc tcccctcctc gctccctccc ctcctctccc cgcccagttc 120 ttctcttccc gtctgaggtg gcggtcggtc tcgccttgtc gccagctcca ttttcctctc 180 tttctcttcc cctttccttc gcgcccaaga gcgcctccca gcctcgtagg gtggtcacgg 240 agcccctgcg ccttttcctt gctcgggtcc tgcgtccgcg cctgccccgc catgaatgag 300 gagtacgacg tgatcgtgct gggcaccggc ctgacggaat gtatcctgtc aggtataatg 360 tcagtgaatg gcaagaaagt tcttcatatg gatcgaaacc cttactacgg aggagagagt 420 gcatctataa caccattgga agatttatac aaaagattta aaataccagg atcaccaccc 480 gagtcaatgg ggagaggaag agactggaat gttgacttga ttcccaagtt ccttatggct 540 aatggtcagc tggttaagat gctgctttat acagaggtaa ctcgctatct ggattttaaa 600 gtgactgaag ggagctttgt ctataagggt ggaaaaatct acaaggttcc ttccactgaa 660 gcagaagccc tggcatctag cctaatggga ttgtttgaaa aacgtcgctt caggaaattc 720 ctagtgtatg ttgccaactt cgatgaaaaa gatccaagaa cttttgaagg cattgatcct 780 aagaagacca caatgcgaga tgtgtataag aaatttgatt tgggtcaaga cgttatagat 840 tttactggtc atgctcttgc actttacaga actgatgatt acttagatca accgtgttat 900 gaaaccatta atagaattaa actttacagt gaatctttgg caagatatgg caaaagccca 960 tacctttatc cactctatgg ccttggagaa ctgccccaag gatttgcaag gctaagtgct 1020 atttatggag gtacctatat gctgaataaa cccattgaag aaatcattgt acagaatgga 1080 aaagtaattg gtgtaaaatc tgaaggagaa attgctcgct gtaagcagct catctgtgac 1140 cccagctacg taaaagatcg ggtagaaaaa gtgggccagg tgatcagagt tatttgcatc 1200 ctcagccacc ccatcaagaa caccaatgat gccaactcct gccagatcat tattccacag 1260 aaccaagtca atcgaaagtc agatatctac gtctgcatga tctcctttgc gcacaatgta 1320 gcagcacaag ggaagtacat tgctatagtt agtacaactg tggaaaccaa ggagcctgag 1380 aaggaaatca gaccagcttt ggagctcttg gaaccaattg aacagaaatt tgttagcatc 1440 agtgacctcc tggtaccaaa agacttggga acagaaagcc agatctttat ttcccgcaca 1500 tatgatgcca ccactcattt tgagacaacg tgtgatgaca ttaaaaacat ctataagagg 1560 atgacaggat cagagtttga ctttgaggaa atgaagcgca agaagaatga catctatggg 1620 gaagactaac agcagtacat gttattatgt aattaggaca catttaaaat ttggcaaata 1680 atgcatataa tgaaatcaat attgtaaggc ctgcttttgt aatgaaaatg gagagaatga 1740 agagcgctgt gccagtaaat actccccttc acctttctaa ttattaactt gttttcatgg 1800 agtggctatt cagcattggc agttaccaca ttctgttcaa tttaaccaaa ctggcttttt 1860 ttttttctag tgaagttaaa caaacattgg gataccgaca cagacaactt gagacagttt 1920 ttttaatctt ttaatcagtg tagctatgtg ctgctgctgc tcaagagctg gatccataca 1980 ggttgtgtgt catctgtcct cttgaggttc aggagattct aaattgaata ttccacggtt 2040 tgggacagca tccggaagtt ttccctatga ctttatattt tgtattatgt caaatgttat 2100 ggcagggccc aaatagcata gccacaagtt tggtttatgt gggcataaaa ttctaaccaa 2160 accccagaca tagggagtca tttggagaaa gcctgtatgt ggtgttttaa cctaataaag 2220 ttgatgagag agaaggggag aggaagcgaa cataaagcgg gtcaagtgta gtgcatcttt 2280 tgtatctcag gcgtggcttc ttcagtggac caagctgcaa tgcagtattg acttgacaga 2340 gcctctactt ctgtctcaaa atggctccaa atgatttctg tactgcaaaa taaagccaaa 2400 ttctggaaac taaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2441 <210> 50 <211> 855 <212> DNA <213> homo sapiens <400> 50 gccagctctg gggtctcggc aggtggtcca caacatgacc tctgagttct tcgctgccca 60 gctccgggcc cagatctctg acgacaccac tcacccgatc tcctactaca agcccgagtt 120 ctacacgccg gttgatgggg gcactgctca cctgtctgtc gtcgcagagg acggcagtgc 180 tgtgtccgcc accagcacca tcaacctcta ctttggctcc aaggtccgct ccccggtcag 240 cgagatcctg ttcaatgatg aaatggatga cttcagctct cccaacatca ccaacgagtt 300 tggggtgccc ccctcacctg ccaatttcat ccagccaggg aagcagccgc tctcgtcaat 360 gtgcccgacg atcatggtgg gccaggacgg ccagccccca agccatgctg atcacactcc 420 catgccccag gccatcatct acaacctctg gttcggctat gacgtgaagc gggccgtgga 480 ggagccccgg ctgcacaacc agcttctgcc caacgtcacg acagtggaga gaaacattga 540 ccaggcagtg actgcagccc tggagacccg gcaccatcac acccagatcg cgtccacctt 600 catcgctgtg gtgcaagcca tcgtccgcac ggctggtggc tgggcagctg cctcggactc 660 caggaaaggc ggggagcctg ccggctactg agtgctccag gaggacaagg ctgacaagca 720 atccagggac aagatactca ccaggaccag gaaggggact ctgggggact ggcttcccct 780 gtgagcagca gagcagcaca ataaatgagg ccactgtgcc aggctccagg tggcctccct 840 gccctgtcaa aaaaa 855 <210> 51 <211> 1898 <212> DNA <213> homo sapiens <400> 51 agccgaccta ctggtgtcat ggcagcccca aagacagcag ctgtggggcc gttggtggga 60 gcggtggtcc agggcaccaa ctccactcgc tttctggttt tcaattcaaa aacagcggaa 120 ctacttagtc atcacaaagt ggaattaaca caagagttcc caaaagaagg atgggtggaa 180 caagacccta aagaaattct tcagtctgtc tacgagtgta tagcgagaac gtgtgagaaa 240 cttgacgaac tgaatattga tatatccaac ataaaagctg ttggtgtcag caatcagagg 300 gaaaccactg taatctggga caagttaaca ggagagcctc tctacaatgc tgtggtgtgg 360 cttgatctaa gaacccagac tactgttgag gatcttagta aaaaaattcc aggaaatagt 420 aacttcgtca agtctaagac aggccttcca ctcagcactt acttcagtgc agtaaaactt 480 cgttggatgc ttgacaatgt gagaaacgtc caaaaggctg ttgaagaagg tagagctctt 540 tttggtacca ttgattcatg gcttatctgg agtttgacag gaggagttaa tggaggcgtg 600 cattgtacag atgtaacaaa tgcaagtagg acaatgcttt ttaatatcca ttctttggaa 660 tgggataaag agctctgtga cttttttgaa attccaatgg accttcttcc aaatgtcttc 720 agttcttctg agatctatgg cctaattaaa actggagccc tggaaggtgt gccaatatct 780 gggtgtttgg gggaccaatg tgctgcatta gtaggacaaa tgtgcttcca ggagggacaa 840 gccaaaaaca cctatggaac aggttgcttc ttactgtgta atacgggtcg taaatgtgtg 900 ttttctgaac atggcctttt gaccacagta gcttacaaac taggcagaga gaagccagca 960 tattatgcac tggaaggttc tgttgctata gcaggtgctg ttattcgttg gctaagagac 1020 aatcttggaa ttatagagac ctcaggagac attgaaagac ttgctaaaga agtaggaact 1080 tcttatggct gttactttgt cccagccttt tcagggttat atgcacctta ttgggagccc 1140 agtgcaagag ggatactctg tggcctcact cagtttacca ataaatgtca tattgctttt 1200 gctgcattag aagctgtttg tttccaaacc cgagagattt tggaagccat gaaccgtgac 1260 tgtggaattc cacttcgtca tttgcaggta gatggaggaa tgaccaacaa caaagttctt 1320 atgcagctac aagcagatat tcttcatatt ccagtaataa aaccctttat gcctgaaaca 1380 actgcactag gagctgccat ggcagcaggg gctgcagagg gagtaagcgt ttggagcctt 1440 gaaccccagg ctttgtcagt tctcaggatg gaacgatttg aaccacagat ccaggccaca 1500 gaaagtgaaa ttcgttatgc cacatggaag aaagccgtaa tgaagtcaat gggttgggtt 1560 accagtcagt ctcctgaagg tggtgatcct tctatcttct ctagtctgcc tttgggattt 1620 tttatagtga gtagcatggt aatgctaatt ggagcaagat atatctcggg tgtgccataa 1680 taataccagc tatggagtcc caagatgtaa acattttaca taatgaaagc atatagcagt 1740 tctgcctctt aatataatga cactattata gactctgatt ttgtttataa accacttgct 1800 acatgaccca tgaaaaccct agacttgtga cctgaaataa agaaaatacg ttagaagagc 1860 actgtaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1898 <210> 52 <211> 4262 <212> DNA <213> homo sapiens <400> 52 gtcagctgcg cgcgaaccag ggctgggagg ctcggctgga ggtgtgacca gggcagggac 60 tgacctggcc cggaacagaa gcgcgcagag tcccatcctg ccacgccacg aggagagaag 120 aaggaaagat acagtgttag gaaagagacc tccctcgccc ctacgccccg cgcccctgcg 180 cctcgcttca gcctcaggac agtcctgccg ggacggtgag cgcattcagc accctggaca 240 gcaccgcggt tgcgctgcct ccagggcggc cccgggctgc tcctgctccg cagagctacg 300 ccctcccccc gggtgccccg gaccctgcac ttgccgccgc tttcctcgcg ctgctctgga 360 ccttgctagc cggctctgca cctcccagaa gccgtgggcg cgccgctcag ctgctccatc 420 gcctcacttt cccaggctcg cgcccgaagc agagccatga gaaccccagg gtgcctggcg 480 agccgctagc gccatgggcc ccggcgaggc gctgctggcg ggtctcctgg tgatggtact 540 ggccgtggcg ctgctatcca acgcactggt gctgctttgt tgcgcctaca gcgctgagct 600 ccgcactcga gcctcaggcg tcctcctggt gaatctgtct ctgggccacc tgctgctggc 660 ggcgctggac atgcccttca cgctgctcgg tgtgatgcgc gggcggacac cgtcggcgcc 720 cggcgcatgc caagtcattg gcttcctgga caccttcctg gcgtccaacg cggcgctgag 780 cgtggcggcg ctgagcgcag accagtggct ggcagtgggc ttcccactgc gctacgccgg 840 acgcctgcga ccgcgctatg ccggcctgct gctgggctgt gcctggggac agtcgctggc 900 cttctcaggc gctgcacttg gctgctcgtg gcttggctac agcagcgcct tcgcgtcctg 960 ttcgctgcgc ctgccgcccg agcctgagcg tccgcgcttc gcagccttca ccgccacgct 1020 ccatgccgtg ggcttcgtgc tgccgctggc ggtgctctgc ctcacctcgc tccaggtgca 1080 ccgggtggca cgcagacact gccagcgcat ggacaccgtc accatgaagg cgctcgcgct 1140 gctcgccgac ctgcacccca gtgtgcggca gcgctgcctc atccagcaga agcggcgccg 1200 ccaccgcgcc accaggaaga ttggcattgc tattgcgacc ttcctcatct gctttgcccc 1260 gtatgtcatg accaggctgg cggagctcgt gcccttcgtc accgtgaacg cccagtgggg 1320 catcctcagc aagtgcctga cctacagcaa ggcggtggcc gacccgttca cgtactctct 1380 gctccgccgg ccgttccgcc aagtcctggc cggcatggtg caccggctgc tgaagagaac 1440 cccgcgccca gcatccaccc atgacagctc tctggatgtg gccggcatgg tgcaccagct 1500 gctgaagaga accccgcgcc cagcgtccac ccacaacggc tctgtggaca cagagaatga 1560 ttcctgcctg cagcagacac actgagggcc tggcagggct catcgccccc accttctaag 1620 aagccctgtg gaaagggcac tggccctgcc acagagatgc cactggggac ccccagacac 1680 cagtggcttg actttgagct aaggctgaag tacaggagga ggaggaggag agggccggat 1740 gtgggtgtgg acagcagtag tggcggagga gagctcgggg ctgggctgcc tggctgctgg 1800 gtggccccgg gacagtggct tttcctctct gaaccttagc ttcctcaccc ttgttctggg 1860 gtcatggcga tgcttcgaga cagtgggtag ggaagtgccc tgtgtggcat atggtactcg 1920 tgggcgtgct ataagtgact gctgttcatg tgggtgaggt ggtcactctt gctcagggtc 1980 tgttgtgcag cccagatgga cacctgtttc tccaacctgg ttattagcat tgttccgatt 2040 tgttctcggc attgcccagg tttgggagat aaatgccggg gcggagtctg gttgggggct 2100 cccagagttc acatctgata gtctgtggtc aggacctggc aggcacgggc agtccctggg 2160 acatgcccat ctctggaagc ctaggggtcc ccagctccag gcctgtccgc tgtgactgcc 2220 tgtgtgggca cgcagatgga gcctgtctcc tgccttcctt tccatggttt gccaggggtt 2280 tggcatcttg actgcggaag ctgtggagtc tgtgtgctca gagccttttc tggtgaagat 2340 atcatcagag catgtgacct ctgtttcctc cccctgaagg ccaccgctgg gcctctggat 2400 cttagacatg agacggtcaa gagattgaag tagtagccag ggcccaggtg tccagagagg 2460 gtggcctggg atggggaggg cccttgctcc ccaacagcag tgctggggga gccaagagaa 2520 ggtggagcat ccctgagtag tggtgtgcat cacccccagt ttagtaatca cggggtgcca 2580 ttccccggtg ggagcaccca ccatcaatgt cattgaatgt ccccatggga cagtgttgag 2640 gacttttgtg acatctgtcc tatttcacag ctcagggaaa ggtgcacagt gcacacgggc 2700 acccggtgga gaggtgtgtg tgtgaatgag tgagcgagtg aatgaatgga cacgattctc 2760 tcttcagcct ctgtcattgc tgttttcttc aaggcccagg gccatcccct gcagaggtag 2820 ggtgggctgc aagacctcag gcccctgcct catgggactc tctgatgggc ttcaaccgtg 2880 ggctcttgca ggcatggagc ctgtatcatg acaccttaca cccaaggcca gcaatgcaag 2940 gagagtatgg acatcaaatt ctttccttcc agaggctgaa ttcttcaaag acacacgcgg 3000 tcgtcacttg ctcttggcat taacggtgga gaacccagct gaggtggctt cacagattct 3060 tccccaaaaa cacaggtgtt attattatac ttttaaaaaa ctttttgaga cagggtctga 3120 ctctgttgcc taggctagag tgcagtggtg caatctcagc tcactgcagc ctccacctcc 3180 catgctcaag ccatcctccc acctcagcct cctgagtagt tgaggacaca ggcacgggac 3240 accatgcctg gctaattttt gtattttttt ttgtagagat ggcggtctca ctttgttgcc 3300 caggctggtc ttgaattcct gagcttaagt gatcctccca cctcagcctc ccaaagtgct 3360 gggattacag gtgtgagcca ccacacccag ccaaaaccag gtgttatttg ctgactcacc 3420 aatgcctccc ccaaaaggat aaatttaaag gtgtgtataa cccatgaagt gtaattcaaa 3480 taaaacaaat tatcgtttgg aataataaca actataggta tgtggtcagg aagcagttaa 3540 aaacattaaa atacagacct ggccagttca atccaaccca ggggttccaa gcaggaggtg 3600 gggcaggtgg gcgtcatgcc ctgattcaca gagggcacag gtgggtgtca tgccctggtt 3660 cacagagggc acgtgaactc gagaccgtgc tgcaccccgg tgcccctgtg cttataaggg 3720 agggcacgtg cacagcagaa gcaggttgtt ccccatttaa agttctggag cccaggctgt 3780 gagctccttg gctgagccct ctcctgtccc tgggagctcc ccaggtgcga ggagcctgcc 3840 agccagtggg gcctacactc tgtgttattg catctccgcc aggctaaaag ccttggtcac 3900 tactttagag ccactcaagg aaacgcgtgc accctgccct gctggaaggc accatggtta 3960 gagggaggca cactgtttct tagagacggg gactgcttgc tgtcatgttt cgccttcctc 4020 ggcagctcca tggaatgttc tggagcaggc atcttagggc attccctccg cacttctctg 4080 ccagcccatg tggctcccac actgggctat cccttgcctt aggcttgtgg cctttttttt 4140 tttttttttt ttaatttgaa aaatattttt catgtgcact taaacgtgtt gtggaatgat 4200 gctgggtctc aagaatgctg tgaatcaata aacattttat tcagaaaaaa aaaaaaaaaa 4260 aa 4262 <210> 53 <211> 1530 <212> DNA <213> homo sapiens <400> 53 gttgcgcgcc gtggcggcct ctgtgcagtc gccggttccg gaggagggcc caacccggct 60 gggtgggtgg gaagtgtggc tggtaacctg gcagccgcgg agagagagaa gattataaat 120 ggcagagcca tttaactgtg gttagctgtt ggattctgat actttcttaa aaatacgttc 180 ttgcaccaac atcttcattg ggaacagttc agaaaaagca aagaggagag ccaacattca 240 catttaccat ggctatacca ataacagtgc ttgactgtga cctcttgcta tatggccgtg 300 gtcaccggac attggaccgt tttaagctgg atgatgtgac tgatgaatac ttgatgtcca 360 tgtatgggtt tccacggcag ttcatttatt acttggtgga gctcttgggg gcgaatcttt 420 ctaggcctac tcagcgatcc agggctatta gcccagagac acaggtcctt gcagcattgg 480 gtttttatac ctcaggttcc ttccagactc ggatgggaga tgccattgga atcagtcagg 540 cgtctatgag tcgttgtgtt gccaatgtca ctgaagcact tgtggaaagg gcctcacagt 600 tcattcgctt tccagctgat gaagcctcca ttcaggctct gaaggatgaa ttctatgggt 660 tggcagggat gccaggggtg atgggggtgg ttgactgtat ccatgtggcc atcaaggcac 720 caaatgctga agacctctcc tatgtgaacc gaaaaggcct gcattcttta aactgcctga 780 tggtgtgtga cattagaggg acactaatga ccgtggagac aaactggccc ggcagcctac 840 aggactgtgc tgtgctgcag cagtcttccc tcagtagtca gtttgaagcg ggtatgcaca 900 aagatagctg gcttctgggt gacagttcct tctttcttcg aacctggctc atgaccccac 960 ttcacattcc tgaaactcca gcagaatatc gctataacat ggcccattct gcaactcaca 1020 gtgtgattga gaagactttc cgaaccctct gctcccgatt ccgctgcctg gatggatcca 1080 agggggcact gcagtactca ccagagaaat ccagccatat catcttggcc tgttgtgtcc 1140 tccacaacat ctccctggag catgggatgg atgtttggtc ctctccaatg acaggaccca 1200 tggaacagcc cccggaagag gagtatgagc acatggagtc cctggactta gaggctgacc 1260 gtattcgtca ggagctaatg ctcactcatt ttagctaatg tagaaggtgg agaggaggga 1320 tacttcccag gagttgtgac agactttcct cctcatcacc ttttacacag ttccatcatc 1380 tagcatgact gagtatacag atacttgtca taaactgaca tttaatatgt gtgttttggt 1440 aaggttgggg ctatgccaga atatcttgat tcatttgcat atgcattaat taaactgaaa 1500 ccaagacagc ggctccctac taaaaaaaaa 1530 <210> 54 <211> 2306 <212> DNA <213> homo sapiens <400> 54 ataaatagca acctatgcta ggggttgcta gcaccagcca tttcccctac tcacacctgt 60 gcagtgtgat aaagatagta gaattagcct gcagttgtgg tccaaccaga taaaactttt 120 aggcgggaag tcaagtgaca ggcaaacttg tgtgtgtggt tttttttttt aagtgttaga 180 tgtttttgat attttaaaaa agcatctagg ctgcttgtgg aagtcagacc aaaatagcag 240 gaaggtattg cagcaagatg gatttgggaa aggaccaatc tcatttgaag caccatcaga 300 cacctgaccc tcatcaagaa gagaaccatt ctccagaagt cattggaacc tggagtttga 360 gaaacagaga actacttaga aaaagaaaag ctgaagtgca tgaaaaggaa acatcacaat 420 ggctatttgg agaacagaaa aaacgcaagc agcagagaac aggaaaagga aatcgaagag 480 gcagaaagag acaacaaaac acagaattga aggtggagcc tcagccacag atagaaaagg 540 aaatagtgga gaaagcactg gcacctatag agaaaaaaac tgagccacct gggagcataa 600 ccaaagtatt tccttcagta gcctccccgc aaaaagttgt gcctgaggaa cacttttctg 660 aaatatgtca agaaagtaac atatatcagg agaatttttc tgagtaccaa gaaatagcag 720 tacaaaacca ttcttctgaa acatgccaac atgtgtctga acctgaagac ctctctccta 780 aaatgtacca agaaatatct gtacttcaag acaattcttc caaaatatgc caagacatga 840 aggaacctga agacaactct cctaacacat gccaagtaat atctgtaatt caagaccatc 900 ctttcaaaat gtaccaagat atggctaaac gagaagatct ggctcctaaa atgtgccaag 960 aagctgctgt acccaaaatc cttccttgtc caacatctga agacacagct gatctggcag 1020 gatgctctct tcaagcatat ccaaaaccag atgtgcctaa aggctatatt cttgacacag 1080 accaaaatcc agcagaacca gaggaataca atgaaacaga tcaaggaata gctgagacag 1140 aaggcctttt tcctaaaata caagaaatag ctgagcctaa agacctttct acaaaaacac 1200 accaagaatc agctgaacct aaataccttc ctcataaaac atgtaacgaa attattgtgc 1260 ctaaagcccc ctctcataaa acaatccaag aaacacctca ttctgaagac tattcaattg 1320 aaataaacca agaaactcct gggtctgaaa aatattcacc tgaaacgtat caagaaatac 1380 ctgggcttga agaatattca cctgaaatat accaagaaac atcccagctt gaagaatatt 1440 cacctgaaat ataccaagaa acaccggggc ctgaagacct ctctactgag acatataaaa 1500 ataaggatgt gcctaaagaa tgctttccag aaccacacca agaaacaggt gggccccaag 1560 gccaggatcc taaagcacac caggaagatg ctaaagatgc ttatactttt cctcaagaaa 1620 tgaaagaaaa acccaaagaa gagccaggaa taccagcaat tctgaatgag agtcatccag 1680 aaaatgatgt ctatagttat gttttgtttt aacaatgctc aaccataaag ttgtggtcca 1740 atggaacata cagcttaata gtttatgcgt gattttctca aaatattgta aaacttttga 1800 caatgctcat taatattatt ttttctattt gtagaccata tctgaaagaa ataacatttt 1860 ttaaggctct accacataga caatatcatg ctagaatgtg tgtgtgtgtg tgtgtgtgtg 1920 tgtgtgtatg tatgtatagg tcggggagag gatagtggtg ggaacagaca aataaggaag 1980 cggggaggac tggataattg gttttccccc ctaagaacat ttatttacgt cttaagagca 2040 gataagtgac taagactgaa cacatacatt ttgtggagta tatagttttc ttgtaaatgc 2100 tgttcaatta ttaatgtaac agtagcatca aaattttatt caggctttag ttgactcttt 2160 tggtcagttt taacaattct ccttaaaaga tattttggag tgatgaatgt agtttacttt 2220 tgtatttgaa ttttgatttt ctatttttat tttttaaata ttgtatttgt gcacaatgta 2280 cattaaatca ttattacatg cttaaa 2306 <210> 55 <211> 500 <212> DNA <213> homo sapiens <400> 55 gtggttctcg tgttgctgca atttgatgcg aggagatgtc tggacgaggg aagcagggag 60 gaaaagcacg cgccaagtct aagtctcgct cttctagagc gggtttgcag tttcccgtag 120 gccggatcca tcgtctgctt cgtaagggaa actatgcaga gcggataggg gcaggcgcac 180 cagtgtattt ggcggcagtg ttagagtatc tcacagcaga aatccttgag ctggcaggca 240 atgcgtctcg cgataacaaa aaaactcgca ttattccccg ccacctgcag ctagcgatcc 300 gcaatgatga ggaactcaat aagcttttgg gcggcgtgac cattgcccag ggcggagtcc 360 tgcctaacat tcaggcagtg ctgctgccca agaagactga gagtcaccac cataaagccc 420 aaagcaagta acttaaggtt gtcattggta aaaagacttc tgtgtcagaa aaaacaaaag 480 gctcttttca gagccaccta 500 <210> 56 <211> 1989 <212> DNA <213> homo sapiens <400> 56 agctgggcca atgaacggcg gcgggaggtg aaatccggtt ctaaccggtc cggggctccc 60 agcgctataa aaactttata aaccccccgg agcccgagca gtgtgaagaa gaggcgagaa 120 cgacccccgg accgaccaaa gcccgcgcgc cgctgcatcc cgcgtccagc acctacgtcc 180 cgctgccgtc gccgccgcca ccatgcccaa gagaaaggct gaaggggatg ctaagggaga 240 taaagcaaag gtgaaggacg aaccacagag aagatccgcg aggttgtctg ctaaacctgc 300 tcctccaaag ccagagccca agcctaaaaa ggcccctgca aagaagggag agaaggtacc 360 caaagggaaa aagggaaaag ctgatgctgg caaggagggg aataaccctg cagaaaatgg 420 agatgccaaa acagaccagg cacagaaagc tgaaggtgct ggagatgcca agtgaagtgt 480 gtgcattttt gataactgtg tacttctggt gactgtacag tttgaaatac tattttttat 540 caagttttat aaaaatgcag aattttgttt tacttttttt ttttttttaa aagctatgtt 600 gttagcacac agaacacttc attgttgttt ttgggggaag gggcatatgt cactaataga 660 atgtctccaa agctggattg atgtggagaa aacacctttc ccttctagtt ttgagagact 720 tcctcttggc tcccaggagg agggattccc tgactttgac acacatggcc accttggcac 780 aaaagccttg tggtatagaa aaacaaattt gtttttatgt cctcttctcc ctttccatcg 840 ttcagcatag acttaactcc cttaagccca gacatctgtt gagacctgac ccctagtcat 900 tggttaccag tgtgtcaggc aatctggact ttccagtgat gccactgaga tggcacctgt 960 caaaagagca gtggttccat ttctagattg tggatcttca gataaattct gccattttca 1020 tttcacttcc tgaaagtcag ggtcggcttg tgaaaagttg ttaaacaaca tgctaaatgt 1080 gaaatgtcaa ccctcactct aaactttccc tgttcagagc atcagatgaa gacttcattg 1140 ggttttatag tggctttctg atttttggta gtccattgaa gaagggagtt tgaaagttgt 1200 tgtatactgt taacgattgt ctgcccatgt cctgcctgaa ataccatgat tgtttatgga 1260 aagtatcttt aataaagctg gatacagttt ggcttggaat gctgcctctg atcttttccc 1320 acaagtgggg taacctggtt tatccaagtc tcttggaaca gggtacgttc tgctttgagg 1380 tactccatgt acagtctaat gatgatcttt cactgattta tagtcagctt ccaaaacaca 1440 cagtgctagg tgcagttagg aaggattcca ggagtagact tagctgatgg tgaaaggctg 1500 ggagtatgga gtgatttctg tacttggtta tgcagcattc cctgcagtgt ttgttttttg 1560 catgactccg aatacatgaa gtgtattaaa tgcagatttt tggtagatct gcggttttgg 1620 ctgggtagct gacaggagcc tctctacttc catctgcatt tgcaacttct ataaaattag 1680 caaattaata gactcatgtc agagagtgtc tctgtgaatg tgtacacagt tgtccatttg 1740 taaggtagat gacactttgc tcctaagtag acctgcaaac aaagacaatg gggtctttcc 1800 tgattccttt agtttggaga tgcagagaac cccacgtttc tctaagtgaa atggcaagaa 1860 gttatttgtt agaatatgga actggtaaca aattcatgtt tgcaccttga atttgctttc 1920 acagacctgg ctgtattgtt ggacaggaat aaagtaaatt ggagactaaa aaaaaaaaaa 1980 aaaaaaaaa 1989 <210> 57 <211> 1144 <212> DNA <213> homo sapiens <400> 57 aagaagggtg agaatgcccc ctgggctgac caaagcccac gggccactgc atcccttgcc 60 aagtgcctac atcccactgc cattgctgcc atcatgccca agacaaagat tgaaggggat 120 gctaaaggag ataaagccaa ggtgaaagac gaaccactga gaagatccgc gaggttgtct 180 actaaacctt ccaaagccag agcccaagcc aaaaaaggct ctcgagaaga agggagagaa 240 ggtacccaat ggaaaaaggg aaaagctgtt gctggcaagg aggggaataa ccctgcagaa 300 aatggagatg ccaaaacaga ccaggcacag aaagctgaag gtgctggaga tgccaagtga 360 agtgtgcaca tttttgataa ctatgtgcct ctagaggtga ctgtagagtg tgaaatactc 420 tttttatcaa gttttataaa aatgcagcat tttgtttcac tttttttaaa agctatgttg 480 ttagcacaca gaacaattca ttgttgtttt tgggaaaaga atgtccgtga agctggattg 540 atgtggagaa gacacctttc ccttctagtt ttgagagact tcctcttggc tcccaggagg 600 agggatttcc tgactttgac acacatggcc accttgtcac aaaagccatt aaaaacaaat 660 tcatttttat gtcctcttct ccctttcaac ctttcagcat agacttaact cccttaaacc 720 cagacacctg ttgggatgtg accccccagt aattggtcac cagtgtgtca ggcaatctgg 780 actttccagt gatagcactg agatggtgct ccttaaaaga gcagtggttc catttgtagg 840 ttgtggatct ttggataaat tctgccattt tcattttact tcctgaaagc cagggttggc 900 tcatgaaaag gtgttgaaca acatgctaaa tgtgaaatgt taaccctcac tctaaacttt 960 ctctgttcag agcatcagat gaagacttaa ttgagtttta tagtggcttt ctgattttgg 1020 gtagtcaact gaagaaggga gtttgaaagt tgttgtgtac tgttaatgat tgtctgccca 1080 agttctgctt gaaataccat gattgtttat ggaaagtacc tttactaaag ctggataaag 1140 tttg 1144 <210> 58 <211> 1927 <212> DNA <213> homo sapiens <400> 58 acctaagcga tgaaatccaa aggtgaatct tttggttggt gattttgatg atagccacaa 60 agcaagcagg ctgtatggta gccttgaaaa ccaacaggcc acaatcacag tgaaaacctc 120 aggttggcag ccactggagg atacaaaatg agtttggatc tccttcaatg ccccattccc 180 agagaactgt cattatttga cctgctggta gttccctaaa ggacgtgcaa ggatgttttt 240 atttgactgg acacttgaag cttgccctgt atgaacagcc cccatcttcc catgcttgtc 300 aaaaatcaga ggcaactaac actgcggctt cctgagagtc tcactctgtc acccaggctg 360 gagagcaatt gcacaaacac ttggctcact gcagcctcaa cttcttgtcc tcaagtgatc 420 ctcccacctt agcctcctaa gtagctggga ccacagggaa ctccggatgt gactcctgtt 480 acatgaaaat ggaagaggtc agagttgtcc aagagggagg ccagccacat ccaggcaggg 540 cccccatggt cagaaccctg ctagagccat caaggtccca gagctcccaa gatggtggca 600 agccttttgt tctctgacca gaggttcctg gcctcacgga ttccaaggaa tggaaccttg 660 ggccatgcgt gcacttgatt ttgcagatga gtctggaagt gttagttgca aagatatgca 720 tttacttctc tggctacaaa aaagaataga aatgcacaaa gcagagcagt gtgaagaaga 780 agaggcgatg acccctagac cgaccaaagc ccgtgctcca ctgcccagtg cctatgtccc 840 accactgtcg ctgccaccct gcccgagaga aaggctgaag gggatgctaa aggagataaa 900 accaaggtta agtaggaact gcagagaaga tccacaaggt tgtctgctaa acctgctcct 960 ccaaagccac agccgaagcc cagaaaggcc tctgcaaaga agagagagaa ggtacctaca 1020 gagaagaagg gaaaagctga tgctggcaag gaggggaata accctgcaga aaatggagat 1080 gccaaaacag actaggcaca gaaagctaaa ggtgctggag atgccaagtg aagtgtgtgc 1140 atttttgata actgtgtact tctggtgact gtacagtttg aaatactatt ttttaatcaa 1200 gttttataaa aatgcagatt ttgtttagct tttttttttt tttttaagct atgttagtac 1260 acagaatact tcattgttgt tttggggaga agggccatat gtcactaata gaaagcccct 1320 gaagctggac tgatgtgggg aaaacacctt ttccttctgg ttttgagaga cttcctcttg 1380 ggtcccagga agagggattc cctgactttg atacacatgg ccaccttggt ataaaagcct 1440 tgtggtatgg aaaaacaaat tcgtttttta tgtcctcttc tctgtttcta cctttcagaa 1500 tggacttaaa tcccttaaac ccagacatct tctgggacct gacccccaat aattggttac 1560 cagtgtgtca ggcaatctgg actttgccct caaaagagca gtggttcctg tttctaggtt 1620 gtggatcttc agataaattc tgtcattttc ctttcacttc ctgaaagcca gggtcggttc 1680 atgaaaagct atgaaacagc atgctaaatg tgaaatgtca accctcacta aactttgccg 1740 gttcagagca tcagatgaag acttcattgg gttttacagt ggctttctga tttttggtag 1800 tccattgaag aagggagttt gaaagttgtt gtatactgtt aacgattgtc tgcccatgtc 1860 ctgcccaaaa taccatgatt ctttatggaa attatcttta ataaagctgg atacagtttg 1920 gcttggg 1927 <210> 59 <211> 2435 <212> DNA <213> homo sapiens <400> 59 aggggtggag agaaaagagg ggagggatgg ggggagggga aacaggagcg aggtgtctcc 60 ctagctcgct gcctctggca agtggagttt ttaaaaagct ccagcagatc atgtcatgac 120 gacttcgctg ctcctgcatc cacgctggcc ggagagcctt atgtacgtct atgaggacag 180 cgcggcggag agcggcatcg gcggcggcgg cggaggagga ggcggcggca cgggcggagc 240 ggggggtggc tgcagcggag cgagccccgg caaagccccg agcatggatg gtctgggcag 300 cagctgcccg gccagccact gccgcgacct gcttccgcac cccgtgctgg gccgcccgcc 360 ggctcccctg ggcgcccctc agggcgccgt ctatacggac atcccggccc cggaggcggc 420 gcgccagtgt gccccgccgc ccgcaccccc cacctcgtcc agcgccaccc tgggctacgg 480 ctaccccttc gggggcagct actacggctg ccgcctgtcg cacaacgtga acctgcagca 540 gaagccttgc gcctaccacc cgggcgataa atacccggag ccgtcgggcg ccctgcccgg 600 tgacgacctg tcctctaggg ccaaggagtt cgccttctac cccagcttcg ccagctccta 660 ccaggcgatg cccggctacc tggacgtgtc ggtggtgccc gggatcagcg ggcacccgga 720 gccgcgtcac gacgccctca tccccgtcga aggctaccag cactgggctc tctccaatgg 780 ctgggacagt caggtgtact gctccaagga gcagtcgcag tccgcccacc tctggaagtc 840 tcccttccca gacgtggttc ccctgcagcc cgaggtgagc agctaccggc gcgggcgcaa 900 gaaacgcgtg ccctacacta aggtgcagct gaaggagcta gagaaggaat acgcggctag 960 caagttcatc accaaagaga agcgccggcg catctccgcc accacgaacc tctctgagcg 1020 ccaggtaacc atctggttcc agaaccggcg ggtcaaagag aagaaggtgg tcagcaaatc 1080 gaaagcgcct catctccact ccacctgacc acccacccgc tgcttgcccc atctatttat 1140 gtctccgctt tgtaccataa ccgaacccac ggaaagacgc tgcgcgggtg cagaagagta 1200 tttaatgtta aggaaagaga agaaccgcgc cgcccggagg cagagaggct ccatggccgt 1260 gctgctgggc catccccaac tccctatccc atccccagcc tccaccccca tccagatggg 1320 actcacgtgg cttcaacagc tttggaaatg ggtcccgagt gggccgtgcg aggaaggctg 1380 tcgacctcta ctcctccttg cgctcacctt gccagaaagt ctggtggcag cgcagagccc 1440 aatcattcca accaaagcag ggttggggaa tcccgaatgg ccccaattct tgcctcatcc 1500 tatgaccagg cttttagagg accttcccta agggcgcagc ttcggagcag gatctgtcca 1560 gctcatactt tccttcgctg tccctcccgc actccttagg caagatttcc cagtaaagat 1620 tttctgtgcg tattttaaaa gtcgtgttaa tactcatgat aattattagg gacctggcag 1680 cgtgattgga gtatggatgt ttccgtaaaa gctggaattc cgtaaaagca ttgacgcagc 1740 ccctacactc catcccaacc aagaaactgc atttcctggg gccaggtggg agctgccttt 1800 gccccactgc ctcccctgtt ctgctctctc agtcaacatg tggaaatcca aggaggacaa 1860 agactccagc cacgctgcta aatagggctc ctctctcctc tctctctctc taggtggtaa 1920 ggttggggat tagtccaggt acagaagcag aacttttttc taaggataaa catctcttcc 1980 aaggggatgg agagtgggtc cctcaacaaa gtccctgtcc agtcaccttt ccatcagggc 2040 actagcccag gaatgactcc tcacactttc acctttactg atttccagag gaaagctaga 2100 ggatctagtt caagaggcaa gaagatctgg ccctcaatta gctagatgta gatgctgcct 2160 aacagttccc tcctcaaagg ccaccttggt gctgtggggg ccccttgcct cttcccttcc 2220 cactggtgca ttacaaaaca gtgttctttt gaaatgttca tcaggaatag gcttttttaa 2280 aaaatgttgt gtatctgtat atagtattgt gatgtctgaa tgacaatgta ctgaatgcaa 2340 aaaggaaaaa aacccacaaa catgttttta aaataaaata tctttttttg ccttgaaaaa 2400 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2435 <210> 60 <211> 1803 <212> DNA <213> homo sapiens <400> 60 gcacaggcac cgcgtggttc tcacaaccag cagctcggct cactgagacc cggtggtcca 60 gacgctgctc ctggctgggg tggcgctgca gggagaaccg cgagctctca ggggtcggcg 120 ggtgacttct ttccggaaga aagcgaggaa cgcgctctgc ggggtgagcc ggactcccca 180 actccggacg atcagcccag gactgagagc cccgaagtcc ccaaccacaa gtaagcggcc 240 ccagaaggac aagtctaggt cgccgtccag agcgccatgg ccgcgcccgc ccttcgtttg 300 tgccacatcg ccttccacgt gcccgccggg cagcccctag cccggaacct gcagcgcctc 360 ttcggcttcc agcccctggc ttcgcgggag gtggacggct ggcggcagct agccctgcgc 420 agcggcgacg cggtcttttt ggtgaacgag ggcgcagggt ctggagagcc gctgtacggc 480 ctggatccgc gtcacgccgt gcccagcgcc acaaacctgt gcttcgacgt ggcggacgcc 540 ggcgctgcaa cccgggagct ggcagcgctg ggctgcagcg tgcctgtccc tcccgttcgc 600 gtgcgggacg cgcagggtgc cgccacttac gccgtggtca gctcgcctgc cggcatcctc 660 agcctgacct tgctggagcg cgctggctac cgcggaccct tcctacccgg cttcaggccc 720 gtgtcctctg cgcctggccc cgggtgggtc agccgcgtgg accacctgac cttggcctgc 780 acccccggca gctcccccac acttttgcgc tggttccacg actgcctggg cttttgccac 840 ttgccgctga gcccaggtga ggatcccgag ctgggcctcg aaatgacagc agggtttggg 900 cttgggggac tgaggcttac agccctgcag gcccagccgg gcagcattgt ccccactctt 960 gttctggctg agtcccttcc gggggcgacg acacgacagg accaggtgga gcagttcctg 1020 gcccggcaca aggggccagg cctgcagcac gtggggctgt atacgcctaa cattgtggag 1080 gccactgagg gggtggcaac tgctggaggc cagttcctgg ctccccctgg ggcatactac 1140 cagcagccag gaaaggagag gcagatccga gctgcagggc acgagcctca tctgcttgct 1200 cgacagggga tcctgctaga tggtgataaa ggcaagtttc tgcttcaggt cttcaccaag 1260 tcccttttta ctgaggacac tttcttcctg gagctgattc agaggcaggg ggccactggc 1320 tttggtcagg gcaacatcag agctctgtgg cagtccgtac aggagcaatc tgccaggagc 1380 caggaagcct aaggatgccc agggctgggt gcagccagct gtcctgcagc tctggggaga 1440 ccagcacaga actgaggaac atctgcagga ggcccaacta gtgaaaggct ttgcctccgg 1500 ggggcaggtg tgacttccat ttcatcagtg cctgccagaa gctgtgtctc tcattgggct 1560 ccaaagaggt gggatttttt aaaactaaaa catttcttat atacagtcta taataaatat 1620 gtaagataca aagaacaata aaagaattac acactaggaa atagaacata accaatactt 1680 tcgagtcctc cctgtgtccc gctgtgattc tatttcctcc cacccactcc tcaaatcctg 1740 tcattattag ccctttgctt ttctgtattg tttcactccg tatgtaacat aaccctaaat 1800 aaa 1803 <210> 61 <211> 971 <212> DNA <213> homo sapiens <400> 61 aacaaagttc agtgactgag agggctgagc ggaggctgct gaaggggaga aaggagtgag 60 gagctgctgg gcagagaggg actgtccggc tcccagatgc tgggcctcct ggggagcaca 120 gccctcgtgg gatggatcac aggtgctgct gtggcggtcc tgctgctgct gctgctgctg 180 gccacctgcc ttttccacgg acggcaggac tgtgacgtgg agaggaaccg tacagctgca 240 gggggaaacc gagtccgccg ggcccagcct tggcccttcc ggcggcgggg ccacctggga 300 atctttcacc atcaccgtca tcctggccac gtatctcatg tgccgaatgt gggcctccac 360 caccaccacc acccccgcca cacccctcac cacctccacc accaccacca cccccaccgc 420 caccatcccc gccacgctcg ctgaggctgc tgtcgccggt gcctgtggac agcagctgcc 480 cctgccctcc catctgttcc caggacaagt ggaccccatg tttccatgtg gaaggatgca 540 tctctggggt gaacgagggg aacaatagac tggggcttgc tccagctgca tttgcatggc 600 atgccccagt gtactatggc agcagagaat ggaggaacac tgggtctgca gtgctgaagg 660 gtttggggag tggagagcaa gggtgctctt tcggggctgg acagcccgtc ttgtgacagt 720 gactcccagt gagccccaga aatgacaagc gtgtcttggc agagccagca cacaagtgga 780 tgtgaagtgc ccgtcttgac ctcctcatca ggctgctgca ggcctctggc gggcagggca 840 ctgggagagg ccctgagaat gtccttttgg tttggagaag gcagtgtgag gctgcacagt 900 caattcatcg gtgccttagt ccaagaaaat aaaaaccact aagaagcttt aaaaaaaaaa 960 aaaaaaaaaa a 971 <210> 62 <211> 4578 <212> DNA <213> homo sapiens <400> 62 atttcaaagc acaccatgcc ggcagcactt ggaggtggta tgtgctggga aactgaccaa 60 cagtttagtc agactgagtc acttcaagga ggggagtgga gacagcagtg ggtgccagat 120 gacacggagc tgtcggcttc cgtgtgcatt ttcttttgat agtagccgta gagaagttgt 180 ccgccaggca gccctcaatg ggatttttca tttaagaaaa atcactctgc tcgtgcactg 240 atggagaaat gaactacaag aagcaagccc tgaggtctgg agacaggaag ctactgaaac 300 cagccaggga gtgagccata actggtggct gctcttgcgc caatgagcct ccccaattcc 360 tcctgcctct tagaagacaa gatgtgtgag ggcaacaaga ccactatggc cagcccccag 420 ctgatgcccc tggtggtggt cctgagcact atctgcttgg tcacagtagg gctcaacctg 480 ctggtgctgt atgccgtacg gagtgagcgg aagctccaca ctgtggggaa cctgtacatc 540 gtcagcctct cggtggcgga cttgatcgtg ggtgccgtcg tcatgcctat gaacatcctc 600 tacctgctca tgtccaagtg gtcactgggc cgtcctctct gcctcttttg gctttccatg 660 gactatgtgg ccagcacagc gtccattttc agtgtcttca tcctgtgcat tgatcgctac 720 cgctctgtcc agcagcccct caggtacctt aagtatcgta ccaagacccg agcctcggcc 780 accattctgg gggcctggtt tctctctttt ctgtgggtta ttcccattct aggctggaat 840 cacttcatgc agcagacctc ggtgcgccga gaggacaagt gtgagacaga cttctatgat 900 gtcacctggt tcaaggtcat gactgccatc atcaacttct acctgcccac cttgctcatg 960 ctctggttct atgccaagat ctacaaggcc gtacgacaac actgccagca ccgggagctc 1020 atcaataggt ccctcccttc cttctcagaa attaagctga ggccagagaa ccccaagggg 1080 gatgccaaga aaccagggaa ggagtctccc tgggaggttc tgaaaaggaa gccaaaagat 1140 gctggtggtg gatctgtctt gaagtcacca tcccaaaccc ccaaggagat gaaatcccca 1200 gttgtcttca gccaagagga tgatagagaa gtagacaaac tctactgctt tccacttgat 1260 attgtgcaca tgcaggctgc ggcagagggg agtagcaggg actatgtagc cgtcaaccgg 1320 agccatggcc agctcaagac agatgagcag ggcctgaaca cacatggggc cagcgagata 1380 tcagaggatc agatgttagg tgatagccaa tccttctctc gaacggactc agataccacc 1440 acagagacag caccaggcaa aggcaaattg aggagtgggt ctaacacagg cctggattac 1500 atcaagttta cttggaagag gctccgctcg cattcaagac agtatgtatc tgggttgcac 1560 atgaaccgcg aaaggaaggc cgccaaacag ttgggtttta tcatggcagc cttcatcctc 1620 tgctggatcc cttatttcat cttcttcatg gtcattgcct tctgcaagaa ctgttgcaat 1680 gaacatttgc acatgttcac catctggctg ggctacatca actccacact gaaccccctc 1740 atctacccct tgtgcaatga gaacttcaag aagacattca agagaattct gcatattcgc 1800 tcctaaggga ggctctgagg ggatgcaaca aaatgatcct tatgatgtcc aacaaggaaa 1860 tagaggacga aggcctgtgt gttgccaggc aggcacctgg gctttctgga atccaaacca 1920 cagtcttagg ggcttggtag tttggaaagt tcttaggcac catagaagaa cagcagatgg 1980 cggtgatcag cagagagatt gaactttgag gaggaagcag aatctttgca agaaagtcag 2040 acctgtttct tgtaactggg ttcaaaaaga aaaaaataat aaaaataaaa gagagagaga 2100 atcagacctg ggtggaactc tcctgctcct caggaactat gggagcctca gactcattgt 2160 aattcaagct ttccgagtca agtgattgac aactgaagag acacgtggct agggttccac 2220 tggagaattg aaaaggactc ttgagccctc ctggaatgga gctgtataac tgtgcagaga 2280 ctttatccat gccaatagtt gctgtcccct tccaggggtc accttgagag gcatgacagc 2340 tgttccacag gggctatccc ttctcagaaa acttctcttc tgagcctctt taacagcttt 2400 ctccagaacc agtgtctgaa ccaccctgga aattctgcct tattatttct tactcaaaca 2460 tgtttagagt ggatagaaaa ttatgcagct tgcacaccca tcgtctttaa ccccaaattt 2520 cctttggcta ttaaaaaagt ggtggcaaaa gacatcctca aaagaaagag aaatgaaata 2580 tttttgaatg gttgcacgtt aaaaattaaa agaaggaatg ggggcagaat gccatatttt 2640 tgagggctgt actaggttta tctcatttaa gccccacaac accccacagg agggtaattt 2700 tctaactcta gtttgcagag gagcaaattg aggttcagca aggtgagaga ggtacccaag 2760 gtcacatagc tagttatgtg agaaagttag agtacagatc ctctggggtt tcagcttatt 2820 gtagcatatt ttctccgaaa ggcaaaaatg tgcccttttg gccgggcatg gtagctcaag 2880 cctataatcc cagcatgttg agaggctgag gtgggcagat catttgaggc caggagttca 2940 agaccagtct ggccaatatg gagaaacctt gtctctacta aaaacacaaa aattatctgg 3000 gcatggtggg gcatgcctgt agtcccactt acttgggagg ccgaggcacg agaattgctt 3060 gaacccggga ggtggaggtt gccgtgagcc aagatcacgc cactgcactc cagcctgggc 3120 aacagagcaa gactctgtct caaaaaaaaa aatacaatat tttaacaatg tgccctctta 3180 agtgtgcaca gatacacata cacggtattc ccaagagtgg tggcagctca aaatgatatg 3240 tttgagtaga cgaacagctg acatggagtt cccgtgcacc tacggaaggg gacgctttga 3300 aggaaccaag tgcattttta tctgtgagtt ctgttgtgtt tgtcaaaaag tcattgtaat 3360 ctttcatagc catacctggt aagcaaaaac tagtaaagac ataggaacat gtagttttac 3420 ttggtgttta tgttgcaatc tggttgtgat ttatatttta aagcttggtg ctaaaccaca 3480 atatgtatag catatggagt gcctgtacaa gctgatgttt tgtattttgt gttcctcttt 3540 gcatgatctg tcaaagtgag atatttttac ctgcctaaaa tatgatgttt aaaagcatac 3600 tctatgtgat ttatttattt ctacctttct gagtctcttg gactaagaag atgttttgaa 3660 atgtaccatc aaatgttaac agagtttgat atgggctttc tctttggttt ctcatcacat 3720 ttgtaaatgt cttttcaaaa ggatttactt tttgtaaaaa gcttcattct cactctgctt 3780 tgcatccccc aaacttcttg ttcaaaacgg ggggagttta ggagacttta atcccggttt 3840 cagaagctgc agctggtctg tttccaggtc agaaaccatt gttcagaaga cctccctgtg 3900 agagagttgc tcctcagggt ccctcaggac caaagaacac tcgaaaagag cacttcacac 3960 agacaagtgg ctaagtgtcc attatttacc ttgaacaatc aaggcaacta gtggagagaa 4020 ctgattgtga gctctgcctc tgggtcagag agacctggat ttgagtctga caagaacaag 4080 aaatggtcaa taaatataaa ttaccagcgt ctaaggaaca aggtctatgc attattgtat 4140 acagtgtctc tagtgcttgt atagtgtctg gtatacagag ggcactccta tgcattttta 4200 aaacatgctg agcacatacc atgtgccagg ctttgtgttt tatctaatgt tatctaatgg 4260 tattggtgcc attatgtaat gttgccttta caacaacctc atgagggaga tttccatctt 4320 tacaaatagg caaactgagg cccagagaga ttgaggaact gctccgaggt ctgattctgg 4380 aatgtgcttc ctttccactt tatcaatctg ctcttcgtac tcctgtctga acgatggaaa 4440 ttaatttttg aatgtataaa agacaacaga ctatgataca gaaatgtcag ccccagccca 4500 ctaagaaagc cccagcccat cagtggctaa tggctttaat aaattggtca tttggctaaa 4560 aaaaaaaaaa aaaaaaaa 4578 <210> 63 <211> 5416 <212> DNA <213> homo sapiens <400> 63 actccacctc ggtccacagc tctcttcctg cgcagttcgc ctctgcagcc tctgcgggga 60 agtgccgggg ctgctcgagg ctcagttctt aggactgcaa ggaggcagcc ccggcgtgcg 120 gcggtgcgca cagtctagag tggccagggc gcgagagtgc aacgtcctcc tggccccgag 180 cgcgtcgtcg cgccccggga gcagaccctc gcccagcagt taccgccgtc ccgactttcc 240 gttccagttg cagctcctgc cgggcaacat gtcaagagcc gccgccgcta cagctgccgc 300 cgccacctgg ggaagagcag cagcagcagc ggcggccgcg ggcacacggg ggcaataaac 360 cgagccaccc gggcgtccag cgtgccgggg aaccctctct gcgctcactg cccggcggga 420 cccacgccat gtgctgagcc atgtccctgg ccgcgcccgc gggcagcgca tggggcagcg 480 cctgagtggc ggcagatctt gcctcgatgt ccccggccgg ctcctaccgc agccgccgcc 540 gcccccgccg ccggtgagga ggaagctcgc gctgctcttc gccatgctct gcgtctggct 600 ctatatgttc ctgtactcgt gcgccggctc ctgcgccgcc gcgccggggc tgctgctcct 660 gggctctggg tcccgcgccg cacacgaccc gccagccctg gccacagctc cggacgggac 720 gccccccagg ctgccgttcc gggcgccgcc agccacccca ctggcttcag gcaaggagat 780 ggccgagggc gctgcgagcc cggaggagca gagtcccgag gtgccggact ccccaagccc 840 catctccagc tttttcagtg ggtctgggag caagcagctg ccgcaggcca tcatcatcgg 900 cgtgaagaag ggcggcacgc gggcgctgct ggagtttctg cgcgtgcacc ccgacgtgcg 960 cgccgtgggc gccgagcccc atttcttcga tcgcagctac gacaagggcc tcgcttggta 1020 ccgggacctg atgcccagaa ccctggacgg gcagatcacc atggagaaga cgcccagtta 1080 cttcgtcacg cgggaggccc ctgcgcgcat ctcggccatg tccaaggaca ccaagctcat 1140 cgtggtggtg cgggacccgg tgaccagggc catctcggac tacacgcaga cgctgtccaa 1200 gcggcccgac atccccacct tcgagagctt gacgttcaaa aacaggacag cgggcctcat 1260 cgacacgtcg tggagcgcca tccagatcgg catctacgcc aagcacctgg agcactggct 1320 gcgccacttc cccatccgcc agatgctctt cgtgagcggc gagcggctca tcagcgaccc 1380 ggccggggag ctgggccgcg tgcaagactt cctgggcctc aagaggatca tcacggacaa 1440 gcacttctac ttcaacaaga ccaagggctt cccctgcctg aagaaggcgg agggcagcag 1500 ccggccccat tgcctgggca agaccaaggg caggacccat cctgagatcg accgcgaggt 1560 ggtgcgcagg ctgcgcgagt tctaccggcc tttcaacctc aagttctacc agatgaccgg 1620 gcacgacttt ggctgggatt gagcagaccc gggctatgta ccttacccac gtggcttatc 1680 tattgacaga gattatatgt atgtaaaatg tacagaaatc tattttataa taatttattt 1740 ttaattcata agcaattaat tcactaagct gcctagccac actctttaga gagttagctt 1800 cataatctgt taacattcca aagtgtttaa ctctagtatt tcgttctctt cttcacaatt 1860 gatggtgctt ctattttttc ttctccccta cctgttatat ttaaaacaaa gaaaagcaca 1920 acttgagatt tttgttgtta cgggtattca gccttcagtc accgtctgag ttctccagtt 1980 gctgcctcct tgtcttgtct tgggtctccc attccagctt ccctgtctct tcctgcctgt 2040 gtacctcgta ggaacgctga gctgcctcaa cagggctgta ttctgaaggg caggcctcat 2100 gcagcagcct ccttgcagat gtggtgtccc gtccaatgat gtagcctgaa agccacagcc 2160 ctagggttct gtccctccct ccattcagca catggggaaa tttctcactc cctttacagg 2220 gacatccaca tccttttttt ttcttttttt tttttttttt tttttgagat ggagtcttgc 2280 tcttgttgcc caggctgggg cgtaatggtg tgatatatgc ttaccacaac ctctggctcc 2340 cggttcaagc gattctcctg tctcagcctc ccaagtatct gggattacag gcatgcacca 2400 ccatgcctgg ctaattttgt atttttagta gagacggggt ttcttcatgt tggtcaggct 2460 ggtatcaaac tcccgacctc aggtgatccg cctgccttgg cctccaaagt gttgggatta 2520 taggcgtgag ccactgcgcc cgctatccac atccttctag agtcagaatg gtagggtctg 2580 ttgacttcag cttttgattt tgcaggatgg ccctgtgtcc tcctctgccc cattccctgg 2640 ttcattaacc agtttgaagt gtatgtagat tgttgccccg tctttcccag gtcacatgtg 2700 tgagatgcct gggtgctgct tcagaaatca agatgatctc ctttaatttg catgaaacta 2760 caccatgctg cgttccccag gcagacagtt ctgctttgac acaccaaaga atcccgtagg 2820 ctagcagagc caccagcaca aaccaagggc gctgggtgtc gagactcaga ggggtcagct 2880 gtgtccctcg gcatcagcgt ctaccaaggt gctgctaggt acagagccag ccagtgttgg 2940 gcagcaggct cacagcctca atagggagaa aagacaaagg cctcaaaatg acaggcagcc 3000 tgacagagga aggagtctga cacctcagct tgatgcgtct ttggaattcc tagctcatct 3060 cagaattata tcttagagtg ataatatggg tggtagccag tggccaaaca gcaagaacta 3120 agagtggccc ttgcaaaaaa aggttgggaa agctgggccc atattgcctg taaacccttg 3180 agcctgatgc tcatacagct gtcccttgtt ttagccaggt cttgacagaa gggttaccag 3240 cactgtcact gctctacaga atgctctccc cgtgcctctc tgttgattta taacagttgg 3300 gtaaccagat agcaatatag tggcaattga gtagccatat agtaatacag gggcagttgg 3360 ttaaacatat agcaatatca cataatgata tgtttaattt aacctcagtt ttttaaacca 3420 gaatgcttct accataaaag aattgtgatt tcagttatac ttccatcaag gaatatgtgg 3480 gaagatatac atattgtcaa aatggttggg atgggatagt tacaaaggac acttttgtat 3540 gttgtatggg atcacttgcc tgatagtata aggaacattg tatgaaaaga tgaaaagata 3600 cttcattttt agaaactgat cagagatgtc actggtcttt aagtgatgtc ttgaaaatcc 3660 agtatgtatt tgcccaaaag ttttagccta catctagcta gcttacactt agcagccaaa 3720 ccatcattgt gtaggttctg ttttggagga agctcatggg ggatctgtgt atttcttagg 3780 tttctccctg ttctccaatg ttttatccat ttcgtagctt ttttactgtc tccagaaagt 3840 agtgtgggac ctgcacttag gggaatacca gaatcatagc gtggttctgc cttcttgatg 3900 agtgattgtg aaaaacacct gcataagggt gctaattggt tgtgtatttt ttcatttatt 3960 tgaaatcaaa ctgagaacac ctcttttcgg tttacagcat aacatggctt gaagtaaaag 4020 gcagtatcca agtccttcac ctggtcttgc cctgtctact ttctgatcat tctgatggtc 4080 tgatgtggct gttgatgtgg aactgcagaa gagttcagag aagagtatgc aacaaagcca 4140 taggaaaaca cacaggagct tttccctccc cttcaggtcc ccgccctctt tccaagctgg 4200 acaatttttt attaagttgt ttattccctg ccttaaaact gaaacaggaa attttctggt 4260 agaaggaggg tcatttagtc acgaacactg aagtgggtca aaattctatt ctgggtcaaa 4320 tccttgaatt caaacagatg tccataatca gtactgatgg aatagagcaa gtttttctat 4380 gtaagacaaa taaatcaaac atcatgtgca tctcctcata agggtctgca agggtctgat 4440 ggtttaaagt tcctaacaga tctggttgca gcatctgccg gagcttgcac cccatcatcg 4500 gacggtcatc ttcctgctgc agaagttagg taacataaga cttagatttc ttcctgttct 4560 agcaatctgc aagaccacca ggcttaactt tttagctgcc agaagacaaa cccccttttc 4620 tgtttcggca atttgtcctg gcacgtgttt tggacttcct ccgatttaca cgaaaagctc 4680 tgatattcat tggagtactt tatttttttt cctcagtttt gtttcttttc tcatgtaaaa 4740 acaaacaaaa aggtcaacaa aaaaaaattg aggtttttct tgtttctatc tagttcatgc 4800 tttctttgcg gtgtttgaac agtagtctgt taacttagta ggtggtacct ggaaaggtat 4860 tttaagtata gtgactgttt aataaatact taattggatg atggaggagg agaaattgtt 4920 ttcttcccag gattctcttt gggggtcatt ttgtgtgaca gatatatttt agacatttgg 4980 agaaacagtt tcagatcctg ccaggatatt tttgtaaaaa aggaaaatgg aagattccaa 5040 taaactagaa acagtacgta tctaagatgc tgacacagaa gctaatgtga cttttcagct 5100 tatcaagagg atggccaata aaacttaaag gtgtggttag atgttttctc acttttgtga 5160 cattaattta tcactgagtc tcattcaacc aagtaatcta aaatactgtg caaattctag 5220 cagtatgtct tcgataactt ggatgttagg atagccaata tgtacaaaaa attaaatcaa 5280 gtattttgtc ctatgtataa cacaaattaa ttttacacag agaaagatgt ttctaggcaa 5340 gtgaaattct ggtaattcat actatttctt tgtatgaaca aataaaatat attttgccaa 5400 aaaaaaaaaa aaaaaa 5416 <210> 64 <211> 1730 <212> DNA <213> homo sapiens <400> 64 gcataaagct ccagtccttc ctccagggat gaggcagtaa ggacttggac tcctctgtcc 60 agcttttaac aatctaagtt acgccctctt ctgggtcacg ctagaatcag atctgctctc 120 cagcatcttc tgtttcctgg caagtgtttc ctgctacttt ggattggcca cgatgggctg 180 gagctgcctt gtgacaggag caggagggct tctgggtcag aggatcgtcc gcctgttggt 240 ggaagagaag gaactgaagg agatcagggc cttggacaag gccttcagac cagaattgag 300 agaggaattt tctaagctcc agaacaggac caagctgact gtacttgaag gagacattct 360 ggatgagcca ttcctgaaaa gagcctgcca ggacgtctcg gtcgtcatcc acaccgcctg 420 tatcattgat gtctttggtg tcactcacag agagtccatc atgaatgtca atgtgaaagg 480 tacccagcta ctgttggagg cctgtgtcca agccagtgtg ccagtcttca tctacaccag 540 tagcatagag gtagccgggc ccaactccta caaggaaatc atccagaacg gccacgaaga 600 agagcctctg gaaaacacat ggcccactcc atacccgtac agcaaaaagc ttgctgagaa 660 ggctgtgctg gcggctaatg ggtggaatct aaaaaatggt gataccttgt acacttgtgc 720 gttaagaccc acatatatct atggggaagg aggcccattc ctttctgcca gtataaatga 780 ggccctgaac aacaatggga tcctgtcaag tgttggaaag ttctctacag tcaacccagt 840 ctatgttggc aacgtggcct gggcccacat tctggccttg agggctctgc gggaccccaa 900 gaaggcccca agtgtccgag gtcaattcta ttacatctca gatgacacgc ctcaccaaag 960 ctatgataac cttaattaca tcctgagcaa agagtttggc ctccgccttg attccagatg 1020 gagccttcct ttaaccctga tgtactggat tggcttcctg ctggaagtag tgagcttcct 1080 actcagccca atttactcct atcaaccccc cttcaaccgc cacacagtca cattatcaaa 1140 tagtgtgttc accttctctt acaagaaggc tcagcgagat ctggcgtata agccactcta 1200 cagctgggag gaagccaagc agaaaaccgt ggagtgggtt ggttcccttg tggaccggca 1260 caaggagacc ctgaagtcca agactcagtg atttaaggat gacagagatg tgcatgtggg 1320 tattgttagg aaatgtcatc aaactccacc cacctggctt catacagaag gcaacagggg 1380 cacaagccca ggtcctgctg cctctctttc acacaatgcc caacttactg tcttcttcat 1440 gtcatcaaaa tctgcacagt cactggccca accagaactt tctgtcctaa tcatacacca 1500 gaagacaaac aatatgattt gctgttacca aatctcagtg gctgattctg aacaattgtg 1560 gtctctctta acttgaggtt ctcttttgac taatagagct ccatttcccc tcttaaatga 1620 gaaagcattt cttttctctt taatctccta ttccttcaca cagttcaaca taaagagcaa 1680 taaatgtttt aatgcttaac atggagagaa aaaaaaaaaa aaaaaaaaaa 1730 <210> 65 <211> 8333 <212> DNA <213> homo sapiens <400> 65 aatgttctga ccggtttggt gtttgtcatt tcactttatt aagtaaagag gaaatcggga 60 aaggaggaat agagagggtc cccgagttca ttcaagagca gaccgagaga tgctccgatc 120 ccgagtcggg ccggtggcgg ggtcaggccg gcgcccgagg ggggcgaacg cggacgccag 180 gtcgcgcggt ttaaatctcc cgcctcccgc agcgggagcc tgacacctcc acgcactggt 240 gcggaggggc actggctgcc ggagggccgg gagtcggcgc ggggctcgcg ggcggtggcc 300 ggaacgggtg ccgggacgga tcaccgtacg gccgaacgcg acccgaggag gcggaagagc 360 ggcgccggcg acgtactgta agacgatatt actttaatca tcttcacatc agtatttatg 420 gaatagccac aggtgcctca tcctttagta ggagttaatt atacatttac tggccgagta 480 aacatctccg aatgtcactc catggattcc tttgggcaac ccagaccaga agataatcag 540 tcagtagtca gaagaatgca aaagaaatac tggaaaacta aacaggtctt tatcaaagca 600 acaggaaaaa aagaggatga gcacttggtg gcgtctgatg ctgaactgga tgctaaactt 660 gaggtttttc actctgttca agagacatgc actgaacttc tgaagataat cgagaaatac 720 cagctaagac tcaatgttat atcagaggaa gaaaatgagc tagggctctt tttaaaattt 780 caagcagaac gggatgcaac tcaagctggc aaaatgatgg atgccactgg caaggcactt 840 tgttcttcag ccaagcaaag attggccctg tgtactcctc tgtctcgtct gaagcaagaa 900 gtagcaacat tcagtcaaag ggcagtatct gataccttga tgacaattaa tcggatggag 960 caggcacgca cagaatacag aggagctcta ctgtggatga aagatgtatc ccaagagctg 1020 gacccagaca ccttaaagca aatggaaaag tttagaaaag tacagatgca agtgagaaat 1080 agcaaagctt cttttgacaa gttaaagatg gatgtttgtc agaaagtgga tttacttgga 1140 gctagtcgct gcaatatgct atctcattcg ctcactacct accagagaac actgcttgga 1200 ttctggaaga aaacagctcg aatgatgtcc caaattcatg aagcctgtat tggctttcat 1260 ccgtatgatt ttgtagctct caagcaacta caagacacgc caagcaagat tagtgaagac 1320 aataaagatg aacaaatagg cggttttctt actgaacagc tcaataagct agttttgtct 1380 gatgaggaag caagctttga gagtgaacaa gcaaacaaag atcacaatga aaaacattct 1440 caaatgagag aatttggagc acctcagttt tctaactctg aaaatgttgc aaaagatcta 1500 cctgtagatt cattggaagg agaagatttt gagaaggaat tctcatttct gaacaacctc 1560 ctaagttctg gttcttcaag tactagtgaa tttacccaag aatgccagac tgcctttggg 1620 agccccagtg ccagtctcac atcccaggag ccttccatgg ggtctgagcc cctcgctcat 1680 tcttctcgat tccttccttc acaactcttt gaccttggct ttcatgtggc tggagcgttc 1740 aacaactggg tctcccaaga ggaatcagaa ctttgtcttt cacacactga taaccagcca 1800 gtgccttcac agagtccaaa gaaattaaca agatccccca acaatggcaa ccaagacatg 1860 tcagcctggt tcaatctgtt tgcagacttg gatccacttt caaacccaga tgctattgga 1920 cactcagatg atgaacttct taatgcttga ctgaagttat aatgtcactt cagtggcctt 1980 gagacatcaa ttttgcaacg tatttccttc gtggaaagga tttagattgt aacccgcaca 2040 caaaagcacg gtgtttgtga atataacacc tgtcagccaa ctttagacag atggtaaaga 2100 ccacatttga ataagtacac atctttcata tcttggattt gcagctgttg gtactatgtg 2160 gaaaatatta gaaacttcta tgtggaaaat attagaaact acagagtttg cgatatttag 2220 atactgaaat ttatgtcaaa ataacggcta ggaataattc tgtcaatatg gagttgagct 2280 tatttctttg gaaacccttt taagttgcct tgctggctgt gagaatttta tatgtggata 2340 acaaagatag atagatagca tgtaaattgg gttgtggttt ggggtcagtt tttaaatgaa 2400 atagtagcga ggaggatttt ctgttttgga aaacaccatt agaaccagac cagctttgtt 2460 ttgggttaga gagagtaaga tttgagaact cagtttgctt taatgaaatc acagagaaac 2520 ttggtacttg tttttcttca tttggaggct aaaatgtaat gttttttcat tcatacaaaa 2580 taatggacac tccctaattc cattattaaa tcttgaaggg gaagtagcag gataattaat 2640 ttgctaagcc catcctctgc agaaacagaa aaatctatct tcccatctcc taaaactcag 2700 aatgcacagt aatacttaag gcttgtacaa gtgtcttcag acccactttt tcatacactt 2760 gctatatagt agtatgcagt atttatatta ttcctgaaaa taaaatgagg ggagaatatt 2820 ccctaagcaa ctggcaatag tattcctgaa atacctagaa atttctatct gaatgaggga 2880 gacacttatg aacaccttat ccttacatat atttgcatac ttatctcata ttttgtgaca 2940 taattattta acccagaata ctttctggca gacatacaga aagctctgtg tgatcaataa 3000 gggagtgtct catttttcta cttccctctt tctgtgggtg acatgatctg aggttctatt 3060 tgattactaa gcaaaatctg ttacccctac agggtttaga acctaagtat tagagaggaa 3120 ggctatttaa tggaagttag tgtaagctga taaaaacgta gctaccgtac acacacatca 3180 atcactcaat ttcctgtcct tttaaattgc ccacccttta attttgaagc aatttcccaa 3240 gtgtgtgttt gttttatatt tgtcatccag tccattgcat ttccataaga agacattttg 3300 actggctggg tgcggtggct cacgcttgta atcccagcac tttgggaggc tgaggcaggc 3360 ggatcacgag gtcaggagat ggagaccatc ctggctaaca tggtgaaacc ccgtctctac 3420 taaaaataca aaaaattagc caggcgtggt ggcacgtgcc tgtagtccca gctactccgg 3480 aggctgaggc aggagaatgg cgtgaacccg ggaggcggag cttgcagtga gctgagatgg 3540 cgccactgca ctccagccta ggcaacagag caagactccg tctcaaaaaa aaaaaaaaaa 3600 aaaaaagaca ttttaactaa gttattcaca gtagcttcca tgtgctctta gttctattct 3660 aaacaggctt atttagaaaa ggattgcttg taatgtttgt catggtacat agaaaacatt 3720 ggaccagagt aggtaaaatg cagtccatgt cccatccata gccatctaca atagtaactg 3780 cccacaggct ctccagaaaa ctactacaat ggccaagtac agtataggct ggaaagacct 3840 tatctgaagg tcagaaacat tgactcagaa aaaaggtatg aagtctttcc ataaaatctt 3900 ttcacaatat tactcctatt tcttttagat tttaatgagc cattacttat ctcttcagaa 3960 gacttaagtc ttcctttata ctcagtgaaa tttcccagaa tgtaatactg tcactgttct 4020 gccaagttcc aatcaccaag atcatgatta cgaatcccaa tctgaattct atacccatgg 4080 tgactctgat gctctcaact tttgagtgcc tcaaaaaatg ctaaaacttt ggctgggcat 4140 ggtggctcac gcctgtaatc ccagcacttt gggaggccat ggcgggtgga acatttgagg 4200 gcatgagttc gagaccagcc tggccaacat ggtgaaaccc tgtctctact aaaaatacaa 4260 aaattagcca ggtgtggagg tacatgcctg taatcccagc tactcaggag gctgaggcag 4320 aagaattgct tgaacccagg cggcagaggt tgcagtgagt cgagattgca ccactacact 4380 ccagcctggg caacagagag cgactctctc aaaaaaaaaa aaaaaaaaaa aaaaaaaagc 4440 taactttatg tcttgagagt ttgtaccatt tttctttgta gtggtcacct tgctaatgca 4500 ttagttctga gatatttatc tccctcacat gtgtgcaagg aagtccctgt tatcgaatac 4560 agatacttta acaagcagac aaagcagaaa cccaaagtcc atactaggaa caccctaaat 4620 tttccaaaag caaaagttct cccgaaatgg agacatacaa gggactttta ttattctgtt 4680 actagtttct ataacatttc ttctttcaac agagtatatg tttcccattt aacccagagc 4740 aacattaact tccttagcaa gtccagttct aacttccaac aagtccaacc actgtttttg 4800 aagagcatat cagtaactat attaagatga aggtaaccac attcgtattt tctcaagatt 4860 agttatttga agctcagcag tttttgtggt cagaaagaaa ttttgctcta ttaaaccaat 4920 actgctaata taaaaaacca ccacactgaa gaaacgaggg aaaggacggg ataagcacag 4980 aacagagaat gactggttgc tttttgtctc aatctagata atccattcaa taagaagtaa 5040 attaattatc cttaaccaat ggtaggctga gaacaaccct caaaatagat attttttatg 5100 ttaaatgggg agaaatatct atactttatg ttatactgga taaaaatgtg ttttaagtct 5160 aaaaaaaacc agacgagcta aactttgcct agtgtgtcta caaccatttt ttaggagacg 5220 caggaatacc agggcataat aagatcagat tggtgtaatt ttgtatgttt ttgaaatcct 5280 tcattaattg tagaaccttg atatgattag aaacaaactg tatttcaaca aacaggtttc 5340 agtatttgca cactgaaaaa gtgttttgta ttttaactat aaatatttca cgtatctgta 5400 tagaccatct agaaatgtag aggtcttaca gcattagaac gaaggaagtt tacatgtgct 5460 ctatctattt ttctgagcct cttttaataa agattgcaag aaggcataaa acaagagttt 5520 gtttcctgaa gtttttagta caattattgt tttcctattc aaaaacttgg gttttacctc 5580 aagatcatag tattaggaaa gtacattgag ttgatacgga catgggagaa cgaaaataaa 5640 accagggcaa ttaatatcct tgtaaggcca ggcgcggtag ctcacgccta tataacagca 5700 ctttgggagg ccaaggcagg cagatcactt gaagttggga gtttgagacc accctggcca 5760 acatggtgaa accccatctc tatgaaaaat ataaaaatta gctgggcatg gtggcagatg 5820 cctgtaatcc cagctacttg ggaggctgag gcaggagaat cgcttgaacc cgggaggtgg 5880 aggttgcagt gagctgagat caggccatgc actccagcct gggtgacaga gtgagactcc 5940 gtctcaaaag aaaatccttg tgagatgaat tcgttcttat ttcatataca aggggactat 6000 gtaagatatg ggaaataata taatgtacgt tatttatgta aatactttca gtaacaaaaa 6060 ctaacaaata tcaaaaatct gagcctagac acaaacaatt aaatataagc catagtatgt 6120 aacctgactt attgaaggca ggaataaaaa gaagagagcc agaattgatt cagttatttt 6180 tgtcttccat agtgttggca gggccctgca tttctctacc ttgagcaatg aagcagtccc 6240 agaattttgg aatatagaaa ttaggaagga aaaacgaact ttaaaatatt aatttagtag 6300 aactgaaagt aatgcatttc atgcaacagt aaagtgctta aacatggcaa agaaaactaa 6360 gggacaagat aagaaaaatg gttggtaaag atgggtcaca tccagaagcc caacataagc 6420 tatttttcca tctttttctg taccatttaa aagactacta aagagttcaa aacaaactgt 6480 ccttggcatt taaagtcaaa acatggttct tcactcagtg gtgtaaatta actactcatt 6540 ggccaaagag taaatacaaa aaggagatga agttctgact ggtgttgtgg gtgagatttt 6600 gcagtgtatg tttttacatt tgtagtgtac gttttaaact tccggttttc ttgctgcctc 6660 aacatctcca caaacaggct gtgagcacct ggcccagtgt gatatgggtg gcccctgcca 6720 caagtttccc ttgctacctt gcccatgacc tagtaacatt taaatgcacc agtgaaattc 6780 tctttttctt gtgtgcttct ccctgaccca aaggctcctg cccatgtctt aggcctctcc 6840 gctccccacc tgcttggctg agccccctcc catgtgaccc cctctcagca tgcagtgact 6900 ggtctctcta ggacctgtga gtatattaca actttttttc ctgtgtctct cctgtgatat 6960 ctcttgtggc taaacctcac tgaccataac ctaaaaaaac acatacaaaa aacatgaaag 7020 aaaaagttgt ttcttgagct ggcctggacg aacggggagc caggggctcg accctggctg 7080 ttggaggcgc agtgaggcct ggtctccggc tgccagacca cgctgagcgg agcgcgcggc 7140 aggctcgcct cagcgctgcg gggaacgcgc gcgccgccgt ccgcggtcgc ccgtaggtgc 7200 ctgcacgcgt cggggtcacg gcctttggcc gacaggagcg agaagactca ggagccgccc 7260 cgcgccttcg atccggcgct gctggagttc ctggtgtgcc cgctctccaa gaagccgctc 7320 agatatgaag catcaacaaa tgaattgatt aatgaagagt tgagaatagc ttatccaatc 7380 attgatggga ttcctaatat tatcatatta ggcagctagg atgacacatc aaagaagcaa 7440 gaagtggagc agcgctagtt cataatttaa aaaaataaaa cagccaactc ttcttagtac 7500 catatacctt ttaaaacaca gtggcaagta ataagcggaa gagaagaatc tttctgtctc 7560 tttctacgtt gactgttctt attccactgg tttatttagc aggactgttc cactcagcct 7620 ctgtagaaga aaacttccca cagggctgca cttgcacagc tagcctttgc ttttacagcc 7680 tgctcttgcc tattaccata ccggtgtatg tattcttcca cctttggacc tggatggtta 7740 ttaaactctt catgcataac tgatgcaact agagtcaata tgctgtatat attaatgata 7800 gctcttgggc atctatctct gaaagctcaa atggatggaa tttagtttgt gggaaagagg 7860 ctttgctttg agcatatcag gcttaggact gtggacggct taagttgcag acgcttcttt 7920 tattgtactc ttgttctgcc cgtgtttttt gaaggctctg acataactgc tttatcagaa 7980 gaaacatttt gacagtgtct tgttggagat aaacatccct aattgacatg tgatgactac 8040 ttcttattcc attcatctaa gagtcattga aattttgttt tctttgtttg tttagcttca 8100 aggtctttgg tagtcacatg ttagggatga ctgaaataat tccaaaggag tgatgttgga 8160 atagtccctc taagggaaag aaatgcattt gaacgaatgt gatataaaac cacataatca 8220 aatagaaatt tcatgtactt acaaaaattt agtttgtaaa attaccttca tttctttgac 8280 attaaatgct tatattagca ataaagatgt tgacactttc tcataaaaaa ttt 8333 <210> 66 <211> 2294 <212> DNA <213> homo sapiens <400> 66 agtccagatg atagttaaga aagcagtaag aatacagaga gtccacaatg agatgaaaat 60 gcactgccag ttgaaacatc ctcctacact ggagctttat aaatatttta aagacaagga 120 ttggattaga tttgacatta gaaatgtacc ataatacaga aggcaatgga cacctaaaga 180 acagaatgaa aaccttctta ggaaatgaag cttgacactt cacccaccag gccaccacaa 240 gaatgttgca ttttcattat tatgatactt caaacaaaat aatggagccc cacagaccga 300 atgtgaagac agcagtgcca ttgtctttgg aaagctatca catatctgaa gagtatggct 360 ttcttcttcc agattctctg aaagaacttc cagatcatta taggccttgg atggaaattg 420 ccaacaaact tcctcaattg attgatgctc accagcttca agctcatgtg gacaagatgc 480 ccctgctgag ctgccagttc ctgaagggtc accgggagca gcgcctggcc cacctggtcc 540 tgagcttcct caccatgggt tatgtctggc aggaaggaga ggcgcagcct gcagaggtcc 600 tgccaaggaa tcttgccctt ccatttgtcg aagtctccag gaacttgggg ctccctccta 660 tcctggtcca ctcagacttg gtgctgacga actggaccaa aaaagatcca gacggattcc 720 tggaaattgg gaacctggag accatcatct catttcctgg gggagagagc ctgcatggtt 780 ttatactggt gactgctttg gtagagaaag aagcagtgcc tgggataaag gctcttgttc 840 aggccacgaa tgctatcttg cagcccaacc aggaggccct gctccaagcc ctgcagcgac 900 tgagactgtc tattcaggac atcaccaaaa ccttaggaca gatgcatgat tatgtagatc 960 cagacatatt ttatgcaggc atccggatct ttctctctgg atggaaagac aacccagcaa 1020 tgcctgcagg gctgatgtat gaaggagttt cccaagagcc cctgaaatac tccggcggga 1080 gtgcagctca gagcacagtg cttcatgcct ttgatgagtt cttaggcatt cgtcatagca 1140 aggaaagtgg tgactttctg tacagaatga gggattacat gcctccttcc cataaggcct 1200 tcatagaaga catccactca gcaccttccc tgagggacta catcctgtca tctggacagg 1260 accacttgct gacagcttat aaccagtgtg tgcaggccct ggcagagctg cggagctatc 1320 acatcaccat ggtcaccaaa tacctcatca cagctgcagc caaggcaaag catgggaagc 1380 caaaccatct cccagggcct cctcaggctt taaaagacag gggcacaggt ggaaccgcag 1440 ttatgagctt tcttaagagt gtcagggata agaccttgga gtcaatcctt cacccacgtg 1500 gttaggaggc tgccctctcc ccagcaatgc agagccccca tggagggcag gtgggcctgg 1560 agaatgaggg tcagggttct gcctgggatc atccaggaag gatctcagcc ctattcatgt 1620 ttctgctcta cagagcacta tattctcctt gttgagagct gttggcttca caaaggagag 1680 ttgatgtggc caagcctttc cctccctacc tgatcactgc ttaacggcat gtataatgga 1740 tacttcctca tgcagaaccc ccagaggagt gactgtatgc cattctcttt gccaagtaat 1800 agaaaaccaa tctaaatgtc aaaaatcaga taaaattgcc tggggataca ttacttgttg 1860 attttcttaa aaaacaaatt cacttaacaa ttcattaagt tcatactgag cactgcctcc 1920 aagattaaaa ccaggatttc tgtggtccca gaccagccct cttctccctg aatgtgttga 1980 gttggtggca ggaggttgga aatgctccag tggagatggg aagatagagg atgctgacaa 2040 taaggacttg gaagtcacta gtgtgaaaat gagcagttaa tgatatggga acggatgaga 2100 ctttccacgt ggtacctaga tttgcaaatt ctattgtaat gcctttattt ttagaagaat 2160 tattctctct tcttactctg aaaatctgta tttgtaaaat gaatgaatgg atcctatata 2220 agtaaataag aaaactggga ataagtagta aatcaatgtg tttagtgtgc aaataaatgt 2280 aaatgctttt attg 2294 <210> 67 <211> 1629 <212> DNA <213> homo sapiens <400> 67 acacatcagg ggcttgctct tgcaaaacca aaccacaaga cagacttgca aaagaaggca 60 tgcacagctc agcactgctc tgttgcctgg tcctcctgac tggggtgagg gccagcccag 120 gccagggcac ccagtctgag aacagctgca cccacttccc aggcaacctg cctaacatgc 180 ttcgagatct ccgagatgcc ttcagcagag tgaagacttt ctttcaaatg aaggatcagc 240 tggacaactt gttgttaaag gagtccttgc tggaggactt taagggttac ctgggttgcc 300 aagccttgtc tgagatgatc cagttttacc tggaggaggt gatgccccaa gctgagaacc 360 aagacccaga catcaaggcg catgtgaact ccctggggga gaacctgaag accctcaggc 420 tgaggctacg gcgctgtcat cgatttcttc cctgtgaaaa caagagcaag gccgtggagc 480 aggtgaagaa tgcctttaat aagctccaag agaaaggcat ctacaaagcc atgagtgagt 540 ttgacatctt catcaactac atagaagcct acatgacaat gaagatacga aactgagaca 600 tcagggtggc gactctatag actctaggac ataaattaga ggtctccaaa atcggatctg 660 gggctctggg atagctgacc cagccccttg agaaacctta ttgtacctct cttatagaat 720 atttattacc tctgatacct caacccccat ttctatttat ttactgagct tctctgtgaa 780 cgatttagaa agaagcccaa tattataatt tttttcaata tttattattt tcacctgttt 840 ttaagctgtt tccatagggt gacacactat ggtatttgag tgttttaaga taaattataa 900 gttacataag ggaggaaaaa aaatgttctt tggggagcca acagaagctt ccattccaag 960 cctgaccacg ctttctagct gttgagctgt tttccctgac ctccctctaa tttatcttgt 1020 ctctgggctt ggggcttcct aactgctaca aatactctta ggaagagaaa ccagggagcc 1080 cctttgatga ttaattcacc ttccagtgtc tcggagggat tcccctaacc tcattcccca 1140 accacttcat tcttgaaagc tgtggccagc ttgttattta taacaaccta aatttggttc 1200 taggccgggc gcggtggctc acgcctgtaa tcccagcact ttgggaggct gaggcgggtg 1260 gatcacttga ggtcaggagt tcctaaccag cctggtcaac atggtgaaac cccgtctcta 1320 ctaaaaatac aaaaattagc cgggcatggt ggcgcgcacc tgtaatccca gctacttggg 1380 aggctgaggc aagagaattg cttgaaccca ggagatggaa gttgcagtga gctgatatca 1440 tgcccctgta ctccagcctg ggtgacagag caagactctg tctcaaaaaa taaaaataaa 1500 aataaatttg gttctaatag aactcagttt taactagaat ttattcaatt cctctgggaa 1560 tgttacattg tttgtctgtc ttcatagcag attttaattt tgaataaata aatgtatctt 1620 attcacatc 1629 <210> 68 <211> 1859 <212> DNA <213> homo sapiens <400> 68 gcaggcacaa actcatccat ccccagttga ttggaagaaa caacgatgac tcctgggaag 60 acctcattgg tgtcactgct actgctgctg agcctggagg ccatagtgaa ggcaggaatc 120 acaatcccac gaaatccagg atgcccaaat tctgaggaca agaacttccc ccggactgtg 180 atggtcaacc tgaacatcca taaccggaat accaatacca atcccaaaag gtcctcagat 240 tactacaacc gatccacctc accttggaat ctccaccgca atgaggaccc tgagagatat 300 ccctctgtga tctgggaggc aaagtgccgc cacttgggct gcatcaacgc tgatgggaac 360 gtggactacc acatgaactc tgtccccatc cagcaagaga tcctggtcct gcgcagggag 420 cctccacact gccccaactc cttccggctg gagaagatac tggtgtccgt gggctgcacc 480 tgtgtcaccc cgattgtcca ccatgtggcc taagagctct ggggagccca cactccccaa 540 agcagttaga ctatggagag ccgacccagc ccctcaggaa ccctcatcct tcaaagacag 600 cctcatttcg gactaaactc attagagttc ttaaggcagt ttgtccaatt aaagcttcag 660 aggtaacact tggccaagat atgagatctg aattaccttt ccctctttcc aagaaggaag 720 gtttgactga gtaccaattt gcttcttgtt tactttttta agggctttaa gttatttatg 780 tatttaatat gccctgagat aactttgggg tataagattc cattttaatg aattacctac 840 tttattttgt ttgtcttttt aaagaagata agattctggg cttgggaatt ttattattta 900 aaaggtaaaa cctgtattta tttgagctat ttaaggatct atttatgttt aagtatttag 960 aaaaaggtga aaaagcacta ttatcagttc tgcctaggta aatgtaagat agaattaaat 1020 ggcagtgcaa aatttctgag tctttacaac atacggatat agtatttcct cctctttgtt 1080 tttaaaagtt ataacatggc tgaaaagaaa gattaaacct actttcatat gtattaattt 1140 aaattttgca atttgttgag gttttacaag agatacagca agtctaactc tctgttccat 1200 taaaccctta taataaaatc cttctgtaat aataaagttt caaaagaaaa tgtttatttg 1260 ttctcattaa atgtatttta gcaaactcag ctcttcccta ttgggaagag ttatgcaaat 1320 tctcctataa gcaaaacaaa gcatgtcttt gagtaacaat gacctggaaa tacccaaaat 1380 tccaagttct cgatttcaca tgccttcaag actgaacacc gactaaggtt ttcatactat 1440 tagccaatgc tgtagacaga agcattttga taggaataga gcaaataaga taatggccct 1500 gaggaatggc atgtcattat taaagatcat atggggaaaa tgaaaccctc cccaaaatac 1560 aagaagttct gggaggagac attgtcttca gactacaatg tccagtttct cccctagact 1620 caggcttcct ttggagatta aggcccctca gagatcaaca gaccaacatt tttctcttcc 1680 tcaagcaaca ctcctagggc ctggcttctg tctgatcaag gcaccacaca acccagaaag 1740 gagctgatgg ggcagaacga actttaagta tgagaaaagt tcagcccaag taaaataaaa 1800 actcaatcac attcaattcc agagtagttt caagtttcac atcgtaacca ttttcgccc 1859 <210> 69 <211> 1151 <212> DNA <213> homo sapiens <400> 69 attctctccc cagcttgctg agccctttgc tcccctggcg actgcctgga cagtcagcaa 60 ggaattgtct cccagtgcat tttgccctcc tggctgccaa ctctggctgc taaagcggct 120 gccacctgct gcagtctaca cagcttcggg aagaggaaag gaacctcaga ccttccagat 180 cgcttcctct cgcaacaaac tatttgtcgc aggaataaag atggctgctg aaccagtaga 240 agacaattgc atcaactttg tggcaatgaa atttattgac aatacgcttt actttataga 300 aaacctggaa tcagattact ttggcaagct tgaatctaaa ttatcagtca taagaaattt 360 gaatgaccaa gttctcttca ttgaccaagg aaatcggcct ctatttgaag atatgactga 420 ttctgactgt agagataatg caccccggac catatttatt ataagtatgt ataaagatag 480 ccagcctaga ggtatggctg taactatctc tgtgaagtgt gagaaaattt caactctctc 540 ctgtgagaac aaaattattt cctttaagga aatgaatcct cctgataaca tcaaggatac 600 aaaaagtgac atcatattct ttcagagaag tgtcccagga catgataata agatgcaatt 660 tgaatcttca tcatacgaag gatactttct agcttgtgaa aaagagagag acctttttaa 720 actcattttg aaaaaagagg atgaattggg ggatagatct ataatgttca ctgttcaaaa 780 cgaagactag ctattaaaat ttcatgccgg gcgcagtggc tcacgcctgt aatcccagcc 840 ctttgggagg ctgaggcggg cagatcacca gaggtcaggt gttcaagacc agcctgacca 900 acatggtgaa acctcatctc tactaaaaat acaaaaaatt agctgagtgt agtgacgcat 960 gccctcaatc ccagctactc aagaggctga ggcaggagaa tcacttgcac tccggaggta 1020 gaggttgtgg tgagccgaga ttgcaccatt gcgctctagc ctgggcaaca acagcaaaac 1080 tccatctcaa aaaataaaat aaataaataa acaaataaaa aattcataat gtgaaaaaaa 1140 aaaaaaaaaa a 1151 <210> 70 <211> 1498 <212> DNA <213> homo sapiens <400> 70 accaaacctc ttcgaggcac aaggcacaac aggctgctct gggattctct tcagccaatc 60 ttcattgctc aagtgtctga agcagccatg gcagaagtac ctgagctcgc cagtgaaatg 120 atggcttatt acagtggcaa tgaggatgac ttgttctttg aagctgatgg ccctaaacag 180 atgaagtgct ccttccagga cctggacctc tgccctctgg atggcggcat ccagctacga 240 atctccgacc accactacag caagggcttc aggcaggccg cgtcagttgt tgtggccatg 300 gacaagctga ggaagatgct ggttccctgc ccacagacct tccaggagaa tgacctgagc 360 accttctttc ccttcatctt tgaagaagaa cctatcttct tcgacacatg ggataacgag 420 gcttatgtgc acgatgcacc tgtacgatca ctgaactgca cgctccggga ctcacagcaa 480 aaaagcttgg tgatgtctgg tccatatgaa ctgaaagctc tccacctcca gggacaggat 540 atggagcaac aagtggtgtt ctccatgtcc tttgtacaag gagaagaaag taatgacaaa 600 atacctgtgg ccttgggcct caaggaaaag aatctgtacc tgtcctgcgt gttgaaagat 660 gataagccca ctctacagct ggagagtgta gatcccaaaa attacccaaa gaagaagatg 720 gaaaagcgat ttgtcttcaa caagatagaa atcaataaca agctggaatt tgagtctgcc 780 cagttcccca actggtacat cagcacctct caagcagaaa acatgcccgt cttcctggga 840 gggaccaaag gcggccagga tataactgac ttcaccatgc aatttgtgtc ttcctaaaga 900 gagctgtacc cagagagtcc tgtgctgaat gtggactcaa tccctagggc tggcagaaag 960 ggaacagaaa ggtttttgag tacggctata gcctggactt tcctgttgtc tacaccaatg 1020 cccaactgcc tgccttaggg tagtgctaag aggatctcct gtccatcagc caggacagtc 1080 agctctctcc tttcagggcc aatccccagc ccttttgttg agccaggcct ctctcacctc 1140 tcctactcac ttaaagcccg cctgacagaa accacggcca catttggttc taagaaaccc 1200 tctgtcattc gctcccacat tctgatgagc aaccgcttcc ctatttattt atttatttgt 1260 ttgtttgttt tattcattgg tctaatttat tcaaaggggg caagaagtag cagtgtctgt 1320 aaaagagcct agtttttaat agctatggaa tcaattcaat ttggactggt gtgctctctt 1380 taaatcaagt cctttaatta agactgaaaa tatataagct cagattattt aaatgggaat 1440 atttataaat gagcaaatat catactgttc aatggttctg aaataaactt cactgaag 1498 <210> 71 <211> 2197 <212> DNA <213> homo sapiens <400> 71 aaattaacgt actatcctcc ttacttttgg gtcgggccct ccgggaagat ggcggccgtg 60 caggcggccg aggtgaaagt ggatggcagc gagccgaaac tgagcaagaa gtggtggtaa 120 tcattagttc cagggtgctc tgccatgttg acgcaagctg ctgtaaggct tgttaggggg 180 tccctgcgca aaacctcctg ggcagagtgg ggtcacaggg aactgcgact gggtcaactt 240 gctcctttca cagcgcctca caaggacaag tcattttctg atcaaagaag tgagctgaag 300 agacgcctga aagctgagaa gaaagtagca gagaaggagg ccaaacagaa agagctcagt 360 gagaaacagc taagccaagc cactgctgct gccaccaacc acaccactga taatggtgtg 420 ggtcctgagg aagagagcgt ggacccaaat caatactaca aaatccgcag tcaagcaatt 480 catcagctga aggtcaatgg ggaagaccca tacccacaca agttccatgt agacatctca 540 ctcactgact tcatccaaaa atatagtcac ctgcagcctg gggatcacct gactgacatc 600 accttaaagg tggcaggtag gatccatgcc aaaagagctt ctgggggaaa gctcatcttc 660 tatgatcttc gaggagaggg ggtgaagttg caagtcatgg ccaattccag aaattataaa 720 tcagaagaag aatttattca tattaataac aaactgcgtc ggggagacat aattggagtt 780 caggggaatc ctggtaaaac caagaagggt gagctgagca tcattccgta tgagatcaca 840 ctgctgtctc cctgtttgca tatgttacct catcttcact ttggcctcaa agacaaggaa 900 acaaggtatc gccagagata cttggacttg atcctgaatg actttgtgag gcagaaattt 960 atcatccgct ctaagatcat cacatatata agaagtttct tagatgagct gggattccta 1020 gagattgaaa ctcccatgat gaacatcatc ccagggggag ccgtggccaa gcctttcatc 1080 acttatcaca acgagctgga catgaactta tatatgagaa ttgctccaga actctatcat 1140 aagatgcttg tggttggtgg catcgaccgg gtttatgaaa ttggacgcca gttccggaat 1200 gaggggattg atttgacgca caatcctgag ttcaccacct gtgagttcta catggcctat 1260 gcagactatc acgatctcat ggaaatcacg gagaagatgg tttcagggat ggtgaagcat 1320 attacaggca gttacaaggt cacctaccac ccagatggcc cagagggcca agcctacgat 1380 gttgacttca ccccaccctt ccggcgaatc aacatggtag aagagcttga gaaagccctg 1440 gggatgaagc tgccagaaac gaacctcttt gaaactgaag aaactcgcaa aattcttgat 1500 gatatctgtg tggcaaaagc tgttgaatgc cctccacctc ggaccacagc caggctcctt 1560 gacaagcttg ttggggagtt cctggaagtg acttgcatca atcctacatt catctgtgat 1620 cacccacaga taatgagccc tttggctaaa tggcaccgct ctaaagaggg tctgactgag 1680 cgctttgagc tgtttgtcat gaagaaagag atatgcaatg cgtatactga gctgaatgat 1740 cccatgcggc agcggcagct ttttgaagaa caggccaagg ccaaggctgc aggtgatgat 1800 gaggccatgt tcatagatga aaacttctgt actgccctgg aatatgggct gccccccaca 1860 gctggctggg gcatgggcat tgatcgagtc gccatgtttc tcacggactc caacaacatc 1920 aaggaagtac ttctgtttcc tgccatgaaa cccgaagaca agaaggagaa tgtagcaacc 1980 actgatacac tggaaagcac aacagttggc acttctgtct agaaaataat aattgcaagt 2040 tgtataactc aggcgtcttt gcatttctgc gaaagatcaa ggtctgcaag ggaattcttg 2100 tgtgctgctt tccatttgac accgcagttc tgttcagcca tcagaagaga gacaaggaat 2160 taaaaatttc tttttaatcc tgttaccaaa taaaaaa 2197 <210> 72 <211> 5228 <212> DNA <213> homo sapiens <400> 72 cattgtcgcc cacgctgcag tagcggcttc tgcggctcca agccagcggg tcctgtgaag 60 gcgagcagac gcggagaaag gacgcgggag tgagagaggg tgagtcagcc actgtctaaa 120 cgataacggg aggcggctct gcggggtagg gttgaattca gtaaatgggc tcgtgctgct 180 gtctcttcgg agacgctgct atcttagcgt cagcgaggga aggttgagga ggagccagag 240 ccgggtcctg cagcgtttct cgccatcagc gcccgtcgcc atctccacca tgcagtcccg 300 ggaagacgcc ccgcgctctc gccgcctagc cagtccccgt ggtgggaagc ggcccaagaa 360 gattcacaaa cccacagttt cggccttttt cacgggtcca gaggaattaa aggacacggc 420 ccattctgca gccctgctgg cacagctcaa gtccttctac gatgcgcggc tgctgtgtga 480 tgtgaccatc gaggtggtga cgcctggcag cgggcctggc acgggtcgcc tgttcccctg 540 caaccgcaat gtgctggccg cggcatgtcc ctacttcaag agcatgttca caggtggcat 600 gtacgagagc cagcaggcca gcgtgaccat gcacgatgtg gacgccgagt ccttcgaggt 660 gttggtcgac tactgctaca cgggtcgtgt gtctctcagt gaggccaacg tggagcgcct 720 gtacgcggcc tccgacatgc tacagctgga atatgtgcgg gaagcctgtg cctccttctt 780 agcccgacgt cttgacctga ccaactgcac cgccatcctc aagtttgcag atgcctttgg 840 ccatcgcaag ctgcgatccc aggcccagtc ctatatagct cagaacttca agcaactcag 900 ccacatgggt tcaattcggg aggagactct agcagatctg accctggccc agctgctggc 960 tgtcctgcgc ttggatagtc tggacgtgga gagtgagcag acagtgtgcc atgtggcagt 1020 gcagtggctg gaggctgctc ccaaagagcg gggtcccagt gctgcagaag tcttcaagtg 1080 cgtgcgctgg atgcacttca ctgaagaaga tcaggactac ttagaagggc tgctgaccaa 1140 gcccatcgtg aagaagtact gcctggacgt tattgaaggg gccctgcaga tgcgctatgg 1200 tgacctgttg tacaagtctc tggtgccagt gccaaacagc agcagcagca gtagcagcag 1260 caactctctt gtatctgcag cagaaaatcc accccagaga ctgggtatgt gtgccaagga 1320 gatggtgatc ttctttggac accccagaga tccctttctc tgctgtgatc catactcggg 1380 ggacctttac aaagtgccgt cacctttgac ctgtctggct cacactagga ctgtcaccac 1440 tctagctgtc tgtatctctc ctgaccatga catctatcta gctgctcagc ccaggacaga 1500 cctctgggtg tataaaccag ctcagaatag ttggcagcaa cttgcagatc gcttgctgtg 1560 tcgtgagggc atggatgtgg catatctcaa tggctatatc tacattttgg gggggcgaga 1620 ccctattact ggagttaagt tgaaggaagt ggaatgctac aatgttaaga gaaaccagtg 1680 ggcattggtg gctccactgc cccattcttt tttatccttt gacctaatgg taattcgaga 1740 ctatctctat gctctcaaca gtaagcgcat gttctgttat gatcctagcc acaatatgtg 1800 gctgaagtgc gtttctctga agcgcaatga ctttcaggaa gcctgcgtct tcaatgagga 1860 gatctattgt atctgtgata tcccagtcat gaaggtctac aacccagtta gggcagaatg 1920 gaggcaaatg aataatattc ccttggtctc agagaccaac aactacagaa ttatcaagca 1980 tggccaaaaa ttgttgctca tcacctctcg caccccacag tggaaaaaga accgggtgac 2040 tgtgtatgaa tatgatatta ggggagacca atggattaat ataggtacca cattaggcct 2100 cttgcagttt gattctaact ttttttgcct ctctgctcgt gtttatcctt cctgccttga 2160 acctggtcag agtttcctca ctgaagaaga agaaatacca agtgagtcta gcactgaatg 2220 ggacttaggt ggattcagtg agccagactc tgagtcagga agttcaagtt ctctttctga 2280 tgatgatttt tgggtgcgtg tagcgcctca gtgaaatgca caggatcaac agggtttgtt 2340 gtaactagat tgaaacacta agttgttttt actgttttgg aaaatatctt aaatatcctt 2400 tttgttccta aaggagagga aaagttgatt aacttctggt ttggtttaga aaaagtaatg 2460 tttgaaatac gaaggtaatt taatgttaca aattttaaca ctcaaatcaa ccttttaata 2520 attttctgtg ctaagggtcc agtatttatt tgattattta gtatgtttat gtttcatgac 2580 actaatttag tcttttgata cattttacat tctgtttact gccacaagca ctgtggcaat 2640 aacttttgaa ttttaatttt tataatagaa aaatgattag gaattgctag atagtgtttt 2700 gaaagcatat ctttttcttc agaacaatgt agacttccaa aatggttaac ctaaggggtc 2760 tttacaaaat gtgttataag ttaaacataa tttgggaagt tttacttttg ttttcttcta 2820 tgaagaaaaa aatgcaggct gggcgcggtg gctcacgcct gtaatcctag cactttggga 2880 ggccgaggca ggtggatcac ctgaggtcag ttcaagacca gcctggccaa catggtgaaa 2940 ccccgtctct actaaaaata caaaaattag ctgggcgtgg tggcatgcgc ctgtaatccc 3000 agctacccag gaggctgagg caggagaatt gctgaaaccc gggagtcaga ggctgcagag 3060 agccgagact gggccactgc actccagcct ggatgacaga gtgagactcc gtctcaaaaa 3120 aaaaaaaaaa aaaaaaagga aaaaaaaaaa agaaaaaaaa ccatatgtgt attagggtga 3180 ctgagtggtg acttcattta taataataca gagaatagct ataagctcat tgacagtaaa 3240 aacaacaaac caggattcta ctgtttgaaa agaagtttcg ttttaatttt ggaatttaga 3300 atgtgtattt gcaaagtcac caattttcat ctaaaaggtt atattctagt tgtgtcacca 3360 aatcatcaaa aaaccttaaa aaagaagtaa cttgctttgt aggtttgtat tgttgatcta 3420 aacctgatac atgcttcatt taatcaggaa taatcctttt ttttctgctg gacatgtata 3480 aatttcactg gattgtataa atttttatct attgccttaa acatttacat gattctcaat 3540 atgttttagc tgtacagttt tggtgttcat cttagaggat tcttcagcag aagtgatatt 3600 tctttactgt tttgtgaggt aatactgatt ttgaaaatat atataagcta aaaacagtat 3660 ttcgttgata tcagtagtca ttgtgttaac tataaagtca agtgccagca aagaacttta 3720 aaactgtaaa gctgtgtata gaactgtttt gtgtagcatg gaaatattct gtcagctttt 3780 taaagtcact aaatgttctt gattatcagc ttgaaggtat ttttgtatta caagttgaca 3840 gttgctgggt gtagtggctc atgcctgtaa tcctagcaac tcggggctga ggtgggagga 3900 ttgcttcagc ccaggagttt gagaccagcc tgggcaacat agcaaaaccc catctctaca 3960 aaaataaaaa atatgtctgg gcatggtggc ccaagtctga gtcccagtta cttgggagga 4020 tcacttgaat gtaggatcac ttgagtctag gagttcgggg ctgcagctat catctgcagc 4080 tataatcata gctcactgca gctatgatca tgtctcagca ctccagcttt ggcaacagaa 4140 cgagatccca tctcttagaa aaacaaagtt gatagttaaa gaacataagt ggatgatggc 4200 atttgaggcc actagtgaaa gtatgttttc tctaaaatat ttctctaata gtgatataaa 4260 tggctatttt attatgatgt ttgtatgtgt tttgtatttc tctgtaaacc atgctccagt 4320 ctttgttttt ctgttaccat aatgtaagag aaggtcctgg aacagagact aaatcccacg 4380 aaactgacat tgttaaacac actaaaacag aagtacttac ctcttgaaga tttaatatat 4440 aatggttgac atgatacatg tacatgatga atgaccagat gcttatggtc tacattttcc 4500 tttatcctgt tagtattacc ttccttaatc tttgttcatt aacatgctaa ttcctcttca 4560 gtgtttattt tctagtgaca gaatgctaac atttcttaca ccctggcaga agggagagaa 4620 atgtgttttg gggtgggtaa ctaaattttt gagtgaaata tcataagatg agaatggaaa 4680 gagggagaca caaagagtta taacaaaaaa acaatggttt ttttagccat ttgactggct 4740 ctttaaatag tctacaagac attcacgttt aacatcactt ttagtgaaat aaaatgtgcc 4800 atactagtat gtgcttcaaa agggcaaatg tgctttagtg ccctaaggct aaattttggt 4860 catttgacat cagagatgtt gtaagtattg cacttaatac gcacctattt ctcaatagtg 4920 ttattttttg gctagcattt tctttaccac tatcttgttg atagcttttt gttctctaag 4980 gttgaaacat gacagtgctt atctcaaaca gattacccat ctgcagaact aaggaaagca 5040 atttatgtat gaaagaaatt cttgaattcg tcattctcaa cctttgaatt aaagcttaga 5100 ctaaatagta atatatcgtg ggaaggattt tggttttgtg atatttctgt gaattaagga 5160 atagatgtta accattattt tgtagaaaag tgatttgtat gtggttaatt ataaataaaa 5220 ctggtacc 5228 <210> 73 <211> 2267 <212> DNA <213> homo sapiens <400> 73 gtgctccctg ccgaggagat gtgagggatt ttctcttggg ggagaaatca gtggtcgagc 60 gcctgcccag ctcaaatgcc acccggctca gagggaggcc tgcggcccag ggatcccgga 120 gggagagcaa cgtcacacct cctgaggaca gccaggactc cagcttttgc tgagctttgc 180 atcttgcctc cttccttcaa aaggctccag gcccatgctc ggctgtcttc aagtcccgca 240 tgcccctggc caggcacctc accgcccctc cagcccagcc caatcctaga gctcacctcc 300 aggacccaga gtctgccctt ctgcccagaa tgactcacca ttatttctag ctcgagtgag 360 aagacgtgat gaggagttgg gctgcctgtt ggtgcatctc agattcctgc agcatctgat 420 cagctctgca aggaagagag cttcacgtct ctggtcagcc aagcgaggct gtctctccag 480 ctctcagaga gctctcgggg ctctcctgca ggagaccagg ccaatgctcc tgtgcttcct 540 ggggccagta gcagcaccct gagctccctg ccaccaggca gctgaaaggc atagcgtgag 600 gtgcttctct cagtcccaat tatgacagtg gccaccggag acccagcaga cgaggctgct 660 gccctccctg ggcacccaca ggacacctat gacccagagg cagaccacga gtgctgtgag 720 agggtggtga tcaacatctc agggctgcgg tttgagaccc agctaaagac cttagcccag 780 tttccagaga ccctcttagg ggacccaaag aaacgaatga ggtactttga ccccctccga 840 aatgagtact ttttcgatcg gaaccgccct agctttgatg ccattttgta ctactaccag 900 tcagggggcc gattgaggcg acctgtgaat gtgcccttag atatattctc tgaagaaatt 960 cggttttatg agctgggaga agaagcgatg gagatgtttc gggaagatga aggctacatc 1020 aaggaggaag agcgtcctct gcctgaaaat gagtttcaga gacaagtgtg gcttctcttt 1080 gaatacccag agagctcagg gcctgccagg attatagcta ttgtgtctgt catggtgatt 1140 ctgatctcaa ttgtcagctt ctgtctggaa acattgccca tcttccggga tgagaatgaa 1200 gacatgcatg gtagtggggt gaccttccac acctattcca acagcaccat cgggtaccag 1260 cagtccactt ccttcacaga ccctttcttc attgtagaga cactctgcat catctggttc 1320 tcctttgaat tcttggtgag gttctttgcc tgtcccagca aagccggctt cttcaccaac 1380 atcatgaaca tcattgacat tgtggccatc atcccctact tcatcaccct ggggacagag 1440 ttggctgaga agccagagga cgctcagcaa ggccagcagg ccatgtcact ggccatcctc 1500 cgtgtcatcc ggttggtaag agtctttagg attttcaagt tgtccagaca ctccaaaggt 1560 ctccagattc taggtcagac cctcaaagcc agcatgagag aattgggcct cctgatattc 1620 tttctcttca taggggtcat ccttttctct agtgctgtgt attttgcaga ggccgatgag 1680 cgagagtccc agttccccag catcccagat gccttctggt gggcagtcgt ctccatgaca 1740 actgtaggct atggagacat ggttccgact accattgggg gaaagatagt gggttcccta 1800 tgtgcgattg caggtgtgtt aactattgcc ttaccggtcc ctgtcattgt gtccaatttc 1860 aactacttct accaccggga gacagaggga gaggaacagg cccaatactt gcaagtgaca 1920 agctgtccaa agatcccatc ctcccctgac ctaaagaaaa gtagaagtgc ctctaccatt 1980 agtaagtctg attacatgga gatccaggag ggtgtaaata acagtaatga ggactttaga 2040 gaggaaaact tgaaaacagc caactgtacc ttggctaaca caaactatgt gaatattacc 2100 aaaatgttaa ctgatgtctg attgaaacct attaccgtac tcacagctca atggaactaa 2160 tgcagatgtt gcataatagc ctgcattgta gtcagtgtgt tctacagtgt gtatctggtt 2220 ctgcatggaa agcaatagtt gtgcaagtga aaaaaaaaaa aaaaaaa 2267 <210> 74 <211> 6079 <212> DNA <213> homo sapiens <400> 74 atcctcagtc tcccagttca agctaatcat tgacagagct ttacaatcac aagcttttac 60 tgaagctttg ataagacagt ccagcagttg gtggcaaatg aagccaggct gtgcggcagg 120 atctccaggg aatgaatgga ttttcttcag cactgatgaa ataaccacac gctataggaa 180 tacaatgtcc aacgggggat tgcaaagatc tgtcatcctg tcagcactta ttctgctacg 240 agctgttact ggattctctg gagatggaag agctatatgg tctaaaaatc ctaattttac 300 tccggtaaat gaaagtcagc tgtttctcta tgacactttc cctaaaaact ttttctgggg 360 tattgggact ggagcattgc aagtggaagg gagttggaag aaggatggaa aaggaccttc 420 tatatgggat catttcatcc acacacacct taaaaatgtc agcagcacga atggttccag 480 tgacagttat atttttctgg aaaaagactt atcagccctg gattttatag gagtttcttt 540 ttatcaattt tcaatttcct ggccaaggct tttccccgat ggaatagtaa cagttgccaa 600 cgcaaaaggt ctgcagtact acagtactct tctggacgct ctagtgctta gaaacattga 660 acctatagtt actttatacc actgggattt gcctttggca ctacaagaaa aatatggggg 720 gtggaaaaat gataccataa tagatatctt caatgactat gccacatact gtttccagat 780 gtttggggac cgtgtcaaat attggattac aattcacaac ccatatctag tggcttggca 840 tgggtatggg acaggtatgc atgcccctgg agagaaggga aatttagcag ctgtctacac 900 tgtgggacac aacttgatca aggctcactc gaaagtttgg cataactaca acacacattt 960 ccgcccacat cagaagggtt ggttatcgat cacgttggga tctcattgga tcgagccaaa 1020 ccggtcggaa aacacgatgg atatattcaa atgtcaacaa tccatggttt ctgtgcttgg 1080 atggtttgcc aaccctatcc atggggatgg cgactatcca gaggggatga gaaagaagtt 1140 gttctccgtt ctacccattt tctctgaagc agagaagcat gagatgagag gcacagctga 1200 tttctttgcc ttttcttttg gacccaacaa cttcaagccc ctaaacacca tggctaaaat 1260 gggacaaaat gtttcactta atttaagaga agcgctgaac tggattaaac tggaatacaa 1320 caaccctcga atcttgattg ctgagaatgg ctggttcaca gacagtcgtg tgaaaacaga 1380 agacaccacg gccatctaca tgatgaagaa tttcctcagc caggtgcttc aagcaataag 1440 gttagatgaa atacgagtgt ttggttatac tgcctggtct ctcctggatg gctttgaatg 1500 gcaggatgct tacaccatcc gccgaggatt attttatgtg gattttaaca gtaaacagaa 1560 agagcggaaa cctaagtctt cagcacacta ctacaaacag atcatacgag aaaatggttt 1620 ttctttaaaa gagtccacgc cagatgtgca gggccagttt ccctgtgact tctcctgggg 1680 tgtcactgaa tctgttctta agcccgagtc tgtggcttcg tccccacagt tcagcgatcc 1740 tcatctgtac gtgtggaacg ccactggcaa cagactgttg caccgagtgg aaggggtgag 1800 gctgaaaaca cgacccgctc aatgcacaga ttttgtaaac atcaaaaaac aacttgagat 1860 gttggcaaga atgaaagtca cccactaccg gtttgctctg gattgggcct cggtccttcc 1920 cactggcaac ctgtccgcgg tgaaccgaca ggccctgagg tactacaggt gcgtggtcag 1980 tgaggggctg aagcttggca tctccgcgat ggtcaccctg tattatccga cccacgccca 2040 cctaggcctc cccgagcctc tgttgcatgc cgacgggtgg ctgaacccat cgacggccga 2100 ggccttccag gcctacgctg ggctgtgctt ccaggagctg ggggacctgg tgaagctctg 2160 gatcaccatc aacgagccta accggctaag tgacatctac aaccgctctg gcaacgacac 2220 ctacggggcg gcgcacaacc tgctggtggc ccacgccctg gcctggcgcc tctacgaccg 2280 gcagttcagg ccctcacagc gcggggccgt gtcgctgtcg ctgcacgcgg actgggcgga 2340 acccgccaac ccctatgctg actcgcactg gagggcggcc gagcgcttcc tgcagttcga 2400 gatcgcctgg ttcgccgagc cgctcttcaa gaccggggac taccccgcgg ccatgaggga 2460 atacattgcc tccaagcacc gacgggggct ttccagctcg gccctgccgc gcctcaccga 2520 ggccgaaagg aggctgctca agggcacggt cgacttctgc gcgctcaacc acttcaccac 2580 taggttcgtg atgcacgagc agctggccgg cagccgctac gactcggaca gggacatcca 2640 gtttctgcag gacatcaccc gcctgagctc ccccacgcgc ctggctgtga ttccctgggg 2700 ggtgcgcaag ctgctgcggt gggtccggag gaactacggc gacatggaca tttacatcac 2760 cgccagtggc atcgacgacc aggctctgga ggatgaccgg ctccggaagt actacctagg 2820 gaagtacctt caggaggtgc tgaaagcata cctgattgat aaagtcagaa tcaaaggcta 2880 ttatgcattc aaactggctg aagagaaatc taaacccaga tttggattct tcacatctga 2940 ttttaaagct aaatcctcaa tacaatttta caacaaagtg atcagcagca ggggcttccc 3000 ttttgagaac agtagttcta gatgcagtca gacccaagaa aatacagagt gcactgtctg 3060 cttattcctt gtgcagaaga aaccactgat attcctgggt tgttgcttct tctccaccct 3120 ggttctactc ttatcaattg ccatttttca aaggcagaag agaagaaagt tttggaaagc 3180 aaaaaactta caacacatac cattaaagaa aggcaagaga gttgttagct aaactgatct 3240 gtctgcatga tagacagttt aaaaattcat cccagttcca tatgctggta acttacagga 3300 gatatacctg tattatagaa agacaatctg agatacagct gtaaccaagg tgatgacaat 3360 tgtctctgct gtgtggttca aagaacattc ccttaggtgt tgacatcagt gaactcagtt 3420 cttggatgta aacataaagg cttcatcctg acagtaagct atgaggatta catgctacat 3480 tgcttcttaa agtttcatca actgtattcc atcattctgc tttagctttc atctctacca 3540 atagctactt gtggtacaat aaattatttt taagaagtaa aactctgggg ctggacgctg 3600 tggctcacac ctgtaatctc agcactttgg gaggccgagg cggggagatc acctgaggtg 3660 aggagttcga gaccagcctg gccaacatgg tgaaaccatg tctctactaa aaatacaaaa 3720 aattagccag gcgtggtgac agtggcacct gtaatcccag ctacttggga ggctgaggca 3780 gaagtttgaa cccaggaaac aggttacagt aggccaaaat tgcgccactg cactccagcc 3840 taggcgacaa cagcaagact gtgtccaaaa aaaaaaaaaa aagcaaaagc aaaactttgt 3900 tttgttagac tctacagcag agatttaaca cccttcttta aactgggtag tcagtgatag 3960 ataatatata ttctgtcact tctaataagg tgccttctcc tttaggtcag ggtggttcta 4020 aaatggaaag aaaacacaat agggtaagta gtgcttgtct aagccagtta caacacagac 4080 tcttaaagag gatcaagccc ttcatttttc taacaacaaa aaatcaccta tagaatatct 4140 aatttgtgat cttttactag atctgatttt ttaaaataat gtaatttccg gccaggcacg 4200 gtggcaccgc ctgtaatccc agcactttgg gaggccaagg caggtggatc acctgaggtt 4260 aggagttcga gactagcctg gccaacatgg caaaacccca tctctactaa aaatacaaaa 4320 gttagccggg catggtggtg ggcacctgta atcccagcta ctcaggaggc cgaggcagga 4380 gaatcgcttg aacccgagag gcagaggttg caatgagcca agatcgtgcc attgcactcc 4440 agcctggggg acagggcaag actgtctctc aaaataaaaa aaaataataa aaataaaaat 4500 aaaagtaatt tccaaaacct catctcatgg aaagatcaca ggatgaagga aagctagact 4560 caactctgtg aatagaagtt gctatactgt aagtaaagca acaattcaga atactgaatg 4620 agtttaaatt gttttatata gcaccctttt gggctagggt taattactag atctgacttg 4680 gataatttga cactttggga aatgaactct gttcttgaga cttgttcagt gtattttaaa 4740 catctgagga agaaaactta aatatgcacc tatttatacc tattctttct ttaggtcaac 4800 atttaacacc cactgcatac attaatttgt ccttgtctgc tcactccagc aatttagacc 4860 ttaacagtca caagagacgt tcttctgtta caaagcctta gtaaattaag gcagttttga 4920 ttatattcta ggtccaccta tgtctgaagc taaattcagt atctaactgc taatgaacaa 4980 gtttccaaaa tactgtaaaa atacaattag tcaatttgag taaatgcaaa tatgatgaga 5040 aatcaatttg ctatttggcc tggcaaatgg gaacagtaaa attctgcttt actcttctct 5100 agtctccttg ccccagctgc acccactacc ccaaagttgg cagttttgag gtatgatttt 5160 caaggaattt ttttagtatt aacatctccc tctgagaact atgtacctaa ggtcacgcat 5220 acaactagtc aattctgttt ttattactct aactatgtag aaacagtaag tcacttaaaa 5280 caatcacttg gctgggtttt ttcccctttg tgccacattg attcaccctg acccaagaac 5340 tccagggaaa attctttaat gtcaactggg caactcatta acctctcttt aacatcaagg 5400 gcttgggaaa aaaaaaaaaa aggttagcca caggaataac aaaaacctgg aatttatctt 5460 tcaggttttg ctttctcttt ctcactttgt ttaaagtatc tcgtactcac agttcacaaa 5520 ttaaccttca ctgtctcttt cacattaaga gcttatgctt aaagcatgcc ccccttttct 5580 aacttgctgg tttaccataa actcccctaa gtaataaaat tcctaaccca gtactgagag 5640 tcctccttct ctgccacttg ggcattattt tactagtttt taagccatca tcgcacaaga 5700 atccaaaaac ccttaaattt tttaaccact ggcaaatatg tacagcaaat taggttaagc 5760 atttaatctg gctcatgctc tatcatacta aatattcagg tttatcataa actccttaaa 5820 aaccatcaaa ggtcaaccag aaactgataa ctcttgaaag gagcaaacag gtaagatctt 5880 tggagtttaa gcttttctga gatgtgttgt gaaaaatcta acgtgtttat cgtatattca 5940 atgtaacaac ctggagaatc acaactatat ttaaagagcc tctggaaaat gaggccagta 6000 cagtgtgact acatgtttaa ttttcaatgt aatttattcc aaataaactg gttcatgctg 6060 accacttgta ttcaactaa 6079 <210> 75 <211> 5266 <212> DNA <213> homo sapiens <400> 75 gcttaaaaat ttctgtgtct tacacagaag atagaaaaaa tagagtgtct ccaattggat 60 ggatttttta aaaaatttgg ttattgtaat ggatttattt tttcttagag ctgagctgat 120 tgtactttgg ccaactaatg ggttaatact gtcaagggaa attagccctg actaaacatt 180 gccgctggct catgaatgca ctaggcttgg ggcagtataa aaactcagag aaatcagtgt 240 gtaggagaca cagaaatcag tgtcactcag tgacagaagc aacaataatt gtgaaaaata 300 cttcagcagt tatggactca tctgtcattc aaaggaaaaa agtagctgtc attggtggtg 360 gcttggttgg ctcattacaa gcatgctttc ttgcaaagag gaatttccag attgatgtat 420 atgaagctag ggaagatact cgagtggcta ccttcacacg tggaagaagc attaacttag 480 ccctttctca tagaggacga caagccttga aagctgttgg cctggaagat cagattgtat 540 cccaaggtat tcccatgaga gcaagaatga tccactctct ttcaggaaaa aagtctgcaa 600 ttccctatgg gacaaagtct cagtatattc tttctgtaag cagagaaaat ctaaacaagg 660 atctattgac tgctgctgag aaatacccca atgtgaaaat gcactttaac cacaggctgt 720 tgaaatgtaa tccagaggaa ggaatgatca cagtgcttgg atctgacaaa gttcccaaag 780 atgtcacttg tgacctcatt gtaggatgtg atggagccta ttcaactgtc agatctcacc 840 tgatgaagaa acctcgcttt gattacagtc agcagtacat tcctcatggg tacatggagt 900 tgactattcc acctaagaac ggagattatg ccatggaacc taattatctg catatttggc 960 ctagaaatac ctttatgatg attgcacttc ctaacatgaa caaatcattc acatgtactt 1020 tgttcatgcc ctttgaagag tttgaaaaac ttctaaccag taatgatgtg gtagatttct 1080 tccagaaata ctttccggat gccatccctc taattggaga gaaactccta gtgcaagatt 1140 tcttcctgtt gcctgcccag cccatgatat ctgtaaagtg ctcttcattt cactttaaat 1200 ctcactgtgt actgctggga gatgcagctc atgctatagt gccgtttttt gggcaaggaa 1260 tgaatgcggg ctttgaagac tgcttggtat ttgatgagtt aatggataaa ttcagtaacg 1320 accttagttt gtgtcttcct gtgttctcaa gattgagaat cccagatgat cacgcgattt 1380 cagacctatc catgtacaat tacatagaga tgcgagcaca tgtcaactca agctggttca 1440 tttttcagaa gaacatggag agatttcttc atgcgattat gccatcgacc tttatccctc 1500 tctatacaat ggtcactttt tccagaataa gataccatga ggctgtgcag cgttggcatt 1560 ggcaaaaaaa ggtgataaac aaaggactct ttttcttggg atcactgata gccatcagca 1620 gtacctacct acttatacac tacatgtcac cacgatcttt cctccgcttg agaagaccat 1680 ggaactggat agctcacttc cggaatacaa catgtttccc cgcaaaggcc gtggactccc 1740 tagaacaaat ttccaatctc attagcaggt gatagaaagg ttttgtggta gcaaatgcat 1800 gatttctctg tgaccaaaat taagcatgaa aaaaatgttt ccattgccat atttgattca 1860 ctagtggaag atagtgttct gcttataatt aaactgaatg tagagtatct ctgtatgtta 1920 attgcaatta ctggttgggg ggtgcatttt aaaagatgaa acatgcagct tccctacatt 1980 acacacactc aggttgagtc attctaacta taaaagtgca atgactaaga tccttcactt 2040 ctctgaaagt aaggccctag atgcctcagg gaagacagta atcatgcctt ttctttaaaa 2100 gacacaatag gactcgcaac agcattgact caacacctag gactaaaaat cacaacttaa 2160 ctagcatgtt aactgcactt ttcattacgt gaatggaact tacctaacca cagggctcag 2220 acttactaga taaaaccaga aatggaaata aggaattcag gggagttcca gagacttaca 2280 aaatgaactc attttatttt cccaccttca aatataagta ttatcatcta tctgtttatc 2340 gtctatctat ctatcatcta tctatctatc tatcatctat ctatctatct atctatctat 2400 ctatctatct atctatctct atttatttat gtatttagag atcaggtctc actctgttga 2460 ccaggctgga gtgcagtggt gagatctggg ttcactgcaa cctctgcctc ctgggctcaa 2520 gcaatcctcc cacttcagcc tcccaaatag ctggggctac catggtattt ttcagtagag 2580 accgggtctt gccatgctgc ccaggccagt ctcaaactcc tggcctcatg tgatctgccc 2640 acctcagcct cccaaagtac agggattaga gttgtgagcc accgctgcca gcccagagtt 2700 accctctaaa gataagaaaa aggctattaa tatcatacta agtgaaggac aggaaagggt 2760 tttattcata aattaaatgt ctacatgtgc cagaatggaa aggaaacaag gggagacaac 2820 ttttatagaa atacaaagcc attactttat tcaatttcag accctcagaa gcaatttact 2880 aatttattct tcgactacat actgcagcag aaccagcaat acacttgatt tttaaaagca 2940 catttagtga aatgttttct ttggttcatc cttctttaac aggctgctga gtcactcaga 3000 aatccttcaa acatgattaa ttatgaagat gaaacactag agtcatataa gaaataaaaa 3060 ttgggcaata aaataaaatg attcagtgtt tcttttctat attgtcaatg aaaaccttga 3120 gttctaataa tccatgttca gtttgtaggg aaagaaaaaa taatttttcc ttctacccac 3180 tttaggttcc ttggctgggg cccctataac aaaagacaga ttgacaagag aaaaacaaac 3240 ataaatttat tagcgggtat atgtaatata tatgtgggaa atacagggga atgagcaaat 3300 ctcaaagagc tggcgtctta gaactccctg gcttatatag catcgacaaa gaacagtaaa 3360 tttttagaga aacaacaaaa caaagaaaaa gagctttgag tctgtagggg cagcaatttg 3420 ggggaagcaa atatatggga gtttgccttg tagattcctc tggtgctggt ctccaggctg 3480 acaaggattc aaagttgtct ctgaaactcc tctttgtcat actgcacata taaaacgtct 3540 tttgtttcca acaagaggat tttctttttc attctagaat tatctccttg ataacttgat 3600 cagatatagg acatgacact gaatagagtc caacagtaca aaaaaaattc agtatgttct 3660 agctacttca cacatgtgta cgcgacagtt atttttacag taaggtattt tcgagaaaaa 3720 tgcattacgt gttttggaaa atagagtaat ttaaaaaata tatttgaaat gaaaatctcc 3780 aacacattag aagatgatga tgttagatgc ccatcgtgtg ccacaagtgg ttttttcatt 3840 atgtaaagca cccgttgaat taaaagaatt tgtttttgtt caacctcttc ctgaggccca 3900 agagcatatg ggcaattcgg atttcctgct ggaccacaag gttctgttga tattacatag 3960 aacgggtatt ccagacactt cttatgatga aagtccaaaa gtggcatcca atttaaggcc 4020 ccatctttcg ttgccattct tcattcctac aaaggacgaa cttggattac atcaactttg 4080 gacccattgg ttttgtcgct gtcgtcaact gacagtgatt catcactggt gatgataaaa 4140 atgatggaag aagagttgaa agtcactttt ttctttggcc tgtccccatc tttctgtgac 4200 atcacaatgg gtctgatctg catttcactt ccagctgctg gtaggtcttt agcaggcctc 4260 tggcacctca gcagtcggag gcacagaagc tgcaaaaggg atcttcgaaa ctgggcagag 4320 aaaaaataaa gtggaatatt aagtaaaagt tgggcactaa tctggattaa cattcgagga 4380 aatcagttga gctgaattta agttgttttt tgtttgttag caggtgtgga tgtggggtta 4440 tgtggtcatg ctcagatcta cctaaatcac cccagagctt tatgtctttt attcattcta 4500 attcttatta accggaatat gtaggaccat ttcaatacct tgtaatcctc caagcttcaa 4560 tctgcacaca ctttctatga gggcaggtac aactattaag agattttgaa cattaagtta 4620 gtccacaaat attcagtggg catctactag gtgacagcca ctgtgctata attagagact 4680 ttttactata agcatcaaaa acagataagg ctcttcctgg cagagtttac agcctggtgt 4740 acttgctaat gtctctttaa ttaggtgaag aatttttttt ttctatcgaa attactaatc 4800 agttggggaa aaaaatacta tagcagacag cactaatgtc atcaacaaac attgttcttc 4860 tccgtgtcct gggtacaaca tcgaataata tttcttggcc tcctttccgc ttctcctctc 4920 tgctgttcct ctctacaaga acctgggagg ccaacgccta aagatcataa tatcacacaa 4980 tggaaggaac ctagattcct aaatgactgc ataggacaga tcccatctcc tccacccaat 5040 acattattag actgaactgt gacctgaaat gagcaataaa ctctgtatta attcactgaa 5100 atgttggggt tgcttgttat agtagtcggt ccatcatgac cagtaaaaca taaatcaaaa 5160 gttaatgtaa ttgttatccc attatttaga gcgaaataaa tgttgaatat atggactttc 5220 tcagattagg aaataccaat taaaaatata ataaatagct acattg 5266 <210> 76 <211> 2162 <212> DNA <213> homo sapiens <400> 76 cactccctgg gctaaacagc atcaccatgt ctgttcgata cagctcaagc aagcactact 60 cttcctcccg cagtggagga ggaggaggag gaggaggatg tggaggagga ggaggagtgt 120 catccctaag aatttctagc agcaaaggct cccttggtgg aggatttagc tcaggggggt 180 tcagtggtgg ctcttttagc cgtgggagct ctggtggggg ctgctttggg ggctcatcag 240 gtggctatgg aggattagga ggttttggtg gaggtagctt tcgtggaagc tatggaagta 300 gcagctttgg tgggagttat ggaggcagct ttggaggggg cagtttcgga ggtggcagct 360 ttggtggggg cagctttggt ggaggcggct ttggtggagg cggctttgga ggaggctttg 420 gtggtggatt tggaggagat ggtggccttc tctctggaaa tgaaaaagta accatgcaga 480 atctgaatga ccgcctggct tcctacttgg acaaagttcg ggctctggaa gaatcaaact 540 atgagctgga aggcaaaatc aaggagtggt atgaaaagca tggcaactca catcaggggg 600 agcctcgtga ctacagcaaa tactacaaaa ccatcgatga ccttaaaaat cagattctca 660 acctaacaac tgataatgcc aacatcctgc ttcagatcga caatgccagg ctggcagctg 720 atgacttcag gctgaagtat gagaatgagg tagctctgcg ccagagcgtg gaggctgaca 780 tcaacggcct gcgtagggtg ctggatgagc tgaccctgac caaggctgac ctggagatgc 840 aaattgagag cctgactgaa gagctggcct atctgaagaa gaaccacgag gaggaaatga 900 aagaccttcg aaatgtgtcc actggtgatg tgaatgtgga aatgaatgct gccccgggtg 960 ttgatctgac tcaacttctg aataacatga gaagccaata tgaacaactt gctgaacaaa 1020 accgcaaaga tgctgaagcc tggttcaatg aaaagagcaa ggaactgact acagaaattg 1080 ataataacat tgaacagata tccagctata aatctgagat tactgaattg agacgtaatg 1140 tacaagctct ggagatagaa ctacagtccc aactggcctt gaaacaatcc ctggaagcct 1200 ccttggcaga aacagaaggt cgctactgtg tgcagctctc acagattcag gcccagatat 1260 ccgctctgga agaacagttg caacagattc gagctgaaac cgagtgccag aatactgaat 1320 accaacaact cctggatatt aagatccgac tggagaatga aattcaaacc taccgcagcc 1380 tgctagaagg agagggaagt tccggaggcg gcggacgcgg cggcggaagt ttcggcggcg 1440 gctacggcgg cggaagctcc ggcggcggaa gctccggcgg cggccacggc ggcggccacg 1500 gcggcagttc cggcggcggc tacggaggcg gaagctccgg cggcggaagc tccggcggcg 1560 gctacggggg cggaagctcc agcggcggcc acggcggcag ttccagcggc ggctacggtg 1620 gtggcagttc cggcggcggc ggcggcggct acgggggcgg cagctccggc ggcggcagca 1680 gctccggcgg cggatacggc ggcggcagct ccagcggagg ccacaagtcc tcctcttccg 1740 ggtccgtggg cgagtcttca tctaagggac caagatacta acaaaaccag agtaatcaag 1800 acaattattg aagaggtggc gcccgacggt agagttcttt catctatggt tgaatcagaa 1860 accaagaaac actactatta aactgcatca agaggaaaga gtctcccttc acacagacca 1920 ttatttacag atgcatggaa aacaaagtct ccaagaaaac acttctgtct tgatggtcta 1980 tggaaataga ccttgaaaat aaggtgtcta caaggtgttt tgtggtttct gtatttcttc 2040 ttttcacttt accagaaagt gttctttaat ggaaagaaaa acaactttct gttctcattt 2100 actaatgaat ttcaataaac tttcttactg atgcaaacta aaaaaaaaaa aaaaaaaaaa 2160 aa 2162 <210> 77 <211> 1735 <212> DNA <213> homo sapiens <400> 77 agactgccgc agcgactcat cctatcgata aggttcagtt agccaaggtg gaggatggga 60 aaagaatgga actgtcccag ctactcaatg agatcagggc aaactatgaa aagatcctca 120 ccagaaatca gatagagacg gtgctctcaa caaggatcca gctagaagaa gacataagca 180 aaaaaatgga caaagatgaa gaggctttga aggcagctca agcagaactc aaggaggccc 240 gacgccagtg gcaccacctg caagtggaaa ttgaatctct ccatgctgtg gaaaggggcc 300 ttgaaaactc cctacatgcc agcgagcagc attaccagat gcagctgcaa gacctagaga 360 ctgtgattga aggactagaa aaagagctac aggaagtaag gcgcggcatc gaaaagcagc 420 ttcaagagca cgagatgctt ctcaacacga agatgaggct ggaacaagaa atagcaactt 480 atcgccacct cctagaaaaa gaagaaatca gatattatgg ttgtatccaa ggtgggaaaa 540 aagacaaaaa gcctaccaca agtagagttg gttttgtttt accatcagcc attataaatg 600 aaatatcttt tactacaaaa gtcccacaaa agtatgagaa tgaaaatgta gaaacagtaa 660 ccaaacaggc aatcttaaat gggagtatcg ttaaggagag cactgaagct catggcacta 720 ttcagacaga gaaagtggat gaagttatta aagaatggga aggttctttc tttaaagata 780 accctcgatt gaggaaaaag tctgtttctc ttcgatttga tcttcattta gcagccactg 840 atgaagggtg tttagagact aagcaggata atctaccaga tatagaagtc aggcttatca 900 tgagaagatc atgcagtatt ccctctatca aacctccatc aacagctaat taatccaaag 960 atagtatttg acttgattgg aaaatgttag gatggaccaa ggtgggccat accaactccc 1020 tctgtcccaa aatgtaagtt attacgtatg tatggaaaat gttatgatca atatgtggtt 1080 ctcttcagaa gaaaaaaaca ataaaggaca tttctctgaa tctaattatg gagatagaca 1140 tatatatata tatatgaatg agagggagta gcttaaaaat aaaatcacaa atccagtaca 1200 gtctctttct ttatattctc ccaatagtct tctttttccc ttgaaacttc atcagagact 1260 gtaagcatta acctggttta gtaaagtctt tgtaattttt ttcaatggct gaatacgcta 1320 aggaaaaaag aattgtttga ataggattgt gttaagagtc acactgagtt attcaccatt 1380 attccatgac tggttaaacc tacaatgttt gttctatttt tcaaaaagag caattataaa 1440 caagttttta aagggggact cactattcac ctaatgagga ttcttctttt tgagataaat 1500 catttgtata ctgagaaaaa tgagttattt tccatgagaa attctgagca aactatagaa 1560 cacaccccag ggctaatttg agataagtac aattaagtta atctacatat atctaaaagg 1620 ttttttttgt aataagtatc tgatttccgg aagatttact ttactcaagg aactttaaag 1680 gttgtatccc ccaccaaaaa aagaaaaaaa atcagaaggc caactgcgca aacaa 1735 <210> 78 <211> 789 <212> DNA <213> homo sapiens <400> 78 acagcctctc ccagccccag caagcgacct gtcaggcggc cgtggactca gactccggag 60 atgaagcccc tgctcctggc cgtcagcctt ggcctcattg ctgccctgca ggcccaccac 120 ctcctggcct cagacgagga gattcaggat gtgtcaggga cgtggtatct gaaggccatg 180 acggtggaca gggagttccc tgagatgaat ctggaatcgg tgacacccat gaccctcacg 240 accctggaag ggggcaacct ggaagccaag gtcaccatgc tgataagtgg ccggtgccag 300 gaggtgaagg ccgtcctgga gaaaactgac gagccgggaa aatacacggc cgacgggggc 360 aagcacgtgg catacatcat caggtcgcac gtgaaggacc actacatctt ttactgtgag 420 ggcgagctgc acgggaagcc ggtccgaggg gtgaagctcg tgggcagaga ccccaagaac 480 aacctggaag ccttggagga ctttgagaaa gccgcaggag cccgcggact cagcacggag 540 agcatcctca tccccaggca gagcgaaacc tgctctccag ggagcgatta ggggcagggg 600 acaccttggc tcctcagcag cccaaggacg gcaccatcca gcacctccgt cattcacagg 660 gacatggaaa aagctcccca cccctgcaga acgcggctgg ctgcacccct tcctaccacc 720 ccccgccttc cccctgccct gcgccccctc tcctggttct ccataaagag cttcagcagt 780 tcccagtga 789 <210> 79 <211> 4077 <212> DNA <213> homo sapiens <400> 79 gccagtgagc ccccgcgacg gtggcccgga cggaaaagat acctcggcgg cgtgggcccg 60 gctccctgct ccaggaccta gggatcttgg ccttccaccc tcctccgagc accaggactc 120 cctccagttc cgtacccgag gcctccgtgg tgaagaggtg ccggacccga tgagctcggg 180 agtccaccat cgctctgcaa gccgcagtta aacgagaaga ttcatcaccg ctttgatggc 240 tgcctcacaa acttcacaaa ctgttgcatc tcacgttcct tttgcagatt tgtgttcaac 300 tttagaacga atacagaaaa gtaaaggacg tgcagaaaaa atcagacact tcagggaatt 360 tttagattct tggagaaaat ttcatgatgc tcttcataag aaccacaaag atgtcacaga 420 ctctttttat ccagcaatga gactaattct tcctcagcta gaaagagaga gaatggccta 480 tggaattaaa gaaactatgc ttgctaagct ttatattgag ttgcttaatt tacctagaga 540 tggaaaagat gccctcaaac ttttaaacta cagaacaccc actggaactc atggagatgc 600 tggagacttt gcaatgattg catattttgt gttgaagcca agatgtttac agaaaggaag 660 tttaaccata cagcaagtaa acgacctttt agactcaatt gccagcaata attctgctaa 720 aagaaaagac ctaataaaaa agagccttct tcaacttata actcagagtt cagcacttga 780 gcaaaagtgg cttatacgga tgatcataaa ggatttaaag cttggtgtta gtcagcaaac 840 tatcttttct gtttttcata atgatgctgc tgagttgcat aatgtcacta cagatctgga 900 aaaagtctgt aggcaactgc atgatccttc tgtaggactc agtgatattt ctatcacttt 960 attttctgca tttaaaccaa tgctagctgc tattgcagat attgagcaca ttgagaagga 1020 tatgaaacat cagagtttct acatagaaac caagctagat ggtgaacgta tgcaaatgca 1080 caaagatgga gatgtatata aatacttctc tcgaaatgga tataactaca ctgatcagtt 1140 tggtgcttct cctactgaag gttctcttac cccattcatt cataatgcat tcaaagcaga 1200 tatacaaatc tgtattcttg atggtgagat gatggcctat aatcctaata cacaaacttt 1260 catgcaaaag ggaactaagt ttgatattaa aagaatggta gaggattctg atctgcaaac 1320 ttgttattgt gtttttgatg tattgatggt taataataaa aagctagggc atgagactct 1380 gagaaagagg tatgagattc ttagtagtat ttttacacca attccaggta gaatagaaat 1440 agtgcagaaa acacaagctc atactaagaa tgaagtaatt gatgcattga atgaagcaat 1500 agataaaaga gaagagggaa ttatggtaaa acaacctcta tccatctaca agccagacaa 1560 aagaggtgaa gggtggttaa aaattaaacc agagtatgtc agtggactaa tggatgaatt 1620 ggacatttta attgttggag gatattgggg taaaggatca cggggtggaa tgatgtctca 1680 ttttctgtgt gcagtagcag agaagccccc tcctggtgag aagccatctg tgtttcatac 1740 tctctctcgt gttgggtctg gctgcaccat gaaagaactg tatgatctgg gtttgaaatt 1800 ggccaagtat tggaagcctt ttcatagaaa agctccacca agcagcattt tatgtggaac 1860 agagaagcca gaagtataca ttgaaccttg taattctgtc attgttcaga ttaaagcagc 1920 agagatcgta cccagtgata tgtataaaac tggctgcacc ttgcgttttc cacgaattga 1980 aaagataaga gatgacaagg agtggcatga gtgcatgacc ctggacgacc tagaacaact 2040 tagggggaag gcatctggta agctcgcatc taaacacctt tatataggtg gtgatgatga 2100 accacaagaa aaaaagcgga aagctgcccc aaagatgaag aaagttattg gaattattga 2160 gcacttaaaa gcacctaacc ttactaacgt taacaaaatt tctaatatat ttgaagatgt 2220 agagttttgt gttatgagtg gaacagatag ccagccaaag cctgacctgg agaacagaat 2280 tgcagaattt ggtggttata tagtacaaaa tccaggccca gacacgtact gtgtaattgc 2340 agggtctgag aacatcagag tgaaaaacat aattttgtca aataaacatg atgttgtcaa 2400 gcctgcatgg cttttagaat gttttaagac caaaagcttt gtaccatggc agcctcgctt 2460 tatgattcat atgtgcccat caaccaaaga acattttgcc cgtgaatatg attgctatgg 2520 tgatagttat ttcattgata cagacttgaa ccaactgaag gaagtattct caggaattaa 2580 aaattctaac gagcagactc ctgaagaaat ggcttctctg attgctgatt tagaatatcg 2640 gtattcctgg gattgctctc ctctcagtat gtttcgacgc cacaccgttt atttggactc 2700 gtatgctgtt attaatgacc tgagtaccaa aaatgagggg acaaggttag ctattaaagc 2760 cttggagctt cggtttcatg gagcaaaagt agtttcttgt ttagctgagg gagtgtctca 2820 tgtaataatt ggggaagatc atagtcgtgt tgcagatttt aaagctttta gaagaacttt 2880 taagagaaag tttaaaatcc taaaagaaag ttgggtaact gattcaatag acaagtgtga 2940 attacaagaa gaaaaccagt atttgattta aagctaggtt tcctagtgag gaaagcctct 3000 gatctggcag actcattgca gcaggtggta atgataaaat actaaactac attttatttt 3060 tgtatcttaa aaatctatgc ctaaaaagta tcattacata taggaaaaca ataattttaa 3120 cttttaaggt tgaaaagaca atagcccaaa gccaagaaag aaaaattatc ttgaatgtag 3180 tattcaatga ttttttatga tcaaggtgaa ataaacagtc taaagaagag gtgtttttat 3240 aatatccata tagaaatcta gaatttttac ttagatacta ataaaataca tttagaaact 3300 tttaaagtca tgaaaaagca ttaaccttct aaacagtata ttctaaaaag tcaaaacgtt 3360 aacaatagtt tttatctaat aaaagcactg caagaaaata gggtagaatt gttacagctg 3420 gacttgtaaa aatatgtctt tttactcagg gtttaaaatg tcccatttaa atatgaaatg 3480 taaacaaatt tgttttttaa ggttaaggcc aaatgtaaca ataaaaccct gtcgatggtt 3540 ttagctaaat tagaggaagt tgtatgagac ttaatgatct aaaaacttaa aattgaattg 3600 gtttgattaa aaataaagct tgcaatttta aaagtagctc acatttaatt tcttgtgtga 3660 aatagaacat gctttaaagg aagtattttt atgtgaattt gcattccagt ataaatagta 3720 ttcacaaaaa agattttcct agattttatc tattgaatag gtgtcaatat ggcatgcata 3780 ttgtaacttt cattagaaat aagttgcttt gacttttaaa aatgacatag ttagattatt 3840 taaagtcaat gtatatagta tatattatgt atggatttat ataccaaatt ttggaataca 3900 gcctatctca tgaccatatt gaaatgtacg gaatttgatc catgcgatac tatgtgtgca 3960 ttatttgaaa gttattggaa attttattca aaccgtggaa caaatgtatg tgattttgtt 4020 atacttctta atttaaataa aatatttaat gcactattaa aaaaaaaaaa aaaaaaa 4077 <210> 80 <211> 2903 <212> DNA <213> homo sapiens <400> 80 ttttcttttg atagaatgtc aaacttacga aaaaagttac aagaagagaa caaagagcta 60 ttagagggtg ttgctgacac aatgctttat cactcttgaa tattttcgtg tgtaattcct 120 acaaataagg acattctccc acatagccac aatacaacca tcaaaatcag gaagttaacg 180 ctgatgtgtt tctaccatgt aatcctcaga tccaattcaa gtgtcaccag ctgtcccaat 240 aatgtctttt ataacaaaaa cattcagtct aagatcactc attctattta gttatcttgt 300 ctattcttca atttggaagt gttctttgtt ctttcctgaa tgttcatgac cttgacatct 360 tagaagatta aaggttattt aaagttgttg agttaaatat ccattaaatt aggtttgtca 420 gatatttcct cgaaattaga ttcagcttat gcattttttg gaaggaatac cacagaagtg 480 atgttgtttt ctttctgttg catccaatca gatgatacag gattttgatt tgttccatta 540 ctgttgacat gaattttgaa catttgataa tgccagtatc agccagattt ttccattgta 600 aagtcattcc tttgtccttt gtatttaata agtatgttta gggactttga gactatgtca 660 atgtcctgtt cttcatcaaa attccactca ctcattctta gtattcattg acgtttactg 720 atcgaactaa ttattattat gatagttgcc aaatgttggt ttttctaatt caatcatttc 780 tttagtgttt attagcattc tactataagg aaaagcacta tcttctcccc atttattaat 840 tcacatattt acatcagctt ggagttattg atttctattt tattaaatag tttataattg 900 attaccatcc ttatttattt taatgctcaa attgtcccaa attatggcca aagaaagctc 960 cttcaaactg gttgctatgt ccttttgaca tggcccatca ttctttaaac acattttaca 1020 tctggcacaa taacgtgcta catacccatc ttgtattttt cctgccccat ctttgaaatc 1080 agccattctc aaggggttcc ttcttaatct ggctgttgtt gtgttggaac tcctggtacc 1140 atcttagaac cttaaggaga caagcgaacc aagccaataa gctttccatg atgctgctta 1200 gagttaaaca gagcccaggt actaagttat gtcatggaga cagtgaacta acctctggac 1260 tgcttgctac atgagacaat tgattttctt attttctatg tagggtggta catttcctca 1320 ttttgagata tttcttcaac atatagcttt tcattagtgg ggattttgtc aattataacc 1380 aaaaacaatg tgacggatac ccaagatgtt tcatgttgta gcttgggtga attacacatt 1440 tctgaagcca ttacacttcc tagtttattt ggatttaagt tgacaaataa aaattgcata 1500 tgtttatggt ctataacatg gtgtttcgat atatgtatac atcgtggaat ggctaaatca 1560 agctaacata tccattacct cacatagtta ttttttgtgg tgagaacatt ttaaaaatat 1620 tgtcttagca attttcaatc aagcctgtcc catggagaca caagcaatag tgacatgagc 1680 acttgactcg ctgggttatc aggctttggc tccaaatgtt tggcttcaaa tatgaaaaag 1740 ttacatgaaa gatgaaacta tgcaatggca tggctgttgg tcattcacat ctctctctgc 1800 caagaatgga gatgacgctg ttgaaggaag aaatgtgttt tctccttttt ctcaagtgat 1860 atttgcctta ggtcagattc tactagttta aagcaaaacg atctcctggt ctgattcctt 1920 tgggtctcta ataatggaaa ctgcaaggat cagcataaag tgttcctttg ttctgacgtt 1980 ggtataacat tgcttcttga aaaatgaaag tatttggaca tgcagacaga agcaatatta 2040 ttcaggtctt ccttgttgca agtgagggaa atccaattaa aactggttta aacctaaaaa 2100 aaaaaaaaag aagaaaagaa aagaaaaaat atgagagggg ttttgctttc tggaatctgc 2160 tttctagtca gaaagtgcag aagaagggct agcttcagga acaattggat gcagtagttc 2220 aaatcacaag ttaagtctct gcttcttttc tccatctctc ttctgtcttc ctccacactg 2280 gctttattct taggtaggct tacccagata gtcataaaca cagccaccag tggcagctgg 2340 gctcactttt gtccttggag ccagtgagcc catgaaaaag gagcttctct ttctggagct 2400 tcccaggggt aactttgatc agccaacaag ggtcagtcct atgcttatcc cttgaccaat 2460 ctctgtgccc agagggcagg gtactctgat tggcaatacc ttcatcgtgg gccaaccact 2520 gtggggaagg gggagggatt agaaaagaca gccacaccca aatctcatga agcagtcccc 2580 tttattttaa aaaagtccct gtgagagcaa caggagcaaa gcatggagaa gaagcaatct 2640 tggagaagct ggaagagaac cgacccaaag aatccaagag actaagactg tgcagggttg 2700 gggaacggaa gctcacacag gaggcctgga cagagctgca gcagagccag gagagaagcc 2760 aagtggcaca gctcatcttg aagtaattat aatgccacta aaattctcat ttgtattaat 2820 tttttttaat tactggcaag ataaggcaaa tgtttttaaa ggcctaaata aaatgatatt 2880 ccctgaaaaa aaaaaaaaaa aaa 2903 <210> 81 <211> 219 <212> DNA <213> homo sapiens <400> 81 atggtggtcc tggggatgca gacagaggag gggcactgca taatgctgag agggctggca 60 ccctctctag gtggaacaca ggtaatttgt aaagttgtag gtctgccaaa cagtattgta 120 ttcaacacat cttctcacct tctctttcca gccaccctcc agggtgccct gactcacctt 180 ccctgcagat ggaggtgagg ttccacagac aaaccccct 219 <210> 82 <211> 930 <212> DNA <213> homo sapiens <400> 82 ggttgaaaga tccttcagta ccagccaact ctctctcctg gttccatgtt cactctgcta 60 ctttctaatt attactccag gttggaggga tggatgatgg acaacaactt ttctcatcac 120 tggaagggca tgttccccac tgaaactgaa tccactgttt tttgtttgtt tgtttatttg 180 tttatttttg tttttgagac agcgtctggc tttgttgccc agactggagt gcactggtgc 240 aatctcggct cactgcaacc tctgcctccg gggttcaaga gattctcctg cctcagcctc 300 ccaagtagct tggactacag gcacgcacca ccatgcctgg ctaattttta tatttttagt 360 ggagacaggg tttcaccatg ttggccagac tggtcttgag ctcctggctg atctgggagc 420 cacagcaggg gtcagggccc tgtgatcccc agcctgaaac tggcagtcag atttcacagg 480 cttcagacca cagaggagca ctaggacccc accagaggtg gtccggaggc tgacctgaag 540 gccctgggga tgggctatgc aagctgattg ctcactgcga gtagcaagag tatgtgtttt 600 tctggaagga atgattggaa tatccaagga catgagggga gaagaaagcg gtaaaatggc 660 atttgctgta aaagagtggg aaaaaaattg aattactcca aggttcgttg tgttcttcca 720 gctccatcta tgataaagag aatgaacaac taggtgtttt ccttctggac aatgattatg 780 acacagatta ctgctgggac cagaagtatt gccactttgg acaacatgga atagaaggat 840 tattgagaat cacttataat gagatgttac ttcaaattag gaaaaatttg ataaacaaat 900 ttataataca aatgattata aaaacctaaa 930 <210> 83 <211> 1234 <212> DNA <213> homo sapiens <400> 83 aaagacttcc ggtcggcgtg agcgtgaggt gtgggtgttc gtttctcagg taaaacatgg 60 ctaaaagctt acggagtaag tggaaaagaa agatgcgtgc tgaaaagaga aaaaagaatg 120 ccccaaagga ggccagcagg cttaaaagta ttctcaaact agacggtgat gttttaatga 180 aagatgttca agagatagca actgtggtgg tacccaaacc caaacattgc caagagaaaa 240 tgcaatgtga ggtaaaagat gaaaaagatg acatgaaaat ggagactgat attaagagaa 300 acaaaaagac tcttctagac cagcatggac agtacccaat atggatgaac caaaggcaaa 360 gaaaaaggct gaaggcaaag cgagagaaaa gaaaggggaa aagcaaagca aaagcagtga 420 aagtggcaaa gggtttggcc tggtagactc ttaaaacctt ggaaaatgcc acatgggata 480 gatgacggat tagaatgtat acacatgtat actttgattt caactgccac caaatgaaaa 540 ccatttgttt tcctatttta acttggcctt ttttcttcaa ttcaaaccca gcataactcc 600 tcaagtttgt tttgggaact tgaataaaat attttctttg atacatccaa gctctactga 660 tactttaact ggatgctacc caatatccag ttataatcag gcctcaacgt tctgtcaggt 720 attaatatgg ttagaattgt tcttacaact ggtaattata gtcaatagag ataaaacaga 780 tgatgtactg acaaattttt gtgaacttag attttaaaga aagttgttgt ataatcatat 840 catttaaaaa tactacatta gggctgggca tggtggctca cacctgtaat cccagcactt 900 tgggaggccg aggcaggtgg atcacgaggt cagttcgaga ctagcctggc taatacagtg 960 aaaccccatc tctactaaaa atacaaaatt agccgggcat gggggcgcgc acctgtagtt 1020 ccagctactc gggaggctga ggcaggataa ttgcttgaac ccaggagatg gaggttgcag 1080 tgagccaaga ttgccccact gcactccacc ctgggcaatg gagtaggact ctgtctcaaa 1140 aaaaaaaaaa ataatggatc ttataaagta cttgtgtgga gctttgattc cacagaataa 1200 aagatatttt gtgtgtaaaa aaaaaaaaaa aaaa 1234 <210> 84 <211> 2338 <212> DNA <213> homo sapiens <400> 84 agcttcaagc ctgacgttct aggggggagc cgcttcttaa gtacgtgcta ggatcaaggg 60 tgcatttgca aacttttcaa aatgccttag aggagtccta accagcccca gggtgtctga 120 ggcacgctgc ccacaggaca cttgctctct ctttcttgtg accccaacat gtcagctggc 180 aagactcaac attcctgtct gggactgagc agcttgaacc acttgtatga gtcacagaaa 240 aggagaatca tacccccatt ccaccacccc actccaaccc ctccactgtg gctccaatgt 300 tacagaccac tcctaacttc agtcccggaa gaatggaagg aaggctgcaa cttaagagac 360 tgcggttaga agtgatcttc ataaattgtt tgccttgcct gtgtctagag tccttaagat 420 ggagtgaagg tacctgagcg caggaaccat ggtcttcatt gctgcctcag cattagcgga 480 agtgccacgg gccggctccc agggggccag agtttcccag gaacaccatt gagtaccact 540 gaactagagt ctgcaagtta aagtaaggca agaaggaaaa ccggaaacaa ctgtaaaaac 600 ctgacctttc gtcaccttaa tactggccat catttatcga gtgcttatta tgtaacagac 660 attgttctca gtgtgtgagt gcagtgttcc tcaaacctaa atgtgggcct gaatcgcagc 720 ggatcttggt aaaatgcagt ttctcattca gtacctctgg ggtgcggcct gagattctgc 780 atttccaaca agctcccagg atactttgta tagaaaggct ttggtgtatt aactaactcg 840 atcttcttaa taatcctatg aaatactact gctattccca ttttacagat gaggaaacag 900 aggttaagca tatatgaact tacatcaaaa taaatagact gcagggcaag gagggagggg 960 agaatagtgt gggcagtgta cagtgcagaa acaaagttct aggcagagga aaaaggattt 1020 acagaaagcc tggcatacag ggcaggggga cggggcctgc acacggggct gtttcaccgt 1080 tagacgttat aagcacagta cttggggcta tgggcttcct gaaggtccca agtatttgag 1140 acctgaaaaa aatttattga cacctacata ggaaaagtga acttttaaat taataattcc 1200 aaaattcaaa tcacgaattg tttcaaaaat tttacatgat agaattcata tttagtaagc 1260 gatacgggta tattttaatg catttgattt taaaaacggg gtagggccta ctaagaacag 1320 gccaagccct ggccccagtg ggtttggata taatcctgag ggcagctggg aaccactgag 1380 agaagcagga gaatgttctc tgtggctaca gtgaggagaa tggattggag ggaggccaga 1440 ctggaggccc agtggctaga gaccagatag gcagttacag tcttccagac tgcgagacaa 1500 tctctcttta gtgccaagat tagcataaaa tcatagcatt atataaccca attattcttt 1560 gattcctgca tccccaatct gactcagcat tctaaattta cttaagatct ggggacaagg 1620 gtttttggca aatccttgaa ggcaaatgat gttacagtca atcagtatat gccttgagcc 1680 agacagacat gggtacgggc ctcagttctg ctgcttgcta gctatgtgac tttgcacaag 1740 tgatttaact tctctgggcc ttggattcct tactggtaac acgagcataa tcgattcctc 1800 acagaattaa gtgagaaaac tatgtatgta ggacttctta tggagtgggt acttagaaat 1860 aaatggtagc cgttatcatt tatgtgcctt tgttctgaaa tctgcttaag ttttctctag 1920 gaagtaacag agggtagaat aaattattta gtattttcat caatcttctg agataaaaat 1980 tattatcctc attttgcaga taaggaaaag ggctcagaga ttagatcaca gctctgtgaa 2040 gtaggggcac aaagtggtca acctggaaga gctggacttt attttgcttg cacttctgtc 2100 catgcactct ctccagcagt tgacatttgc cctctttgat ggctccacga ccaatttccc 2160 ttagtcatgg catgagtcag ctgtgagggc tgatggcaca ccaccgaata ctctgctgtg 2220 gcgccactag cctccattta ccttcttctc caacgttttc cagcctccct cataccttgc 2280 cccccagttt tatagcttct ggattttcct tattaaagag cttgtttctg agactcag 2338 <210> 85 <211> 2129 <212> DNA <213> homo sapiens <400> 85 aagtactgca ttcaaagaaa tacaaacaca accagaaagt attataagtc tatattcagc 60 atttcaaatc tgtcctgtct atcaaggaaa caccgaagga ggaggtaaat tcttaatgca 120 tagcagacat ttaaaaattc tctctcacca ttgctgccca gtcactaccc tgcatgtgaa 180 tgccagcttg tctcttgagt tgtctctttc ctattctcaa cttccacccc caaacacatt 240 tagagcacag gtcttttctg tcacacttgc cagtcttcct tgcctgctct tattatgtaa 300 atcaaattca ccactctgtc ctgttttgtt ttcatctctg cttcactcaa taccccgact 360 ccctcaggac cgtgttgctt ctgccctgaa tgagttcttt tctcccgggc tgcagggacc 420 acagaggtct tcttcctatt acttcatgga ctgtatgaat tccacccagc tggtgacatc 480 atggcaggtg gtttggagat gaactggtat cctgccctgt gttaaatgtc ctcagactgg 540 agctcagaac ttttgagtat tttcaaaagg gtcaccgtgt ctccagagaa atgctcccaa 600 cagtcctaac tgaagtcagc actgaactgg gcaaaggact caagaaaaaa agtttccttc 660 ctcctcgatg tgttgctcaa agcactgcgt gagaccacac ggagcagtat ctaagcattg 720 agcaacactc agaagggcag caggacaaat gcgtagctgc taatgacccc tctcctgcca 780 atgctttcct ccctcagccc cctctagggt caccgaacag ctgtaaatac aagctgacca 840 ccctcaagga gctgggatgg agggaggttt tctccagtct ccagttctgc ctttgcacct 900 ctgtggcctc tcaaatgctc agccagtatt ttgagtacac ccaacctcac ccaggagata 960 tatgtcaccc agaaacatgt gctctccaga aagtcttcct gacatcatcg gggcagtcct 1020 cctccacctc ctcctcttcc cagcaattcg ttctgcaaat taatgccatc caaacaatcc 1080 tcgagaacta tctaggaaag gacgaggacc aaattaccaa gcctttggat ctaatccatg 1140 tggcatccca tctgtgagct ccagggagat tcaaagttgg ccagtgctgg aggccaatca 1200 tatttatacc atttccatat ggcacctttt gattgagact tggcaagcac atgatcggat 1260 tggaggaaga cagagagcaa gacgttggaa caagcagcag gggtggagcc tgggacacaa 1320 ggtcagcaca tagcaagccc ttgctttgga gcagaggtgg ccggtttcca gggcagtgag 1380 tatttgaggc agtaattgtg atcttcagct tcactggtgc aagtatcacc tgtgagaaag 1440 caggcattgg gtgtgattaa ttagtatgct tctttagcat atggggtgag ggagggacag 1500 gggctaattt gagcagtcag ggacaaggag tcaacatcag tgtggagtga taacgtttgt 1560 acaccaagct ggtaaataga catcctagtt acatatgatt ctattggcat tgcctacaga 1620 ggagaaaaaa gtgatcaagt ggttgtggat tttatgtttg cttacctgtt ttttaaaaaa 1680 aaggtgaata aggaacttta taaagatgtt ggattccagc atgttagaca ttgtagtgga 1740 ttgaattttg atccccaaaa agatatgtcc caagtcttaa cctcacagta gctgtcaatg 1800 tgagcttata tagagccttt gcaaatgtat taagttaagc atctccagac gagatcatcc 1860 tggattcagt gtgggctcta aattcaatga ctggtggtgg tataagagaa aggagagaga 1920 gacaaacaga cccagagaca cacagagggg aaggccatca gaagacgagg cagctattgg 1980 agttacgcag ccagagccaa gggatgccag aagccaacag aagctggagg agtcaaggaa 2040 ggattctccc ctagaaccct ggaagggact gtggccctgc tgacgctttc tgggctccaa 2100 aactgagtga gaataaattt ctgttgttt 2129 <210> 86 <211> 1489 <212> DNA <213> homo sapiens <400> 86 ctttgaatga ggctttttgc ttttatattc ttggatgccc caagggtttg accttgatat 60 aagttgagtt tagtcgactg gcatagtttc ttgatgattt ctgggtacca aggctcagct 120 cagcactcct ggcatgcatg ctataaccct ggggtgttag gactaggcac atgactttgt 180 tctctgtctc ctcgaggtta agcacccatt gcactggtgg ggccaaggtg ttcccggtct 240 gctgggcaac aacactctga tggtggggcc ggcaaaagtg cttggttggg gtggtgacag 300 tagggtggta aggcctgcat atacattgga aaagccgtcg ggggaggctg tgggtgacgg 360 tgtcctggca aaacagtgcg gggaagctgt gcgtgggtgg atgctggtgg aggcccatgt 420 gcaggtgctc tctggtggtt acctggggct tgccagcaaa ggagctatag tggtggctgt 480 cgggaagtgc tgcggttggg catcagcgtc cattgcaatt ggatgtggcc aggcagggac 540 tgtggaacag gcaaccaggg atgggggttg gggggggcgc tcaaatctga caagccctgt 600 gccatgggca agatagttct gttctgtcta ggtccaatag tcagcaaaga ccaaagctac 660 ctagaggtgt gtggtgagct ttgggagatg gacatacctg gccatgctcc actgcagcca 720 ttcccacacc aggccttctg ggctccgtgc agactggagt cctgtttctg ccaacttccc 780 aagcagctgt ctttgcaacc tcaaatgtct gtaggggtca tggagcctcc ttcagctagg 840 attctagagg tccatgacaa gaacaggcta ctccatgcct gtttaactca tcctttcccc 900 aggagcattt ggggtcagaa tgagtcatgg tgctagggga gctccctgta aggttcccag 960 ctttctcctc cttcagccca ggatccgcat cctccttctg ttcactctca gtgccttcct 1020 tccaaagatc tgctcagagt gtgctggtct tcttgatggc ctggtctctt ggtggtggaa 1080 gctcttcctg actctgtgtc tacttggcca ccctgactcc tctctgttgt ctgttcactg 1140 tatatagtgt catgtgagga ataaaagttt taacatttga cgaagtccaa ttcacctatt 1200 ttttttcttt tgttgcctat gcttttggtg ttatatccaa gaaatcattg caaaatgcag 1260 tgtcacagaa ctttctccct atgctttatt ctaagtttta tagttttcag ttttacattt 1320 agctcttgga tccattttga gttaattttt gaatatggta taagcctgtc acacaggctg 1380 gagtgcagtg gcgcagtctc ggctcactgg aaactccgct tcccgggttc acgccattct 1440 gctgcctcag cctcccgagt ggctggtact gcaggtgccc gccacaaca 1489 <210> 87 <211> 1110 <212> DNA <213> homo sapiens <400> 87 gggcttgcct cctcctgcgt cctgctagct atttttaaat gtgagctcta ttttgttcca 60 agatcattag gatatttagc cccttcacca atttccacaa gaaaattaat tcattccaat 120 attcagaggt tcctttttta tttcttagcc agtgattaag gaatccatta tgtaacccag 180 agccattctc tctactcttt tcttaatttt tccttctaaa atggggagtt ccattttctt 240 aatttttcat tctaaattgg ggagttccaa attttttttc tctctctctc ttaggcaaag 300 cagttcatgt ccttcctgga agttttagta tctgccagta ctgatgccca gtttgcattt 360 taaaagctcc ttctagctgc tagatgctga aaagactgaa aggaggcaag gggataggca 420 aagggaccag tatcaggtta ttttaggaga tgatggtggc ttgaaccagg tagtggcaaa 480 gctcgtaaag acaagtgcat gaataggaat attttggagg agatgctgca gtacttgctt 540 atagattgga ttgtaggtga ccagtttgaa attcagctaa accagcagct atggtccctc 600 atccccaaca acgatgtgag aaggcttgtt tctcatgtta tccggacctt gaagacggac 660 tgcactgaga cccatttgca actggcctgt gccaagctca tctctaggac aggcctccta 720 atgaagcttc tcagtgagca gcaagaattg agaactgtat caatgacagc atggaagccc 780 agaatgaaca gaaagagcag aagtcgaatg aggtcctgat atggaagaaa ctactgatgt 840 cagctgaagg accacactga tgcagctgtc ctgaaggact ccccgaggag ctacctcatc 900 aaaaaataca gtttccactt tgcgatgatt ttatccccct tgccccaacc gaccagcaac 960 cccaattttc cagcccctca ctctccacaa tcctcttaaa gccccaggcc agaacttctt 1020 gggagacaga tttgagggtt tccttccact tccttgctgg gtggcctgtg atcattaaac 1080 tctttctttg ctgcaaaaaa aaaaaaaaaa 1110 <210> 88 <211> 4733 <212> DNA <213> homo sapiens <400> 88 gtacagaaat aatggacagt gaatgccaac attatgatat acattgccct ctactttcct 60 ttcaggtgga tggctggtac tctttgccat catgttgcgg ttggtggcag cttgccctga 120 gtcatgtgtg gtgtgcacca aagatgtaac cctctgtcac cagctaacct atatagtagc 180 agcccctatg accacgaggg ttttaatcat caccgatgga tatctctcct ctattgagag 240 cacaaacctg tctctcttgt ttaatcttgc cctgctctcc ctaagcagaa atggtatcga 300 ggatgttcag gaagatgccc tgcatgggct tacgatgttg cggaccttgt tgctggagca 360 caaccaaata tccagctctt cgctcactga tcacaccttc agcaagcttc acagcctgca 420 ggtactggtg ctgagcaata atgctctccg caccctacga gggtcttggt tccgaaacac 480 aagcggcctg acccggctcc agctggatgg gaatcagatt actaatctca cagacagttc 540 tttcggaggc acgaatctcc acagtctcag gtatctggat ttatccaaca attttatttc 600 ctacattggg aaagatgcct tccggcccct gcctcaacta caggaagtgg acctttcccg 660 aaataggtta gcccacatgc cggatgtgtt tactccactg aagcagttaa tccttctgag 720 cttagataag aaccagtgga gctgcacttg tgatctccat ccccttgctc ggtttttaag 780 aaactacatt aagtcttctg ctcacacgct caggaatgcc aaggacctaa attgccagcc 840 atctaccgca gctgtggcag ctgcacagag tgtgctgagg ctgtctgaga ccaactgtga 900 ttccaaagct cccaacttca ctctggttct aaaggacaga agtcccctcc tcccaggacc 960 agatgtggcc ctgctgactg tccttggctt cgcaggagct gttggtctca cttgcctagg 1020 tttagttgta tttaactgga aactccacca aggcaaagca aatgaacaca catcagaaaa 1080 cctttgttgc agaaccttcg atgaacccct gtgtgctcat gaggcaagaa attaccacac 1140 taagggatac tgcaactgcc acttaactca ggaaaacgag ataaaggtca tgtccactgt 1200 ggggtccaga aaagaaatgc cacttttaca ggaaaatagc catcaagcaa catcggcctc 1260 tgagtctgca acccttgacg gatcatttag aaacctgaaa aagaaagacc gtggggtagg 1320 cagcacttta ttttgccagg atggtagatt gctgcattcg gaatgttcag agcctcctgg 1380 aaatatgaga gcttttaatg aagcaggctt acttacaaca tataatccaa ggaaagttca 1440 aaagctatgg aatcttgagc ctggagaagt ccagcctcaa actctgcaac accatataat 1500 aagaacagaa gatatcagca gtgacatatt tagaagaaga tatgcaacac ccgcttcagc 1560 cttggcagga gaaagtcttg agaagcgttt aacaaatgaa tcatggcagc ctccaataga 1620 aaaagaagac aatggcttac accctcatag gcaaagacat tttattacaa gctcatcatc 1680 caagccttgt gagcctgagg aacactatgt acaaaagatc gtacaaaaaa atagatcaaa 1740 atatgatgat ccttgtggac tgttaaaaca gagcaaacct aggtattttc agccaaacaa 1800 ttctcttatc tgtaaatatg tgccctgtga gcaatttgaa gattacatga aagaaaagaa 1860 gccaaatcgt agacaacact caaagcctga gaaagagcaa atccaaatta acagtgcaat 1920 agaaaaattt cttatgagtg aggacaacat agatttatca ggattatcaa caaaaaccaa 1980 gaaagcatat tccccaaaga gggttatctt ccatgatcct gatttagtag aaataaatag 2040 gtcgatgatg tcacccaaaa tatcaacccc ttggaaacga cagaaaaatc aaagtaacca 2100 actgactaag ttggatgtta aaaaatttag caacactggg gagagaaaca aaggagaaaa 2160 atggtttact aattcatggg ttctgaaaag gaagagaacc cctcagtctg acctcaaagg 2220 gaaaattaaa ggacaaaact taaaattaaa tttacatcct tttagaaaag tcagagtcca 2280 tccagaaaaa tccttgtcaa gtctcccaaa gcaatgcaag caggtattgt tgcctcctaa 2340 gaaattatcc aaaacttctg agacagaagc caaaataaat actgtgtgtt ctgcagattt 2400 tcttcaacag tcagagagta gcaactatgt tagactcact tcaaagaggc tgcctctgaa 2460 acatgactca aagcagaccc catattatca acgaaacact aaacgtgccc ccctgctcag 2520 tgctaacaac ttgcgtgtag tcaaccagag ctctatagaa agcagctgtt actcagctgg 2580 ccacattcct gatggaaaca catcaaaatt gccccaacct acacccactg atgctgagca 2640 caggcactca cattctcaat tctcaactga gcaaatggaa gatgcaactc agcttgaatc 2700 aaaagtgctt agttatttag caactacttg ggaaaataca ggaagtgatg ttttaccatt 2760 ccaacattcc aggagggcta ctgaccaagg gacaacggag tccactgagc acatgggaca 2820 gaatgtatca aagaccagtg agttaaatca gttttctttg tccccgagga atcaaacaca 2880 acttttagat gctcacaaga ctgacagcta caacaaggaa tacactttag accaaaatga 2940 agccttacaa cacagagagc aaaattcaag tcatgcacag cttgaaaata aagaaaaaac 3000 attaatgaca aaaccccaaa tatcacatca aattgtggaa aattgtatta tggataagga 3060 agaaaatgat gtagaaaaaa aactttcaaa aacagaaact tatgattcct ctctcattcc 3120 ccaaacacaa tccaagaaca acctatcatt tatgaagaca aattcaattc cataccaaaa 3180 tagaatagaa cttcccaagg atatcagtac ttctcctgtt agtagtcaag ccgtttggca 3240 cctaaccaat agtagcgaaa aaggaattga cagcacaaat gcattgccca gaaatgacgg 3300 cactgaagca ctagagataa aaatagtagg gaaagaagag aaaaatatgc ttgatgaaag 3360 caagacagat tctagtatgt taactcagat ctcacaaatg accttaaaag gcatcacaaa 3420 agaaaggcag caaacttggg aaaatggaac aagtgaaaaa tatatattac atgatgcaag 3480 ctctgccgag gagaccatta cagctaaaga tttaagtatc acaagttccc atgaaaccca 3540 aaatagaata ctttgcagtg aagtagatcc tgaagttaac agtaatgtac ataattttag 3600 agaagttcaa aatattcaac cagataaaga tagtgcacat aaagaaggcg caatgacagt 3660 ggagacacat gaagcgcttt ccttcttacc agggttaaaa gacagttttg aggcagaaaa 3720 tgaggtgttt ttagttccta gcagaataaa tgaagctgaa aactctgctc caaaacctgt 3780 actgtatcca ccatctgctg aatatgctac tacatcacct ttagaaacag aataaagtga 3840 acaaaataac tcaaataata atccttttct actttagctt tcttcaagag gacaaacacc 3900 cactagcctt tgcatgcatt agaagtggat cattttggag gacaacaacg tcctcagtaa 3960 ctctttgtta tcaataaaat aaaaccagag ttgaatatat gacaaaaatc aaagatggag 4020 tcataggata cgtctgacac aattaactga gtatgcttct ctaaggaatg aaaaaacaag 4080 taagaaaagt tttgccaagt cttgcaaaag caagcaaaca ttgaaaaaaa aaaagcctta 4140 aacaaatgaa aaactacata agaagagtat ttgagcagat ttacatttga tgtttatttc 4200 atgtaaatta ttatacatat ctcaattagt ggtattacaa tattgctttc tacatggata 4260 attatatatt catatttgtg tttgatctgt tttcctaatt atagtatgaa aataaaaatt 4320 cagctttgtt aactgtagtg taactgatat gcatattggt atgtttcata catttgcaat 4380 tgtcctgttg acaatcatcc cagatttaag tagaagtctt taaaacttgt tatttctcta 4440 agagaaaaaa attaaggatt tccagggata gttggctgtt cccataaaga tctgcaaaat 4500 cctatatatc cactaggtgg agatctcagc ttcaatcatt ttagaagaac agggcttgaa 4560 gatcgacaca atggatcctg aacaaaagga attttaatga gctttattgc caattgttat 4620 taatttaaga ttttgaaaac taaataacct attagtgcat agctttcaag gtctgatctc 4680 ttgggtttcg catgccactg ttgtttggag tgagaactcc tccttataca ctg 4733 <210> 89 <211> 1474 <212> DNA <213> homo sapiens <400> 89 agtcgcctga acccccagcc tgtggttctc tcctaggcct cagcctttcc tgcctttgac 60 tgaaacagca gtatcttcta agccctgggg gcttccccgg gccccagccc cgacctagaa 120 cccgcccgct gcctgccacg ctgccactgc cgcttcctct ataaagggac ctgagcgtcc 180 gggcccaggg gctccgcaca gcaggttctc cccatgacac cacctgaacg tctcttcctc 240 ccaagggtgt gtggcaccac cctacacctc ctccttctgg ggctgctgct ggttctgctg 300 cctggggccc aggggctccc tggtgttggc ctcacacctt cagctgccca gactgcccgt 360 cagcacccca agatgcatct tgcccacagc accctcaaac ctgctgctca cctcattgga 420 gaccccagca agcagaactc actgctctgg agagcaaaca cggaccgtgc cttcctccag 480 gatggtttct ccttgagcaa caattctctc ctggtcccca ccagtggcat ctacttcgtc 540 tactcccagg tggtcttctc tgggaaagcc tactctccca aggccacctc ctccccactc 600 tacctggccc atgaggtcca gctcttctcc tcccagtacc ccttccatgt gcctctcctc 660 agctcccaga agatggtgta tccagggctg caggaaccct ggctgcactc gatgtaccac 720 ggggctgcgt tccagctcac ccagggagac cagctatcca cccacacaga tggcatcccc 780 cacctagtcc tcagccctag tactgtcttc tttggagcct tcgctctgta gaacttggaa 840 aaatccagaa agaaaaaata attgatttca agaccttctc cccattctgc ctccattctg 900 accatttcag gggtcgtcac cacctctcct ttggccattc caacagctca agtcttccct 960 gatcaagtca ccggagcttt caaagaagga attctaggca tcccagggga ccacacctcc 1020 ctgaaccatc cctgatgtct gtctggctga ggatttcaag cctgcctagg aattcccagc 1080 ccaaagctgt tggtctgtcc caccagctag gtggggccta gatccacaca cagaggaaga 1140 gcaggcacat ggaggagctt gggggatgac tagaggcagg gaggggacta tttatgaagg 1200 caaaaaaatt aaattattta tttatggagg atggagagag gggaataata gaagaacatc 1260 caaggagaaa cagagacagg cccaagagat gaagagtgag agggcatgcg cacaaggctg 1320 accaagagag aaagaagtag gcatgaggga tcacagggcc ccagaaggca gggaaaggct 1380 ctgaaagcca gctgccgacc agagccccac acggaggcat ctgcaccctc gatgaagccc 1440 aataaacctc ttttctctga aaaaaaaaaa aaaa 1474 <210> 90 <211> 638 <212> DNA <213> homo sapiens <400> 90 cctgctcgcg gatcccgagt agagaacgca agcacccacg cccgcctgca agctcccggg 60 cgcccccggc ctctcctgct cggcggaacg aggataaccc agtagagccg gacccaggga 120 tattattgat aataaggcct ctgtaaccat ggctagttct gacgtaaaac caaaatcagt 180 aagtcatgcc aaaaaatggt cagaagagat agaaaatctg tacagatttc aacaagcagg 240 atatcgggat gaaaccgaat atagacaagt gaaacaagtt tctatggtag atcgttggcc 300 ggagacagga tatgtgaaga aacttcagag aagggacaat acgttctatt actacaacaa 360 acagagggaa tgtgatgaca aagaagtcca caaagtgaaa atttatgctt actagcctgt 420 cttctttgta ttacttgtca attatatttt aagtattcat catttccttc tacatcatgt 480 gtttgtcatt tgatgaaata attcaagatg cagtctgcag tttaatgttt tgtgaaacac 540 aaaagccatg agaattggta tctgctaatc accttgtcct gttctaagaa ctggctgcag 600 atgcattaaa gttgtacttt cttggaaaaa aaaaaaaa 638 <210> 91 <211> 2519 <212> DNA <213> homo sapiens <400> 91 gtttccggct ccggtgtcat ggccggctcc taccctgaag gtgcacctgc agtcctcgcc 60 gataagaggc agcagttcgg aagccggttc ctgagagatc cggcgcgcgt cttccaccac 120 aatgcctggg acaatgtgga gtggtcggaa gagcaagccg cggcggcgga gagaaaagtc 180 caggagaaca gtatccagcg ggtgtgccag gagaaacaag ttgattatga gatcaatgcc 240 cacaaatact ggaatgactt ctacaaaatc cacgaaaatg ggtttttcaa ggatagacat 300 tggcttttta ccgaattccc tgagctggca cctagccaaa atcaaaatca tttgaaggac 360 tggttcttgg agaacaagag tgaagtacct gaatgtagaa acaatgagga tggacctggt 420 ttaataatgg aagaacagca caagtgttct tcaaagagcc ttgaacataa aacacagaca 480 cttcctgtgg aggagaatgt aactcagaaa attagtgacc tggaaatttg tgctgatgag 540 tttcctggat cctcagccac ctaccgaata ctggaggttg gctgtggtgt gggaaacaca 600 gtctttccaa ttttacaaac gaacaatgac ccaggactct ttgtttattg ctgtgatttt 660 tcttccacag ctatagaact ggtccagaca aattcagaat atgatccttc tcggtgtttt 720 gcctttgttc acgacctgtg tgatgaagag aagagttacc cagtgcccaa gggcagtctt 780 gatattatca ttctcatatt tgttctttca gcaattgttc cagacaagat gcagaaggct 840 atcaacaggc tgagcaggct tctgaaacct ggcgggatga tgcttctgcg agattacggc 900 cgctatgaca tggctcagct tcggtttaaa aaaggtcagt gtctatctgg aaatttctac 960 gtgagaggtg atggaaccag agtttacttc ttcacacaag aggaactgga cacgcttttc 1020 accactgctg gactggaaaa agttcagaac ctggtggatc gccgactgca ggtgaaccga 1080 ggaaagcaac tgacaatgta ccgggtttgg attcagtgca aatactgcaa gccccttctg 1140 tccagcacca gctgagaggc acctgctgcc aacacgatgc aagcccattg tgtttccggg 1200 cttttttaaa aaaaaaattg tagcactggg cgtggtgcat gcctgtaatc ccagccactc 1260 aggaggctga ggcggggagg atccattgag cccagcagtc caacctgggc aaaatagtga 1320 gagaccctgt atctgaaagt aataataaaa ataaaaaata taaatgaggt ctcgttgatg 1380 ttggacaatt caagaattca gacttgaacc ttaaacctag gaaaagttac tttgtatcag 1440 gattctaaca attatgcttc atatttgtga agtcctttaa aacataattt tctcaagttc 1500 tttctttgag atctcaatct gtcttagcat tttgtaacta ataactgaaa ttttattcaa 1560 aggaattgta aaccttaaac caccaattta tttccatgtg aaaaagtgtt acatatgaca 1620 agtgtttttt gactgtaatt gcgttaaatc ttttgagaat gtaaatgccg ggctaggcaa 1680 ttgcagttaa tacatacaga ggttagtgaa gggcttatta agttgtaggg gaagcaagct 1740 gggaagaatc agatcagata ttttcctgac aaaaaaaaat gaccctacag agagcatcaa 1800 aatgtggtgt tcttgttaag taattgatcg tggtcttcgc tttaatctta gttccgccag 1860 gcacggtggc tcacacctgt aatcccagca ctttgggagg ccaaggcggg cggatcagct 1920 gaggtcagga gttggagacc agcgtggcca acatggtgaa accccgtctc tactaaagat 1980 aaaaaaatta gctgagtgtg ttggtgggtg cctgtaatcc agctacttgg gagactgagg 2040 caggagaatt gcttgaaccc aggaggcaga ggttgcagtg agctgagatt gtgccactgc 2100 actccagcct gggcaacaaa gcaagactct gtctcaaaaa aataaaaata aaaaaaaaat 2160 cttagttcca tggaatttta agcattgttc cccctctaac ctgtgtctaa agaattaaaa 2220 gaatttggcc gggtgcggca gctcatgcct gtaatcccaa cactttggga ggctgaggca 2280 ggcggatcac gaggtcagga gatcgagacc atcctggcca acacggtgaa acctcgtctc 2340 cactaaaaat accaaaaaaa ttagctgggc atggtggcac acacctgtag tcccctgtag 2400 tcccagctac tcgggaggct gaggcaggag aatcgtttga acctgggagg tggaggttgc 2460 agtgagccaa gatcatgtca ctgcattcca gcctgggcaa cagaggaaga ctccgtctc 2519 <210> 92 <211> 2728 <212> DNA <213> homo sapiens <400> 92 gggccggagg gccgcggtgt gccgcggggc agttgcgggt tgtcataacg gtccccgccg 60 gagtgaggcg aggccgcgtc gctcagttct ggccgtctag ggcccctgta aggatgagag 120 cgcagaggac gcagggccgc tggaggcgca ggtaacgaag ctagggtgcg gttgggaccg 180 cggctgagct ttttccggga cccgtggtgc tgaatggaga ggacggagac gaagccgagc 240 cgcggctcct agcggcggcg ccgatgctcg agctgtagct gccaggcgag gatgtgtgga 300 gcgcaggcgg cgcggggtaa atgagaggtc tcgggcccca ggacccccgg ggcccgggat 360 gagttagcga gggcagccgc gggggccagt tccgaccgtg acaggccaag gcgacggccg 420 ccgcccgccc gccccttccg tgcagaagca gctgctcctt tccgcgcccg cccgcctgcg 480 ctcccggccc tggagaccat gaggttccgc atctacaaac ggaaggtgct aatcctgacg 540 ctcgtggtgg ccgcctgcgg cttcgtcctc tggagcagca atgggcgaca aaggaagaac 600 gaggccctcg ccccaccgtt gctggacgcc gaacccgcgc ggggtgccgg cggccgcggt 660 ggggaccacc cctctgtggc tgtgggcatc cgcagggtct ccaacgtgtc ggcggcttcc 720 ctggtcccgg cggtccccca gcccgaggcg gacaacctga cgctgcggta ccggtccctg 780 gtgtaccagc tgaactttga tcagaccctg aggaatgtag ataaggctgg cacctgggcc 840 ccccgggagc tggtgctggt ggtccaggtg cataaccggc ccgaatacct cagactgctg 900 ctggactcac ttcgaaaagc ccagggaatt gacaacgtcc tcgtcatctt tagccatgac 960 ttctggtcga ccgagatcaa tcagctgatc gccggggtga atttctgtcc ggttctgcag 1020 gtgttctttc ctttcagcat tcagttgtac cctaacgagt ttccaggtag tgaccctaga 1080 gattgtccca gagacctgcc gaagaatgcc gctttgaaat tggggtgcat caatgctgag 1140 tatcccgact ccttcggcca ttatagagag gccaaattct cccagaccaa acatcactgg 1200 tggtggaagc tgcattttgt gtgggaaaga gtgaaaattc ttcgagatta tgctggcctt 1260 atacttttcc tagaagagga tcactactta gccccagact tttaccatgt cttcaaaaag 1320 atgtggaaac tgaagcagca agagtgccct gaatgtgatg ttctctccct ggggacctat 1380 agtgccagtc gcagtttcta tggcatggct gacaaggtag atgtgaaaac ttggaaatcc 1440 acagagcaca atatgggtct agccttgacc cggaatgcct atcagaagct gatcgagtgc 1500 acagacactt tctgtactta tgatgattat aactgggact ggactcttca atacttgact 1560 gtatcttgtc ttccaaaatt ctggaaagtg ctggttcctc aaattcctag gatctttcat 1620 gctggagact gtggtatgca tcacaagaaa acctgtagac catccactca gagtgcccaa 1680 attgagtcac tcttaaataa taacaaacaa tacatgtttc cagaaactct aactatcagt 1740 gaaaagttta ctgtggtagc catttcccca cctagaaaaa atggagggtg gggagatatt 1800 agggaccatg aactctgtaa aagttataga agactgcagt gaaaatcaca gttacaaaag 1860 cgacagtctt ctatttttga tatttgtcca aacaggacat acaattgaat aaaagagttt 1920 aggaactggt ttctgcttta atacaaaaac aaaatcttgt aaaaggtgtc caaatacata 1980 gtaatctttt ccagttatgt ctgattaaga tttaaaactg aaggtttcat tttgggagta 2040 gggttttaaa gctcaatctg ttatctgcta aaattgatta ttgttgatat gagagaagag 2100 gggaaatttt atttaaattg catttattaa tctttttatc tgaaactttg tacacttttc 2160 cactttcaaa acctatttta agtacagcaa aatttattta aaactgtcat agcagtaaaa 2220 agtattacga tgaaattgtt agggtattaa tggaacaaac ccagtttcac tctcttgaca 2280 cacttattag gaagggattg cttcactggt ttaataattt aaaagttatg tttgttaaac 2340 accctgtcag aacagtcatt ttcagtatta gattcctgta ctattgtgtt ttgagtgtgt 2400 tttggaacct tcatagaaca cactttcttt tggaatgtat ttgattgata agaaagttta 2460 aacattgttt tcacctcaat gtagaaatac agtggttttg tttttttttt tcttttagtg 2520 ctgacaaaat aaaatactca tttttgcata aaaaggttcc taatcctttt gcagaataag 2580 ttttgtttac tctttatacc aaaattcagt gaaggcattc tacaagtttt gagttagcat 2640 tacattttaa tatttactat tgctacattg tataattgag tttgaaataa aacccagctt 2700 atgacaatgc aaaaaaaaaa aaaaaaaa 2728 <210> 93 <211> 1488 <212> DNA <213> homo sapiens <400> 93 accactgtgg ttctactatg ccttctgacc ccgtcttgga cttcaactgg gagaatgtgg 60 agccatttga acaggctcct cttctggagc atattttctt ctgtcacttg tagaaaagct 120 gtattggatt gtgaggcaat gaaaacaaat gaattccctt ctccatgttt ggactcaaag 180 actaaggtgg ttatgaaggg tcaaaatgta tctatgtttt gttcccataa gaacaaatca 240 ctgcagatca cctattcatt gtttcgacgt aagacacacc tgggaaccca ggatggaaaa 300 ggtgaacctg cgatttttaa cctaagcatc acagaagccc atgaatcagg cccctacaaa 360 tgcaaagccc aagttaccag ctgttcaaaa tacagtcgtg acttcagctt cacgattgtc 420 gacccggtga cttccccagt gctgaacatt atggtcattc aaacagaaac agaccgacat 480 ataacattac attgcctctc agtcaatggc tcgctgccca tcaattacac tttctttgaa 540 aaccatgttg ccatatcacc agctatttcc aagtatgaca gggagcctgc tgaatttaac 600 ttaaccaaga agaatcctgg agaagaggaa gagtataggt gtgaagctaa aaacagattg 660 cctaactatg caacatacag tcaccctgtc accatgccct caacaggcgg agacagctgt 720 cctttctgtc tgaagctact acttccaggg ttattactgt tgctggtggt gataatccta 780 attctggctt tttgggtact gcccaaatac aaaacaagaa aagctatgag aaataatgtg 840 cccagggacc gtggagacac agccatggaa gttggaatct atgcaaatat ccttgaaaaa 900 caagcaaagg aggaatctgt gccagaagtg ggatccaggc cgtgtgtttc cacagcccaa 960 gatgaggcca aacactccca ggagctacag tatgccaccc ccgtgttcca ggaggtggca 1020 ccaagagagc aagaagcctg tgattcttat aaatctggat atgtctattc tgaactcaac 1080 ttctgaaatt tacagaaaca aactacatct caggatggag tctcactctg ttgcccaggc 1140 tggagttcag tagcgcgatc ttggctcact tcaatctcca tcttcccagt tcaagcgatt 1200 ctcatgcctc gacctcccga gtagctggga ttacaggtgc ccgctaccac gcccagctaa 1260 tttttgtatt tttagtagag atggggtttc actatggtgg ccaggctggt cttgaactcc 1320 tgacctcaga tgatctgcct gcctcggcct cccaaagtgc tggaactaca agcctgagcc 1380 accgtgcccg gccctgaatc gctttagtaa ataaagggtc tccaagaata aattcatccg 1440 aacatgcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1488 <210> 94 <211> 68 <212> DNA <213> homo sapiens <400> 94 gaggcaaagt tctgagacac tccgactctg agtatgatag aagtcagtgc actacagaac 60 tttgtctc 68 <210> 95 <211> 110 <212> DNA <213> homo sapiens <400> 95 gtgataatgt agcgagattt tctgttgtgc ttgatctaac catgtggttg cgaggtatga 60 gtaaaacatg gttccgtcaa gcaccatgga acgtcacgca gctttctaca 110 <210> 96 <211> 84 <212> DNA <213> homo sapiens <400> 96 gtgctcggtt tgtaggcagt gtcattagct gattgtactg tggtggttac aatcactaac 60 tccactgcca tcaaaacaag gcac 84 <210> 97 <211> 81 <212> DNA <213> homo sapiens <400> 97 gatactcgaa ggagaggttg tccgtgttgt cttctcttta tttatgatga aacatacacg 60 ggaaacctct tttttagtat c 81 <210> 98 <211> 85 <212> DNA <213> homo sapiens <400> 98 tctcatgatg tgaccatctg gaggtaagaa gcactttgtg ttttgtgaaa gaaagtgctt 60 cctttcagag ggttactctt tgaga 85 <210> 99 <211> 1647 <212> DNA <213> homo sapiens <400> 99 gcttcagctg aagaaagaga ggaatgaagc gccttctgct tctgtttttg ttctttataa 60 cattttcttc tgcatttccc ttagtccgga tgacggaaaa tgaagaaaat atgcaactgg 120 ctcaggcata tctcaaccag ttctactctc ttgaaataga agggaatcat cttgttcaaa 180 gcaagaatag gagtctcata gatgacaaaa ttcgggaaat gcaagcattt tttggattga 240 cagtgactgg aaaactggac tcaaacaccc ttgagatcat gaagacaccc aggtgtgggg 300 tgcctgatgt gggccagtat ggctacaccc tccctgggtg gagaaaatac aacctcacct 360 acagaataat aaactatact ccggatatgg cacgagctgc tgtggatgag gctatccaag 420 aaggtttaga agtgtggagc aaagtcactc cactaaaatt caccaagatt tcaaagggga 480 ttgcagacat catgattgcc tttaggactc gagtccatgg tcggtgtcct cgctattttg 540 atggtccctt gggagtgctt ggccatgcct ttcctcctgg tccgggtctg ggtggtgaca 600 ctcattttga tgaggatgaa aactggacca aggatggagc aggattcaac ttgtttcttg 660 tggctgctca tgaatttggt catgcactgg ggctctctca ctccaatgat caaacagcct 720 tgatgttccc aaattatgtc tccctggatc ccagaaaata cccactttct caggatgata 780 tcaatggaat ccagtccatc tatggaggtc tgcctaagga acctgctaag ccaaaggaac 840 ccactatacc ccatgcctgt gaccctgact tgacttttga cgctatcaca actttccgca 900 gagaagtaat gttctttaaa ggcaggcacc tatggaggat ctattatgat atcacggatg 960 ttgagtttga attaattgct tcattctggc catctctgcc agctgatctg caagctgcat 1020 acgagaaccc cagagataag attctggttt ttaaagatga aaacttctgg atgatcagag 1080 gatatgctgt cttgccagat tatcccaaat ccatccatac attaggtttt ccaggacgtg 1140 tgaagaaaat agatgcagcc gtctgtgata agaccacaag aaaaacctac ttctttgtgg 1200 gcatttggtg ctggaggttt gatgaaatga cccaaaccat ggacaaaggg ttcccgcaga 1260 gagtggtaaa acactttcct ggaatcagta tccgtgttga tgctgctttc cagtacaaag 1320 gattcttctt tttcagccgt ggatcaaagc aatttgaata cgacattaag acaaagaata 1380 ttacccgaat catgagaact aatacttggt ttcaatgcaa agaaccaaag aactcctcat 1440 ttggttttga tatcaacaag gaaaaagcac attcaggagg cataaagata ttgtatcata 1500 agagtttaag cttgtttatt tttggtattg ttcatttgct gaaaaacact tctatttatc 1560 aataaattca tagacctaaa ataaacctca acaggtcttt taatataaat tctgcttcaa 1620 aatagaataa aaccattctt taacaac 1647 <210> 100 <211> 2067 <212> DNA <213> homo sapiens <400> 100 agctccgtcc gcgccctccc ggcgcaccgc ctgcggggcg gtgactggcc cagccgcacc 60 gcgtctcccg ccttctccgc agccccgcag gccccgggcc ctgtcattcc cagcgctgcc 120 ctgtcttgcg ttccagtgtt ccagcttctg cgagatgacc ctcaaggcga gcgagggcga 180 gagtgggggc agcatgcaca cggcgctctc cgacctctac ctggagcatt tgctgcagaa 240 gcgtagtcgg ccagaggctg tatcgcatcc attgaatact gtgaccgagg acatgtacac 300 caacgggtct cctgccccag gtagccctgc ccaggtcaag ggacaggagg tgcggaaagt 360 gcgactcata cagtttgaga aggtcacaga agagcccatg ggaatcacgc tgaagctgaa 420 tgaaaaacag tcctgtacgg tggccagaat tcttcatggt ggcatgatcc atagacaagg 480 ctcccttcac gtgggggatg agatcctaga aatcaatggc acaaatgtga caaatcattc 540 agtggatcag ctgcagaagg cgatgaaaga aaccaaagga atgatctcat taaaagtaat 600 tcccaaccag caaagccgtc ttcctgcact acagatgttc atgagagcgc agtttgacta 660 tgatcccaaa aaggacaatc tgatcccttg caaggaggcg ggactgaagt ttgctactgg 720 ggacattatc cagattatca acaaggatga cagcaattgg tggcagggac gggtggaagg 780 ctcctccaag gagtcagcag gattgatccc ttcccctgag ctgcaggaat ggcgagtggc 840 aagtatggct cagtcagctc ctagcgaagc cccgagctgc agtccctttg ggaagaagaa 900 gaagtacaaa gacaaatatc tggccaagca cagctcgatt tttgatcagt tggatgttgt 960 ttcctacgag gaagtcgttc ggctccctgc attcaagagg aagaccctgg tgctgatcgg 1020 agccagtggg gtgggtcgca gccacattaa gaatgccctg ctcagccaga atccggagaa 1080 gtttgtgtac cctgtcccat atacaacacg gccgccaagg aagagtgagg aagatgggaa 1140 ggagtaccac tttatctcaa cggaggagat gacgaggaac atctctgcca atgagttctt 1200 ggagtttggc agctaccaag gcaacatgtt tggcaccaaa tttgaaacag tgcaccagat 1260 ccataagcag aacaagattg ccatccttga cattgagccc cagaccctga aaattgttcg 1320 gacagcagaa ctttcgcctt tcattgtgtt cattgcacct actgaccagg gcactcagac 1380 agaagccctg cagcagctgc agaaggactc tgaggccatc cgcagccagt acgctcacta 1440 ctttgacctc tcactggtca ataatggtgt tgatgaaacc cttaagaaat tacaagaagc 1500 cttcgaccaa gcgtgcagtt ctccacagtg ggtgcctgtc tcctgggttt actaagcttg 1560 tagaatgggg gaacccactg tatgcccctc tccagcattt ggaattccac ccgccttgct 1620 ttaagacaaa cagggctgct ccaactagtt ttgtgtcagc ttccagctct ctgcagctat 1680 cctaattcag ccagtaaggt tcagtcttct tgctcaggct cctgaagggt tgattctcct 1740 gatagatggg gccccactga tctggatttg aaaaggattt ctagaaattg ggggtaagaa 1800 gtactaccaa aatgtaactg ctaatcaagg gtgatgcaca gcaaaagcaa tggaccccat 1860 ccctctaaag cctgccctcc tttgccttca actgtatatg ctgggtattt catttgtctt 1920 tttattttgg agaaagcgtt tttaactgca actttctata atgccaaaat gacacatctg 1980 tgcaatagaa tgatgtctgc tctagggaaa ccttcaaaag caataaaaat gctgtgttga 2040 aatgccaaaa aaaaaaaaaa aaaaaaa 2067 <210> 101 <211> 4554 <212> DNA <213> homo sapiens <400> 101 ctctttctag ggactttcct gagtgggagg gatttcgccg gaacaaaaat gcctcagttt 60 ggaggtcgcg ctcactgcga cggcaggctt tgagtgtagc acttggtagt tcttcctctg 120 ctctgcttcc cttcggagga aaatttcagg ctgaaggttt agcgggtgcc gcctctaaag 180 agagcaatca ctacacttat ggctgggatt ttgcgcttag tagttcaatg gcccccaggc 240 agactacaga ctgtgacaaa aggtgtggag tctcttattt gtacagattg gattcgtcac 300 aaattcacca gatcaagaat tccagaaaaa gtgtttcagg cctcacctga agatcatgaa 360 aaatacggtg gggatccaca gaaccctcat aaactgcata ttgttaccag aataaaaagt 420 acaagaagac gtccatattg ggaaaaagat ataataaaga tgcttggatt agaaaaagca 480 catacccctc aagttcacaa gaatatccct tcagtgaatg caaaattgaa agtagttaag 540 catttgataa gaatcaagcc cttgaagttg ccacaaggac ttccagcaga ggagaacatg 600 tctaacacgt gcctcaaaag cactggggag ttagtagtgc agtggcatct gaaacctgtg 660 gagcagaaag cacatgagtc ctaatgcccc agcagcttcc gattggaaaa tgcaaattgt 720 ttttatttaa agatggtgag aaagtgtttt cattaaaata tgttttcaaa accattttca 780 ggccgggcac ggtggctcac ctgtaatccc agcactttgg gaggccaagg cgggcagatc 840 acctgaggtc aagagttcga gaccagcctg accaacatgg agaaaccccc atctctactg 900 aaaatacaga attagccagg catggtggca catgcctgta acccagctac tcgggaggct 960 gaagcaggag aatcacttga acccgggagg cagaggttgc agtgagctga gatggtgcca 1020 ctgtactcca gcctgggtga taggatgaga ctccatctca ggggaaaaaa aaaaattttt 1080 ttttcactga ctaaacctgc tgcagctctc ttttactaca gacttggaga ttttagttta 1140 atttggttta attctctgtc ctttcccttt cactgtttca ctccaaaaca tgtaagaatg 1200 gcaatgtttg aacatctgcg tttgggtcta ctgccacctt agcaagcctc attaaccatt 1260 ttataaaaat tgcgttagta ttgttgttgt tgtttttgag acagggtctt gctctgtcac 1320 ccaagctgga atacagtggc atgatttcag ttcactgcag cctcgacctc ccaggctcaa 1380 gtgatcctcc cacctcagcc tccagagtag ctaggactac aggcagtgtg ccaccacatc 1440 cagctaattt tttaaagttt tttcatagag acagggactc actatgttgt ccaagctggt 1500 ctcaaactcc tgggttcaag ccatcctccc acctcagcct cccaaaatgc tgggattaca 1560 ggcatgagcc actgtaccca gccaaaattg ttttcttttt taagtgaatt caacaatttc 1620 tgtgagtggc tctttgcatg aacactgtgc aaggtgttgg agaaatccaa agctgaccaa 1680 aacatggtcc ccaccttttg gagcttacag tctgttctgg ggaacagaga ttcagccaaa 1740 gtcaagaaac actggatgcc agctagatta tctgttctgt gctttggtgt ctataagtac 1800 atatgtggat atgggttcat tttatcccta aacttagtac caaaccagca tttaatatct 1860 aattataaat ctaatttggc ctaaacttta ttattgcaca ctgcctgaac aaaacctatt 1920 tgtctctatg taaatttttt cctcatggaa caagggtgtg aaatgaaaat attttaggat 1980 ttattcaaaa acagactatt ctgttttcag cttcagaatt gttctttgaa tcctaaggaa 2040 cctctgtcaa cagttgaggt tgctgttgaa aagaaagaag aaggaggcgg aaatctctca 2100 gggagaatta tttcctttct tttctatttt agatacctgg aggggtgggg agaagtaaga 2160 attgtaaggg aggttcagta gtggggaatt ctgtgacagc tgattgaaga tgatgatgaa 2220 gaacctctgc attctagtta ccctttgctt cccttcacct cttgtaaaat ttggcttggc 2280 aacaatgaca ttgtcatgct tattgtccca atatccatcc tgtcgtagat cttaatgttt 2340 ttgatcgttg cgttaaagtg gaagtgccac ccacagtgaa accagatccc attaataaat 2400 aagcttaaag gcaactgcag ttttaattcc atagttattg aatatccagt gtgtgtaagg 2460 cctggagggg agccaaagga cactaacttc taagagctcc gtctagttgg agagaaacct 2520 gtgtgccaca acatacagtg tccttgctta tgtggggtcg aagacatctg tgaaaataaa 2580 agcagcctct gctaatttag cgccatctct tttactgtgc taattttttt ttctttagag 2640 acagggtctc actctgtcgc ccagcctgga gggcagtggt gtgatcgtag ctcactatta 2700 cctccaactc ttgggctcaa gtgatcctcc cacctcagcc tcctgagcag ctaggactac 2760 agatacatgc caccgctccc ggctagtatt ttttaaaatt ttttgtagag ccaagtgttg 2820 ctatgttgtc cacactgatc tggagcttct aatctcaaat gattctcctg cctcagcctc 2880 ccaaagtgct gggaatacag gtgtgagcca ccatacctgg ccttactgta ctaatattaa 2940 tattgtgtaa ataggggaaa ataccatggt taatttttac tcaaacagta agaaagtttg 3000 agtaactaat tttaatctca acagcccata gctagaagag gggatctaaa tgttaagttg 3060 aatatttaga aataaaagtg tctacaagaa gaaaagtctt tagtgaaaat atgggcatag 3120 gccagcagca ttagctttct attgctgcag aacaaattac cacaaactta gctgcttaaa 3180 acaacacaca cttattgtct cacaatgttt gtgggtcgga agtctaggcg tggcttagct 3240 gggtagtctg tttaggatct cagtgctgga aaaacgtgtc tggccaggtg ctcattgtag 3300 ctttgacagg gaagggatct gctcccaagc actctcaggt tgttggcaga atttgtttcc 3360 ttatggctgt aggattcatg gcaagttgct tcttccaaaa ccagcattgg agacagacta 3420 gcaagatggg cactacactc ttagataatc aaataaatgc aatcatgtgc ctcgtgtcac 3480 cttttttgca ttccattcat taagaacaag ttgcagttcc tacctacact caaggaaggg 3540 aggaattaca cagaagtgtg accacaggag gcagggctca tggaggcctc cttaaagtcc 3600 cccagccaaa cctgaaaagt caatcctgga ccttatcata gtggctgtat agtttagaag 3660 gtttcttcag attggcattc ctttgcctca tatcatcact tcaaaaccct ataagggttt 3720 gttcctcggt cttgactttg tgtctttgag gattgctttg tttagtgtca cctgccttct 3780 ttcaggaggt tttgcctgac atctggtggt gaccgtggcc accaagtcaa cccaaacact 3840 acctttaagg acgactgcag ttctcttagg gtctcctcaa tctaaaattg tacctctttc 3900 aggccaaaca cctattttct tcattttttt tttctcataa gaatgctagc tagtatgcct 3960 attatctaac tggcacagtt tcaccaagga cagtttggaa ctacacaggc cattttaggg 4020 agattttgac atgaacaaga ttgcttcttt gggaggtacc ttaaaatgaa aagcaaagaa 4080 acttccatgc ggagattgtc ttgtttttct caaaatggga taattttgct taacataagt 4140 agtatccctt ccttcctttc catactttga gaattaataa ggactagctt tttgatcaca 4200 cagcttgata aaattttcaa gggtccaaat tactgtctaa accatttgcc actctttgtg 4260 tatatttgtc aaaatctgct tttctatatc aaaacttttc tctcaagacc tgagggaatt 4320 aattaataag gaatccttgg aacactggaa attctaaaat aagagtcaga tacaaaacac 4380 tggtcactaa aattcttacc tttatgtatt agaatggcaa tcaatgaaca aactgaaaat 4440 gtctttggat attatttctg tttatttttt gcctcaaaat tattaaatga catgaaataa 4500 gtgctcaaga agaaaaataa acaattcttc atttccaaaa aaaaaaaaaa aaaa 4554 <210> 102 <211> 1905 <212> DNA <213> homo sapiens <400> 102 cagccggagc cgcggtgtac aacggaactt gtagtctcct cgtggctagt tcaggcggaa 60 ggagcagtcc tctgaagctt gaggagcctc tagaactatg agcccgaggc cttcccctct 120 cccagagcgc agaggctttg aaggctacct ctgggaagcc gctcaccgtc ggaagctgcg 180 ggagctgaaa ctgcgccatc gtcactgtcg gcggccatga caccgctcgt ctcccgcctg 240 agtcgtctgt gggccatcat gaggaagcca cgagcagccg tgggaagtgg tcacaggaag 300 caggcagcca gccaggaagg gaggcagaag catgctaaga acaacagtca ggccaagcct 360 tctgcctgtg atggcctggc caggcagccg gaagaggtgg tattgcaggc ctctgtctcc 420 tcataccatc tattcagaga cgtagctgaa gtcacagcct tccgagggag cctgctaagc 480 tggtacgacc aagagaaacg ggacctacca tggagaagac gggcagaaga tgagatggac 540 ctggacaggc gggcatatgc tgtgtgggtc tcagaggtca tgctgcagca gacccaggtt 600 gccactgtga tcaactacta taccggatgg atgcagaagt ggcctacact gcaggacctg 660 gccagtgctt ccctggagga ggtgaatcaa ctctgggctg gcctgggcta ctattctcgt 720 ggccggcggc tgcaggaggg agctcggaag gtggtagagg agctaggggg ccacatgcca 780 cgtacagcag agaccctgca gcagctcctg cctggcgtgg ggcgctacac agctggggcc 840 attgcctcta tcgcctttgg ccaggcaacc ggtgtggtgg atggcaacgt agcacgggtg 900 ctgtgccgtg tccgagccat tggtgctgat cccagcagca cccttgtttc ccagcagctc 960 tggggtctag cccagcagct ggtggaccca gcccggccag gagatttcaa ccaagcagcc 1020 atggagctag gggccacagt gtgtacccca cagcgcccac tgtgcagcca gtgccctgtg 1080 gagagcctgt gccgggcacg ccagagagtg gagcaggaac agctcttagc ctcagggagc 1140 ctgtcgggca gtcctgacgt ggaggagtgt gctcccaaca ctggacagtg ccacctgtgc 1200 ctgcctccct cggagccctg ggaccagacc ctgggagtgg tcaacttccc cagaaaggcc 1260 agccgcaagc cccccaggga ggagagctct gccacctgtg ttctggaaca gcctggggcc 1320 cttggggccc aaattctgct ggtgcagagg cccaactcag gtctgctggc aggactgtgg 1380 gagttcccgt ccgtgacctg ggagccctca gagcagcttc agcgcaaggc cctgctgcag 1440 gaactacagc gttgggctgg gcccctccca gccacgcacc tccggcacct tggggaggtt 1500 gtccacacct tctctcacat caagctgaca tatcaagtat atgggctggc cttggaaggg 1560 cagaccccag tgaccaccgt accaccaggt gctcgctggc tgacgcagga ggaatttcac 1620 accgcagctg tttccaccgc catgaaaaag gttttccgtg tgtatcaggg ccaacagcca 1680 gggacctgta tgggttccaa aaggtcccag gtgtcctctc cgtgcagtcg gaaaaagccc 1740 cgcatgggcc agcaagtcct ggataatttc tttcggtctc acatctccac tgatgcacac 1800 agcctcaaca gtgcagccca gtgacacctc tgaaagcccc cattccctga gaatcctgtt 1860 gttagtaaag tgcttatttt tgtagttaaa aaaaaaaaaa aaaaa 1905 <210> 103 <211> 6038 <212> DNA <213> homo sapiens <400> 103 atttccacca agaacccaga gagtggaaca cttctgaacc tgcattttta tctggaactc 60 cagaggcaga atcctttgct aaataaatcg cagccatgag tgcgagctca gacgctgaga 120 tggctgtttt tggcgaagct gctccctacc ttcgaaaatc agaaaaggag cggattgagg 180 cccaaaacaa gccgtttgat gctaaaacat ctgtctttgt ggcggagccc aaggaatcct 240 atgtgaagag cactatacaa agcaaagaag gagggaaagt aaccgtaaag actgaaggtg 300 gagcaactct aactgtcagg gaagaccaag tcttccctat gaaccctccg aaatatgaca 360 aaattgagga catggccatg atgactcatc tacacgagcc tggagtgctg tacaacctca 420 aagagcgcta tgcagcctgg atgatctaca cctactcagg cctcttctgt gtcaccgtca 480 acccctacaa gtggctgccg gtgtacaagc ccgaggtggt ggctgcctac agaggcaaaa 540 agcgccagga ggccccgccc cacatcttct ccatctctga caatgcctat cagttcatgt 600 tgactgatcg agagaatcag tccatcctga tcaccggaga atctggtgcc ggaaagactg 660 tgaacaccaa gcgtgtcatc caatactttg caacaattgc agttactgga gagaagaaga 720 aggatgaatc tggcaaaatg caggggactc tggaagatca aatcatcagc gccaatcccc 780 tactggaggc ctttggcaat gccaaaactg tgaggaatga caactcctct cgctttggta 840 aattcattag aatccacttt ggtactacag ggaagctggc atctgctgat atagaaacat 900 atcttttaga aaagtccaga gttactttcc agctaaaggc ggaaagaagc taccatattt 960 tttatcagat cacttccaat aagaagccag atctaattga aatgctcctg atcaccacca 1020 acccatatga ctatgccttc gtcagtcagg gggagatcac agttcccagt attgatgacc 1080 aagaagagtt gatggccact gatagtgcca ttgacatcct gggcttcact cctgaagaga 1140 aagtgtccat ctataaactc acaggggctg tgatgcatta tgggaacatg aaattcaagc 1200 aaaagcagcg tgaggagcaa gctgagccag atggcacaga agtcgctgac aaggcagcct 1260 atctccagag tctgaactct gcagacctac tcaaagccct ctgctaccct agggtcaagg 1320 ttggcaatga gtatgtcacc aaaggccaga ctgtgcagca ggtgtacaat gcggtgggtg 1380 ctctggccaa agccgtctac gagaagatgt tcctgtggat ggtcacccgc atcaaccagc 1440 agctggacac caagcagccc aggcagtact tcatcggggt cttggacatt gctggctttg 1500 aaatctttga ttttaacagc ctggagcagc tgtgcatcaa cttcaccaac gagaaactgc 1560 aacagttttt caaccaccac atgtttgtgc tagagcagga ggagtacaag aaggaaggca 1620 tcgagtggac gttcattgac tttgggatgg acctggctgc ctgcattgag ctcattgaga 1680 agccactggg catcttctcc atcctggaag aggagtgcat gttccctaag gcaacggaca 1740 cctccttcaa gaacaagctg tatgaccagc acctgggcaa gtctgccaac ttccagaagc 1800 ccaaggtggt caaaggcaag gctgaggccc acttctctct gattcactat gctggcactg 1860 tggactacaa cattactggc tggctggaca aaaataagga ccccctgaat gatactgtgg 1920 ttgggctgta ccagaagtct gcaatgaaga ctctagccag tctcttttcc acgtatgcta 1980 gtgctgaagc agatagcagc gcgaagaaag gtgctaagaa aaagggctct tctttccaga 2040 ctgtgtctgc ccttttcagg gaaaatttaa ataaattgat gacgaatctg aggagcacac 2100 accctcactt cgtacggtgt atcattccca atgaaaccaa aactcctggg gcaatggaac 2160 atgaacttgt gttgcaccag ctgaggtgta atggtgtgct ggaaggcatc cgcatctgta 2220 ggaaaggatt cccaagcaga atcttatatg gtgatttcaa acaaagatac aaggttttaa 2280 atgcaagtgc tattccagag ggacagttca ttgacagcaa gaaggcttct gagaaacttc 2340 ttgcatctat tgatattgat catactcaat ataaatttgg acataccaag gttttcttca 2400 aagctggact tctgggtctt ctggaagaaa tgagagatga aaaattagcc caaattataa 2460 caagaacaca agctgtctgt aggggattcc taatgagggt agaatatcag aagatgttgc 2520 aaaggagaga agcacttttc tgcatccagt ataatgtccg tgccttcatg aacgtcaagc 2580 actggccctg gatgaaactc tttttcaaga ttaagcccct cctcaagagt gcagagaccg 2640 agaaagagat ggccaccatg aaggaagaat tccagaaaac caaagatgaa ctcgccaagt 2700 cagaggcaaa acggaaggag ctagaggaaa aaatggtcac tctcttaaaa gagaaaaatg 2760 acctgcaact ccaggttcaa tctgaagcag atagcttggc tgatgcagag gaaaggtgtg 2820 agcaactgat taaaaacaaa atccaacttg aggccaaaat caaagaggtg actgaaagag 2880 ctgaggagga ggaagagatc aatgctgagc tgacagccaa gaagagaaaa ctggaggatg 2940 aatgttcaga actcaagaaa gacattgatg accttgagct gacactggcc aaggttgaga 3000 aggagaaaca tgccacggag aacaaggtga aaaatcttac agaagagatg gcaggcctgg 3060 atgaaaccat tgcaaaactg tccaaggaga agaaggctct ccaagagacc caccagcaga 3120 ccctggatga cctgcaggca gaggaggaca aagtcaacat cctgaccaaa gctaaaacca 3180 agctagaaca gcaagtggat gatcttgaag ggtctctgga acaagaaaag aagcttcgaa 3240 tggatctaga aagagcaaag cggaaactgg agggtgacct caaattggcc caagaatcca 3300 caatggatat ggaaaatgac aaacagcaac ttgatgaaaa gcttgaaaag aaagaatttg 3360 aaatcagcaa tttgataagc aaaattgaag atgagcaagc tgtagaaatt caactacaga 3420 agaagatcaa agagttgcag gcccgcattg aggagctggg ggaagaaatc gaggcagaga 3480 gggcgtcccg agccaaagcg gagaagcagc gctctgacct ctcccgggaa ctggaggaga 3540 tcagcgagag gctggaagaa gccggtgggg caacttctgc tcaggtggaa ttgaacaaga 3600 agcgggaggc tgagtttcag aaactgcgca gggacctgga ggaggccacc ctgcagcatg 3660 aagctatggt ggctgctctt cggaagaagc acgcagacag tatggctgag cttggggagc 3720 agattgacaa cttgcagcgg gtcaaacaga agctggagaa ggagaagagt gagctgaaga 3780 tggagactga tgacctcagc agtaacgcag aggccatttc caaagccaag ggaaaccttg 3840 aaaagatgtg ccgctctcta gaagatcaag tgagtgagct taagaccaag gaagaggagc 3900 agcagcggct gatcaatgac ctcacagcac agagagcgcg cctgcagaca gaagcgggtg 3960 aatattctcg acaattagat gagaaagatg ctttagtctc tcagctttca aggagcaagc 4020 aagcatctac tcagcagatt gaagagctga aacatcaact agaggaagaa actaaagcca 4080 agaacgccct ggcacacgcc ctgcagtcct cccgccatga ctgcgacctg ctgcgggaac 4140 agtatgagga agagcaggaa ggcaaagctg agctgcagag ggcgctgtcc aaggccaaca 4200 gtgaggttgc ccagtggaga accaaatacg agacggatgc catccagcgc acagaggagc 4260 tggaggaggc caagaaaaag ttggcccagc gcctgcaaga agctgaggaa catgtagaag 4320 ctgtgaacgc caaatgtgct tcccttgaga agacgaagca gcggctccag aatgaagttg 4380 aagacctcat gcttgatgtg gaaaggtcta atgcagcctg tgcagccctt gataagaagc 4440 aaaggaactt tgacaaggtc ctatcagaat ggaagcagaa gtatgaggaa actcaggctg 4500 aacttgaggc ctcccagaag gagtcacgtt ctcttagcac tgagctgttc aaggtgaaga 4560 atgtctatga ggaatccctg gatcaactcg aaacgctaag aagagaaaat aagaacttgc 4620 aacaggagat ttctgacctc actgagcaga ttgcagaggg aggaaagcaa attcatgaat 4680 tggagaaaat aaagaagcaa gtagaacaag agaaatgtga aattcaggct gctttagagg 4740 aagcagaggc atctcttgaa catgaagaag gaaagattct gcgtatccag cttgagttaa 4800 accaagtcaa gtctgaagtt gatagaaaaa tcgcagaaaa ggatgaggaa attgaccagc 4860 tgaagagaaa ccacactaga gtcgtggaga caatgcagag cacgctggat gcagagatta 4920 gaagcagaaa tgatgctctg agagtcaaga agaaaatgga aggagatctg aatgaaatgg 4980 aaatccagct gaaccatgcc aatcgcttag ctgcagagag tttaaggaac tacaggaaca 5040 cccaaggaat cctgaaggaa acccagctcc acctggatga tgctctccgg ggccaggagg 5100 acctcaagga acagctggca attgtggagc gcagagccaa cctgctgcag gctgagatcg 5160 aggagctgtg ggccactctg gaacagacag agagaagcag gaaaatcgcc gaacaggagc 5220 tcctggatgc cagtgagcgt gtccagctcc tccacaccca gaataccagt ctcattaaca 5280 ccaagaagaa attagaaaat gacgtttccc aactccaaag tgaagtggaa gaagtaatcc 5340 aagaatcacg caatgcagaa gagaaagcca agaaggccat cactgatgct gccatgatgg 5400 ctgaggagct gaagaaggaa caggacacca gcgcccacct ggagcggatg aagaagaacc 5460 tggagcagac ggtgaaggac ctgcagcatc gtctagatga ggccgagcag ctggcgctga 5520 agggtgggaa gaagcagatc cagaaactgg aggccagggt acgtgagctt gaaggagagg 5580 ttgaaaatga acagaaacgt aatgcagagg ctgttaaagg tttacggaaa catgagcgac 5640 gagtaaaaga actcacctac cagactgaag aagatcgcaa gaatgttctc aggctgcagg 5700 acttggtaga taaattacag gcgaaggtga aatcatacaa gagacaagct gaggaggctg 5760 aggaacaatc caatgctaat ctatctaaat tccgcaaact ccagcatgag ctggaggagg 5820 ccgaggaacg ggctgacatt gctgagtccc aggtcaacaa attgcgagtg aagagccgag 5880 aggttcacac aaaaatcagt gcagagtaaa cacacctgcc tgatgctatc aagaggctga 5940 agaaaggcac aaaatgtgct atttttggtc acttgcttta tgacgtttat tttcctgtta 6000 aagctgaata aataaaaact acagtaaatg tatacatt 6038 <210> 104 <211> 883 <212> DNA <213> homo sapiens <400> 104 ggataatgca agtgtttaac agatgcttca ctattaaaat attttccccc caagtctcaa 60 atattgaaga atctctaacc aggtacagta tcactctgct ctcttttctg gttgaaaaga 120 aagaaagaaa gaaaacgcag gtattgcttt tcgaagtgct ttgtaggtaa tcgagggaca 180 ccagtcccta cgaagacctt gggcgatttt gaagtgcggg cacctcgatt ccccgaatct 240 gtagtgtggc tggtatcggt gttcccctgg tttaactagc ctgtttgaag gcacagatca 300 ttcatgggga tgtataaccg aaaccagtcc tctccaccgc ctggggatct tcactttcgc 360 agtctacgac tgcctgtgac tccagaaaga caaactgcag attggccaag tgcctttcaa 420 actgtttttt actggatgaa gaaactcaac caagaaaata tatgtcgatt cttgtatatg 480 ggacaatatt agctgctgtg atttttaata ctagcataaa atataagaat ctttttatta 540 ctgtgatatt gttttttcct aaatgaatgc atagtgtaac aattggtgtc aaaaagcatt 600 gaattttttt cagatggatt aagctggaat aataaagtat atctatgaga tgatttctgt 660 aaactctgac ttgctgagaa aaaagtgaaa aagctttttc tggaagaaac atggcaactt 720 aaccgttatt aatctggact aaataaaaca ggaaactgct tctttacatt tctagtaatt 780 ttttctgctt ttccaaacat tgttaagttc tatgcaactt gtgctattca agtaaagatg 840 atgtcagtaa taaaattaca gaatctaaaa aaaaaaaaaa aaa 883 <210> 105 <211> 646 <212> DNA <213> homo sapiens <400> 105 aatcgtcaat gcgacgtcct cctactccca cctcagagct gtcacagaga ctgtcagttc 60 cgtccctccc cttcagccct ttaacgcacg tcttcccgac cgcataactt gctcagtccc 120 tgcggccaac tggggcgggc caatggctgt gacggataag gggtgtgggg tgcggggaca 180 atgggccaga gcttctcatg cagcctgcac cagcgccggg tcggagagtc agaggccacc 240 ctgagatgga ccgagatctt cagttgggga ggcgcctccg gtgagcttgc ggccagatgc 300 cccctcagta gtcctccgca acaggtgccg cgcagccgag tggcgggcta gcataccgcc 360 tgcccgcaat tcggccaggc ctcgagcctg ctccgccttc ccgctgcggt agcgccgccg 420 gggaaacgcc gccacgggct gcatgggcag cgctcgcgcc ccgccgctga gccgccgggg 480 agccgtccag tcttcgaatc ccagcttggt ggcatgcatg tttagtccca gctacacagc 540 agggaggctg aggctgaagg aatacttgag cccaggaatt caagactagc ctgcacaaca 600 tagtgagacc ctgactttaa aataaattta aaaaaattaa aagcaa 646 <210> 106 <211> 525 <212> DNA <213> homo sapiens <400> 106 atgatgtatg ctttgtttct gttgagtgtg ggtttagtaa tggggtttgt ggggttttct 60 tctaagcctt ctcctattta tgggggttta gtattgattg ttagcggtgt ggtcgggtgt 120 gttattattc tgaattttgg gggaggttat atgggtttaa tagttttttt aatttattta 180 gggggaatga tggttgtctt tggatatact acagcgatgg ctattgagga gtatcctgag 240 gcatgggggt caggggttga ggtcttggtg agtgttttag tggggttagc gatggaggta 300 ggattggtgc tgtgggtgaa agagtatgat ggggtggtgg ttgtggtaaa ctttaatagt 360 gtaggaagct gaataattta tgaaggagag gggtcagggt tgattcggga ggatcctatt 420 ggtgcggggg ctttgtatga ttatgggcgt tgattagtag tagttactgg ttgaacattg 480 tttgttggtg tatatattgt aattgagatt gctcggggga atagg 525 <210> 107 <211> 3271 <212> DNA <213> homo sapiens <400> 107 gctgtgacag ccacacgccc caaggcctcc aagatgagct acacgttgga ctcgctgggc 60 aacccgtccg cctaccggcg ggtaaccgag acccgctcga gcttcagccg cgtcagcggc 120 tccccgtcca gtggcttccg ctcgcagtcg tggtcccgcg gctcgcccag caccgtgtcc 180 tcctcctata agcgcagcat gctcgccccg cgcctcgctt acagctcggc catgctcagc 240 tccgccgaga gcagccttga cttcagccag tcctcgtccc tgctcaacgg cggctccgga 300 cccggcggcg actacaagct gtcccgctcc aacgagaagg agcagctgca ggggctgaac 360 gaccgctttg ccggctacat agagaaggtg cactacctgg agcagcagaa taaggagatt 420 gaggcggaga tccaggcgct gcggcagaag caggcctcgc acgcccagct gggcgacgcg 480 tacgaccagg agatccgcga gctgcgcgcc accctggaga tggtgaacca cgagaaggct 540 caggtgcagc tggactcgga ccacctggag gaagacatcc accggctcaa ggagcgcttt 600 gaggaggagg cgcggttgcg cgacgacact gaggcggcca tccgcgcgct gcgcaaagac 660 atcgaggagg cgtcgctggt caaggtggag ctggacaaga aggtgcagtc gctgcaggat 720 gaggtggcct tcctgcggag caaccacgag gaggaggtgg ccgaccttct ggcccagatc 780 caggcatcgc acatcacggt ggagcgcaaa gactacctga agacagacat ctcgacggcg 840 ctgaaggaaa tccgctccca gctcgaaagc cactcagacc agaatatgca ccaggccgaa 900 gagtggttca aatgccgcta cgccaagctc accgaggcgg ccgagcagaa caaggaggcc 960 atccgctccg ccaaggaaga gatcgccgag taccggcgcc agctgcagtc caagagcatc 1020 gagctagagt cggtgcgcgg caccaaggag tccctggagc ggcagctcag cgacatcgag 1080 gagcgccaca accacgacct cagcagctac caggacacca tccagcagct ggaaaatgag 1140 cttcggggca caaagtggga aatggctcgt catttgcgcg aataccagga cctcctcaac 1200 gtcaagatgg ctctggatat agaaatcgct gcgtacagaa aactcctgga gggtgaagag 1260 actagattta gcacatttgc aggaagcatc actgggccac tgtatacaca ccgaccccca 1320 atcacaatat ccagtaagat tcagaaaccc aaggtggaag ctcccaagct taaggtccaa 1380 cacaaatttg tcgaggagat catagaggaa accaaagtgg aggatgagaa gtcagaaatg 1440 gaagaggccc tgacagccat tacagaggaa ttggccgttt ccatgaagga agagaagaaa 1500 gaagcagcag aagaaaagga agaggaaccc gaagctgaag aagaagaagt agctgccaaa 1560 aagtctccag tgaaagcaac tgcacctgaa gttaaagaag aggaagggga aaaggaggaa 1620 gaagaaggcc aggaagaaga ggaggaagaa gatgagggag ctaagtcaga ccaagccgaa 1680 gagggaggat ccgagaagga aggctctagt gaaaaagagg aaggtgagca ggaagaagga 1740 gaaacagaag ctgaagctga aggagaggaa gccgaagcta aagaggaaaa gaaagtggag 1800 gaaaagagtg aggaagtggc taccaaggag gagctggtgg cagatgccaa ggtggaaaag 1860 ccagaaaaag ccaagtctcc tgtgccaaaa tcaccagtgg aagagaaagg caagtctcct 1920 gtgcccaagt caccagtgga agagaaaggc aagtctcctg tgcccaagtc accagtggaa 1980 gagaaaggca agtctcctgt gccgaaatca ccagtggaag agaaaggcaa gtctcctgtg 2040 tcaaaatcac cagtggaaga gaaagccaaa tctcctgtgc caaaatcacc agtggaagag 2100 gcaaagtcaa aagcagaagt ggggaaaggt gaacagaaag aggaagaaga aaaggaagtc 2160 aaggaagctc ccaaggaaga gaaggtagag aaaaaggaag agaaaccaaa ggatgtgcca 2220 gagaagaaga aagctgagtc ccctgtaaag gaggaagctg tggcagaggt ggtcaccatc 2280 accaaatcgg taaaggtgca cttggagaaa gagaccaaag aagaggggaa gccactgcag 2340 caggagaaag agaaggagaa agcgggagga gagggaggaa gtgaggagga agggagtgat 2400 aaaggtgcca agggatccag gaaggaagac atagctgtca atggggaggt agaaggaaaa 2460 gaggaggtag agcaggagac caaggaaaaa ggcagtggga gggaagagga gaaaggcgtt 2520 gtcaccaatg gcctagactt gagcccagca gatgaaaaga aggggggtga taaaagtgag 2580 gagaaagtgg tggtgaccaa aacggtagaa aaaatcacca gtgagggggg agatggtgct 2640 accaaataca tcactaaatc tgtaaccgtc actcaaaagg ttgaagagca tgaagagacc 2700 tttgaggaga aactagtgtc tactaaaaag gtagaaaaag tcacttcaca cgccatagta 2760 aaggaagtca cccagagtga ctaagatttg agtccattgc aaaaggttaa gccatatgac 2820 aatttcaaaa tgcatgtgat tggcagcttc aaaacagaac gggttctccc atgggggctc 2880 cagacattgt attttacttt gtgcaatatg aggggactgc atgcaagctc agggtgctcc 2940 ctcctcagtc tttgggggat tcaaatgcat gatattgtat gtacctggga aatttgccga 3000 tttcctaagc tgttggaagg gggtcactta aggggggatg tcttgagatg tattatgcaa 3060 agtaccaact gagccaaaaa caataaacga aacacagaac tcagccttaa gaaagctata 3120 tatgaataat tatgtttacc tcactggtgc atttaaaatg gacttttgtt catgggagaa 3180 cctcgttgac atgcacagtt tgcaatctta tgttgatcga tgttaaacgt cacagcagta 3240 cttgctcaat aaaggtcata ttggaaacat a 3271 <210> 108 <211> 3002 <212> DNA <213> homo sapiens <400> 108 ggggaggagg ggagaacggg gagcgcacag cctggacgcg tgcgcaggcg tcaggcgcat 60 agacctgcta gcccctcagc tagcggcccc gcccgcgctt agcatcacta actgggctat 120 ataacctgag cgcccgcgcg gccacgacac gaggaattcg cccacgcagg aggcgcggcg 180 tccggaggcc ccagggttat gagactatca ctgctcagga cctactaaca acaaaggaaa 240 tcgaaacatg accaaatcgt acagcgagag tgggctgatg ggcgagcctc agccccaagg 300 tcctccaagc tggacagacg agtgtctcag ttctcaggac gaggagcacg aggcagacaa 360 gaaggaggac gacctcgaag ccatgaacgc agaggaggac tcactgagga acgggggaga 420 ggaggaggac gaagatgagg acctggaaga ggaggaagaa gaggaagagg aggatgacga 480 tcaaaagccc aagagacgcg gccccaaaaa gaagaagatg actaaggctc gcctggagcg 540 ttttaaattg agacgcatga aggctaacgc ccgggagcgg aaccgcatgc acggactgaa 600 cgcggcgcta gacaacctgc gcaaggtggt gccttgctat tctaagacgc agaagctgtc 660 caaaatcgag actctgcgct tggccaagaa ctacatctgg gctctgtcgg agatcctgcg 720 ctcaggcaaa agcccagacc tggtctcctt cgttcagacg ctttgcaagg gcttatccca 780 acccaccacc aacctggttg cgggctgcct gcaactcaat cctcggactt ttctgcctga 840 gcagaaccag gacatgcccc cccacctgcc gacggccagc gcttccttcc ctgtacaccc 900 ctactcctac cagtcgcctg ggctgcccag tccgccttac ggtaccatgg acagctccca 960 tgtcttccac gttaagcctc cgccgcacgc ctacagcgca gcgctggagc ccttctttga 1020 aagccctctg actgattgca ccagcccttc ctttgatgga cccctcagcc cgccgctcag 1080 catcaatggc aacttctctt tcaaacacga accgtccgcc gagtttgaga aaaattatgc 1140 ctttaccatg cactatcctg cagcgacact ggcaggggcc caaagccacg gatcaatctt 1200 ctcaggcacc gctgcccctc gctgcgagat ccccatagac aatattatgt ccttcgatag 1260 ccattcacat catgagcgag tcatgagtgc ccagctcaat gccatatttc atgattagag 1320 gcacgccagt ttcaccattt ccgggaaacg aacccactgt gcttacagtg actgtcgtgt 1380 ttacaaaagg cagccctttg ggtactactg ctgcaaagtg caaatactcc aagcttcaag 1440 tgatatatgt atttattgtc attactgcct ttggaagaaa caggggatca aagttcctgt 1500 tcaccttatg tattattttc tatagctctt ctatttaaaa aataaaaaaa tacagtaaag 1560 tttaaaaaat acaccacgaa tttggtgtgg ctgtattcag atcgtattaa ttatctgatc 1620 gggataacaa aatcacaagc aataattagg atctatgcaa tttttaaact agtaatgggc 1680 caattaaaat atatataaat atatattttt caaccagcat tttactactt gttacctttc 1740 ccatgctgaa ttattttgtt gtgattttgt acagaatttt taatgacttt ttataatgtg 1800 gatttcctat tttaaaacca tgcagcttca tcaattttta tacatatcag aaaagtagaa 1860 ttatatctaa tttatacaaa ataatttaac taatttaaac cagcagaaaa gtgcttagaa 1920 agttattgtg ttgccttagc acttctttcc tctccaattg taaaaaaaaa aaaaaaaaaa 1980 aaaaaaaaaa aaaaattgca caatttgagc aattcatttc actttaaagt ctttccgtct 2040 ccctaaaata aaaaccagaa tcataatttt caagagaaga aaaaattaag agatacattc 2100 cctatcaaaa catatcaatt caacacatta cttgcacaag cttgtatata catattataa 2160 ataaatgcca acataccctt ctttaaatca aaagctgctt gactatcaca tacaatttgc 2220 actgttactt tttagtcttt tactcctttg cattccatga ttttacagag aatctgaagc 2280 tattgatgtt tccagaaaat ataaatgcat gattttatac atagtcacaa aaatggtggt 2340 ttgtcatata ttcatgtaat aaatctgagc ctaaatctaa tcaggttgtt aatgttggga 2400 tttatatcta tagtagtcaa ttagtacagt agcttaaata aattcaaacc atttaattca 2460 taattagaac aatagctatt gcatgtaaaa tgcagtccag aataagtgct gtttgagatg 2520 tgatgctggt accactggaa tcgatctgta ctgtaatttt gtttgtaatc ctgtatatta 2580 tggtgtaatg cacaatttag aaaacattca tccagttgca ataaaatagt attgaaagtg 2640 agagcaattg ttgcatttct tcttaaaggg attctgtttt tatttttggg gaaagtagtt 2700 gcttttttgc tgagttaaaa aatactaaac actatatgta gaataaaaga aaagaaaaaa 2760 gtttaccttg gcatatgctc ttgtctgttt atcttgcaca gggagtcacc agttctatgt 2820 agataatgaa aagacctaac tgatatttca ttatttggaa tatgggactg gacggcagta 2880 caaacagtgt gtttttttct ttgttttaag tggcttagcc tttaggtttt ttatttccat 2940 ttttaaaaat gattgttaca tgttttcttc tatttctttt tttaaaaggt ggattttaat 3000 aa 3002 <210> 109 <211> 3228 <212> DNA <213> homo sapiens <400> 109 caggcgcagt gcaggactgc tccgagcacg cctacgcgcg cattttctcc ccttcctctc 60 cctctttcca ctttcctctc cctttttctc ctctcctttc cccctcccac cacttggtct 120 ttcagtcttt cagtcagttc gtttaggtct ctccttccga cccccacccc cagctcctct 180 ccctttcctt ttccccctcc ccctttcctt tcccgtctca cgcgccaggc cgcttgcaca 240 tgcgcattag gtacaaagcc tcgctctttg tccccatctg tcgttcacac gaactcaagc 300 ctttggcatt cggcagccaa tagaatctaa gaaatggcgg aaaaatgatt ccgcctcggg 360 agctaaacct tgattggcag tttagctaac caatcgagaa cgccattttg taccccttgg 420 caggcaccga gctccgtcgt ctcgtttccg gcggtcgcgc gctcttttct cgggacggga 480 gaggccgtgt agcgtcgccg ttactccgag gagataccag tcggtagagg agaagtcgag 540 gttagaggga actgggaggc actttgctgt ctgcaatcga agttgagagg cccagtattt 600 aggcgacagt gaatttatta ctctgaagag ggttctgcac atatttccaa attatattgg 660 tggtcatcag aagtaggtga taggaagaaa tacttctcaa gggtgcaaaa atgcagagta 720 ataaaacttt taacttggag aagcaaaacc atactccaag aaagcatcat caacatcacc 780 accagcagca gcaccaccag cagcaacagc agcagccgcc accaccgcca atacctgcaa 840 atgggcaaca ggccagcagc caaaatgaag gcttgactat tgacctgaag aattttagaa 900 aaccaggaga gaagaccttc acccaacgaa gccgtctttt tgtgggaaat cttcctcccg 960 acatcactga ggaagaaatg aggaaactat ttgagaaata tggaaaggca ggcgaagtct 1020 tcattcataa ggataaagga tttggcttta tccgcttgga aacccgaacc ctagcggaga 1080 ttgccaaagt ggagctggac aatatgccac tccgtggaaa gcagctgcgt gtgcgctttg 1140 cctgccatag tgcatccctt acagttcgaa accttcctca gtatgtgtcc aacgaactgc 1200 tggaagaagc cttttctgtg tttggccagg tagagagggc tgtagtcatt gtggatgatc 1260 gaggaaggcc ctcaggaaaa ggcattgttg agttctcagg gaagccagct gctcggaaag 1320 ctctggacag atgcagtgaa ggctccttcc tgctaaccac atttcctcgt cctgtgactg 1380 tggagcccat ggaccagtta gatgatgaag agggacttcc agagaagctg gttataaaaa 1440 accagcaatt tcacaaggaa cgagagcagc cacccagatt tgcacagcct ggctcctttg 1500 agtatgaata tgccatgcgc tggaaggcac tcattgagat ggagaagcag cagcaggacc 1560 aagtggaccg caacatcaag gaggctcgtg agaagctgga gatggagatg gaagctgcac 1620 gccatgagca ccaggtcatg ctaatgagac aggatttgat gaggcgccaa gaagaacttc 1680 ggaggatgga agagctgcac aaccaagagg tgcaaaaacg aaagcaactg gagctcaggc 1740 aggaggaaga gcgcaggcgc cgtgaagaag agatgcggcg gcagcaagaa gaaatgatgc 1800 ggcgacagca ggaaggattc aagggaacct tccctgatgc gagagagcag gagattcgga 1860 tgggtcagat ggctatggga ggtgctatgg gcataaacaa cagaggtgcc atgccccctg 1920 ctcctgtgcc agctggtacc ccagctcctc caggacctgc cactatgatg ccggatggaa 1980 ctttgggatt gaccccacca acaactgaac gctttggtca ggctgctaca atggaaggaa 2040 ttggggcaat tggtggaact cctcctgcat tcaaccgtgc agctcctgga gctgaatttg 2100 ccccaaacaa acgtcgccga tactaataag ttgcagtgtc tagtttctca aaacccttaa 2160 aagaaggacc ctttttggac tagccagaat tctaccctgg aaaagtgtta gggattcctt 2220 ccaatagtta gatctaccct gcctgtacta ctctagggag tatgctggag gcagagggca 2280 agggaggggt ggtattaaac aagtcaattc tgtgtggtat attgtttaat cagttctgtg 2340 tggtgcattc ctgaagtctc taatgtgact gttgagggcc tggggaaacc atggcaaagt 2400 ggatccagtt agagcccatt aatcttgatc attccggttt tttttttttt tgtccatctt 2460 gtttcatttg cttgccccgc ccccgagacg gagtcttact ctgtcgccca ggctggagtg 2520 tagtggcatg atctcggctc actgcaatct ctgcctcccg ggttcaagct tgtccaggtt 2580 gatcttgaac tcctgacctc gtgatctacc cacctcggcc tcccaaaatg ctgggattac 2640 aggggtgagc caccgtgccc aacctcactt gcttcttatc cttacactcc cccagcccca 2700 gagaaactgc cacatacacc acaaaaacca aacatccccc aatgacctta gccccattgc 2760 tccattcact cccaggtgag aattcaggca aacgtccaca aaggtcacag gcagcgtaca 2820 tacggttctg ttatacccca tatattaccc cttcatgtcc taaagaagac attttctctt 2880 agagattttc attttagtgt atctttaaaa aaaaatcttg tgttaacttg cctccatctt 2940 tttcttgggt gaggacaccc aggaatgacc cttttgtgtc tatgatgttg ctgttcacag 3000 cttttcttga taggcctagt acaatcttgg gaacagggtt actgtatact gaaggtctga 3060 cagtagctct tagactcgcc tatcttaggt agtcatgctg tgcatttttt ttttcattgg 3120 tgtactgtgt ttgatttgtc tcatatattt ggagtttttc tgaaaaatgg agcagtaatg 3180 cagcatcaac ctattaaaat acattttaag ccttttaaaa aaaaaaaa 3228 <210> 110 <211> 3197 <212> DNA <213> homo sapiens <400> 110 ccctgggagc ccgcacccgt ctctggtgcc agggcgttgt cgggggtccc aagagagcgg 60 ggtggggaag gtgaagggag cgcggctgga aaaatgggga ttagggtggc ggaacaggca 120 cttgtcagga gtgaagagac agcggagagg gtactgggct gaattctttc gtgccgagca 180 ggtccctccg gttcccaact cacccgggtg gagcaggcgc gggccgaacc cgggaggaga 240 gtgtcgggga tccgcgaagg agcctcctgg ggatggggcg ggggatggac aaagcgctgc 300 ccccggctgg acgcgctctg gctgcagccc ggctggcatc cggagctggg aacagcagcc 360 cgcggggtgc ccgggtcagg gctcaaccct agcgggtctc tggcgaggcc gggggcgcag 420 cccgcggggc gccactcagg ccgtccagct gccgcgcggt ccagcgctga cccgagcccg 480 ggaggcagct gcgctctaag gtttgcgctc ctgtttgcga ggtgtcttca tataacaaat 540 gcgagcaata acaaacatcc atagaactcg aattccagaa acgggaattc ttttttccaa 600 gttcacagac ctttagttaa tcttttaaag gaactgaggc gttgtgttgg accaaagcca 660 aaacgatttt accttagacc atggaaaata gcctaaggct ctttcagcag aattttgcag 720 tccgaatgca attttagatt tcagatttct caagggaaga gaaactctgc tgttagaatt 780 tggaagggag ggtggtgcat gcctgtgtgt ttgtcagctg agcagagctg tatttatctt 840 tccaattcaa attgtgccag attctggctt taagaacaaa ccatgggaat atttgagaac 900 atggaatcat gctgctgttc cacgatcaca gcaaaacaga caatagttga tattgtatca 960 ttgcaggagg aaaaagaatt acatatattt tattcttttg tgtgattgtc atcctttgtg 1020 aaaagaatga tgtgtatttt cataaagcaa aaaattattc aaacaaagaa accttattta 1080 aatgtacaag tcagactttt aatatccttt gaattccctg cagttcctcc tattattctt 1140 gagaactatc tactttctta aaatacttaa aatctattca gaaggtttca tttgtctagg 1200 tgtcagatat agaagagttt ataagaaaat tccagtaaac ctttaaaaag atattatttt 1260 ttataagttg ccatagttta ataaagaact tttatttttc acacttttta ctcagagatt 1320 aaagttctgt gtttcagcct ggaaattctg atggtgggag atacaactaa tacaaaagag 1380 aatgagtaaa tatagtaatt aggtctgctc attgtgtttt tcaggaaaaa ggaagggaaa 1440 gggtgttaca aggaaaggct atcggtaaca actgacctgc cacaaagtta gaagaaagga 1500 ttgattcaag aaagactata atatggattt agagctcgac gagtattata acaagacact 1560 tgccacagag aataatactg ctgccactcg gaattctgat ttcccagtct gggatgacta 1620 taaaagcagt gtagatgact tacagtattt tctgattggg ctctatacat ttgtaagtct 1680 tcttggcttt atggggaatc tacttatttt aatggctctc atgaaaaagc gtaatcagaa 1740 gactacggta aacttcctca taggcaatct ggccttttct gatatcttgg ttgtgctgtt 1800 ttgctcacct ttcacactga cgtctgtctt gctggatcag tggatgtttg gcaaagtcat 1860 gtgccatatt atgccttttc ttcaatgtgt gtcagttttg gtttcaactt taattttaat 1920 atcaattgcc attgtcaggt atcatatgat aaaacatccc atatctaata atttaacagc 1980 aaaccatggc tactttctga tagctactgt ctggacacta ggttttgcca tctgttctcc 2040 ccttccagtg tttcacagtc ttgtggaact tcaagaaaca tttggttcag cattgctgag 2100 cagcaggtat ttatgtgttg agtcatggcc atctgattca tacagaattg cctttactat 2160 ctctttattg ctagttcagt atattctgcc cttagtttgt cttactgtaa gtcatacaag 2220 tgtctgcaga agtataagct gtggattgtc caacaaagaa aacagacttg aagaaaatga 2280 gatgatcaac ttaactcttc atccatccaa aaagagtggg cctcaggtga aactctctgg 2340 cagccataaa tggagttatt cattcatcaa aaaacacaga agaagatata gcaagaagac 2400 agcatgtgtg ttacctgctc cagaaagacc ttctcaagag aaccactcca gaatacttcc 2460 agaaaacttt ggctctgtaa gaagtcagct ctcttcatcc agtaagttca taccaggggt 2520 ccccacttgc tttgagataa aacctgaaga aaattcagat gttcatgaat tgagagtaaa 2580 acgttctgtt acaagaataa aaaagagatc tcgaagtgtt ttctacagac tgaccatact 2640 gatattagta tttgctgtta gttggatgcc actacacctt ttccatgtgg taactgattt 2700 taatgacaat cttatttcaa ataggcattt caagttggtg tattgcattt gtcatttgtt 2760 gggcatgatg tcctgttgtc ttaatccaat tctatatggg tttcttaata atgggattaa 2820 agctgattta gtgtccctta tacactgtct tcatatgtaa taattctcac tgtttaccaa 2880 ggaaagaaca aatgctgggg tcatataaaa tatatttatg ataactattt acatataata 2940 aatagaaatt ttgttaacat ggaatttaat ttatgtgaaa gagttctgga ttcaaatgtc 3000 agttcataat atatggaaga taattttatg tgttatagta ggattaattt atttagttgt 3060 gcagtcagtg tcaatccaat ctgtaatttc actttagaag gttgtattac cttccacttc 3120 catgttgtct tataaacaaa tgaattgtat tttttgttga aagtaaaagt tatatctaac 3180 caaaaaaaaa aaaaaaa 3197 <210> 111 <211> 744 <212> DNA <213> homo sapiens <400> 111 cagtgggcct gggaagatgt gtttcccctg gatgtgcaca ttcctgtttg tggcttatcg 60 cctctcattt attctgtgtg agtaggtaga aaatgagcat cacggacgtg ctcagtgctg 120 acgacattgc agcagcgctc caggaatgcc gagacccaga cacttttgaa ccccaaaaat 180 tcttccagac atcaggcctc tccaagatgt cagccaatca ggtgaaggat gttttccggt 240 tcatagacaa cgaccagagc gggtacctgg atgaagaaga gcttaagttt ttcctccaga 300 agtttgagag tggtgccaga gaactgaccg agtcagaaac caagtccttg atggctgcgg 360 cggataatga tggagatggg aaaattggag cagaggaatt ccaggaaatg gtgcattctt 420 aaaagcccca gtctctggag aaaagagaga aagggataat cacctggaag gattccaaag 480 ccctgggaat ggggaacccc acatcccatc cctacctaat ttgttaattt tccctgaaaa 540 ccttctgcag tttgctcatt gttttagtga ggtcacgagg gagtcactcc tgactttctt 600 ggtggtgggt atatgccctg acaacttctg taagcccccc ttcccccaac aggcaatgcc 660 tctaaaaatc acccaataaa gacaggcttc tcatcaaaaa aaaaaaaaaa aaaaaaaaaa 720 aaaaaaaaaa aaaaaaaaaa aaaa 744 <210> 112 <211> 588 <212> DNA <213> homo sapiens <400> 112 atgagcatca cggacgtgct cagtgctgat gacattgcag cagcgctcca ggaatgccaa 60 gacccagaca cttttgaacc ccaaaaattc ttccagacgt caggcctctc caagatgtca 120 gccagtcagg tgaaggatgt tttccggttc atagacaacg accagagcgg gtatctggat 180 gaagaagagc ttaagttttt cctccagaag tttgagagtg gtgccagaga actgaccgag 240 tcagaaacca agtccttgat ggctgcggcg gataatgatg gagatgggaa aattggagca 300 gaggaattcc aggaaatggt gcattcttaa aagccccagt ctctggagaa aagagagaaa 360 gggataatca cctggaagga ttccaaagcc ctgggaatgg ggaaccccac atcccatccc 420 tacctaattt gttaattttc cctgaaaacc ttctgcagtt tgctcattgt tttagcgagg 480 tcacgagaga gtcactcatg actttcttgg tggtgggtat atgccctgac aacttctgta 540 agcccccctt cccccaacag gcaatgcctc taaaaatcac ccaataaa 588 <210> 113 <211> 912 <212> DNA <213> homo sapiens <400> 113 atgagcttct cttccctgcc tactgaaata cagtcattac tctttctgac atttctaacc 60 atctacctgg tcaccctgat gggaaactgc ctcatcattc tggttaccct agctgacccc 120 atgctacaca gccccatgta cttcttcctc agaaacttat ctttcctgga gattggcttc 180 aacctagtca ttgtgcccaa aatgctgggg accctgcttg cccaggacac aaccatctcc 240 ttccttggct gtgccactca gatgtatttc ttcttcttct ttggagtggc tgaatgcttc 300 ctcctggcta ccatggcata tgaccgctat gtggccatct gcagtccctt gcactaccca 360 gtcatcatga accaaaggac tcgtgccaaa ctggctgctg cctcctggtt cccaggcttt 420 cctgtagcta ctgtgcagac cacatggctc ttcagttttc cattctgtgg caccaacaag 480 gtgaaccact tcttctgtga cagcccacct gtgctgaggc tggtctgtgc agacacagca 540 ctctttgaga tctacgccat cgtcggaacc attctggtgg tcatgatccc ctgcttgctg 600 atcttgtgtt cctatactca cattgctgct gccatcctca agatcccatc agctaaaggg 660 aagaataaag ccttttctac atgttcctca cacctccttg ttgtctctct tttctatata 720 tcattaagcc tcacctactt ccggcctaaa tcaaataatt cacctgaggg caagaagctg 780 ctatcattgt cctacactgt tatgactccc atgttgaacc ccattatcta cagcctgaga 840 aataacgagg tgaagaatgc cctcagcagg acggtctcta aggccctagc cctcagaaac 900 tgtatcccat ag 912 <210> 114 <211> 933 <212> DNA <213> homo sapiens <400> 114 atggaaagca atcagacctg gatcacagaa gtcatcctgt tgggattcca ggtggaccca 60 gctctggagt tgttcctctt tgggtttttc ttgctattct acagcttaac cctgatggga 120 aatgggatta tcctggggct catctacttg gactctagac tgcacacacc catgtatgtc 180 ttcctgtcac acctggccat tgtggacatg tcctatgcct cgagtactgt ccctaagatg 240 ctagcaaatc ttgtgatgca caaaaaagtc atctcctttg ctccttgcat acttcagact 300 tttttgtatt tggcgtttgc tattacagag tgtctgattt tggtgatgat gtgctatgat 360 cggtatgtgg caatctgtca ccccttgcaa tacaccctca ttatgaactg gagagtgtgc 420 actgtcctgg cctcaacttg ctggatattt agctttctct tggctctggt ccatattact 480 cttattctga ggctgccttt ttgtggccca caaaagatca accacttttt ctgtcaaatc 540 atgtccgtat tcaaattggc ctgtgctgac actaggctca accaggtggt cctatttgcg 600 ggttctgcgt tcatcttagt ggggccgctc tgcctggtgc tggtctccta cttgcacatc 660 ctggtggcca tcttgaggat ccagtctggg gagggccgca gaaaggcctt ctctacctgc 720 tcctcccacc tctgcgtggt ggggcttttc tttggcagcg ccattgtcat gtacatggcc 780 cccaagtcaa gccattctca agaacggagg aagatccttt ccctgtttta cagccttttc 840 aacccgatcc tgaaccccct catctacagc cttaggaatg cagaggtgaa aggggctcta 900 aagagagtcc tttggaaaca gagatcaatg tga 933 <210> 115 <211> 993 <212> DNA <213> homo sapiens <400> 115 atgtgttctt ttttcttgtg ccaaacaggt aaacaggcaa aaatatcaat gggagaagaa 60 aaccaaacct ttgtgtccaa gtttatcttc ctgggtcttt cacaggactt gcagacccag 120 atcctgctat ttatcctttt cctcatcatt tatctgctga ccgtgcttgg aaaccagctc 180 atcatcattc tcatcttcct ggattctcgc cttcacactc ccatgtattt ttttcttaga 240 aatctctcct ttgcagatct ctgtttctct actagcattg tccctcaagt gttggttcac 300 ttcttggtaa agaggaaaac catttctttt tatgggtgta tgacacagat aattgtcttt 360 cttctggttg ggtgtacaga gtgtgcgctg ctggcagtga tgtcctatga ccggtatgtg 420 gctgtctgca agcccctgta ctactctacc atcatgacac aacgggtgtg tctctggctg 480 tccttcaggt cctgggccag tggggcacta gtgtctttag tagataccag ctttactttc 540 catcttccct actggggaca gaatataatc aatcactact tttgtgaacc tcctgccctc 600 ctgaagctgg cttccataga cacttacagc acagaaatgg ccatcttttc aatgggcgtg 660 gtaatcctcc tggcccctgt ctccctgatt cttggttctt attggaatat tatctccact 720 gttatccaga tgcagtctgg ggaagggaga ctcaaggctt tttccacctg tggctcccat 780 cttattgttg ttgtcctctt ctatgggtca ggaatattca cctacatgcg accaaactcc 840 aagactacaa aagaactgga taaaatgata tctgtgttct atacagcggt gactccaatg 900 ttgaacccca taatttatag cttgaggaac aaagatgtca aaggggctct caggaaacta 960 gttgggagaa agtgcttctc tcataggcag tga 993 <210> 116 <211> 939 <212> DNA <213> homo sapiens <400> 116 atggcaaggg agaattcgac cttcaactcc gacttcatcc tcctgggaat cttcaatcac 60 agccccaccc acaccttcct cttctttctg gtcctggcca tcttttcagt ggccttcatg 120 ggaaactctg tcatggttct cctcatctac ctggacaccc agctccacac ccccatgtac 180 ctcctcctca gccaactgtc cctcatggac ctcatgctca tctgcaccac cgtacccaag 240 atggccttca actacctgtc tggcagcaag tccatttcta tggctggttg tgccacacaa 300 attttcttct atacatcact gcttggctct gagtgctttc ttttggctgt tatggcttat 360 gaccgctaca ctgccatttg ccaccctcta agatacacca atctcatgag ccctaaaatt 420 tgtggactta tgactgcctt ttcctggatc ctgggctcta cggatggaat tattgatgtt 480 gtagcaacat tttccttctc ctactgtggg tctcgggaaa tagcccactt cttctgtgac 540 ttcccctccc tactaatcct ctcatgcagt gacacatcaa tatttgaaaa gattcttttc 600 atctgctgta tagtaatgat tgttttccct gttgcaatca tcattgcttc ctatgctcga 660 gttatcctgg ctgtcattca catgggatct ggagagggtc gtcgcaaagc ttttactact 720 tgttcctctc acctcttggt ggtgggaatg tactatggag cagctttgtt catgtacata 780 cggcccacat ctgatcgctc cccaacacag gacaagatgg tgtctgtatt ctacaccatc 840 ctcactccca tgttgaatcc cctcatctac agcctccgca acaaggaggt gaccagagca 900 ttcatgaaga tcttaggaaa gggcaagtct ggagagtga 939 <210> 117 <211> 975 <212> DNA <213> homo sapiens <400> 117 atgggcatgg agggtcttct ccagaactcc actaacttcg tcctcacagg cctcatcacc 60 catcctgcct tccccgggct tctctttgca atagtcttct ccatctttgt ggtggctata 120 acagccaact tggtcatgat tctgctcatc cacatggact cccgcctcca cacacccatg 180 tacttcttgc tcagccagct ctccatcatg gataccatct acatctgtat cactgtcccc 240 aagatgctcc aggacctcct gtccaaggac aagaccattt ccttcctggg ctgtgcagtt 300 cagatcttcc tctacctgac cctgattgga ggggaattct tcctgctggg tctcatggcc 360 tatgaccgct atgtggctgt gtgcaaccct ctacggtacc ctctcctcat gaaccgcagg 420 gtttgcttat tcatggtggt cggctcctgg gttggtggtt ccttggatgg gttcatgctg 480 actcctgtca ctatgagttt ccccttctgt agatcccgag agatcaatca ctttttctgt 540 gagatcccag ccgtgctgaa gttgtcttgc acagacacgt cactctatga gaccctgatg 600 tatgcctgct gcgtgctgat gctgcttatc cctctatctg tcatctctgt ctcctacacg 660 cacatcctcc tgactgtcca caggatgaac tctgctgagg gccggcgcaa agcctttgct 720 acgtgttcct cccacattat ggtggtgagc gttttctacg gggcagcctt ctacaccaac 780 gtgctgcccc actcctacca cactccagag aaagataaag tggtgtctgc cttctacacc 840 atcctcaccc ccatgctcaa cccactcatc tacagcttga ggaataaaga tgtggctgca 900 gctctgagga aagtactagg gagatgtggt tcctcccaga gcatcagggt ggcgactgtg 960 atcaggaagg gctag 975 <210> 118 <211> 972 <212> DNA <213> homo sapiens <400> 118 atgggcatgg agggtcttct ccagaactcc actaacttcg tcctcacagg cctcatcacc 60 catcctgcct tccccgggct tctctttgca gtagtcttct ccatctttgt ggtggctata 120 acagccaact tggtcatgat tctgctcatc cacatggact cccgcctcca cacacccatg 180 tacttcttgc tcagccagct ctccatcatg gataccatct acatctgtat cactgtcccc 240 aagatgctcc aggacctcct gtccaaggac aagaccattt ccttcctggg ctgtgcagtt 300 caaatcttct acctgaccct gattggaggg gaattcttcc tgctgggtct catggcctat 360 gaccgctatg tggctgtgtg caaccctcta cggtaccctc tcctcatgaa ccgcagggtt 420 tgcttattca tggtggtcgg ctcctgggtt ggtggttcct tggatgggtt catgctgact 480 cctgtcacta tgagtttccc cttctgtaga tcccgagaga tcaatcactt tttctgtgag 540 atcccagccg tgctgaagtt gtcttgcaca gacacgtcac tctatgagac cctgatgtat 600 gcctgctgcg tgctgatgct gcttatccct ctatctgtca tctctgtgtc ctacacgcac 660 atcctcctga ctgtccacag gatgaactct gctgagggcc ggcgcaaagc ctttgctacg 720 tgttcctccc acattatggt ggtgagcgtt ttctacgggg cagccttcta caccaacgtg 780 ctgccccact cctaccacac tccagagaaa gataaagtgg tgtctgcctt ctacaccatc 840 ctcaccccca tgctcaaccc actcatctac agcttgagga ataaagatgt ggctgcagct 900 ctgaggaaag tactagggag atgtggttcc tcccagagca tcagggtggc gactgtgatc 960 aggaagggct ag 972 <210> 119 <211> 936 <212> DNA <213> homo sapiens <400> 119 atggagatgg aaaactgcac cagggtaaaa gaatttattt tccttggcct gacccagaat 60 cgggaagtga gcttagtctt atttcttttc ctactcttgg tgtatgtgac aactttgctg 120 ggaaacctcc tcatcatggt cactgttacc tgtgaatctc gccttcacac gcccatgtat 180 tttttgctcc ataatttatc tattgccgat atctgcttct cttccatcac agtgcccaag 240 gttctggtgg accttctgtc tgaaagaaag accatctcct tcaatcattg cttcactcag 300 atgtttctat tccaccttat tggaggggtg gatgtatttt ctctttcggt gatggcattg 360 gatcgatatg tggccatctc caagcccctg cactatgcga ctatcatgag tagagaccat 420 tgcattgggc tcacagtggc tgcctggttg gggggctttg tccactccat cgtgcagatt 480 tccctgttgc tcccactccc tttctgcgga cccaatgttc ttgacacttt ctactgtgat 540 gtccaccggg tcctcaaact ggcccataca gacattttca tacttgaact actaatgatt 600 tccaacaatg gactgctcac cacactgtgg tttttcctgc tcctggtgtc ctacatagtc 660 atattatcat tacccaagtc tcaggcagga gagggcagga ggaaagccat ctccacctgc 720 acctcccaca tcactgtggt gaccctgcat ttcgtgccct gcatctatgt ctatgcccgg 780 cccttcactg ccctccccat ggataaggcc atctctgtca ccttcactgt catctcccct 840 ctgctcaacc ccttgatcta cactctgagg aaccatgaga tgaagtcagc catgaggaga 900 ctgaagagaa gacttgtgcc ttctgataga aaatag 936 <210> 120 <211> 924 <212> DNA <213> homo sapiens <400> 120 atggaaacag ggaacctcac gtgggtatca gactttgtct tcctggggct ctcgcagact 60 cgggagctcc agcgtttcct gtttctaatg ttcctgtttg tctacatcac cactgttatg 120 ggaaacatcc ttatcatcat cacagtgacc tctgattccc agctccacac acccatgtac 180 tttctgctcc gaaacctggc tgtcctagac ctctgtttct cttcagtcac tgctcccaaa 240 atgctagtgg acctcctctc tgagaagaaa accatctctt accagggctg catgggtcag 300 atcttcttct tccacttttt gggaggtgcc atggtcttct tcctctcagt gatggccttt 360 gaccgcctca ttgccatctc ccggcccctc cgctatgtca ccgtcatgaa cactcagctc 420 tgggtggggc tggtggtagc cacctgggtg ggaggctttg tccactctat tgtccagctg 480 gctctgatgc tcccactgcc cttctgtggc cccaacattt tggataactt ctactgtgat 540 gttccccaag tactgagact tgcctgcact gacacctcac tgctggagtt cctcaagatc 600 tccaacagtg ggctgctgga tgtcgtctgg ttcttcctcc tcctgatgtc ctacttattc 660 atcctggtga tgctgaggtc acatccaggg gaggcaagaa ggaaggcagc ttccacctgc 720 accacccaca tcatcgtggt ttccatgatc ttcgttccaa gcatttacct ctatgcccgg 780 cccttcactc cattccctat ggacaagctt gtgtccatcg gccacacagt catgaccccc 840 atgctcaacc ccatgatcta taccctgagg aaccaggaca tgcaggcagc agtgagaaga 900 ttagggagac accggctggt ttga 924 <210> 121 <211> 939 <212> DNA <213> homo sapiens <400> 121 atggctgatg ataattttac agttgtcact gagtttattc ttttgggatt gacagatcat 60 gctgaactaa aagctgtgct ttttgtggtg ttcctggtga tttacgccat taccttgttg 120 aggaatctgg gcatgatcct cttaatccaa atcacctcca aactccacac acccatgtac 180 tttttactca gctgtctttc atttgtggat gcctgctatt catctgcaat tgcacccaaa 240 atgctggtga acctcctggt tgtgaaggca acaatttctt tctctgcttg catggtacag 300 catttgtgtt tcggagtgtt catcaccaca gaaggcttct tactgtcagt gatggcctat 360 gaccgctatg tggccattgt gagtcccttg ctttacactg tagccatgtc tgatagaaag 420 tgtgtggagc ttgtcacagg atcatggata ggtggaatag ttaacacatt aatccacaca 480 atcagcttga ggagactgtc cttttgtagg ctaaatgctg tcagccactt cttctgtgac 540 attccttcac tgctaaagct gtcatgttct gacacctcca tgaatgagtt gttgctgtta 600 accttctccg gagtcattgc catggccacc ttcttgactg tgatcatttc ctacatcttc 660 attgcttttg ctagcctaag gatccactca gcatcaggca gacagcaagc cttctccacc 720 tgtgcctctc acctgactgc tgtgaccata ttctatggta ccttaatctt tagctacatt 780 cagccaagct cccagtattt tgtggaacaa gagaaagtgg tttctatgtt ctatacgcta 840 gggattccca tgttaaacct gttgatacac agtttgagaa acaaggacgt aaaggaggca 900 gtgaaaaggg ccatagaaat gaaacatttc ctctgttaa 939 <210> 122 <211> 948 <212> DNA <213> homo sapiens <400> 122 atgttgtccc caaaccacac catagtgaca gaattcattc tcttaggact gacagacgac 60 ccagtgctag agaagatcct gtttggggtg ttcctggcga tctacctaat cacactggca 120 ggcaacctgt gcatgatcct gctgatcagg accaattccc aactgcaaac acccatgtat 180 ttcttccttg gtcacctctc ctttgtagac atttgctatt cttccaatgt tactccaaat 240 atgctgcaca atttcctctc agaacagaag accatctcct acgctggatg cttcacacag 300 tgtcttctct tcatcgccct agtgatcact gagttttact tccttgcttc aatggcattg 360 gatcgctatg tagccatttg cagcccttta cattacagtt ccaggatgtc caagaacatt 420 tgcatctctc tggtcactgt gccttacatg tatggcttcc ttaatgggct ctctcagaca 480 ctgctgacct ttcacttatc cttctgtggc tcccttgaaa tcaatcattt ctactgcgct 540 gatcctcctc ttatcatgct ggcctgctct gacacccgtg tcaaaaagat ggcaatgttt 600 gtagttgcag gctttactct ctcaagctct ctcttcatca ttcttctgtc ctatcttttc 660 atttttgcag cgatcttcag gatccgttct gctgaaggca ggcacaaagc cttttctacg 720 tgtgcttccc acctgacaat agtcactttg ttttatggaa ccctcttctg catgtacgta 780 aggcctccat cagagaagtc tgtagaggag tccaaaataa ttgcagtctt ttatactttt 840 ttgagcccaa tgctgaaccc attgatctat agcctacgga acagagatgt aatccttgcc 900 atacaacaaa tgattagggg aaaatccttt tgtaaaattg cagtttag 948 <210> 123 <211> 939 <212> DNA <213> homo sapiens <400> 123 atgatgggta gaaggaatga cacaaatgtg gctgacttca tccttacggg actgtcagac 60 tctgaagagg tccagatggc tctgtttatg ctatttctcc tcatatacct aattactatg 120 ctggggaatg tggggatgct attgataatc cgcctggacc tccagcttca cactcccatg 180 tattttttcc ttactcacct gtcatttatt gacctcagtt actcaactgt cgtcacacct 240 aaaaccttag cgaacttact gacttccaac tatatttcct tcacgggctg ctttgcccag 300 atgttctgtt ttgtcttctt gggtactgct gaatgttatc ttctctcctc aatggcctat 360 gatcgctatg cagcgatctg cagtcctcta cactacacag ttattatgcc caaaaggctc 420 tgcctcgctc tcatcactgg gccttatgtg attggcttta tggactcctt tgtcaatgtg 480 gtttccatga gcagattgca tttctgtgac tcaaacataa ttcatcactt tttctgtgac 540 acttccccaa ttttagctct gtcctgcact gacacagaca acactgaaat gctgatattc 600 attatcgctg gttccaccct gatggtgtcc cttatcacaa tatctgcatc ctatgtgtcc 660 attctctcta ccatcctgaa aattaattcc acttcaggaa agcagaaagc tttctctact 720 tgcgtctctc atctcttggg agtcaccatc ttctatggaa ctatgatttt tacttactta 780 aagccaagaa agtcttattc cttgggaaga gatcaagtgg ctcctgtgtt ttatactatt 840 gtgattccca tgctgaatcc actcatttat agtcttagaa acagagaagt gaaaaatgct 900 ctcattagag tcatgcagag aagacaggac tccaggtag 939 <210> 124 <211> 918 <212> DNA <213> homo sapiens <400> 124 atgcagagga gcaatcatac agtgactgag tttatactgc tgggcttcac cacagaccca 60 ggaatgcagc tgggcctctt cgtggtgttc ctgggcgtgt actctctcac tgtggtagga 120 aatagcaccc tcatcgtgtt gatctgtaat gactcctgcc tccacacacc catgtatttt 180 ttcactggaa atctgtcgtt tctggatctc tggtattctt ctgtctacac cccaaagatc 240 ctagtgacct gcatctctga agacaaaagc atctcctttg ctggctgcct gtgtcagttc 300 ttcttctctg cagggctggc ctatagtgag tgctacctgc tggctgccgt ggcttatgac 360 cgctacgtgg ccatctccaa gcccctgctt tatgcccagg ccatgtccat aaagctgtgt 420 gcattgctgg tagcagtctc atattgtggt ggctttatta actcttcaat catcaccaag 480 aaaacgtttt cctttaactt ctgccgtgaa aacatcattg atgacttttt ctgtgatttg 540 cttcccttgg tggagctggc ctgtggcgag aagggcggct ataaaattat gatgtacttc 600 ctgctggcct ccaatgtcat ctgccccgca gtgctcatcc tggcctccta cctctttatc 660 atcaccagtg tcttgaggat ctcctcctcc aagggctacc tcaaagcctt ctccacatgc 720 tcctcccacc tgacctctgt cactttatac tatggctcca ttctctacat ctacgctctc 780 cccagatcta gctattcttt tgatatggac aaaatagttt ctacatttta cactgtggta 840 ttccccatgt tgaatctcat gatctacagc ctaaggaata aggatgtgaa agaggctctg 900 aaaaaacttc tcccataa 918 <210> 125 <211> 844 <212> DNA <213> homo sapiens <400> 125 cagacacaga gtaaactttt gctgggctcc aagtgaccgc ccatagttta ttataaaggt 60 gactgcaccc tgcagccacc agcactgcct ggctccacgt gcctcctggt ctcagtatgg 120 cgctgtcctg ggttcttaca gtcctgagcc tcctacctct gctggaagcc cagatcccat 180 tgtgtgccaa cctagtaccg gtgcccatca ccaacgccac cctggaccgg atcactggca 240 agtggtttta tatcgcatcg gcctttcgaa acgaggagta caataagtcg gttcaggaga 300 tccaagcaac cttcttttac tttaccccca acaagacaga ggacacgatc tttctcagag 360 agtaccagac ccgccagaac cagtgcttct ataactccag ttacctgaat gtccagcggg 420 agaatgggac cgtctccaga tacgagggag gccgagaaca tgttgctcac ctgctgttcc 480 ttagggacac caagaccttg atgtttggtt cctacctgga cgatgagaag aactgggggc 540 tgtctttcta tgctgacaag ccagagacga ccaaggagca actgggagag ttctacgaag 600 ctctcgactg cttgtgcatt cccaggtcag atgtcatgta caccgactgg aaaaaggata 660 agtgtgagcc actggagaag cagcacgaga aggagaggaa acaggaggag ggggaatcct 720 agcaggacac agccttggat caggacagag acttgggggc catcctgccc ctccaacccg 780 acatgtgtac ctcagctttt tccctcactt gcatcaataa agcttctgtg tttggaacag 840 ctaa 844 <210> 126 <211> 8778 <212> DNA <213> homo sapiens <400> 126 atgggagtcc tggcgtctgc gctctgctgg ctgctttgtg tctggctgcc ctggggtgag 60 caggcagccg agtccctgcg ggtgcagcgc ctcggtgaga gggttgtgga ctcagggagg 120 tcgggggctc gaggaatgag aaacgttaaa ggaatgagga atgggcccgc gcagactcgt 180 gtttcctcca gcagcagcca ccaggaggcg acccttgcca tgggggacaa ggctacagtc 240 gtgggaggcc agcaggctga agccccagac tccgtggcca tgtcttcctg ggaaaggcgg 300 ctccatcggg ccaagtgtgc accatcctac ttgttctcct gcttcaatgg aggcgagtgt 360 gtgcacccag ccttctgtga ctgcagacgc ttcaatgcca ctggaccgcg ctgccagatg 420 gtgtacaatg ccggccctga gagggacagc atttgccggg cgtgggggca gcaccacgtg 480 gagacatttg atgggctcta ctactacctc tccggaaagg gcagctacac cctggtgggt 540 cgccatgagc ccgagggaca gagcttctcc atccaggtac acaatgaccc gcagtgtggc 600 tcttcaccct acacctgctc cagggctgtc agcctcttct ttgtgggtga gcaggagatc 660 catctggcca aggaggtcac ccatggaggc atgagggtcc aactgccaca tgtcatgggg 720 agcgcgcgtc tgcagcagct tgccggctat gtcatcgtgc ggcatcagtc agccttcaca 780 ctggcctggg atggtgcctc ggctgtctac atcaagatga gtccagagct tctgggctgg 840 acccatgggc tgtgtgggaa caacaatgct gaccccaagg atgatctggt gaccagctct 900 gggaagctga ctgacgacgt ggttgagttt gtgcacagct ggcaggagca ggcccctaac 960 cagcctccag ggcccacaac ttcctccctg cctcgcccac cgtgcctaca gcagaaccca 1020 ggaaccatgc agggcgtgta cgagcagtgt gaggctctac tgcggccccc ctttgacgcc 1080 tgccacgcct acgtcagccc tctgcccttc acagccagtt gtaccagtga tctctgccaa 1140 tcaatgggtg atgtagccac ctggtgccgg gcactggcgg agtatgcccg ggcgtgtgcc 1200 caggcagggc ggcccttgca aggctggagg acccagctcc ggcaatgcac tgtgcactgc 1260 aaggagaagg cctttaccta caatgagtgc atcgcctgct gccctgcctc ctgccatccc 1320 cgggcatcct gtgtggacag tgagatcgcc tgtgtggacg gctgctattg ccccaatggg 1380 ctcatcttcg aggatggggg ctgcgtggca ccagctgagt gtccctgtga gtttcacggg 1440 actctgtacc cacctggctc tgtggtgaag gaagactgca atacttgcac atgcacctca 1500 ggcaagtggg agtgcagcac agctgtctgc ccagctgagt gctcagtgac tggtgacatt 1560 cacttcacaa cctttgatgg ccgccggtac acgttccccg ccacatgtca gtacatcctg 1620 gccaagagcc gctcttcggg caccttcacc gtgacattgc agaatgcccc atgtggcctg 1680 aaccaagatg gagcctgtgt ccagtcagtg tcagtgattc tgcaccagga ccctcggagg 1740 caggtgaccc tgacccaggc aggggatgtc cttctgtttg accagtacaa gatcatcccg 1800 ccatacacag atgatgcctt tgagatccgt aggctgtcct ccgtgttcct gcgggtgagg 1860 acgaacgtgg gcgtgcgggt gctctacgac cgtgaagggc tccgactgta cctgcaagtg 1920 gaccagcgat gggtggagga taccgtgggc ctctgcggca ccttcaatgg caacacgcag 1980 gatgacttcc tgtctccagt gggtgtacct gagagcaccc cacaactttt tggcaattcc 2040 tggaaaacac tttctgcttg ctccccgctg gtctctggct cccctctgga cccctgcgat 2100 gtgcacctgc aagccgcctc ctactcagtg caggcctgca gcgtgctcac gggggagatg 2160 tttgcgccct gctctgcgtt cctgagcccc gtgccctact ttgagcagtg ccgcagggat 2220 gcctgccgct gcgggcagcc ctgcctgtgc gccacactgg cccactacgc ccacctgtgc 2280 cggcgccatg ggctccccgt tgatttccgc gcccgcctgc cagcctgtgc actgtcctgt 2340 gaggcctcca aggagtatag cccctgcgtg gccccgtgtg gacgtacctg ccaggacctg 2400 gccagccctg aggcctgtgg ggttgatggt ggcgatgacc tgagcagaga cgagtgtgtg 2460 gagggctgtg cctgcccacc ggacacctat ctggacaccc aggctgacct ctgtgtcccc 2520 cggaaccagt gctcctgcca cttccaggga gtggactatc cccccggaga cagtgacatc 2580 ccatccctgg gccactgcca ctgcaaagat ggagtcatga gctgtgatag cagagcccca 2640 gctgctgcct gcccagcagg ccaggtcttc gtgaactgca gcgacctgca cacggacctg 2700 gagctgagca gggagaggac gtgtgagcag caactgctga acctgagcgt gtcagcccgt 2760 ggcccctgcc tctcgggctg cgcctgtccc cagggtctgc tcagacacgg ggatgcatgt 2820 ttcctgccag aggagtgccc ctgcacttgg aaggggaagg agtatttccc tggggaccag 2880 gtgatgtctc cttgccatac ctgtgtgtgc cagcggggct cattccagtg caccctgcac 2940 ccttgcgcct ccacctgcac tgcctatggg gaccggcatt accgcacgtt tgatgggctc 3000 ccgtttgact tcgtgggggc atgcaaagtg cacctggtca agagcacatc agatgtcagc 3060 ttctctgtga ttgtagagaa tgtgaactgc tacagctctg gcatgatctg caggaaattt 3120 atttccatca acgttgggaa ctcactcatt gtctttgatg atgactccgg aaatcctagt 3180 ccagagagct tcctggatga caagcaggag gtccacacat ggcgagtggg atttttcaca 3240 ctggtgcatt tcccacagga gcacatcacc ctcttgtggg accagagaac cacagtgcac 3300 gtccaggctg ggcctcagtg gcagggccag ctggcgggcc tctgtgggaa ctttgactta 3360 aaaaccatca atgagatgag gaccccggag aacctagagc taactaaccc ccaggagttt 3420 ggcagcagtt gggctgcagt tgagtgccca gacaccctcg atcctcggga tatgtgtgtc 3480 ctgaatcctc tccgagaacc atttgccaag aaggagtgca gcatcctgct cagtgaggtg 3540 tttgagatct gccaccctgt ggttgatgtc acttggtttt actcaaactg cctgacagac 3600 acatgtggct gcagccaggg tggtgactgt gagtgcttct gtgccagcgt ctccgcttat 3660 gcccaccagt gttgccagca tggggtggct gttgactggc gaaccccccg cctctgcccg 3720 tatgactgtg acttctttaa caaagtgcta ggtaagggcc cctatcagct atccagcttg 3780 gcagccggtg gtgctctggt gggcatgaag gcggtgggcg atgacatagt cctagtgagg 3840 acagaggatg tggcgccagc agacattgtg agcttcctgc tgacagctgc tctgtacaag 3900 gccaaggccc atgacccaga tgtggtgtcc ctggaggcag cagacagacc caacttcttc 3960 cttcacgtca cagccaacgg gtctctggag ctggctaagt ggcagggccg tgacaccttc 4020 caacagcatg cctccttctt gctgcaccgg gggacacggc aggcaggcct ggtggccctg 4080 gagtccctgg ccaagcccag ctccttcctc tatgtgtcgg gcgcggtgct ggccctgcgg 4140 ctgtacgaac acacagaggt gttccgccgg ggcacactct tccgccttct ggatgccaag 4200 ccctcggggg ctgcctaccc catctgcgag tggcgctacg atgcctgtgc cagcccctgc 4260 ttccaaacct gccgggaccc acgggcagcc agctgccggg acgtacccag ggtagaaggc 4320 tgtgtccctg tgtgccccac cccccaggtc ctggatgaag tcacacagag atgtgtctac 4380 ttggaggact gtgtggagcc agcagtttgg gttcccacag aggcccttgg caatgagacc 4440 ctccctccca gtcaagggtt gcccactccc agtgatgagg agccacagct gtcacaggaa 4500 agccccagga cccccaccca caggccagcc ctcaccccag ctgccccact caccacagcc 4560 ctgaacccac cagtgacagc cactgaggag ccagtggtgt ctccaggccc cacccagacc 4620 accctgcagc agccactgga gctcactgca tctcaactcc ccgccggccc cacggagtcc 4680 ccagccagca agggagtgac tgccagcctc ctggccatcc cccatacacc agagtcctca 4740 tccctccctg ttgcactgca gacacccaca cctggcatgg tgtcaggtgc catggagaca 4800 acaagggtga ctgtgatctt tgcaggaagc cctaacatca cagtctcctc ccggtcgccc 4860 cctgcccctc gcttcccgct catgaccaag gctgtgacag tccgaggcca tggctccttg 4920 cctgttagga cgacaccccc acagccctcc ttgacagcaa gtccctcctc cagacctgtg 4980 gcttcccctg gagccatctc caggtccccc acctcctcgg gatcccacaa ggctgtgctg 5040 acacctgcag taactaaggt cataagcagg acaggggtcc cccagcccac ccaggcccag 5100 agtgcttcaa gtcccagcac ccctctaact gtggctggaa cagcagcaga acaggttcct 5160 gtcagtcccc ttgcaaccag gagcttggag atagtgctat ccacagagaa gggcgaagcc 5220 gggcacagcc agcccatggg ctcgcctgcc tccccacagc cacacccact cccctctgca 5280 ccaccccgcc cagcccagca taccaccatg gccaccaggt ctccagctct gcccccagag 5340 accccagctg ccgccagcct gtcaacagcc actgatgggc tggcagccac acccttcatg 5400 tcccttgagt caactcgtcc ctcccagctc ctctctggcc tgcctcccga caccagcctg 5460 cccctggcca aggtgggcac atctgcccca gtggccacac ccggccccaa agcctctgtc 5520 atcaccactc cactccagcc acaggccacg actctgcctg ctcagacact tagcccagta 5580 ctgcctttca ctccagcagc aatgacccag gcgcacccac ccactcacat agcaccccca 5640 gcagcaggca cagctccagg cctgctgctg ggagccacat tgccaacctc tggagtcctg 5700 cctgtggctg agggcacggc ctccatggta tctgttgtcc cacgaaagag caccacaggg 5760 aaggtggcca tcctatccaa gcaagtgtct ctgcccactt ccatgtatgg ttctgcagag 5820 ggtgggccca cagagctcac gcctgctacg agccaccctc tcacgccctt ggtggctgag 5880 cccgagggag cccaggcagg cacagctctg ccagtgccca catcctatgc cctgagccgt 5940 gtctcagcca ggacggcccc ccaagacagc atgctggttc tgttgcctca gctggctgag 6000 gcccatggaa cctcggcagg gcctcacctg gcagcagagc cggtggacga ggccaccaca 6060 gaaccatctg ggcgctcagc cccagccctg agcatcgtag agggtttggc ggaggctttg 6120 gcaactacca ctgaggccaa tacatccacc acctgtgttc caatcgccga gcaggactgc 6180 gtccgccaca tctgcctgga gggccagctg attcgcgtga atcagtccca gcactgtccc 6240 cagggtgctg ctccccctcg ctgtgggatc ctgggcctcg ccgtgcgggt gggtggggac 6300 cgctgctgcc cactctggga gtgtgcctgc cggtgctcaa tcttccctga cctgagcttc 6360 gtgaccttcg atgggagcca cgtagctctg ttcaaggagg ccatctacat cctcagccag 6420 agcccagatg aaatgctcac cgtccatgta ctggactgca aaagtgccaa cctggggcac 6480 ctgaactggc ccccgttctg tctggtgatg ttgaacatga ctcacttggc ccatcaggtc 6540 actattgatc gcttcaaccg aaaggtgact gtggacttgc agcctgtgtg gccaccggtg 6600 agcaggtatg gattcagaat tgaggacaca ggccacatgt acatgatcct gactccctca 6660 gacatccaga tccagtggct ccacagctca ggactcatga tcgtggaggc cagcaaaacc 6720 agcaaggccc agggccatgg cctgtgcggt atctgtgatg gagatgcagc caatgacctt 6780 accctgaagg atggctcagt ggtgggtggg gctgaggacc ctgctccctt tctggacagc 6840 tggcaggtgc ccagctccct gacctcagtg ggccagaccc gcttccgccc agacagctgc 6900 gccacaactg actgctcgcc ctgccttcgc atggtgtcca accgcacctt cagtgcctgc 6960 caccgctttg tgcctccgga gtcattctgt gagctgtgga tccgggacac caagtacgtg 7020 cagcagccct gcgtggccct gactgtgtac gtggccatgt gccacaaatt tcatgtgtgc 7080 atcgagtggc ggcgctctga ctactgcccc ttcctgtgct ccagcgactc cacataccag 7140 gcatgtgtga cagcctgtga gccacccaag acatgccagg atgggatact agggcctctg 7200 gacccagagc actgccaggt gctgggcgag ggctgcgtct gctccgaggg caccatctta 7260 caccggcgcc actctgcact ctgcatcccg gaggccaagt gcgcctgcac tgacagcatg 7320 ggggtgccga gggccctggg ggagacctgg aacagctccc tcagcggctg ctgccagcac 7380 cagtgccaag ccccagacac cattgtcccg gtggatctgg gctgccccag tccccgccct 7440 gagagctgcc tgcgattcgg ggaggtggcc ttgctcctac ccaccaagga cccctgctgc 7500 ctggggactg tctgtgtgtg taaccagact ctgtgtgagg gtctcgcccc cacatgccgc 7560 ccaggccacc gcctcctcac ccacttccag gaggactcct gctgccccag ctacagctgt 7620 gagtgtgacc cagatctctg tgaggcagag ctggtcccca gctgccgaca ggaccagatc 7680 ctgatcacgg gccgcctggg ggactcctgc tgcacctcct acttctgcgc ctgtggtgac 7740 tgtccagact ccatccccga atgtcaagaa ggggaggcgc tcactgtgca caggaatacc 7800 acggaactct gctgccctct gtaccagtgt gtgtgtgaga acttccgctg tccccaagtg 7860 cagtgtggcc tgggcactgc cctggtggag gtgtggagcc ccgaccgctg ctgcccctac 7920 aaatcctgtg aatgtgactg tgacacaatc ccggtgcccc ggtgccatct gtgggagaaa 7980 tcccagctgg atgaggagtt catgcacagc gtggagaatg tgtgtggctg cgccaagtac 8040 gagtgtgtga aggccccggt gtgtctgagc cgcgagctgg gtgtgatgca gcccggccag 8100 acagtggtgg agctctcagc agatggcgtg tgccacacct cccgctgcac caccgtgctc 8160 gaccctctca ccaacttcta ccagatcaac accacctccg tgctctgtga catccactgt 8220 gaggcgaacc aggagtacga gcacccgcgg gacctcgctg cctgctgcgg ctcctgcagg 8280 aacgtgtcct gtctcttcac cttccccaat ggcaccacct ccctgttctt gcccggggca 8340 tcctggatcg cagactgcgc ccgccaccac tgcagcagca cgcccctggg tgccgtgctg 8400 gtccgctctc ccataagctg cccaccgctc aatgagactg agtgtgccaa ggttgggggt 8460 tccgtggtac cttccttgga aggatgctgc aggacctgta aggaggatgg gcgctcctgc 8520 aagaaggtga ccatccgcat gaccatccgc aagaatgaat gcaggagcag cacccctgtg 8580 aacctagtgt cctgcgatgg gaggtgccca tccgccagca tctacaacta caacatcaac 8640 acctatgccc gattctgcaa gtgctgccgt gaggtgggcc tgcagcggcg ctctgtgcag 8700 ctcttctgtg ccaccaatgc cacctgggtg ccctatacag tgcaggagcc caccgactgt 8760 gcctgccagt ggtcctga 8778 <210> 127 <211> 513 <212> DNA <213> homo sapiens <400> 127 gagagtgtct tcattctttc cgccatcttg attctttgtc actgaccgag actcagccgt 60 gggaaatatg agtgagcatg tgagaacaag atcccaatcc tcagaaagag gaaatgacca 120 agagtcttcc cagccagttg gatctgtgat tgtccaggag cccactgagg aaaaacgtca 180 agaagaggaa ccaccaactg ataatcaggg tattgcacct agtggggaga tcgaaaatga 240 aggagcacct gccgttcaag ggcctgacat ggaagctttt caacaggaac tggctctgct 300 taagatagag gatgagcctg gagatggtcc tgatgtcagg gaggggatta tgcccacttt 360 tgatctcact aaagtgctgg aagcaggtga tgcgcaacca taggtttcaa gcaagacaaa 420 tgaagactga aaccaagaac gttattctta atctggaaat ttgactgata atattctctt 480 aataaagttt taagttttct gcaaagaaaa aaa 513 <210> 128 <211> 7233 <212> DNA <213> homo sapiens <400> 128 agctgcaagt tgggctgcag gggcagcgca tacactacaa tggctgctgg aaagaggcgt 60 aaggaaacaa tttccaggcc cgccgcgtcc agcccgaaat atgagaaaaa aattattaga 120 aattccgcgg gcggtgtaga ggcggcggac gggccggagg gaggatgtta aagccccgcg 180 attggccaaa atgggaagga ttggattcca ctctcttcca cgaagagtca atgggactgg 240 ctaagatcaa agtctgaggc tttttccatc agtaatcagt ccctttttgc tttcttttac 300 gaccacatga aacttgagaa gccacctaaa gctatatcat ttagtggagt tgggcagttc 360 ccaagtgtcc aacaagaagg cctggtttag gctgcgatgg ccactgtcat tcctggtgat 420 ttgtcagaag taagagatac ccagaaagtc ccttcaggga aacgtaagcg tggtgaaacc 480 aaaccaagaa aaaactttcc ttgccaactg tgtgacaagg cctttaacag tgttgagaaa 540 ttaaaggttc actcctactc tcacacagga gagaggccct acaagtgcat acaacaagac 600 tgcaccaagg cctttgtttc taagtacaaa ttacaaaggc acatggctac tcattctcct 660 gagaaaaccc acaagtgtaa ttattgtgag aaaatgtttc accggaaaga tcatctgaag 720 aatcacctcc atacacacga ccctaacaaa gagacgttta agtgcgaaga atgtggcaag 780 aactacaata ccaagcttgg atttaaacgt cacttggcct tgcatgccgc aacaagtggt 840 gacctcacct gtaaggtatg tttgcaaact tttgaaagca cgggagtgct tctggagcac 900 cttaaatctc atgcaggcaa gtcgtctggt ggggttaaag aaaaaaagca ccagtgcgaa 960 cattgtgatc gccggttcta cacccgaaag gatgtccgga gacacatggt ggtgcacact 1020 ggaagaaagg acttcctctg tcagtattgt gcacagagat ttgggcgaaa ggatcacctg 1080 actcgacata tgaagaagag tcacaatcaa gagcttctga aggtcaaaac agaaccagtg 1140 gatttccttg acccatttac ctgcaatgtg tctgtgccta taaaagacga gctccttccg 1200 gtgatgtcct taccttccag tgaactgtta tcaaagccat tcacaaacac tttgcagtta 1260 aacctctaca acactccatt tcagtccatg cagagctcgg gatctgccca ccaaatgatc 1320 acaactttac ctttgggaat gacatgccca atagatatgg acactgttca tccctctcac 1380 cacctttctt tcaaatatcc gttcagttct acctcatatg caatttctat tcctgaaaaa 1440 gaacagccat taaaggggga aattgagagt tacctgatgg agttacaagg tggcgtgccc 1500 tcttcatccc aagattctca agcatcgtca tcatctaagc tagggttgga tcctcagatt 1560 gggtccctag atgatggtgc aggagacctc tccctatcca aaagctctat ctccatcagt 1620 gaccccctaa acacaccagc attggatttt tctcagttgt ttaatttcat acctttaaat 1680 ggtcctccct ataatcctct atcagtgggg agccttggaa tgagctattc ccaggaagaa 1740 gcacattctt ctgtttccca gctcccccca caaacacagg atcttcagga tcctgcaaac 1800 actatagggc ttgggtctct gcactcactg tcagcagctt tcaccagcag tttaagcaca 1860 agtaccaccc tcccacgttt ccatcaagct tttcagtagg attctgggac atggattcat 1920 tacagaaatg tatgtgtagc tgtgccctag atgaccattt ttattttagt gcctacttta 1980 aaacagtata aaaatttctg cttttgtata atacaaattt tcattaagcc agtataaaat 2040 agaaactagc ttttaaactg agctttggaa ccatttgtgt tcagttaagt ttacctgggt 2100 attttgtcct gattcactgc caattgtcac attttaagac tttttttttt ccatatagga 2160 aagccattat tagtagtaaa cttttacaaa tcccattttc aaattacttt tagatcttaa 2220 aattttcatt tttgtctaat aacagtggct ctaccttttg acatctggct cattaaaaaa 2280 tttagcaata gaatgtaaat tgtataaaaa gtttgtgaat aactcaaggg tttaaatttt 2340 cttactagct tctaaatgga ttaataatca agtgcttcaa atgaattaag agtccagttt 2400 cggaagataa taaatgtttg ttagatacac cataatttca gatcagtata ttctgaagac 2460 tccctgttgt ctggctaaaa tatttgccat ctttattatg agcctttaag gaaaacaaac 2520 cctaaacaca aagcatcagt atttatagca aaaagagact ctgttaggtg acatggcatt 2580 tcgtgtcact taatagttgg ccctaaatta gtacacagga tattttgtcg tgtttcatcc 2640 ttcttaacat gctatctttt catttaataa tagtaatagt gtatggcatt ggggtcttca 2700 gagtcgatat ataggtagat ctctttagtc ttttccacct ttcacatcca aggggtgggt 2760 caagtgcagc cagcaattta ttttcattgt tggcccacgg ttagtccata atctagagcc 2820 attgtggaac tgcagccatg aggtgtgttt atcccacagt ggattgactc agcctctgtg 2880 ggtgacagac ttctaagcag gaagatagac gtgaagcaca tggttacatt tgggaacttg 2940 tgtagggatc atggcccctg tagccagggt taaaaactgg actttttaga agtaaagtaa 3000 aagcatatcg cttatatcat ttcttgctga atttgatatg tttttctttc ccttaagaat 3060 caaaagcaga aaacaaaaac aacagtccta ctccgatgtt atctttctga ttcaatgtga 3120 atccatcttt ccttgcaata ttttggatgg agaatttgaa gttaaatgca ttagaaaact 3180 acctgatgaa ctaccacaaa gttttaagtg actagaaata tatacagtaa aatcccactt 3240 tcatgcatct ctgggaaatg ataggagtat tgcaaataag ttgagtttgt agagggtaac 3300 aaagtaaagt aaaacaaacc tatcttggtt aacatgaaaa taacaattga gaatatatta 3360 tattcactga ataattatag gcttttcctc acattagaca accaacataa tcttcttaaa 3420 ggtctaatta atatattttt ctaagggtca gttgggacat taacctaaga aacatatcta 3480 ttaagcactt gttaacacct tattttagga ccctttccgt tggggatggg ggcaagggtg 3540 ggaggttttt agaagagtat atatctcttt aaaaaaaaac agaaagaaaa atatttctga 3600 gcactcatta gccctatatg gaaacttctt tcctttttgt agggccagtt atcactgcag 3660 attgcaatgt ttaccaagaa tttctaaaaa tgagtgcaga ttactgaata taatacatta 3720 tttaaaatat ttgggagtag tataatttgt ggagaaatgt aaattgtaat aatgtaaatg 3780 ggggcttcaa tatatatata taatacacac acacacacac atgcacacat accgcacttc 3840 atagaatcaa agttgctctc tgaaggagct ttggctcctg atattttatc atgctcctat 3900 atttttttaa tccttggagc agtagttttt atacttatgt atttaaattt tattatgaaa 3960 aattacattt attaaaaaag tgtgttccaa aggcattaaa attatatatg ttaataagga 4020 agtacatttt taaatttttc aaactgctcc tagcttttga ttaggagaat attttttctg 4080 aaagtaggct tttcgctctg cttcattact gcttccttta gtttctatga aacagattgc 4140 ttacctaaat ctttagttga atgattagtg ttcaatattg ctttaatcac catataaaag 4200 gaaaaaaatt ggtgacagag cacaaataga aaacctattt ttaaatagaa atcacaaata 4260 gcaagtgtgg aagcactact ttattctgtt taaaatgtac ttaagaagtc atcaaattag 4320 tgaactgaga cattggcctt agtaggctgt attcactgct aatttaaaaa agggagtacc 4380 aggatttatt aagtaaagca ttttggaaat ggggaatagc gccatatatg tatgtatgtg 4440 tatgtgtgtg tgtgtgtgtg tatatataca cacacacaca catacttaaa tcttgccctg 4500 catgaaattc aaatacatgg aggcacatct tcagggcacc agtgttaaaa ttttggagtc 4560 ttaattttca tgtgtacacc tctttgcctg ttcccacccc cagacttgaa ataacacttc 4620 agagtaagag ggaattcagc taatttgttt ttaaaattga ctgtagtggt cactaaaccc 4680 tttttgagag aatttctatt aaagatgagg cagactcgct tatttgaatt gcacaatgtt 4740 ctaacaagga tgtaacacag aattggcttt tttttcccta gaaaaagatt gtttgtttct 4800 atgtcaacta gatatgatta aaaataagta ttgccaatgc tgttttcatt ctctagtggc 4860 cagaatcatt atccttgaaa tttctggtag tgccttagct tggttaaaaa aaaaaaaaaa 4920 aaaaaaaaaa agggattaac attaaataaa agtagtttag aatttgggcc tcagacaaga 4980 tattgaacct cattcagttt cacttccaca tgtatgtaca agttaggtca ccaaacacgg 5040 aagtgtgagt gtggaaggat cttggcactg taagcaatgc tatccattga tgtatacaag 5100 tacctttata gttatcgatc actgttaaaa ctttcatttt aaaatcctat taccaagttc 5160 agttttttaa aacttcaatt gtcctggctg attatgcatc actctgtgtg caactttttt 5220 atttcattta gtgtttcttt caagctgtgt atttttgcct atttgttgct tgtgctttat 5280 ttttcttagt catttgtgga atatagtgat atattgtgtt aatttggaca gtagcggttt 5340 ttaaaaacca tatactgact gaaacatgag ccagagccga ttgctttatt aagctaataa 5400 tgaatgttaa agagtacata ttttcaggat cgttcatcta gtgagcaata cacatattat 5460 aggccaatat ttttttaaaa aatagagctt ggtcaacctc tatactacac atattacaag 5520 atatagcact ttcaaaatga atctaaacct ttacagaaac tttcttatag gttatgcctt 5580 ttattttaag acttattata attcaagtgc cattagatga tatatatgta ggcctttgat 5640 atataatgct ttgtgtacaa aaatggtaga tggtatttta aacaggtaca tttttacagt 5700 gttttcttat caatttgcta tattgcacag aatcagtgtg tgtcttttca taaggtttta 5760 caatggttta tttttttaca aggtttacgt gtctcaaagc acactgtctt cccagtacgt 5820 aagttaaaaa ataccagttc acccaagttg cttctagcct actgagatcc atgtgacatt 5880 ggaggagatc ttttaaatgt ttagtattcg tcattagcaa tggctggctg ttagttctgg 5940 taaatgtgtg cctaagttga atttgtcttg tttttctcac actgtgtcag cagccatgtc 6000 tacaacacag ataagtctgt tgtgatcaca tagatctaca taagttgtgc agttttgtgc 6060 taaaaaccca tagggagctc ctttgggatc atagaaaaga agatcatgca accagcattg 6120 gtgaaggcac actcagattg cacttagggc ctttctatga tgttgtcaac cctctgagga 6180 tggaaggcag tgtcttttga tgttatctag cctagaaatg acacagaact attgctaatg 6240 tataaaacac ttcattatat aagcttcagt ggtacagatg aaccagaatg aatgtttatc 6300 ttctcagaaa cactccttca atattatatt ggatcatgct gctaatgtaa cttgggctac 6360 aactcttcat ggtgctacaa acttctctgt ctcattcagt cgtatttttt tatccataga 6420 aaaaggacta cattaggtgt aaaagtgtac aatatatttt tatactgtga cttaatttgt 6480 cattaacaaa cttttacacc accacaatgt attcatgtgc acttgcaaaa ggagatctcg 6540 gacatgcaaa tgttaccaga acaaacccag cttttgtcca caaggtgact gtaactcaga 6600 atggaaagtg ggctttataa tagggtgtgg agtgaagaac atgctgtatg ttactaacag 6660 ccctttgaat ttaacaaaaa ctgggaatcc attaggaaac ggattgcatc atacctgaac 6720 ataagctgga ctgctgaaat tgtattttta gctaatgaaa aagtgtttgg actagtactc 6780 taaaaatgtt ctaatgataa agttttgagt caaaatagaa aagaaaaaaa tctgcattcc 6840 aggccgaatt ttgtatattt ttattgcatt taaaattgct attctgtaat attgggaaat 6900 caagtggctt atcatgtata tcgtgtactt aaaatgtatt cacaaactac tgttgtattt 6960 gtataaaata tagacaaaga tcatattttt tgtgtgtgta taagctctgt aaaatagcaa 7020 tcacattatg aagctgcagt gatactacat tttaaacatt cacatccaaa gaagcagact 7080 atttattgtc catataccag atttaaaata ttaatttgct gctaattaaa taatagtact 7140 gcagcttctt gtggcctaca gtgttatgtt tgctgtaaga ataagatatg tgaattccac 7200 aaaatatatg aataaaatta tagaatggct tta 7233 <210> 129 <211> 1371 <212> DNA <213> homo sapiens <400> 129 atccttattc tatatctctt ggtatttagt gtaaaaattt taaaatcttt acctagcaat 60 cttgaggaag aaacttgata actgataata catgagattg ttacctaagt gaaatataat 120 cctatatatt caacaaactt tagagaaata agataaattt taaagtaaat gacttctgta 180 gttttataga tcctccaaac caatctagtc tcagatctca ccttcatcat ttctctcatt 240 tccttttggc ctaattaatc aaaatccttc ctagaatgtt catttctggc cagtatgtct 300 tcctgaatat gaataagaaa taaaatacca tttgatgttt gaaattatgg gggtaatctc 360 aatgacggaa atagatgacc aggaaaaggg aaacgaatgc ctgattcatt atattcatga 420 agatatcaaa ggtttataaa gccaatatct gggaaagaga aaaccgtgag acttccagat 480 cttctctggt gaagtgtgtt tcctgcaacg atcacgaaca tgaacatcaa aggatcgcca 540 tggaaagggt ccctcctgct gctgctggtg tcaaacctgc tcctgtgcca gagcgtggcc 600 cccttgccca tctgtcccgg cggggctgcc cgatgccagg tgacccttcg agacctgttt 660 gaccgcgccg tcgtcctgtc ccactacatc cataacctct cctcagaaat gttcagcgaa 720 ttcgataaac ggtataccca tggccggggg ttcattacca aggccatcaa cagctgccac 780 acttcttccc ttgccacccc cgaagacaag gagcaagccc aacagatgaa tcaaaaagac 840 tttctgagcc tgatagtcag catattgcga tcctggaatg agcctctgta tcatctggtc 900 acggaagtac gtggtatgca agaagccccg gaggctatcc tatccaaagc tgtagagatt 960 gaggagcaaa ccaaacggct tctagagggc atggagctga tagtcagcca ggttcatcct 1020 gaaaccaaag aaaatgagat ctaccctgtc tggtcgggac ttccatccct gcagatggct 1080 gatgaagagt ctcgcctttc tgcttattat aacctgctcc actgcctacg cagggattca 1140 cataaaatcg acaattatct caagctcctg aagtgccgaa tcatccacaa caacaactgc 1200 taagcccaca tccatttcat ctatttctga gaaggtcctt aatgatccgt tccattgcaa 1260 gcttctttta gttgtatctc ttttgaatcc atgcttgggt gtaacaggtc tcctcttaaa 1320 aaataaaaac tgactcctta gagacatcaa aatctaaaat gaaaaaaaaa a 1371 <210> 130 <211> 7311 <212> DNA <213> homo sapiens <400> 130 gaactcgggt tgcgcacttc ccggcgctgg gaacgcggag cggacgcagt ctggccgcca 60 ttgcgctgcg gggaaagcgg cctcttgtgt gagggcctgt gggattctcc ggatatggcc 120 ggagtgtttc cttatcgagg gccgggtaac ccggtgcctg gccctctagc cccgctaccg 180 gactacatgt cggaggagaa gctgcaggag aaagctcgaa aatggcagca attgcaggcc 240 aagcgctatg cagaaaagcg gaagtttggg tttgtggatg cccagaagga agacatgccc 300 ccagaacatg tcaggaagat cattcgagac catggagaca tgaccaacag gaagttccgc 360 catgacaaaa gggtttactt gggtgcccta aagtacatgc cccacgcagt cctcaaactc 420 ctggagaaca tgcctatgcc ttgggagcag attcgggatg tgcctgtgct gtaccacatc 480 actggagcca tttccttcgt caatgagatt ccctgggtca ttgaacctgt ctacatctcc 540 cagtgggggt caatgtggat tatgatgcgc cgagaaaaaa gagataggag gcatttcaag 600 aggatgcgtt ttcccccttt tgatgatgag gagccgccct tggactatgc tgacaacatc 660 ctagatgttg agccactgga ggccattcag ctagagctgg accctgagga ggacgcccct 720 gtgttggact ggttctatga ccaccagccg ttgagggaca gcaggaagta tgtaaatggc 780 tccacttacc agcgctggca gttcacacta cctatgatgt cgactctcta ccgcctggct 840 aatcagctcc tgacagactt ggtggatgac aactacttct acctgtttga tttgaaggcc 900 ttctttacgt ccaaggcact caatatggcc attcctggag gccccaaatt tgaacctctt 960 gttcgagaca tcaacctaca ggatgaagac tggaatgaat tcaatgatat taacaagatt 1020 atcatccggc agcctatccg cactgagtac aagattgctt ttccttactt gtacaacaat 1080 cttccacacc atgtccacct cacctggtac catactccca atgttgtatt catcaaaact 1140 gaggatcctg acttgccagc tttctacttt gaccctttga tcaacccaat ctcccatagg 1200 cactcagtca agagccagga accattgccg gatgatgatg aggaatttga gctcccggag 1260 tttgtggagc ccttcctgaa ggacacaccc ctctatacag acaatacagc caatggcatt 1320 gccctgctct gggccccgcg gcccttcaac ctacgctctg gtcgcacccg tcgggccctg 1380 gacatacccc ttgtcaagaa ctggtatcgg gagcattgtc ctgccgggca gcctgtgaaa 1440 gtgagggtct cctaccagaa gctgcttaag tactatgtgc tgaatgccct gaagcatcgg 1500 ccccctaagg ctcaaaagaa gaggtatttg ttccgctcct tcaaagccac caaattcttt 1560 cagtccacaa agctggactg ggtggaggtt gggctccagg tttgccgcca gggctacaac 1620 atgctcaacc ttctcattca ccgcaaaaac ctcaactacc tgcacctgga ctacaacttc 1680 aacctcaagc ctgtgaaaac gctcaccacc aaggaaagaa agaaatctcg ttttgggaat 1740 gctttccacc tgtgtcggga agttctgcgt ttgactaagc tggtggtgga tagtcacgtg 1800 cagtatcggc tgggcaatgt ggatgccttc cagctggcag atggattgca gtatatattt 1860 gcccatgttg ggcagttgac gggcatgtat cgatacaaat acaagctgat gcgacagatt 1920 cgcatgtgca aggacctgaa gcatctcatc tattatcgtt tcaacacggg ccctgtaggg 1980 aagggtcctg gctgtggctt ctgggctgcc ggttggcgag tctggctctt tttcatgcgt 2040 ggcattaccc ctttattaga gcgatggctt ggcaacctcc tggcccggca gtttgaaggt 2100 cgacactcaa agggggtggc aaagacagta acaaagcagc gagtggagtc acattttgac 2160 cttgagctgc gggcagctgt gatgcatgat attctggaca tgatgcctga ggggatcaag 2220 cagaacaagg cccggacaat cctgcagcac ctcagtgaag cctggcgctg ctggaaagcc 2280 aacattccct ggaaggtccc tgggctgccg acgcccatag agaatatgat ccttcgatac 2340 gtgaaggcca aggctgactg gtggaccaac actgcccact acaaccgaga acggatccgc 2400 cgaggggcca ctgtggacaa gactgtttgt aaaaagaatc tgggccgcct cacccggctc 2460 tatctgaagg cagaacagga gcggcagcac aactacctga aggacgggcc ttacatcaca 2520 gcggaggaag cagtggcagt atataccacc acagtgcatt ggttggaaag ccgcaggttt 2580 tcacccatcc cattcccccc actctcctat aagcatgaca ccaagttgct catcttggca 2640 ttggagcggc tcaaggaagc ttatagtgtg aagtctcggt tgaaccagtc tcagagggag 2700 gagctaggtc tgatcgagca ggcctacgat aacccccacg aggcgctgtc ccgcatcaag 2760 cgtcacctcc tcacacagag agccttcaaa gaggtgggca ttgagttcat ggatctgtat 2820 agccacctcg ttccagtata tgatgttgag cccctggaga agataactga tgcttacctg 2880 gaccagtacc tgtggtatga agccgacaag cgccgcctgt tcccaccctg gattaagcct 2940 gcagacacag aaccacctcc gctgcttgtt tacaagtggt gtcaaggcat caataacctg 3000 caggacgtgt gggagacgag tgaaggcgag tgcaatgtca tgctggaatc ccgctttgag 3060 aagatgtatg agaagatcga cttgactctg ctcaacaggc tgctgcgcct catcgtggac 3120 cacaacatag ccgactacat gacagccaag aacaacgtcg tcatcaacta taaggacatg 3180 aaccatacga attcatatgg gatcatcaga ggcctgcagt ttgcctcatt catcgtgcag 3240 tattatggcc tggtgatgga tttgcttgta ttgggattgc accgggccag tgagatggct 3300 gggccccctc agatgccaaa tgactttctc agtttccagg acatagccac tgaggctgcc 3360 caccccatcc gtctcttctg cagatacatt gatcgcatcc atattttttt caggttcaca 3420 gcagatgagg ctcgggacct gattcaacgt tacctgacag agcaccctga ccccaataat 3480 gaaaacatcg ttggctataa taacaagaag tgctggcccc gagatgcccg catgcgcctc 3540 atgaaacatg atgttaactt aggccgggcg gtattctggg acatcaagaa ccgcttgcca 3600 cggtcagtga ctacagttca gtgggagaac agcttcgtgt ctgtgtacag taaggacaac 3660 cccaacctgc tgttcaacat gtgtggcttc gagtgccgca tcctgcctaa gtgccgcacc 3720 agctatgagg agttcaccca caaggacggg gtctggaacc tgcagaatga ggttactaag 3780 gagcgcacag ctcagtgttt cctgcgtgtg gacgatgagt caatgcagcg cttccacaac 3840 cgcgtgcgtc agattctcat ggcctctggg tccaccacct tcaccaagat tgtgaataag 3900 tggaatacag ctctcattgg ccttatgaca tactttcggg aggctgtggt gaacacccaa 3960 gagctcttgg acttactggt gaagtgtgag aacaaaatcc agacacgtat caagattgga 4020 ctcaactcca agatgccaag tcggttcccc ccggttgtgt tctacacccc taaggagttg 4080 ggtggactcg gcatgctctc aatgggccat gtgctcatcc cccaatccga cctcaggtgg 4140 tccaaacaga cagatgtagg tatcacacac tttcgttcag gaatgagcca tgaagaagac 4200 cagctcattc ccaacttgta ccgctacata cagccatggg agagcgagtt cattgattct 4260 cagcgggtct gggctgagta cgcactcaag aggcaagagg ccattgctca gaacagacgc 4320 ctgactttag aagacctaga agattcatgg gatcgtggca ttcctcgaat caataccctc 4380 ttccagaagg accggcacac actggcttat gataagggct ggcgtgtcag aactgacttt 4440 aagcagtatc aggttttgaa gcagaatccg ttctggtgga cacaccagcg gcatgatggg 4500 aagctctgga acctgaacaa ctaccgtaca gacatgatcc aggccctggg cggtgtggaa 4560 ggcattctgg aacacacact ctttaagggc acttacttcc ctacctggga ggggcttttc 4620 tgggagaagg ccagtggctt tgaggaatct atgaagtgga agaagctaac taatgctcag 4680 cgatcaggac tgaaccagat tcccaatcgt agattcaccc tctggtggtc cccgaccatt 4740 aatcgagcca atgtatatgt aggctttcag gtgcagctag acctgacggg tatcttcatg 4800 cacggcaaga tccccacgct gaagatctct ctcatccaga tcttccgagc tcacttgtgg 4860 cagaagatcc atgagagcat tgttatggac ttatgtcagg tgtttgacca ggaacttgat 4920 gcactggaaa ttgagacagt acaaaaggag acaatccatc cccgaaagtc atataagatg 4980 aactcttcct gtgcagatat cctgctcttt gcctcctata agtggaatgt ctcccggccc 5040 tcattgctgg ctgactccaa ggatgtgatg gacagcacca ccacccagaa atactggatt 5100 gacatccagt tgcgctgggg ggactatgat tcccacgaca ttgagcgcta cgcccgggcc 5160 aagttcctgg actacaccac cgacaacatg agtatctacc cttcgcccac aggtgtactc 5220 atcgccattg acctggccta taacttgcac agtgcctatg gaaactggtt cccaggcagc 5280 aagcctctca tacaacaggc catggccaag atcatgaagg caaaccctgc cctgtatgtg 5340 ttacgtgaac ggatccgcaa ggggctacag ctctattcat ctgaacccac tgagccttat 5400 ttgtcttctc agaactatgg tgagctcttc tccaaccaga ttatctggtt tgtggatgac 5460 accaacgtct acagagtgac tattcacaag acctttgaag ggaacttgac aaccaagccc 5520 atcaacggag ccatcttcat cttcaaccca cgcacagggc agctgttcct caagataatc 5580 cacacgtccg tgtgggcggg acagaagcgt ttggggcagt tggctaagtg gaagacagct 5640 gaggaggtgg ccgccctgat ccgatctctg cctgtggagg agcagcccaa gcagatcatt 5700 gtcaccagga agggcatgct ggacccactg gaggtgcact tactggactt ccccaatatt 5760 gtcatcaaag gatcggagct ccaactccct ttccaggcgt gtctcaaggt ggaaaaattc 5820 ggggatctca tccttaaagc cactgagccc cagatggttc tcttcaacct ctatgacgac 5880 tggctcaaga ctatttcatc ttacacggcc ttctcccgtc tcatcctgat tctgcgtgcc 5940 ctacatgtga acaacgatcg ggcaaaagtg atcctgaagc cagacaagac tactattaca 6000 gaaccacacc acatctggcc cactctgact gacgaagaat ggatcaaggt cgaggtgcag 6060 ctcaaggatc tgatcttggc tgactacggc aagaaaaaca atgtgaacgt ggcatcactg 6120 acacaatcag aaattcgaga catcatcctg ggtatggaga tctcggcacc gtcacagcag 6180 cggcagcaga tcgctgagat cgagaagcag accaaggaac aatcgcagct gacggcaaca 6240 cagactcgca ctgtcaacaa gcatggcgat gagatcatca cctccaccac cagcaactat 6300 gagacccaga ctttctcatc caagactgag tggagggtca gggccatctc tgctgccaac 6360 ctgcacctaa ggaccaatca catctatgtt tcatctgacg acatcaagga gactggctac 6420 acctacatcc ttcccaagaa tgtgcttaag aagttcatct gcatatctga ccttcgggcc 6480 caaattgcag gatacctata tggggtgagc ccaccagata acccccaggt gaaggagatc 6540 cgctgcattg tgatggtgcc gcagtggggc actcaccaga ccgtgcacct gcctggccag 6600 ctgccccagc atgagtacct caaggagatg gaacccttag gttggatcca cactcagccc 6660 aatgagtccc cgcagttatc accccaggat gtcaccaccc atgccaagat catggctgac 6720 aacccatctt gggatggcga gaagaccatt atcatcacat gcagcttcac gccaggctcc 6780 tgtacactga cggcctacaa gctgaccccc agtggctacg aatggggccg ccagaacaca 6840 gacaagggca acaaccccaa gggctacctg ccttcacact atgagagggt gcagatgctg 6900 ctgtcggacc gtttccttgg cttcttcatg gtccctgccc agtcctcgtg gaactacaac 6960 ttcatgggtg ttcggcatga ccccaacatg aaatatgagc tacagctggc gaaccccaaa 7020 gagttctacc acgaggtgca caggccctct cacttcctca actttgctct cctgcaggag 7080 ggggaggttt actctgcgga tcgggaggac ctgtatgcct gaccgtttcc ctgcctcctg 7140 cttcagcctc ccgaggccga agcctcagcc cctccagaca ggccgctgac attcagcagt 7200 ttggcctctt tccctctgtc tgtgcttgtg ttgttgacct cctgatggct tgtcatcctg 7260 aataaaatat aataataaat tttgtataaa taggaaaaaa aaaaaaaaaa a 7311 <210> 131 <211> 1038 <212> DNA <213> homo sapiens <400> 131 atttgaggcc atataaagtc acctgaggcc ctctccacca cagcccacca gtgaccacga 60 aggctgtgct gcttgccctg ttgatggcag gcttggccct gcagccaggc actgccctgc 120 tgtgctactc ctgcaaagcc caggtgagca acgaggactg cctgcaggtg gagaactgca 180 cccagctggg ggagcagtgc tggaccgcgc gcatccgcgc agttggcctc ctgaccgtca 240 tcagcaaagg ctgcagcttg aactgcgtgg atgactcaca ggactactac gtgggcaaga 300 agaacatcac gtgctgtgac accgacttgt gcaacgccag cggggcccat gccctgcagc 360 cggctgctgc catccttgcg ctgctccctg cactcggcct gctgctctgg ggacccggcc 420 agctctaggc tctggggggc cccgctgcag cccacactgg gtgtggtgcc ccaggcctct 480 gtgccactcc tcacacaccc ggcccagtgg gagcctgtcc tggttcctga ggcacatcct 540 aacgcaagtc tgaccatgta tgtctgcgcc cctgtccccc accctgaccc tcccatggcc 600 ctctccagga ctcccacccg gcagatcggc tctattgaca cagatccgcc tgcagatggc 660 ccctccaacc ctctctgctg ctgtttccat ggcccagcat tctccaccct taaccctgtg 720 ctcaggcacc tcttccccca ggaagccttc cctgcccacc ccatctatga cttgagccag 780 gtctggtccg tggtgtcccc cgcacccagc aggggacagg cactcaggag ggcccggtaa 840 aggctgagat gaagtggact gagtagaact ggaggacagg agtcgacgtg agttcctggg 900 agtctccaga gatggggcct ggaggcctgg aggaaggggc caggcctcac attcgtgggg 960 ctccctgaat ggcagcctca gcacagcgta ggcccttaat aaacacctgt tggataagcc 1020 agaaaaaaaa aaaaaaaa 1038 <210> 132 <211> 3087 <212> DNA <213> homo sapiens <400> 132 gcaggtggga ttggatagcg acgaaggccg gcaggctagg cgtggaccca actggcgagg 60 ctgctggggt tgcagcggga cagttggggc ggccccgcag gcccaggtga acaaaaattg 120 tttgctggcc cccaggatac taactagacc tttggcctga ctcacaggac actaaggctc 180 cttttctgaa gaagcctttt accagtctca tttaggggat gggaacaaca tgtcttcacc 240 tagggacttt agagcagagc ctgtaaacga ttatgaggga aatgactctg aagcagaaga 300 cttgaatttc agggagactt tgccttcatc aagtcaggaa aacacaccta gatcaaaggt 360 ttttgaaaat aaagttaatt cagagaaggt aaaactttct cttcggaatt tcccacataa 420 tgattatgag gatgtttttg aagagccttc agaaagtggc agtgatccca gcatgtggac 480 agccagaggc cccttcagaa gagacaggtg gagcagtgag gatgaggagg ctgcagggcc 540 atcacaggct ctctcccctc tactttctga tacgcgcaaa attgtttctg aaggagaact 600 agatcagttg gctcagattc ggccattaat attcaatttt catgagcaga cagccatcaa 660 ggattgtttg aaaatccttg aggaaaaaac agcagcgtat gatatcatgc aggaatttat 720 ggctttagaa cttaagaatc tgcctggtga gttcaactct gggaatcaac caagcaacag 780 agaaaaaaat agataccgag atattcttcc atatgattca acacgcgttc ctcttggaaa 840 aagcaaggac tacatcaatg ctagttatat tagaatagtc aattgtggag aagagtattt 900 ttatatcgct actcaaggac cactgctgag caccatagat gacttttggc aaatggtgtt 960 ggaaaataat tcaaatgtta ttgccatgat aaccagagag atagaaggtg gaattatcaa 1020 atgctaccat tactggccca tttctctgaa gaagccattg gaattgaaac acttccgtgt 1080 attcctggag aactaccaga tacttcaata tttcatcatt cgaatgtttc aagttgtgga 1140 gaagtccacg ggaactagtc actctgtaaa acagttgcag ttcaccaagt ggccagacca 1200 tggcactcct gcctcagcag atagcttcat aaaatatatt cgttatgcaa ggaagagcca 1260 ccttacagga cccatggttg ttcactgcag tgccggcata ggccggacag gggtgttcct 1320 atgtgtggat gtcgtgttct gtgccatcgt aaagaactgt tcattcaaca tcatggatat 1380 agtggcccaa atgagagaac aacgttctgg catggttcaa acgaaggagc agtatcactt 1440 ttgttacgat attgtgcttg aagttcttcg gaaacttctg actttggatt aagaaagact 1500 tctgttgcct ctcacttgaa attaccaagt gggtttgcac ctcctcataa agaacatgtt 1560 tgcactgtgc tgaagggctt tgctatgcat acaatctgct ttcttggttt atcagtttat 1620 tttctttcta aaagctccct gaagggcaat atcatttggc ttggggtgat cagtgtttac 1680 ttattgatct tgctagacaa tatcaaaata acttcccaca ttttccagtg aaacagatgt 1740 tacataaaac gattgcagct tggctatttg gttgaaggga ttacagagcc caataaagga 1800 tttaaaatat attcattaag attttatttg gaaaggtggc tggagagagc tgaggatttc 1860 caggactttg taagttctta ttctgggaga acataaggcc aataatcatg acctcttcca 1920 ggcattttta agacagatgt ctattcatgt tctttagcta gagcctgtac tttttgctgg 1980 catttgaata acccagttta aaaagagtcc agttagggtg gactaacttt ggacacaaat 2040 tggcttccat ttcctacatt ttcatactgc tgccttccta cagctgctag accaagacct 2100 gttggtctgg gaagcatttc atggataggg agagctcctc tcggtgaaca gtccaaaact 2160 aaaatagatg tttatataga aagcccaaga ggagactttt gccatgcctg agttctttcc 2220 tatcccaccc taacacttaa catattactt agtctgcttt gttaaaagca agtattacct 2280 ttaacttgcc tcttactctt tgccctttag ctaactaata aagtttgata taggcattat 2340 tatataattc tgagtcattc atggtatctc tcatgtttga tgtatttttc aaactaagat 2400 ctatgatagt tttttttcca gagttccatt aaatcattta tttcctttac tttctcacct 2460 ctgttgaaac atttagaaac tggatttggg aacccaattt tggaaaacca gattcatagt 2520 catgaaaatg gaaacttcca tattctgttt ttgaaaagat gtggccatta ttacagtaat 2580 tttattatag gactttgcct cgtacaatta atagtgatat tttggacaag gagttctggt 2640 gacaagctat acctaattat aagctataaa acaatagata tgagtgtttg tacagtttaa 2700 ctcaatggag atcagaatat tctatgtatt gagaaaatgt ttaatatcaa tctataaatc 2760 ttgaatttct aagaggctta ttttgttctt ttggctgaat gagtatattt gaattggttg 2820 aataattaat aattctcatt gtaaaaataa ttatatgcca aaaatatatt tgatgttaaa 2880 tcaaatagat gattctgttt acattgttca tatgaataat aatctgtgtt aatttcattt 2940 tgataattgg cctttaatat ttgtatctct aattttattt tctctctgtt actgtaaaat 3000 aatagctata atgtataaca attttcttca gaagaattct atgctattat taaaataaaa 3060 tatttactgt gaaaaaaaaa aaaaaaa 3087 <210> 133 <211> 4294 <212> DNA <213> homo sapiens <400> 133 gttacccaac aggcgccgcg gctgctccgg tggcgccact gactcggagg cggctgcgga 60 gagcggggcg ctggcccgtg gaggcggcag cggcggcggc tttctagcgg atccgagatt 120 atatatcttt gaatgatgca ggccactgca gtggtggaga cagcatctgg taaaggctac 180 cacagtaatg gaggcaacct ccaaaaagat aaaccttcaa atccaaagaa agaaaatttg 240 ttattatcct ccaatggttg tgatgaagtc aaattgactt ttcctgatga tgactggaat 300 tcttcgacac tagagcaaag agctaataat aaagaaatca gcaatattga caaaatggat 360 ttattagagc catttttttc agtgagtcaa gatactaaca cagagagtac tcagtttcag 420 tcaagtgaac ttgaagacag tactgactat gctttcttga ataaaacata ttctatacct 480 tattcagagt caaaactaaa gaaggaaagt cttactcctt taagttcaga attagatcct 540 gaagtgcaga aaaaagagga ggtttttttt aatattttgg aacatcaaga taagactgtt 600 ggcttggaaa gaatctacaa tatttcagat gctaattata gagaaagtgc tgaagataca 660 caaaagcatg atacagatga agactcacag caggaatatc acagtgcaga agaacaagaa 720 tacataagta accatttatc ttttgaccaa acaaaagcat tagatatatc taatccagaa 780 gttgttgaat taggaaattc gggttatgaa gttaaatgtg ctagcaatgt agaagataat 840 cgtgttaact cgggaagtgg ttctatcatc tctttcgatt cacttgatgt ttatggacaa 900 gaagagtcac ttcatgtctc caaatttcag aattctgtta tgttaagaga atatcatgac 960 ctaaagcatg aaaagtataa ggaacaagag actaattcaa tgtaccacac tgtatttgat 1020 ggcagtgtac taagaagcaa ttctccagga aaccaggaat ctcaatctaa gagtggttcc 1080 ttgagccctc aaaaagtatt aaaaatgaaa atttatactg aaaacatgaa atctcaaata 1140 aatgaaggta aagatttttg tggaaataaa attgttgaga acaaaatatt actgcacctt 1200 gaaaatccta gcacattacc acaggataaa gctttagaga cattactcca accctgtaaa 1260 gattgtcaaa cttcctggac ctctgttttt gatgattcga taatttctgc ctgtggatat 1320 tatgaaagcc tacaaaacac tgctgactca gccttagatt tttctgctat gctaccaaag 1380 atcgcagtca gagataatca ggcaatagaa gataatacgt ccctaaaagt tgctcatagc 1440 agtaccacaa agaaaacatg ctttcacaat ataggagaaa tgtgtactaa atcattgaca 1500 gatgcagcaa gttgtacagt cacaattaat cagacagtgg acgttagcac tgattttagg 1560 gcttgtttca caaccagcag ggcaacaagt gcaagacctt ctgtagtatc tacatcaagc 1620 aacacagaga taacaatgat gaataaaaaa cgacctgatg aatggcaaaa tgagaaacaa 1680 aaaagtgtgg cttgtagtac agattggtca tacagtgaag attgtataga tacacagatg 1740 gctataacaa aaggatcagg aaaatctctc tccgttgaca gtttaaaacc taatggaaat 1800 tttctaaata aggatttcct ggaattaaga aaagcatgtg gtatcacaga cctaaagaaa 1860 catcctgaga gggaatttca actttttaaa gatacagaga aggatttgcc atcaatgtgc 1920 tgtcagaaga taatgcagag agccataaaa gcagagctgc accttttaaa tgttcactat 1980 cagatgtgtc gtcgccattg ttgtgatatt tacaaacttg tcatggaaaa tagggaagga 2040 ttaaatatga atttatcaag taattctgct aagaaggaat tgggatcagc actactgtct 2100 cttttggggg acttaaaagt tagatatgtg actttgaaag aaaaaataca caaaggcata 2160 ccactggaag agctgccccc actgtcacta gaatcaaaat tattatctac cttctctact 2220 tttgcttcca ggctaatgaa aaaagaaaca catgtctttt cagaagcaga tgctgaacaa 2280 gataatcaga gggctcatga tgttgatgtt tcttcaaacc taaaaaagac actctctcaa 2340 atgtctttat catctgacaa tagtcatgct acacaaaaca tatcacccaa gaaagatgac 2400 tttaaaaatg gtgatataaa tgcagacttt agtcaactga aacttggtga taaagactgc 2460 agacattacc aagagacaag cgaagactgg tctgatgcta aagagagcct gacaggagtt 2520 gacgtctcag ggacacaggg aaatcaagta gaacaagaca catggaattt ggatcttaca 2580 ggagaaatga agaatgttga accctcacaa agagataaag gttatttgat acatgttggt 2640 ggcctctgcc cttcagtatc tgaggccgat ttaaggtctc atttccaaaa ataccaagtt 2700 tctgaaattt caatttatga ttctactaat tacagatatg catctcttgc ttttacaaaa 2760 aacagcgatg caaagatagc tgtgaaagaa atgaatggga tagaaataaa tggaaagtca 2820 gtaaatgtgt ggcctgttaa aattcttgga gaatatacat caccactttc ctccaaaaat 2880 gggaatagaa ttagttcgaa taatttagag aaaagcacca acaaacaaat ccactcagaa 2940 ttctccattt ctagattgcc cagaactagg ccacggcagc tgggttctga gcaagacagt 3000 gaggttttcc cttccgacca gggtgtcaag aagaattgta agcagattga atctgctaaa 3060 ttattacctg atacacccgt tcaattcata cctccaaata cattgaacct tcgtagcttt 3120 accaagatca taaagagact ggctgaactg catccagaag tcagcagaga ccatattata 3180 aatgcacttc aggaagtgag aataagacat aaaggttttc tgaatggctt atctattact 3240 actattgtgg agatgacttc atctcttctg aaaaactctg cttccagtta ggaattcaaa 3300 aaacaataaa gagaacttcc ttggaaagtg tgtttcctcc ttcagagaat gttctacagc 3360 acttaggaaa aagtagtaat aacaagatga tgtaattaaa taggctctat aaatgggcta 3420 agctgttaaa atattctact ttatatccct cctttaaaat ctagcaacag ttgtctatac 3480 aatattaaga tcttctctat atatttaaag ttaaaatata atttttaata agtttttaaa 3540 tttttttatt tcaattttgt tacttagaac attaagatgc atatttgtga tctaaagaaa 3600 ttgtcttgtc cattttaaaa acctttatta agtcactttt aaaatgtatt gaccaagaag 3660 gaggtttgtt gttacatcaa tgtttgtgaa atgatttcca tacataaaaa atgtaattta 3720 cctgaacttt gtcttaagac tcttacattg gattatagga taacagataa ataaactgta 3780 tagatacatt cagtatcata caacattttg gaatgtgtat gctttcaggc ttccaagata 3840 attaaattac tgtcatgata catttcatgc attttttatg acttcagtat aaaacattca 3900 ggtgtgttag ccttccctgg gaagggtaaa cttgtatgtg ctttggtaaa gtacttaaat 3960 tccaatgttc cctatagtgc ttgcattcat tttgtgaaaa gttttgttgt attgttagaa 4020 caattttcaa aggctgattt tatgccttat ctgatagaaa tatagaatag atagttcttt 4080 aattgcttac tttttaaaag taatataata tttaagttgc atttttatta atagtaagat 4140 taacatttaa gtctgcattt tctttaaatg ttttaaatgt ttatagcatt caatgtgtag 4200 ttggatttac ttgactaaaa attagccctt taacgtttat atttgttgta tttatattta 4260 ataaaggcat ctaatcttta gtaaaaaaaa aaas 4294 <210> 134 <211> 1895 <212> DNA <213> homo sapiens <400> 134 agctccagct gtccctcccg cagttggccc tgtggtgttc cgaagccggt tacgtacggc 60 ctgagggcca ggcgaacctc aggctctttg tcctactaaa aagcgcagca caatggtaga 120 agcagatcat cctggcaagc ttttcattgg tggcctcaat agagaaacca atgagaagat 180 gcttaaagca gtatttggga aacatggtcc catatcagaa gttcttttga taaaggatcg 240 aaccagcaaa tccagaggct ttgcatttat tacttttgag aaccctgcag atgctaagaa 300 tgctgcgaaa gatatgaatg gaacgtcttt gcatggaaaa gcaataaaag tagaacaagc 360 caagaaacca tcttttcaaa gtggtggtag gcggagacca ccagcttctt cgagaaacag 420 aagcccttca ggaagtctga gatctgcaag aggaagcagt ggaggaacaa gagggtggct 480 tccctcacat gaagggcacc tggatgatgg tggatacact cctgatctca agatgagtta 540 ttctagggga ctcattccag ttaaaagagg tccatcttca agaagtggag gtcctcctcc 600 gaaaaaatct gctccttctg ctgtggcaag aagcaatagt tggatgggaa gccaaggtcc 660 catgtcacaa agaagagaga attatggagt tcctccacgc agagcgacaa tatcttcctg 720 gagaaatgat cgcatgtcaa caagacatga tggttatgca actaacgatg gaaatcatcc 780 aagttgccaa gaaacgaggg attatgctcc accatctaga ggctatgcat accgtgataa 840 tggtcattct aatcgggatg aacattcctc tagaggatat agaaatcatc gaagttcccg 900 agaaactagg gattatgctc caccatctag aggccatgca taccgtgatt atggtcattc 960 tcgtcgggat gaaagttatt ctagaggata cagaaatcat cgaagttccc gagaaactag 1020 ggagtatgct ccaccatcta gaggccatgg ataccgtgat tatggtcatt ctcgtcgaca 1080 tgaaagttat tctagaggat atagaaatca tccaagttcc cgagaaacca gggattatgc 1140 tccaccacat agagactatg cataccgtga ttatggtcat tctagttggg atgaacattc 1200 ctctagagga tatagttatc atgatggcta cggtgaggcc cttggtagag atcattctga 1260 acatctaagt ggaagttctt atagagatgc acttcagagg tacgggacct ctcatggtgc 1320 accacctgca agagggcctc ggatgtctta tggtggaagc acctgccacg catatagtaa 1380 tacacgagat agatatggca gaagttggga gagttactcg agctgtggtg attttcatta 1440 ttgtgatcgt gagcatgttt gcagaaaaga ccaaaggaat ccgccttctc tgggtagggt 1500 gctccctgat cctcgtgaag catatggtag ctcaagttat gtggcatcta tagtagatgg 1560 tggggagagt cgatctgaaa aaggagactc gagcagatat taaagcaagc attgaaaata 1620 atagttattg cataccaatc cttgtttgca aatcaaaaat tgaaatgtta tttctgcatt 1680 gttacctgca tattactgaa agaaacatgt tggttttgtg gagagaggta gatactaact 1740 tcctccatga attttttgag gtattcaaag gaaaaggaat tgttttcaaa gtaatttcat 1800 acttgttgat gctatttgaa aagtgtttag atgtaatatc taccttaaaa ttttcacaat 1860 aaaattttac atgtactgca aaaaaaaaaa aaaaa 1895 <210> 135 <211> 2707 <212> DNA <213> homo sapiens <400> 135 gggctcgagg cgttcggctg aggaagggag cgcacgccgg cggcgcggag gccggctctg 60 cgcttcgggc cgccccctcc ccccaccccg ctcacacccg gcacttactt cggctgtctc 120 cgctgccctc cagcggagac gcagctcctc aggcgcccgg cggtatttgt tgggtcggcg 180 gcgtcaggga ttcgcagtgg cctgtggtcg gcgtcgtccg gccactggtg cgcccccgcg 240 gcaggcagag ctcacgctcc tgtcccccgg ctggtccggg gtctgggcgc cgcgtcgacg 300 gcggctccgc aggacgcgca gaccgggccg cagcccattc cccgagcgga ctgcattatg 360 aggcacctgc cttacttctg ccggggtcaa gtggtgcggg gcttcggccg cggctccaag 420 cagctgggca tccccacagc taattttcct gagcaagtgg tagataatct tccagctgat 480 atatccactg gtatttacta tggttgggcc agtgttggaa gtggagatgt ccataagatg 540 gtggtgagca taggatggaa cccatattac aagaatacga agaagtctat ggaaacacat 600 atcatgcata ccttcaaaga ggacttctat ggggaaatcc tcaatgtggc cattgttggc 660 tacctgagac cagaaaagaa ctttgattct ttagagtcac ttatttcagc aattcaaggt 720 gatattgaag aagctaagaa acgactagag ttaccagaac atttgaaaat caaagaagac 780 aatttcttcc aggtttctaa aagcaaaata atgaatggcc actgatgaaa aattgtatta 840 tttattcatt cactgttttc tagtgtttct gtgtttatta ctgttcagca tcatcttggt 900 tatatactga aaatcaaaca ctttactaca gttgtgaatt agtttaaacc gtacaatgtt 960 gttatcatat catgcttcaa ctattaaatt aagcccatca tatcatagca ctaaaaagat 1020 tgagttaaaa ataagattta aaaaatatat attgattaaa atgtaccact agaaaggtat 1080 tacatgtgta taagtatggg taaaaaggca agtcactagt ttgagatgaa aactaaaatt 1140 ttcatggtaa aatgccagca tgtatgtact tgtgtagtgt gtacttctaa acagagaagg 1200 cttataaaag taaatgcatt aaggccaagt gcagtggctc acaccggtaa tcccagcact 1260 ttgggaggcc gaggtgggag gattgcttga gctcatgagt tcaagaccag cctgggcaac 1320 atagcgagac tccatctcta taaataaaaa aaaaggaaat gcattaaata gaaggttgat 1380 agtttatcat aaacctgcgg ggaagaaact cagactttct atttttgata ttttgtgcat 1440 taatacatta caaacatgaa gatgtttgta aagttttgtt ttagtcattt tctttgcagt 1500 cacatcattg taccaccttc attattgtat agagctgctt caattctgag tcctctggac 1560 ttcccctgcc tatctgtttg ttgttgttgt tgaagacagt aaaataagtg ttttcaaatc 1620 tatatgtctc ctttttgttg gataatgttt cttcttttta atggtaaata ttcttgttct 1680 tcaacatttt tctttggttc ttttttcctt ttttaggaaa aacaaaacaa cagacttcat 1740 ccttaggttt tctcaagatt taagtgaaca catttacaca tatcaatttc ttaaagaaca 1800 caaaatgttt cctccctagc aaaactattt aagagccaat taaactatga aatagttata 1860 aaattatttt taatatttaa ggccttgaaa ttatattcca aggcaaatct aaatgggtgt 1920 agttgtatat gcacgatgta atttaatgct aaagagtact tacagcttga gggaaaagca 1980 taaagtttta gttaaatagc cttcatactg tggatttttc ctcctactaa ctaatatgtg 2040 ggaaattaag attacagatg ctttgggccc cctcaaacag tacattgcta cagttcactg 2100 tagcaacaga tttggtggtg atggggggat agaggtagaa gcagatagaa ggtaatttta 2160 aagttaattt attatgaatc attttcccct aatctgcata aatgaattag aactgatttt 2220 aataaaaata ttctgtgtaa aaagtactca gaaaaacatc taaagctgtt ggagaagagg 2280 gactcatata aatagttgga ttgcgttttg ctttttattt ctttataaaa atatgtcaaa 2340 aacagttttt aattttagaa atcttatact tgaaagaaac ctcaattatc agtggcttta 2400 tgaagtaaag ttaaaaacaa acataggaaa tgtgaaaata tttgtgtttg ttttgtctga 2460 ctaacttgct gctaaatgct atctttaggt gtgtgaaagt tctttgatat gttattgtcc 2520 ttttacatct tgttaaatag ccattgcttt tgagaatcag atagtgtgtt gtttaggggt 2580 taattgtgtc tatatctttc aaaaactttt atattatgta ttataagaag ttacagtagt 2640 accattttga ttagtctgaa tgttttcagg ccttgaaata aattttgact aagtgatatt 2700 ttttctt 2707 <210> 136 <211> 5796 <212> DNA <213> homo sapiens <400> 136 ccagccacct gacccaaata caccacctga acccacgacc aggtatgccc acaccccatg 60 ggtggcctta acacacacac cctgcccctt tctccaagta caggagcagc agcccagact 120 tccctcgggg caccgcggcc tgcttgggac tgcacagtgc ctgggagggt gcctggggag 180 ggtcacaagg gacttggtgc tagaagcagg aaaagtgtag ggaccggaaa agcccccgtg 240 catcctggaa gggacatggg ccagtttgag caggggtgtg ggagtccagc cctggccttg 300 ccaggtggag aggcgcctgg gccagacatc cgcggcagga ggcgggggaa catgccaaga 360 ggcggaaggg gcacgcggag acccccaggg ggcgccggaa ggggcgcgcc gggcggtcgg 420 cggcggccgt tggcgagctg aggcctgcca ggcgaagtct ggagaccagc cgggccgcgg 480 ccgcaatggc caaggactcg cccagcccct tgggcgcgtc gcccaagaag ccgggctgct 540 ccagcccggc ggcggcagtg ctggagaacc agaggcggga gctggagaag ctacgggcgg 600 agctggaggc ggagcgggca ggctggcggg cggaacggcg gcgcttcgct gcccgggagc 660 gccagctgcg tgaggaggcc gagcgggagc ggcgacagct ggctgaccgt ctgcgctcca 720 agtgggaggc acagcgcagc cgggagttgc ggcagctgca agaggagatg cagcgggaac 780 gcgaggccga gatccggcag ctgctgcgct ggaaggaggc cgagcagcgg cagctgcagc 840 agctgctgca ccgggagcgc gatggcgtgg tgcgccaagc ccgggagctg cagcgccagc 900 tggccgagga gctggtgaac cgcggccact gtagccgccc gggggcgtcc gaggtttccg 960 cggcgcagtg ccgctgtcgc ctgcaggaag tgttggcgca gcttcgctgg cagactgacg 1020 gcgagcaggc ggcgcgcatc cgctatctgc aggcggcgct ggaggtggag cgccagctct 1080 tcctcaagta catcctggcg cacttccgcg ggcacccggc tttgtcggga tcaccggacc 1140 cccaagctgt gcattccttg gaagaaccgc tgccccagac ctccagcggc tcttgccacg 1200 cccccaaacc cgcctgccaa ctcggatctc tagacagcct gagtgctgaa gtcggtgtgc 1260 gctcccgctc gctaggcctg gtgtcctctg cgtgctccag ctccccagac ggcctgctct 1320 ccacgcacgc cagctccctt gattgcttcg cacctgcgtg ttcccgctcg cttgacagca 1380 cccggagcct ccccaaggcc tccaaatccg aggagcggcc ctcctcacca gacacctcca 1440 cccctggctc ccggaggctc tcgccgccac catcgccact cccgccgcca ccaccaccgt 1500 cagcccacag gaaactcagc aacccgcggg gaggagaagg ctctgagagc cagccctgcg 1560 aagtcctgac tccctcaccc ccgggcctgg gccaccacga gctgataaag ctgaactggc 1620 tgctggccaa ggcgttgtgg gtgctggcgc gccgctgtta taccctgcaa gcggagaaca 1680 agcagctgcg gcgtgcaggc tgcccctacc aggcagacga gaaggtgaag cggctcaagg 1740 taaagcgcgc ggagctgacc gggctcgcgc ggcgcctagc tgaccgcgcc cgcaagctgc 1800 aggagaccaa cctccgggcc gtgagcgcgc ctatacccgg cgagagttgc gccggcctgg 1860 agctgtgcca agtctttgcc cgccagcgcg ctcgggacct gtcggagcag gcgagcgcgc 1920 cgctggccaa ggacaagcag atcgaagagc tgcggcagga gtgccacctc ctgcaggcgc 1980 gtgtcgcctc gggtccctgc agcgacctgc atactggaag gggcggcccc tgcacccagt 2040 ggctcaacgt cagagactta gaccgcctgc agcgcgagtc ccagcgggaa gtgctgcgcc 2100 tgcagaggca gttgatgctt cagcagggca acggtggcgc ttggcccgag gcgggcggcc 2160 agagcgcaac ctgcgaggag gtgcgacggc agatgctggc gctggagcgc gagctggacc 2220 agcggcggcg cgagtgccag gagctgggcg cgcaggcggc cccggcgcgg cgacgtggcg 2280 aggaggccga gacacagctg caggcggcgc tgctcaaaaa cgcctggctg gcggaggaga 2340 atgggcggct gcaggccaag accgactggg tgcggaaggt ggaggctgag aatagcgaag 2400 tgcgcggcca cctgggccgc gcgtgtcaag agcgcgatgc ctccggcttg atcgccgaac 2460 agctgctgca gcaggcggcg cgcgggcagg acaggcagca gcagctgcaa cgcgacccgc 2520 agaaggccct gtgtgacctc catccttcct ggaaggagat acaggcgctc cagtgtcggc 2580 ctggtcaccc tcctgaacag ccctgggaga ccagtcaaat gccggagtcc caagttaaag 2640 gtagcagaag gcccaagttc cacgcacggc ctgaagacta cgcagtgtca cagcccaaca 2700 gagacataca ggagaaaagg gaagcctccc tcgaggagag cccagttgcc cttggggagt 2760 cagccagtgt cccccaagtt tcagagacag tccctgccag ccaacctctg tccaagaaaa 2820 ccagctccca gtcaaactcc tcctctgagg ggtcgatgtg ggccaccgtg ccgtcctccc 2880 ctactctgga cagggacaca gccagtgagg tggatgacct ggagcctgac agcgtgtccc 2940 tggccctgga aatggggggc tcggcggctc ctgctgcccc caagctcaag atcttcatgg 3000 ctcagtataa ctacaaccca tttgaggggc ccaatgatca ccctgagggt gagctgcccc 3060 tcacagctgg ggactacata tatatcttcg gggacatgga tgaggatggc ttctatgagg 3120 gggagcttga ggatggccgg cgggggctgg tgccctccaa cttcgtggag cagattccgg 3180 acagctacat cccaggctgc ctgcctgcca aatcccctga tcttggcccc agtcaactcc 3240 cagcggggca ggatgaagct ctggaggaag acagcttatt atctgggaaa gcccagggag 3300 tggtggacag agggctgtgc cagatggtca gggtgggctc caagacagaa gtagcaacag 3360 agatcctgga taccaagacg gaagcctgcc agctgggctt gctgcagagc atggggaagc 3420 agggcctctc cagacccctt ctggggacca aaggggtgct ccgtatggct cccatgcagc 3480 tacacctgca gaatgtcaca gccacatcag ccaacatcac ctgggtctac agcagccacc 3540 gccaccccca tgtggtatat cttgatgacc gagagcatgc cctgacccca gcgggcgtga 3600 gctgctacac cttccagggc ctgtgccccg gcacgcacta ccgggcgcgg gtggaggtgc 3660 ggctgccacg ggacttgctg caggtgtatt ggggaactat gtcctccacc gtcaccttcg 3720 acacactctt ggcaggacct ccctacccac cgctggatgt gctggtggag cgccatgcct 3780 cgccaggtgt cctggtggtc agctggctcc ctgtgaccat tgactcagct gggtcctcca 3840 atggagtcca ggtcaccggt tatgctgtgt atgcagatgg gcttaaggtt tgtgaggtcg 3900 ccgatgccac tgctgggagc accctattgg aattctccca gctacaggtg cccctcacgt 3960 ggcagaaggt ctcagtgaga accatgtcac tctgtggtga gtccctggat tcagtgcctg 4020 ctcagatccc cgaggacttc ttcatgtgtc accgatggcc agagactcca ccctttagct 4080 acacttgtgg cgacccatcc acctacagag tcaccttccc cgtctgcccc cagaagctgt 4140 cactggctcc tccgagtgcc aaggccagcc cccacaaccc tggaagctgc ggggagcccc 4200 aggccaagtt cctagaagca ttctttgaag aacccccaag gaggcaatcc ccagtgtcca 4260 acctgggctc agaaggagaa tgtccgagtt caggggctgg cagccaagcc caggagcttg 4320 cagaggcctg ggagggctgt agaaaggacc tgctctttca gaagagtccc cagaaccaca 4380 ggccaccttc agtcagtgac cagcctgggg agaaggaaaa ttgctcccag cacatgggca 4440 ccagcaaaag ccctgctcca ggattcatcc atctacgcac cgagtgtggg cccaggaaag 4500 aaccgtgtca ggaaaaggct gcccttgaga gggtacttcg gcaaaagcaa gatgcccaag 4560 ggttcacacc tccccagctg ggcgccagcc aacagtatgc atctgacttc cataacgttt 4620 tgaaggagga gcaggaggca ctgtgcttgg atctgtgggg cacagagagg cgagaggaga 4680 ggagggagcc tgagccccac agcaggcaag gacaagctct gggggtgaag agagggtgcc 4740 agctccatga gcccagctcg gcactgtgtc cagctccatc cgccaaagtc atcaagatgc 4800 ccaggggtgg cccccaacag ctggggacgg gggccaacac tccagccagg gtctttgtgg 4860 ccctctctga ttacaacccc ctggtgatgt ctgccaacct caaggctgca gaggaggagc 4920 tggtcttcca gaaaaggcag ttgctaagag tgtggggctc tcaggacacc catgatttct 4980 acctcagcga gtgcaacagg caagtgggca atatccccgg gcgcctagtg gctgagatgg 5040 aggtggggac agagcagact gataggaggt ggcgttctcc ggcccaaggg aacctgcctt 5100 ctgtggccca cctcgaggac tttcaggggc tcaccatccc ccagggttcc tccctggtgc 5160 tccaggggaa ctccaagaga ctcccactgt ggactccaaa gatcatgata gcagctctgg 5220 actatgatcc tggggatggg caaatggggg gccaggggaa gggcaggctg gcgctgaggg 5280 caggagacgt ggtcatggtt tacgggccca tggatgacca aggattctat tatggagagt 5340 tgggcggcca caggggcctg gttcctgccc acctgctgga tcacatgtcc ctccatggac 5400 actgagcaag catccttgcc caggtagtgg cctctggctg ctcacaccct gccagaggag 5460 aagcaagcgt tcagaccctc acaccagcac ccctcctcac caccataagt agcatgtgct 5520 ccaagtgcca ctgtgttaaa ctgatggtag tccttaagcg tcccctaggc tctgaaagta 5580 gcaggactta agcctgagtt atttgcaaaa gcaaacacaa caagccaacc cctgagagtc 5640 tgagaagcca tttcaaagtt gctgataact atggcaggta tacggagaag cgcctttttc 5700 tgtggccaat gtgtgttttc tctgggaggt taaggttatc tgtccattgc cttgtacgaa 5760 agtctcaaga aaagtctaca tcttaaaaaa gaaaaa 5796 <210> 137 <211> 1869 <212> DNA <213> homo sapiens <400> 137 tacctggttg atcctgccag tagcatatgc ttgtctcaaa gattaagcca tgcatgtctg 60 agtacgcacg gccggtacag tgaaactgcg aatggctcat taaatcagtt atggttcctt 120 tggtcgctcg ctcctctcct acttggataa ctgtggtaat tctagagcta atacatgccg 180 acgggcgctg acccccttcg cgggggggat gcgtgcattt atcagatcaa aaccaacccg 240 gtcagcccct ctccggcccc ggccgggggg cgggcgccgg cggctttggt gactctagat 300 aacctcgggc cgatcgcacg ccccccgtgg cggcgacgac ccattcgaac gtctgcccta 360 tcaactttcg atggtagtcg ccgtgcctac catggtgacc acgggtgacg gggaatcagg 420 gttcgattcc ggagagggag cctgagaaac ggctaccaca tccaaggaag gcagcaggcg 480 cgcaaattac ccactcccga cccggggagg tagtgacgaa aaataacaat acaggactct 540 ttcgaggccc tgtaattgga atgagtccac tttaaatcct ttaacgagga tccattggag 600 ggcaagtctg gtgccagcag ccgcggtaat tccagctcca atagcgtata ttaaagttgc 660 tgcagttaaa aagctcgtag ttggatcttg ggagcgggcg ggcggtccgc cgcgaggcga 720 gccaccgccc gtccccgccc cttgcctctc ggcgccccct cgatgctctt agctgagtgt 780 cccgcggggc ccgaagcgtt tactttgaaa aaattagagt gttcaaagca ggcccgagcc 840 gcctggatac cgcagctagg aataatggaa taggaccgcg gttctatttt gttggttttc 900 ggaactgagg ccatgattaa gagggacggc cgggggcatt cgtattgcgc cgctagaggt 960 gaaattcttg gaccggcgca agacggacca gagcgaaagc atttgccaag aatgttttca 1020 ttaatcaaga acgaaagtcg gaggttcgaa gacgatcaga taccgtcgta gttccgacca 1080 taaacgatgc cgaccggcga tgcggcggcg ttattcccat gacccgccgg gcagcttccg 1140 ggaaaccaaa gtctttgggt tccgggggga gtatggttgc aaagctgaaa cttaaaggaa 1200 ttgacggaag ggcaccacca ggagtggagc ctgcggctta atttgactca acacgggaaa 1260 cctcacccgg cccggacacg gacaggattg acagattgat agctctttct cgattccgtg 1320 ggtggtggtg catggccgtt cttagttggt ggagcgattt gtctggttaa ttccgataac 1380 gaacgagact ctggcatgct aactagttac gcgacccccg agcggtcggc gtcccccaac 1440 ttcttagagg gacaagtggc gttcagccac ccgagattga gcaataacag gtctgtgatg 1500 cccttagatg tccggggctg cacgcgcgct acactgactg gctcagcgtg tgcctaccct 1560 acgccggcag gcgcgggtaa cccgttgaac cccattcgtg atggggatcg gggattgcaa 1620 ttattcccca tgaacgagga attcccagta agtgcgggtc ataagcttgc gttgattaag 1680 tccctgccct ttgtacacac cgcccgtcgc tactaccgat tggatggttt agtgaggccc 1740 tcggatcggc cccgccgggg tcggcccacg gccctggcgg agcgctgaga agacggtcga 1800 acttgactat ctagaggaag taaaagtcgt aacaaggttt ccgtaggtga acctgcggaa 1860 ggatcatta 1869 <210> 138 <211> 121 <212> DNA <213> homo sapiens <400> 138 gtctacggcc ataccaccct gaacgcgccc gatctcgtct gatctcggaa gctaagcagg 60 gtcgggcctg gttagtactt ggatgggaga ccgcctggga ataccgggtg ctgtaggctt 120 t 121 <210> 139 <211> 332 <212> DNA <213> homo sapiens <400> 139 ggatgtgagg gcgatctggc tgcgacatct gtcaccccat tgatcgccag ggttgattcg 60 gctgatctgg ctggctaggc gggtgtcccc ttcctccctc accgctccat gtgcgtccct 120 cccgaagctg cgcgctcggt cgaagaggac gaccatcccc gatagaggag gaccggtctt 180 cggtcaaggg tatacgagta gctgcgctcc cctgctagaa cctccaaaca agctctcaag 240 gtccatttgt aggagaacgt agggtagtca agcttccaag actccagaca catccaaatg 300 aggcgctgca tgtggcagtc tgcctttctt tt 332 <210> 140 <211> 299 <212> DNA <213> homo sapiens <400> 140 gccgggcgcg gtggcgcgtg cctgtagtcc cagctactcg ggaggctgag gctggaggat 60 cgcttgagtc caggagttct gggctgtagt gcgctatgcc gatcgggtgt ccgcactaag 120 ttcggcatca atatggtgac ctcccgggag cgggggacca ccaggttgcc taaggagggg 180 tgaaccggcc caggtcggaa acggagcagg tcaaaactcc cgtgctgatc agtagtggga 240 tcgcgcctgt gaatagccac tgcactccag cctgggcaac atagcgagac cccgtctct 299 <210> 141 <211> 1805 <212> DNA <213> homo sapiens <400> 141 tgacgccccc ttctcggccg ccagccctcc acacctcatc tgccttgctc cacctcccta 60 gtgcacccgc tccagccccg tctgcccagg agggcgcttg gatttccttc tccgcggcgc 120 gtatctaacc cttcctgcat gtatttcact gcaggctgaa gaaagctcag tctcaattgt 180 gtttcctgcc tgtcagcctc ttgcctccta aacgtgtacc atttccactt gatgtcatca 240 cgcagaaggg gtgaaagaga ctcggtgaca gatacagaaa tgaacacacc tgtgagtact 300 ggatgcctgt gagcttgcca ttacctgcac tgcaaagaca cagggcggtg gcctctgaga 360 agcagctcct tccccttcac cttggccttg cccttcctgc tcacggtcca ccatggagac 420 gctgtcccag gactctctgc tggaatgtca gatctgtttc aattactaca gcccccggcg 480 caggcccaag ttgctggact gcaagcacac ctgctgttca gtgtgcctgc agcagatgag 540 gaccagccag aaggatgtgc ggtgcccctg gtgccgcggt gtcaccaagc tgcctcccgg 600 cttctccgtg tcgcagctcc cggacgaccc ggaggtcctg gctgtcatcg ccattccaca 660 cacttccgaa cacaccccgg tcttcatcaa acttcccagc aatgggtgct acatgctgcc 720 cctgcccatc tccaaggagc gtgcgctgct gcccggagac atgggctgcc gcctgctgcc 780 cgggagccag cagaagtccg tcaccgtggt gaccatccct gctgaacagc agcctctgca 840 aggtggggct ccccaggagg cggtggagga ggagcaggac aggcggggcg tggtgaaaag 900 ctccacctgg tcgggggtgt gcactgtcat cttggtggct tgcgtcttgg tcttcctcct 960 cggcatcgtg cttcacaaca tgtcttgcat ttctaagcgc ttcactgtga tatcctgtgg 1020 ctgaagaggg ctgcagggaa gtctcttgtg ggtgccaact taggggttga gcaggttgat 1080 gatgagatcc cagtgagaag atggggggca acactgacca tttggtgctg agcgctggcc 1140 tctgggttgc ctcttgatta ccccaagaca gacacaaagg gcagaaggtg cggtctcaac 1200 aagataccag gtgaattgtt ctgagtgttg atggcaacag cttggaagat gattgcatgc 1260 atcctcataa tcatgtattc aatggactgt aatttatgat ttttcaaaat catgttacaa 1320 gatagacata ttctacttag acgttaaact gtacaagtgc gtacaatgtg accttctcta 1380 aatgcggtag attcaaacaa agatgctctg tagacaagta gaattaaacc tgcgaatccg 1440 tgtaaaaatt cagtgaagac atgcactgct ggcttcttta tttttttttt ctttttattg 1500 aaacccagtc ttcatttagt tgctaaggct tttaatacat tttgaatggc accaaaacaa 1560 aataagtcaa aatggacagt cattttattt ggaggaaata tttgaacaag tgtctccaat 1620 gtgttgtgtt ttgtcatgaa ccttcatttt cttcacttgt aattagagct tgctacgtgt 1680 ttatggaact gaaagctcaa caggggagca ataaaccgag aaatcatgag aaatgtctaa 1740 tcccatggga aaacctgtat gccgattttc ctcaagccat ctcacaaaat aagaatttca 1800 aatgt 1805 <210> 142 <211> 3050 <212> DNA <213> homo sapiens <400> 142 aagtccctcc gagaggggcg gctccgcgtc atgtgactgg agtccgcgta ggaggggtcg 60 gaggtcttac ccaacagatt gacgcggcgt tagtattggc cgtgtacccg aaaaactgat 120 tgactgggct ggcgttaact gtgcggaggc aggatttccc tggggaaagt cttcactcag 180 agcttcgctg acagccaagg atggcaagca aggggccctc ggcctctgca tctcctgaga 240 actccagtgc aggggggccc agtgggagca gcaatggcgc tggcgagagc ggagggcagg 300 acagcacttt cgagtgcaac atctgcttgg acacagccaa ggatgccgtc atcagcctgt 360 gtggccacct cttctgttgg ccgtgtttac atcagggatt tcaaggattt ggatttggag 420 atggtggctt ccagatgtct tttggaattg gggcatttcc ctttgggata tttgccacag 480 catttaatat aaatgatggg cggcctcctc cagctgtccc tgggacaccc cagtatgtgg 540 acgagcagtt cctgtcacgc ctcttcctat ttgtggccct ggtgatcatg ttctggctcc 600 tgattgccta atgctgggct cctgcctaca tccgtggcag ggctctggac tggtgacgtg 660 ccaccccaac tcctggtgtt tggcttcctg gctaatcttg actcctggaa tcagtgggat 720 cagtaacaca tcaaggagtc ttgtttcttc atcagagctt tggaactcga gaccagttgg 780 cgatgacccc tgaatatcgc caccgctgta aacactctat aacttcaggc cttggcattg 840 agtcatctct catgggtgac accatgaaat cttgtttcag ccagttctgc aggtcctgac 900 tctgcagagg gaagaggcag aaagagagaa actgtcagag tataatttca cctgagttta 960 atattacaga aacaaaggga tgcaccaaat ggtatttctg gaaattttca tgtctttaaa 1020 taccccttgg taagttgctt ctgaagccag tgggggctcc tcagatagag aggttcccct 1080 ttcaaatccc agtgccgctc tgttctcttt ccttcccctc ccactccccc tcttcttcct 1140 ctgtagagat gcaagaaatt gctgtcccat aaaaatcata attgcagtag ctaaagctgg 1200 ggtcacttcg tgaattcacc agagactcaa agatctttta ttggctctgg gctgtgctca 1260 gtgtctttgg cctcagagaa caacttgaat gacttcctgg tttcctggca taaattattc 1320 ctggtgagac atgtggctta actcacaggt ttcccatcag ctttctccct aaaactatgt 1380 tcatctgcct ctctctgcca gagaacatac agccgagaat actgccgaag ctgagactga 1440 ctactgtgca ttaggaaaga cctggagtca ggactttggt gggatttgga gctccgaggc 1500 agtaataact gaacaagcag ccctgtcccc taggctgcag aagcttgaat gcatcctctc 1560 ccagaacctg ccacaggaaa ctgggggctt tgtcaggtca gcccaactgc atgcaaaaga 1620 ccaccatcct cagaagccaa gttgtctttt atgaagaggc aaggaaaggg gaaacccaca 1680 tgtgaccctg attttggtat ggcttgatag agttccctga aaactccttg tatgtgtgct 1740 aaaaccaggg aagcatgtga ctgccaagca ggcaacccct gatgatttgt aaagccaggt 1800 ggcagggcct tggggagccc cagcacaatg atattgtgtg gtcttccctc ctgtggaatc 1860 gaggggaaat tattcttccc aataccttga tttgattttc agtttcataa gcttcttcct 1920 ctgaatctta ttgagggact atggtaccaa gcaggtagga ctgttcacct ggtggaacag 1980 ttcttgctct gccttctagg cttcatccca gaaatccagc ctctttctgg agaccccaaa 2040 gctggaggga gatgggcttt cctctgggcc tctctcctac tttgccatcc acactgctcc 2100 tggctaaccc cagcaataac caacaaatgg taggaagccc catctattgc tttttctcaa 2160 ttatgactgc atagtttatg gaaacaaaga tcttgaggaa gatgagggaa gccctcccct 2220 cttcacagtc cccatctctt ctcctttgta cctgtcaaca ccagagttca gtgtttaaac 2280 agacaaaata taaagtattg agtaggtggt tcatatgccg aatccacttg gtaggaagaa 2340 accaccagct ttatagtgtg cctgatagat tttaaacatt cctgggcacc cactcaagag 2400 tgctcttttt atcaccttct ggaaatccgc aaagttgcag gggcctctgg agtgtctctt 2460 ctctagagag aattggtggg acccccctca gtgcagtggc cccaactagt ggagggagag 2520 aggacttaag tcagatggac tcaacagaaa tgggtttcca gaagaataat gaaaagttgt 2580 gggtaggaaa atgaatcatt tggactcttc aatgaaatgg agtgagccca ggagagctca 2640 gccaacagag gcactctggg aacctgttag taaagccagg ctggccaaat gccatttgat 2700 tttgaacctc gtaggtcccc actcaccctc tgccaggagc taagtaaggc aggagagctg 2760 acttgggact cctggctcgg ccccaacagg gagccccctt cccaccatcc ctcggcaagc 2820 tcaccacctc atccttctgc caaggcagct ttcctttctt ttgtgtgttt tctgtgttct 2880 tagcctccac cctcctcctg ccacccttgt ggactaggac caggtcctga ccccagtcag 2940 aaaatgatga tatgtacagt ggcacacctt aaccagtcac taattttcac tgttgtgaaa 3000 gtgatttgat ttagaattaa acaaatggtt ttacattact atgaaaaaaa 3050 <210> 143 <211> 2117 <212> DNA <213> homo sapiens <400> 143 ggaggtgtcg aggccgtggc ccggaagtgg tcggggccgc tgcggacgga agggcgcctg 60 tgcttcgtcc gctcggcggt ggcccagcca ggcccgcggg actcagacca gcggggagcg 120 cggcctccgc ccttggggcc ctcccgccgg gccggagacc caagccccca acgccaggcc 180 ctgccctgga agcgctcgcg gcccggcgcc tggacggggg agttgctgct ctttggcgta 240 aattgcaatc gattagggat cgtttctcag aatcaagtta gaagtgagag ttcagataag 300 tgaggccgcc attgctgctt tgaacacctc agaaggggag aatggattta tcaggagtga 360 aaaagaagag cttgctagga gtcaaagaaa ataataaaaa gtccagcact agggctcctt 420 cacctaccaa acgcaaagac cgctcagatg agaagtccaa ggatcgctca aaagataaag 480 gggccaccaa ggagtcgagt gagaaggatc gcggccggga caaaacccga aagaggcgca 540 gcgcttccag tggtagcagc agtaccaggt ctcggtccag ctcgacttcc agctcaggct 600 ccagcaccag cactggctca agcagtggct ccagctcttc ctcagcatcc agccgctcag 660 gaagctccag cacctcccgc agctccagct ctagcagctc ttctggctct ccaagtcctt 720 ctcggcgcag acacgacaac aggaggcgct cccgctccaa atccaaacca cctaaaagag 780 atgaaaagga gaggaaaagg cggagcccat ctcctaagcc caccaaagtg cacattggga 840 gactcacccg gaatgtgaca aaggatcaca tcatggagat attttccacc tatgggaaaa 900 ttaaaatgat tgacatgccc gtggaaagga tgcatcccca tctgtccaaa ggctatgcgt 960 acgtagagtt tgagaatcca gatgaagccg agaaggcgct gaagcacatg gatggaggac 1020 aaattgatgg ccaggagatc actgccaccg ccgtgctggc cccctggcct aggccacccc 1080 ccaggagatt cagccctccc aggagaatgt tgccaccacc gcctatgtgg cgcaggtctc 1140 ccccacggat gaggagaagg tcccgctccc cgaggcgcag gtcccccgtg cgccggagat 1200 cacggtcccc gggccgccgc cgccacagga gccgctccag ctccaactcc tcccgataaa 1260 caggccactg aagctctcgc ccctgtaact tataccccac ccagctcagt tttgtcactt 1320 ttctagccaa aggaagacca gtaggaaagc aaacccttga ctctggcagg atttgcaggc 1380 agcaggcagc acccctctgc cagccgggcc ccggctgcag aagtgctgtt ggtttggatg 1440 ctgtgtgcct gtcaagattc cctccggttt tctggctaga aagctcatcc gtttccggtt 1500 tctaagagtc agttcagtgg cagagccacc agggaaaagt gaggctcttg ggggtggttt 1560 gaccctgctt acctgggagc acacttttcc cttccccgat gacctgggat ggtggccagg 1620 ccgtgccctt gctgttgctg ggcagtgtcc ttttggaaag ggagctgccc caggctttag 1680 tgcagctgcc aaccctgtta ggcctggcct ctcgaggcct cttctgacct caagggtcac 1740 accccctcaa agatcctctc acccatggta gttgctgctc gtggttctgt ctgtccgtgc 1800 accgatgcac acaccgcacc ccaccactgt actctgaaat tggcgagtga gtggagagcc 1860 agctctgcgg agtcatcacg cagccatggt tgtgcctgcc gttcatggtg gtctttcagg 1920 ttatcttggc aacatgtaca ttgcttttat tttttttctt ttttgctttc attgtacagt 1980 cagtactata aaatttctct tttgagtttt atacctttgt agcattttag atgacattgt 2040 gtttgtactt tgttgtgtag agtggaagaa ttgtgttgaa taaacccaag atcggaatgc 2100 aaatctaaaa aaaaaaa 2117 <210> 144 <211> 135 <212> DNA <213> homo sapiens <400> 144 aaaaagggct tctgtcgtga gtggcacacg tagggcaact cgattgctct gcgtgcggaa 60 tcgacatcaa gagatttcgg aagcataatt ttttggtatt tgggcagctg gtgatcgttg 120 gtcccggcgc ccttt 135 <210> 145 <211> 164 <212> DNA <213> homo sapiens <400> 145 atacttacct ggcaggggag ataccatgat cacgaaggtg gttttcccag ggcgaggctt 60 atccattgca ctccggatgt gctgacccct gcgatttccc caaatgtggg aaactcgact 120 gcataatttg tggtagtggg ggactgcgtt cgcgctttcc cctg 164 <210> 146 <211> 188 <212> DNA <213> homo sapiens <400> 146 atcgcttctc ggccttttgg ctaagatcaa gtgtagtatc tgttcttatc agtttaatat 60 ctgatacgtc ctctatccga ggacaatata ttaaatggat ttttggagca gggagatgga 120 ataggagctt gctccgtcca ctccacgcat cgacctggta ttgcagtacc tccaggaacg 180 gtgcaccc 188 <210> 147 <211> 141 <212> DNA <213> homo sapiens <400> 147 agctttgcgc agtggcagta tcgtagccaa tgaggtttat ccgaggcgcg attattgcta 60 attgaaaact tttcccaata ccccgccatg acgacttgaa atatagtcgg cattggcaat 120 ttttgacagt ctctacggag a 141 <210> 148 <211> 116 <212> DNA <213> homo sapiens <400> 148 atctctggtt tctcttcata acgaataaat ctttcgcctt ttactaaaga tttccgtgga 60 gaaaaacaac tatgagttta tggttaaatt ttttgaagtc ttgcctaggc aaggct 116 <210> 149 <211> 107 <212> DNA <213> homo sapiens <400> 149 gtgctcgctt cggcagcaca tatactaaaa ttggaacgat acagagaaga ttagcatggc 60 ccctgcgcaa ggatgacacg caaattcgtg aagcgttcca tattttt 107 <210> 150 <211> 113 <212> DNA <213> homo sapiens <400> 150 ggctggtccg aaggtagtga gttatctcaa ttgattgttc acagtcagtt acagatcgaa 60 ctccttgttc tactctttcc ccccttctca ctactgcact tgactagtct ttt 113 <210> 151 <211> 2201 <212> DNA <213> homo sapiens <400> 151 tagtttcctg tttccggctt cgcttcggcc cacccccacg tccaccccga atccctgctt 60 aaaggccttg ctttcttgtc taacgccgca accagtcctc tgagttgcca acgtctttct 120 tcttgtctcg acgccccgtc gtccggccac agcgattctc tgcttagcag gatcggtcca 180 cagcgggacg tgagtccctt tcctcctcgc ggcttaccgc ctctctccgc ctagtgccag 240 gtgctaataa agttgttgtt tcaaatgcgg ccaggaacat cgcgagcggg gaccaatcag 300 agagtagctt tgcctctata acggcgcgag agtgagacgt catcggtgag cgactaacgc 360 tagaaacagt ggtgcgcgga gaggagaggc ctcgggatgt ctctggcaga tgagctctta 420 gctgatctcg aagaggcagc agaagaggag gaaggaggaa gctatgggga ggaagaagag 480 gagccagcga tcgaggatgt gcaggaggag acacagctgg atctttccgg ggattcagtc 540 aagaccatcg ccaagctatg ggatagtaag atgtttgctg agattatgat gaagattgag 600 gagtatatca gcaagcaagc caaagcttca gaagtgatgg gaccagtgga ggccgcgcct 660 gaataccgcg tcatcgtgga tgccaacaac ctgaccgtgg agatcgaaaa cgagctgaac 720 atcatccata agttcatccg ggataagtac tcaaagagat tccctgaact ggagtccttg 780 gtccccaatg cactggatta catccgcacg gtcaaggagc tgggcaacag cctggacaag 840 tgcaagaaca atgagaacct gcagcagatc ctcaccaatg ccaccatcat ggtcgtcagc 900 gtcaccgcct ccaccaccca ggggcagcag ctgtcggagg aggagctgga gcggctggag 960 gaggcctgcg acatggcgct ggagctgaac gcctccaagc accgcatcta cgagtatgtg 1020 gagtcccgga tgtccttcat cgcacccaac ctgtccatca ttatcggggc atccacggcc 1080 gccaagatca tgggtgtggc cggcggcctg accaacctct ccaagatgcc cgcctgcaac 1140 atcatgctgc tcggggccca gcgcaagacg ctgtcgggct tctcgtctac ctcagtgctg 1200 ccccacaccg gctacatcta ccacagtgac atcgtgcagt ccctgccacc ggatctgcgg 1260 cggaaagcgg cccggctggt ggccgccaag tgcacactgg cagcccgtgt ggacagtttc 1320 cacgagagca cagaagggaa ggtgggctac gaactgaagg atgagatcga gcgcaaattc 1380 gacaagtggc aggagccgcc gcctgtgaag caggtgaagc cgctgcctgc gcccctggat 1440 ggacagcgga agaagcgagg cggccgcagg taccgcaaga tgaaggagcg gctggggctg 1500 acggagatcc ggaagcaggc caaccgtatg agcttcggag agatcgagga ggacgcctac 1560 caggaggacc tgggattcag cctgggccac ctgggcaagt cgggcagtgg gcgtgtgcgg 1620 cagacacagg taaacgaggc caccaaggcc aggatctcca agacgctgca gcggaccctg 1680 cagaagcaga gcgtcgtata tggcgggaag tccaccatcc gcgaccgctc ctcgggcacg 1740 gcctccagcg tggccttcac cccactccag ggcctggaga ttgtgaaccc acaggcggca 1800 gagaagaagg tggctgaggc caaccagaag tatttctcca gcatggctga gttcctcaag 1860 gtcaagggcg agaagagtgg ccttatgtcc acctgaatga ctgcgtgtgt ccaaggtggc 1920 ttcccactga agggacacag aggtccagtc cttctgaagg gctaggatcg ggttctggca 1980 gggagaacct gccctgccac tggccccatt gctgggactg cccagggagg aggccttgga 2040 agagtccggc ctggcctccc ccaggaccga gatcaccgcc cagtatgggc tagagcaggt 2100 cttcatcatg ccttgtcttt tttaactgag aaaggagatt ttttgaaaag agtacaatta 2160 aaaggacatt gtcaagatct gtcaaaaaaa aaaaaaaaaa a 2201 <210> 152 <211> 760 <212> DNA <213> homo sapiens <400> 152 aagtctagac actaaatgat acaaccttca ccatgtccat catctaatcc aagattctaa 60 cgcagagaag caagaaaatg tgacccaaaa acaaaaccag ccttttggcc agaaccgtca 120 tcttccagta atttgccaaa atgatgaata caaaggcaaa aaggaaaggc actggatata 180 tgttctctag gcctttacaa aaacatggag ttgttccttt ggccacatat atgctaatct 240 ataagaaagg tgatattgca gacatcaagg gaaggggtac tgttcaaaaa ggaatgcccc 300 acaggtgtta ccatggcaaa actggaagag tctacaattt tacccagcat gcttttggca 360 ttgttttaaa caaacaagtt aagggcaaga ttcttgccaa gagaattaat gtgcatattg 420 agcacattaa acactctaag agccgaggta gcttcctgaa atgcgtgaag gaaaatgatc 480 agaaaaagaa ggaagccaaa gagaaaagta cctgggttca actgaagcac cagcctgctc 540 cacccagaga agcacactgt gtgagaacca acgggaaaga gcttgagctg ctggaatcta 600 ttccctatga attcatgcat aataggtgtt aaagaaataa aataaaagac ctctggacta 660 tttaaaaaaa aaaaaaaaaa aaggccaggc gcggtggctc gcgcctgtaa tcccagcact 720 ttgggaggcc agggcgggca gatcacaatg tcaggagatc 760 <210> 153 <211> 893 <212> DNA <213> homo sapiens <400> 153 taagaaccca tctagttttg atggtccttg tattcctagc aaatgttaca gcacctgcct 60 cagagtggga atgtaataaa tattttttgg atttttaaaa atgcagatct ttgtaaaaat 120 ggagaagacc atcattctca acattgaacc attggataca atagaaaatg taaaggccaa 180 gacccaggat aaggaaggaa tttctcctga ccagcaaaga ctgatcttcg ctgtcaagca 240 actggaagat ggacgtactt tgtctgacta caacattcaa gaggagtcca ctcttcatca 300 tgtgttgaga tttcatggtg gtgctaagaa aatgaagaag tcttatgcca ttgccaaaaa 360 gaatatgcat tacagaaaga agattaagct ggctgtcctg aaaaactcca aggtgcatga 420 caatggcaaa attggttgcc ttcatgggaa gtgcctttta gatgaatgtg gtgcaggagg 480 ttttatggcc agccactttg acaggcatta ttgtggcaaa tgttgtctta ttgcttcaac 540 aaaccagaca agtaatcgtg tatgagttaa taagagacat gaactaagaa aataaaagtc 600 ataagttgaa atagagattg ttcagccagt tgacataagg tagagcactg acaaagagaa 660 gctgctcacc tttagtggtg gttatgttcg gagctagcag aaaagcctcc tgacttcctc 720 caggactcag ggaaggcagg ggaaggagga ctttggtgtc ttagtccctt ctcacctctt 780 tggcattact tccttccctc ccaacgtcgc accttataat ctactaactc caaaccaaca 840 ggaactctcc tcccacgccc tacattcaaa caccctaggt ttacatgtgc agg 893 <210> 154 <211> 4404 <212> DNA <213> homo sapiens <400> 154 gagcgcgggt cccgccccgg cgggccgctg gaaaagttta gtctctgact cgctcgggca 60 gaggccgagg aagccggttc cggggacggg caacagggac tcagggacca gaaggcggct 120 gcaggacgcg accgagcagg accccaggcc cgggaacgac gtcgcgagcg ctgagactgc 180 cgggcctccc agcccatctg gcattcgagc gcaggaccgg gcgccccggc accgccgcgc 240 gccacccgct aggatgccgg tggccccagc gccctcagcc gacggaggag ccctttttca 300 acgccctcgc tggagtctgg cctgcacgcc ttgctgaatg aagccggaac ctcagccccg 360 cttccctttg aaatgaatgt tcctggggcg ccctctcgtg gattttggag ctaatcgtct 420 gtgaatgcca agtgatggca actgccctcc cgccgcgtct ccagccggtg cgggggaacg 480 agaccctgcg ggagcattac cagtacgtgg ggaagttggc gggcaggctg aaggaggcct 540 ccgagggcag cacgctcacc accgtgctct tcttggtcat ctgcagcttc atcgtcttgg 600 agaacctgat ggttttgatt gccatctgga aaaacaataa atttcacaac cgcatgtact 660 ttttcattgg caacctggct ctctgcgacc tgctggccgg catcgcttac aaggtcaaca 720 ttctgatgtc tggcaagaag acgttcagcc tgtctcccac ggtctggttc ctcagggagg 780 gcagtatgtt cgtggccctt ggggcgtcca cctgcagctt actggccatc gccatcgagc 840 ggcacttgac aatgatcaaa atgaggcctt acgacgccaa caagaggcac cgcgtcttcc 900 tcctgatcgg gatgtgctgg ctcattgcct tcacgctggg cgccctgccc attctgggct 960 ggaactgcct gcacaatctc cctgactgct ctaccatcct gcccctctac tccaagaagt 1020 acattgcctt ctgcatcagc atcttcacgg ccatcctggt gaccatcgtg atcctctacg 1080 cacgcatcta cttcctggtg aagtccagca gccgtaaggt ggccaaccac aacaactcgg 1140 agcggtccat ggcactgctg cggaccgtgg tgattgtggt gagcgtgttc atcgcctgct 1200 ggtccccact cttcatcctc ttcctcattg atgtggcctg cagggtgcag gcgtgcccca 1260 tcctcttcaa ggctcagtgg ttcatcgtgt tggctgtgct caactccgcc atgaacccgg 1320 tcatctacac gctggccagc aaggagatgc ggcgggcctt cttccgtctg gtctgcaact 1380 gcctggtcag gggacggggg gcccgcgcct cacccatcca gcctgcgctc gacccaagca 1440 gaagtaaatc aagcagcagc aacaatagca gccactctcc gaaggtcaag gaagacctgc 1500 cccacacagc cccctcatcc tgcatcatgg acaagaacgc agcacttcag aatgggatct 1560 tctgcaactg atcgtctcca tgcgccctgc tctgcggctg tgttcttatt tattgcatgc 1620 gtcgcttcca caggggcccc tcaagagctg tgactcggga gagctacctt actttgacca 1680 acagcctgcc cagtgtggat gtctcttaca gagggggccc aaggaatcac caccccgctt 1740 cagtgtaaac aacgtgcctt gtccactttg ggctccagag tctttcagat gtactaagct 1800 gctgacatca tccactgcct tctgctgcat cctagacacc ctccctgttg ttcacagaga 1860 gggaaggtcg tgggccacac aatgctgtgt gaccctctcc gtgtgcctct gaatggtgtt 1920 ttgatgattt tacactacat ttcctgtgcg tagaatggat gcttgtatat tcgtacatct 1980 ctatgttaca cagaatttgt gttgcaggtg tttgccatgt ggtacctaca tagaatctcc 2040 atacaacaca caggtaacag gttatacaag tggattcaga ctgaaccccc agtacaagga 2100 cattgttttg aactaggtgg acatgccatc cctggtctcc ttagactgac atgattctca 2160 tgttaaccaa gttttaaaag ttcaaattcc ccaaaaaggc ttgtccaagg ctggccccag 2220 atgtgtgggt ctgacccaca ccagccctgt gtcctgtcct ttcagtcatt tgtccctgcg 2280 taattttaat cgtattccaa agcccaatta tgtgatggtt ttcaggtttc tgcaaattac 2340 agaagagcca gccaagatca cccaggagct tgtgccccca gatgggccaa agaaagagcc 2400 tatgaaggag aagcagaagc agacggctgg cctggctcac cttcccacgc cagtggggca 2460 ggggtctgct tcaggaaatg gaagctgtcc aggaaatgag cagagattca caagacagca 2520 ctttgattct atgttgagtt tgtttctata ttagaaaagc agcaagtcag taatcccccg 2580 tggcatcaca gctaagtagc tgtggccacc ggcagtttca cagcatcctg aaagctggca 2640 ctgatcgtga ctatcagtga aagaagttta attttcaggt tagaaaatgt gatctggcag 2700 tttatgcatt cttcagagta atgtaataat acctatgtga tgctgtaatt ttacttttca 2760 acataagttg aacccgtagc agtctgttta ccttgtaaag ggattactta gaagacattt 2820 ttgtacatgc tcttccccaa ggattgtacg tattatacaa atagatggaa agaaaagtga 2880 acacgtttgt agaactttca taagcacaca gttgctgtgt tgagttctct ttaaaaacaa 2940 ggacaaaacc aaccagcgtt caaaggaacc tcccatcaga gtcccctaaa gtattttagg 3000 ttcagtgagc atttgcctga ataaaaccta aaagagtagt cttaacacat tactaacttt 3060 ttctaagaga aattgattcc tgttttgtca tctgatgcaa tttgctctta taaagagaca 3120 ttttcatagg ttcagagtaa ctcacctcca tgggctgacc aaaggctttt ctaatttttg 3180 ttactgatga gatgaaacct atttgtaagg agatcttccc caggagcatt tctgttgcct 3240 tcttgacatc aatgaaaagt agcatattct cttatgaaat agcatgagaa aacacagggc 3300 atttctagga cagtaaaacg ttaaagtact ggattaagaa aacaacaaca ggctgggcgc 3360 agtggctcac acctgtaatc ccagcacttt gggaggctga ggcgggtgga tcacctgagg 3420 tcaggagttt gtgaccagcc tggccaacat agtgaaatcc tgtttctact aaaaatacaa 3480 aaattagctg gatgcgatag cacgtgcctg tagtcccagc tactcgggag gctgaggctg 3540 gagagttgct caaacccggg aggcggagat tgcagtgagc caagatcgca ccgctgcact 3600 ccagcctggg tgacagagcg accctctgtc tcaaaaaata ataataataa taaataaaac 3660 aacaacaaaa tgcatcagag agccaaaaca ttcagtattg cattttcaca taggtgatga 3720 aatgactttg gaactttatc tgtgttatag ttatgagttg ctttgggaga cttggagctc 3780 tctgtagcta ttgttcataa cactttgctc cataaccctg atgtccgcag tatctaagta 3840 tctcagcctt catccattaa ctctactagg gagcccacag ccaccatttc cactaggagg 3900 tatcaatatt tgtggtatga cataaggctc ccttgaaata acaagacttt tgagcaatct 3960 gaattaaaaa tacatcaaaa aagtaatagc gctcatttgc taaatgcaaa aaataatcac 4020 ctttgatacc aatgtgcacc aatatgccta actagctagc cagctggaga taatttacca 4080 gggaatgttt caaagcccta accttgaagt ttggaaacag gtggtcttct atgctgcaga 4140 gaaactatgc attaggtctc ttttcaatta gaaaccttta ctatttccaa tgtatgtttg 4200 ttaaaaataa taataataaa accaaaagcc tttgtggaaa cccactcttc gtagtccatg 4260 tgatgggatt gttttatcgt tttcaccggg tgccctcccc actgcagggg tgcgcactgt 4320 tgttgcaggc ttgctaccca cctgtgtttc ttagcatttc aggaattaaa ccacattcag 4380 aaccccaaaa aaaaaaaaaa aaaa 4404 <210> 155 <211> 3601 <212> DNA <213> homo sapiens <400> 155 aacacgacag cggctgccga gcgacccgga agtattccca ttttgcgttg tctgggctcg 60 gcggcagccg ggctcggagt ggacgtgcca ctatggggtc gtccaagaag catcgcggag 120 agaaggaggc ggccgggacg acggcggcgg ccggcaccgg gggtgccacc gagcagccgc 180 cgcggcaccg ggaacacaaa aaacacaagc accggagtgg cggcagtggc ggtagcggtg 240 gcgaacgacg gaagcggagc cgggaacgtg ggggcgagcg cgggagcggg cggcgcgggg 300 ccgaagctga ggcccggagc agcacgcacg ggcgggagcg cagccaggca gagccctccg 360 agcggcgcgt gaagcgggag aagcgcgatg acggctacga ggccgctgcc agctccaaaa 420 ctagctcagg cgatgcctcc tcactcagca tcgaggagac taacaaactc cgggcaaagt 480 tggggctgaa acccttggag gttaatgcca tcaagaagga ggcgggcacc aaggaggagc 540 ccgtgacagc tgatgtcatc aaccctatgg ccttgcgaca gcgagaggag ctgcgggaga 600 agctggcggc tgccaaggag aagcgcctgc tgaaccaaaa gctggggaag ataaagaccc 660 taggagagga tgacccctgg ctggacgaca ctgcagcctg gatcgagagg agccggcagc 720 tgcagaagga gaaggacctg gcagagaaga gggccaagtt actggaggag atggaccaag 780 agtttggtgt cagcactctg gtggaggagg agttcgggca gaggcggcag gacctgtaca 840 gtgcccggga cctgcagggc ctcaccgtgg agcatgccat tgattccttc cgagaagggg 900 agacaatgat tcttaccctc aaggacaaag gcgtgctgca ggaggaggag gacgtgctgg 960 tgaacgtgaa cctggtggat aaggagcggg cagagaaaaa tgtggagctg cggaagaaga 1020 agcctgacta cctgccctat gccgaggacg agagcgtgga cgacctggcg cagcaaaaac 1080 ctcgctctat cctgtccaag tatgacgaag agcttgaagg ggagcggcca cattccttcc 1140 gcttggagca gggcggcacg gctgatggcc tgcgggagcg ggagctggag gagatccggg 1200 ccaagctgcg gctgcaggct cagtccctga gcacagtggg gccccggctg gcctccgaat 1260 acctcacgcc tgaggagatg gtgaccttta aaaagaccaa gcggagggtg aagaaaatcc 1320 gcaagaagga gaaggaggta gtagtgcggg cagatgactt gctgcctctc ggggaccaga 1380 ctcaggatgg ggactttggt tccagactgc ggggacgggg tcgccgccga gtgtccgaag 1440 tggaggagga gaaggagcct gtgcctcagc ccctgccgtc ggacgacacc cgagtggaga 1500 acatggacat cagtgatgag gaggaaggtg gagctccacc gccggggtcc ccgcaggtgc 1560 tggaggagga cgaggcggag ctggagctgc agaagcagct ggagaaggga cgccggctgc 1620 gacagttaca gcagctacag cagctgcgag acagtggcga gaaggtggtg gagattgtga 1680 agaagctgga gtctcgccag cggggctggg aggaggatga ggatcccgag cggaaggggg 1740 ccatcgtgtt caacgccacg tccgagttct gccgcacctt gggggagatc cccacctacg 1800 ggctggctgg caatcgcgag gagcaggagg agctcatgga ctttgaacgg gatgaggagc 1860 gctcagccaa cggtggctcc gaatctgacg gggaggagaa catcggctgg agcacggtga 1920 acctggacga ggagaagcag cagcaggatt tctctgcttc ctccaccacc atcctggacg 1980 aggaaccgat cgtgaatagg gggctggcag ctgccctgct cctgtgtcag aacaaagggc 2040 tgctggagac cacagtgcag aaggtggccc gggtgaaggc ccccaacaag tcgctgccct 2100 cagccgtgta ctgcatcgag gataagatgg ccatcgatga caagtacagc cggagggagg 2160 aataccgagg cttcacacag gacttcaagg agaaggacgg ctacaaaccc gacgttaaga 2220 tcgaatacgt ggatgagacg ggccggaaac tcacacccaa ggaggctttc cggcagctgt 2280 cgcaccgctt ccatggcaag ggctcaggca agatgaagac agagcggcgg atgaagaagc 2340 tggacgagga ggcgctcctg aagaagatga gctccagcga cacgcccctg ggcaccgtgg 2400 ccctgctcca ggagaagcag aaggctcaga agacccccta catcgtgctc agcggcagcg 2460 gcaagagcat gaacgcgaac accatcacca agtgacagcg ccctcccgcc ccggccctgc 2520 ctcaaccttc atattaaata aagctccctc cttatttttt cctccctggt cgtggtacag 2580 attccagggt tggatctttg gttgggtgtg gcacagagtc tggctcctgc taggtgagac 2640 ctggccatca aatgacacaa acaactaaac gatggaagag agagcgagcc cgggtcctct 2700 aaggctcctt ccttctcccc tggctgtcgg tcacacctct gcagggccgg ctctctgata 2760 gaaagtggaa ggcggtttta gaaactcatc accctgctct ctcctggcct cgggggctgc 2820 acaggtcact gtcctgtaat gtctcccggt cagggcagcc caggactgcc cagcctggtg 2880 ggctggggat tgggctttgg gtagggcaca ggtgccacct tctgtcctgg ctgtcctgtg 2940 ccaccctggt ctgtgtctag aggagtgaaa ctcccagggt tgggctggga gtatttggtg 3000 cacgcggtat ggggagggct gagctcagtg cctcctggga gacttgtccc gtgtacagtg 3060 acccagaaag atgagattcc ttggcctgaa ctctgtgata gagtgtgact gagctgctgg 3120 gggacatgtg agcctcaaat ccatagaaag acaaacggcc accttgggtg cccaggatac 3180 tggtgcctgg ccccacgtac acccacatac ttctcagatg gctcccacat tttaagattt 3240 taaaaatgaa accaaaaaat aaattgaaga aaactgtaaa ctttaaagaa taatcagctg 3300 ggcgcagtgg ctcatgcttg taatcacagc actttaggag gctgaggcag gaggactgtt 3360 tgagcccagg agtttgagac caacctgagt aaggtggcaa aaccccatct ctaccaaaaa 3420 tacaaagatt agccaggcgt ggtggtgagc gcctgtagtc ccagctactt gggatgctga 3480 ggtgggagga tcacttgaac ctgggagaca caggctgcag tgggccctga ttgagccacc 3540 acactgcagc ctaggtgaca gtcagaccct gtctcaaaaa aaataaaaaa aatttaaaat 3600 a 3601 <210> 156 <211> 3044 <212> DNA <213> homo sapiens <400> 156 atgcgctatt tccggtcata cccggaaaca cgagtccaag ctgcagctgg cagggattgc 60 ggggtgccgg ccgtctgagt ttttttaaaa ctgctcgccg cgaagtctgt ctgcagccaa 120 aatgtccaac agaaacaaca acaagcttcc cagcaacctg ccgcagttac agaatctaat 180 caagcgagac ccgccggcct acatcgagga gtttctacag cagtataatc actacaaatc 240 caatgtggag attttcaaat tgcaaccaaa taaacccagc aaagaactag cagagctggt 300 gatgtttatg gcacagatta gtcactgcta cccagagtac ctaagtaatt ttcctcaaga 360 ggtgaaagat cttctctcct gcaatcatac cgtattggat ccagatctgc gaatgacatt 420 ttgcaaagct ttgatcttgc tgagaaataa gaatctcatc aatccatcaa gcctgctaga 480 actcttcttt gaactttttc gttgccatga taaacttctg cgaaagactt tatacacaca 540 tattgtgact gatatcaaga atataaatgc aaaacacaag aacaataaag tgaatgtagt 600 attgcaaaat ttcatgtaca ccatgttaag agatagcaat gcaaccgcag ccaagatgtc 660 tttagatgta atgattgaac tctacagaag gaacatctgg aatgatgcaa aaactgtcaa 720 tgttatcaca actgcatgtt tctctaaggt caccaagata ttagttgccg ctttgacatt 780 ctttcttggg aaagatgaag atgaaaaaca ggacagtgac tccgaatctg aggatgatgg 840 accaacagca agagacctgc tagtacaata tgctacaggg aagaaaagtt ccaaaaacaa 900 gaaaaagttg gaaaaggcaa tgaaagtgct caagaaacaa aaaaagaaga aaaaaccaga 960 ggtgtttaac ttttcagcca ttcacttgat tcatgatccc caagattttg cggaaaaact 1020 actaaagcag cttgagtgct gtaaggagag gtttgaagtg aagatgatgc tcatgaacct 1080 tatctccaga ttggtgggaa ttcatgagct tttcctcttc aatttctatc cctttttgca 1140 aaggtttctg cagccccacc aaagagaagt aaccaagatc cttctgtttg ctgcacaagc 1200 atctcatcac ctagtacccc cagagattat tcaatcattg cttatgactg tggcaaacaa 1260 ttttgttacc gacaagaact ctggagaagt catgacagta ggaatcaatg ctataaagga 1320 gataacagct cgatgtcctc tggccatgac tgaagaactt ctccaagacc tggctcagta 1380 taaaacacac aaggataaga atgtaatgat gtctgctaga actttgattc acctcttccg 1440 aacactgaat cctcagatgc tgcagaagaa attccggggt aagcctacag aggcctccat 1500 agaagcaaga gtacaagaat atggagaatt agatgctaaa gattacattc caggagcaga 1560 agttctggaa gttgagaaag aagagaatgc tgaaaatgat gaagatggat gggaaagtac 1620 cagtctcagt gaggaggagg atgctgatgg tgaatggatt gatgtgcaac actcttccga 1680 tgaagaacag caagaaatct ccaagaagct gaacagcatg cccatggagg agcggaaggc 1740 caaagctgca gccatcagca ctagccgagt tttaactcag gaagacttcc agaaaatccg 1800 catggcccaa atgagaaaag aacttgatgc tgcccccggg aaatcccaga agaggaaata 1860 cattgaaata gacagtgatg aagagcccag gggtgaatta ctttctcttc gggacattga 1920 acgccttcat aaaaagccaa agtctgacaa agagacaaga ctagcaactg caatggctgg 1980 aaagacagac cgaaaagaat ttgtgaggaa gaaaaccaaa acaaatccat tttccagttc 2040 gacaaataaa gagaagaaaa aacagaagaa ctttatgatg atgcggtata gccagaatgt 2100 ccggtcaaaa aataagcgtt ccttccgaga aaaacagttg gcactacgag atgcactttt 2160 gaaaaagaga aaaagaatga agtaacttcc tggcaagttt tccattccta gaagaatgct 2220 aagtttgtgt ccttgctctg aaaattggta aatcaagcat gtttgtttac attaaaaagt 2280 ccagacacac tgtattgtga aaactgctga acatgtggca gcaattttgt gtttttattt 2340 tggagacggc taatggtagg aatgttaatg taaatagtgg tggtaatgta aaatcatttc 2400 atttatcatt catgcaaaaa aaagtatgta ttgagtgcct attcattgtc actgtagatg 2460 caaaacgaat gagctgtaac cccttcactc aaggcattga cagcttagct gtgagggtgg 2520 acacacatat gtgtatttac agtgcagtgt aaatagttct gtagtagagg ttaactccat 2580 atttctgtga ggtcactgag gccttatgga ctaactctgt gaggatagga gttatatatt 2640 cttataagac aaaacaaaac aggacaatgt tacaagagta agaggttctt acttgtacat 2700 aggctttcct gctgaaaaca ggcccctgct gtacagattt tgggtacata atttagctct 2760 tttagtcaat ccaagagatt taagtgaccc cccccccccc gtgttttttt tgtttttgtt 2820 tttgttttga atgccatgta aaggcttttt ggttaagacc tcacttttaa aactgcctta 2880 agtataaata gtacctttgg aatatattta gttcatcatt tgagctgcct tcatactggt 2940 ttcctcagcc ttccttcagc ctgtaatatt ttcagcccac tgtttacctt gtctcaataa 3000 aaggtttcta atgccaaata cgtaccttta aaaaaaaaaa aaaa 3044 <210> 157 <211> 2164 <212> DNA <213> homo sapiens <400> 157 ataaatatca gagtgtgctg ctgtggcttt gtggagctgc cagagtaaag caaagagaaa 60 ggaagcaggc ccgttggaag tggttgtgac aaccccagca atgtggagaa gcctggggct 120 tgccctggct ctctgtctcc tcccatcggg aggaacagag agccaggacc aaagctcctt 180 atgtaagcaa cccccagcct ggagcataag agatcaagat ccaatgctaa actccaatgg 240 ttcagtgact gtggttgctc ttcttcaagc cagctgatac ctgtgcatac tgcaggcatc 300 taaattagaa gacctgcgag taaaactgaa gaaagaagga tattctaata tttcttatat 360 tgttgttaat catcaaggaa tctcttctcg attaaaatac acacatctta agaataaggt 420 ttcagagcat attcctgttt atcaacaaga agaaaaccaa acagatgtct ggactctttt 480 aaatggaagc aaagatgact tcctcatata tgatagatgt ggccgtcttg tatatcatct 540 tggtttgcct ttttccttcc taactttccc atatgtagaa gaagccatta agattgctta 600 ctgtgaaaag aaatgtggaa actgctctct cacgactctc aaagatgaag acttttgtaa 660 acgtgtatct ttggctactg tggataaaac agttgaaact ccatcgcctc attaccatca 720 tgagcatcat cacaatcatg gacatcagca ccttggcagc agtgagcttt cagagaatca 780 gcaaccagga gcaccaaatg ctcctactca tcctgctcct ccaggccttc atcaccacca 840 taagcacaag ggtcagcata ggcagggtca cccagagaac cgagatatgc cagcaagtga 900 agatttacaa gatttacaaa agaagctctg tcgaaagaga tgtataaatc aattactctg 960 taaattgccc acagattcag agttggctcc taggagctga tgctgccatt gtcgacatct 1020 gatatttgaa aaaacagggt ctgcaatcac ctgacagtgt aaagaaaacc tcccatcttt 1080 atgtagctga cagggacttc gggcagagga gaacataact gaatcttgtc agtgacgttt 1140 gcctccagct gcctgacaaa taagtcagca gcttataccc acagaagcca gtgccagttg 1200 acgctgaaag aatcaggcaa aaaagtgaga atgaccttca aactaaatat ttaaaatagg 1260 acatactccc caatttagtc tagacacaat ttcatttcca gcatttttat aaactaccaa 1320 attagtgaac caaaaataga aattagattt gtgcaaacat ggagaaatct actgaattgg 1380 cttccagatt ttaaatttta tgtcatagaa atattgactc aaaccatatt ttttatgatg 1440 gagcaactga aaggtgattg cagcttttgg ttaatatgtc tttttttttc tttttccagt 1500 gttctatttg ctttaatgag aatagaaacg taaactatga cctaggggtt tctgttggat 1560 aattagcagt ttagaatgga ggaagaacaa caaagacatg ctttccattt ttttctttac 1620 ttatctctca aaacaatatt actttgtctt ttcaatcttc tacttttaac taataaaata 1680 agtggatttt gtattttaag atccagaaat acttaacacg tgaatatttt gctaaaaaag 1740 catatataac tattttaaat atccatttat cttttgtata tctaagactc atcctgattt 1800 ttactatcac acatgaataa agcctttgta tctttctttc tctaatgttg tatcatactc 1860 ttctaaaact tgagtggctg tcttaaaaga tataagggga aagataatat tgtctgtctc 1920 tatattgctt agtaagtatt tccatagtca atgatggttt aataggtaaa ccaaacccta 1980 taaacctgac ctcctttatg gttaatacta ttaagcaaga atgcagtaca gaattggata 2040 cagtacggat ttgtccaaat aaattcaata aaaaccttaa agctgaaaaa aaaaaaaaaa 2100 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160 aaaa 2164 <210> 158 <211> 1722 <212> DNA <213> homo sapiens <400> 158 agacagccgt gacagagaaa ctaggcggtc cgctcctggg acgcggtctc gggggcgggt 60 tcgcccctga ggcccggtga cccttcgccc gcaaccaggg ctagcgcttg tgtgcgccca 120 cggaagcacc cgagcgaccg gagaaagaaa aagtggtcaa ggggacctcc ttccagctct 180 acgcgcctct cattcagaga ggtgaggtca ggaaagggga aggacgaagc cccagagcaa 240 cagaagtcag gcggtgccag gaacactgag agcggagcca ggggaaggcg gccgagcgcg 300 gccccctctc ctcccgggcc ggggcgggcc cgaggcctcg atccgccttc cccgcgccgt 360 cctggtcacg gccccgcggg gcagccatgc ctggccgtct gctgcggggc ctgtggcagc 420 gatggcgccg ttacaagtac cgcttcgttc cctggatcgc actgaaccta agccacaacc 480 cgaggaccct ccgatatgtt ccagaggaat ccaaagacaa agttatctca gatgaagatg 540 tcctaggaac attactgaaa gttttccagg ctctattctt aaatgatttc aataaacaat 600 cagaaatctt gtctatgctt ccagaatctg ttaaatcaaa atatcaagac ctactggcag 660 ttgaacatca aggggtgaaa ctgcttgaaa acagacatca acagcaaagt acctttaaac 720 cagaagaaat tctttacaag actttgggtt tcagtgttgc ccaagcaact agctcattga 780 tttctgctgg aaaaggtgtc ttcgttacta aaggattggt accaaaaggc gcagtcgtat 840 ctatgtatcc tggtacagta tatcagaagt atgagccgat ctttttccag tccattggaa 900 atccgtttat ttttagatgc ctggatgggg tactcattga tgggaatgac aaagggatat 960 caaaagttgt gtacagatct tgcaatggga gggatcgact cggcccttta aaaatgagtg 1020 atagtacatg gctaacgtca gaaattcata accctctggc tgtgggacag tatgtcaaca 1080 attgttccaa tgacagagca gctaatgtct gttatcagga atttgatgtg cctgcagttt 1140 tccctataga actgaagcag tatcttccaa acattgccta cagctatgac aaacaaagcc 1200 cacttcgatg tgttgttctt gtcgcactta gggacatcaa tcaaggagaa gagctttttt 1260 caaactacta cacaattgtc agctaactct gtgaatcaga aattattagg ttttctactc 1320 agctattaat tctaagtgtt ttttgttaat cacttctctg agttctacct gtaaaacaaa 1380 tattttgaga cttaattgga ataggaattt cttatgtttt tgttgatatt atatttatgt 1440 tccaatttca tgataaaagc tacttgcttc attacaattt caaatttgta atgcaattcc 1500 aagtttaatt ggttttcacc taaatacaca atagcttatt aaattaaaac ctactctttg 1560 aacttataat ttcaattttt cttttgttta ttttgtaagc tctgtggtgg tttataaaat 1620 tgtagccagg catcagcagt tcttgtagta ctgctgatgt gtacaaactt ctgtaaaaac 1680 tttattttta cagaattgag taaaaaatac ctattgtgtt gc 1722 <210> 159 <211> 2113 <212> DNA <213> homo sapiens <400> 159 actcaccctc cggcttcctg tcggggcttt ctcagcccca ccccacgttt ggacatttgg 60 agcatttcct tccctgacag ccggacctgg gactgggctg gggccctggc ggatggagac 120 atgctgcccc tgctgctgct gcccctgctg tggggggggt ccctgcagga gaagccagtg 180 tacgagctgc aagtgcagaa gtcggtgacg gtgcaggagg gcctgtgcgt ccttgtgccc 240 tgctccttct cttacccctg gagatcctgg tattcctctc ccccactcta cgtctactgg 300 ttccgggacg gggagatccc atactacgct gaggttgtgg ccacaaacaa cccagacaga 360 agagtgaagc cagagaccca gggccgattc cgcctccttg gggatgtcca gaagaagaac 420 tgctccctga gcatcggaga tgccagaatg gaggacacgg gaagctattt cttccgcgtg 480 gagagaggaa gggatgtaaa atatagctac caacagaata agctgaactt ggaggtgaca 540 gccctgatag agaaacccga catccacttt ctggagcctc tggagtccgg ccgccccaca 600 aggctgagct gcagccttcc aggatcctgt gaagcgggac cacctctcac attctcctgg 660 acggggaatg ccctcagccc cctggacccc gagaccaccc gctcctcgga gctcaccctc 720 acccccaggc ccgaggacca tggcaccaac ctcacctgtc aggtgaaacg ccaaggagct 780 caggtgacca cggagagaac tgtccagctc aatgtctcct atgctccaca gaacctcgcc 840 atcagcatct tcttcagaaa tggcacaggc acagccctgc ggatcctgag caatggcatg 900 tcggtgccca tccaggaggg ccagtccctg ttcctcgcct gcacagttga cagcaacccc 960 cctgcctcac tgagctggtt ccgggaggga aaagccctca atccttccca gacctcaatg 1020 tctgggaccc tggagctgcc taacatagga gctagagagg gaggggaatt cacctgccgg 1080 gttcagcatc cgctgggctc ccagcacctg tccttcatcc tttctgtgca gagaagctcc 1140 tcttcctgca tatgtgtaac tgagaaacag cagggctcct ggcccctcgt cctcaccctg 1200 atcagggggg ctctcatggg ggctggcttc ctcctcacct atggcctcac ctggatctac 1260 tataccaggt gtggaggccc ccagcagagc agggctgaga ggcctggctg agcccctccc 1320 gctcaagaca gaactgaggt gtggacactt agccctgtgg gacacatgca ggacatcact 1380 gtcagcttct ttctggaagc tcacatccca ctgactaccc ctcttttcct tcctgcccca 1440 taccccttct acttattccc ctctgcttgt gagtcttgcc ccaccacacc tgcatcccca 1500 tctgcacccc atcccctctc cacctgccct tctcttccct ctccatccac catctccagc 1560 cctgtgaagg gaatgtactt tcggtcttat acccccatta cccattaccc aaaagttacc 1620 tttttttttt tttttttttt ttgagacaga gtctcactct gttgcacagg ctggagttca 1680 gtggcacaat ctccgttcac tgcaacctcc acctctgggg ttcaagcaat tctcctgcct 1740 cagcctccct agtagctggg attacaggtg cctgccacca catccagtta attttttttt 1800 tttgtatgtt agtagagatg gggttttacc atgttggcca ggtctcgaac tcctgacctc 1860 aagcaatcca ctgcattggc ctcccaaagt gctggcatta caggtatgag ccaccgtgcc 1920 tggctgccaa aagttacctt cttaacactt gaatttctgg tctcctcagc ttccctatcc 1980 atataggcac agagaggcag catttgtttt ccagttaaaa ctctacctca ttgtgattat 2040 tatccaatac aattgttaca aaataagtaa aacttttatg aaacaataca acataactga 2100 ttttactctt taa 2113 <210> 160 <211> 1601 <212> DNA <213> homo sapiens <400> 160 ggcgaccgcg gctgaggtac aggtgcctcg cggtgcagcc gggtcgcctt ccagcccgtc 60 cgcctcccga ccagggcccg cgccccgtcc cgcctctctc ccgcccagcc aaatgcaggc 120 cgccgccctc cctgaggaga tccgttggct cctggaagat gctgaagagt ttctggcaga 180 aggtttgcgg aatgagaacc tcagcgctgt tgcaagggat cacagagacc atattctacg 240 gggctttcag caaatcaaag ccaggtacta ttgggatttt cagccccaag ggggagacat 300 tggacaggac agctctgatg ataatcacag cgggactctt ggcctgtccc tcacatccga 360 tgcacccttt ttgtcagatt atcaggatga gggaatggaa gacatcgtaa aaggagctca 420 agaacttgat aacgtaatca agcaaggata cttggagaag aaaagcaaag atcatagttt 480 ctttggatcg gagtggcaga agcgatggtg tgttgtcagc agaggtctct tctactacta 540 tgctaatgag aagagcaagc agcccaaagg gaccttcctc attaagggct acggtgtacg 600 gatggccccc cacctgcgaa gagattccaa gaaagaatcc tgctttgaac tgacctccca 660 ggataggcgc agctatgagt ttacagctac tagtccagca gaagccagag actgggtgga 720 tcaaataagt ttcttgttaa aggatctgag ctccttaacc attccatatg aagaggatga 780 ggaggaagaa gaaaaagaag agacatatga tgatattgat ggttttgact ccccaagttg 840 tggttcccag tgcagaccca ctatcttgcc tgggagtgtg gggataaaag agcctacaga 900 ggagaaagaa gaagaagata tttatgaagt cttgccagat gaagagcatg atctagaaga 960 ggatgagagt ggcactcgac gaaaaggagt agactatgcc agttactacc agggcctatg 1020 ggattgccat ggtgaccagc cagatgaact gtccttccaa cggggtgacc tcatccgtat 1080 tctgagcaag gagtataaca tgtatggctg gtgggtggga gaactgaaca gcctcgttgg 1140 gattgttcca aaggagtatc tcaccactgc ctttgaagtg gaagaaagat gaaacccagg 1200 aaatatattc ttccctctct cctgccttta tgaggaaact gatcatcaaa agttcccact 1260 ccctacttct gccaccccac caacgccttg gactcctctc tttgctgaag agacccaagt 1320 ctcttgacac ctcagagtga ctgtaagcta ccagtaagac aagtgggaag aggcacgttc 1380 atcaaacctg ttactaaacc agcctagtca tagctcatcc ccatctctaa atgtgtccac 1440 acaaccacat ctgccttttc cacaagcttt tcacaaagaa ggtgagagag aaggaaacct 1500 tgggaggagg acattactgg ttgttctggc tggtttgaaa agcacaaata aacttgggat 1560 gtggttcctt gccatgaaaa aaaaaaaaaa aaaaaaaaaa a 1601 <210> 161 <211> 2983 <212> DNA <213> homo sapiens <400> 161 aagcactgag cctggcccca cgtccaggca ccaggacctc caatccaatg gtgtcttctt 60 cctcccagtc acactgttca ctttgcccta cagcagcaag ggctaaacta ggagaggcca 120 aaagcccagg caagtcctgg ttgggcaagc aattgcgagt gaaactgagg accatcctga 180 ctgagatggg tctttcataa gtcccccaag agccaggtga ggcatcatca acatcagcct 240 ctcctgccac caccgcttcc ctgattcatg cacttcaggc ttcagccagc agcacgcatc 300 cttggggtta ggagccagca tctcaggtca gcagccatgg tttctctgga gaaagaccca 360 tcagaggctc attcagagcc ttaaccctga gcctctgcca cctacccacc gtgttgaaga 420 tgtcattgct tggaagggac tacaacagtg agctgaactc cttggacaac ggacctcagt 480 caccctcaga gagcagcagt agcattactt cagagaatgt ccatcctgct ggagaagctg 540 gactatcgat gatgcaaact ttgatccact tgttgaaatg caacattggc acagggctcc 600 tggggcttcc cctggccata aagaatgccg gcttgttggt cggtcctgtc agccttctgg 660 ccatcggggt cctcaccgtg cactgcatgg tcatcctgtt gaactgtgct caacacctca 720 gccagagact gcagaagact tttgtgaact atggagaggc cacgatgtac ggccttgaaa 780 cctgcccgaa cacctggctg agggcccatg cagtgtgggg aagatggaat ttggctctgt 840 cacccaggct ggagtgcagt ggcaagatct cagctcactg caacccccac cttcagggtt 900 caagcaattc tcctgcccaa gcctcccgag tagctgggat ttacaggtac actgtcagct 960 tcttattagt catcacccag ctgggcttct gcagtgttta ttttatgttt atggcagaca 1020 atttacaaca gatggtggaa aaagcccacg tgacctccaa catctgccag cccagggaga 1080 ttctgacgct gacccccatc ctggacattc gtttctacat gctgataatc ctgcccttcc 1140 tgatcctgtt ggtgtttatc cagaacctca aggtgctgtc cgtcttctcg acattggcca 1200 acatcaccac ccttgggagc atggctctga tctttgagta tatcatggag gggattccat 1260 atcccagcaa cctacccttg atggcaaact ggaagacctt cttgctgttc tttggtacag 1320 ccatcttcac atttgaaggc gtcggtatgg ttctgcctct caaaaaccag atgaagcatc 1380 cacagcagtt ttcttttgtt ctgtacttgg ggatgtccat tgtcatcatc ctctatatct 1440 tactggggac actgggctac atgaagtttg ggtcagacac ccaggccagc atcaccctca 1500 acttgcccaa ttgctggttg taccagtcag tcaagctgat gtactctatc ggcatcttct 1560 tcacctatgc cctccagttc cacgtcccag ctgagatcat catcccgttt gccatctccc 1620 aagtgtcaga gagctgggca ctgtttgtag acctgtctgt ccgctcagcc ttggtctgtc 1680 taacctgtgt ctcagccatc ctcatccccc gcctggactt ggtcatctcc ctggtaggct 1740 ccgtgagcag cagcgccctg gctctcatca tcccagccct cctggagatc gtcatctttt 1800 actctgagga catgagctgt gtcaccattg ccaaggacat catgattagc atcgtgggcc 1860 ttttagggtg tatatttggg acataccaag ccctctatga gttgccccaa cccatcagcc 1920 attccatggc caactccaca ggtgtccatg cataattatc tgtttttatt ctaatagctc 1980 tcccttcctc ccatccccag tttgacttcc atgtggatgt tatatacctt catcaaatcc 2040 caacatctct atattaatta gtggcgtctt tatctttcca agagaaatgc agatgagaaa 2100 agttagcact gatgtctctc aggctacacc tcttttggtt ttatattttt tggatggcct 2160 tttgtacctc tgaaccaaaa ttagattcaa ctattcatat tatcagcctc attttatgga 2220 aaagggatgc cacttacccc aatagccctt gaaacagaga ccaagcataa atacaaaagt 2280 aactgttttc tctacactgc agtagctgcc cttaaagcat cagatttaga aaagtgtatg 2340 ttgggcgaag ggagttttct atttagatat tctaagtaga agagtcatag acagaacaaa 2400 aacagaactc agcagtaatt ttgtccaacc actggctccg ccactgattt cctactggcc 2460 ctcaggcaag ttcctcccca tctctcagtc tatgaagtga acagttggac taactgatta 2520 ttaaggactc tgtcaactct gatattctga aagtgaataa aagaaattaa cttatccacc 2580 aaccacaaaa actggccatg ctagtgttgg tgaggaggtg gagtaactga aactccatac 2640 cctgctatgt ggatagaaag tagtacaatc agtttgataa acatcttgta gtttctttaa 2700 aacttaaaca tatacctacc atatgatcca actattccac tccagaaaaa agaaatatat 2760 atccataaaa agacttgtac aaaaatattc atggtaactt tacttataaa agcaaagaag 2820 ttggaaatac tctaaatgtc tataaacaag agaatggata aataaattgt gatgtagcca 2880 tacaatggaa tattcctcag caaggaacag aaacaaactg ttgaaataca caataaaatg 2940 tatgaatctt aaaataaata tgctgaatga caaaatccag acc 2983 <210> 162 <211> 6053 <212> DNA <213> homo sapiens <400> 162 taggttgtga cagttggaag tgtcatgtac aacatgcggc gattaagtct ttcacccacc 60 ttttcaatgg gatttcatct gttagttact gtgagtctct tattttccca tgtggaccat 120 gtaattgctg agacagaaat ggaaggagaa ggaaatgaaa ctggtgaatg tactggatca 180 tattactgta agaaaggggt gattttgccc atttgggaac cccaagaccc ttcttttggg 240 gacaaaattg ctagagctac tgtgtatttt gtggccatgg tctacatgtt tcttggagtc 300 tctatcatag ctgatcggtt catgtcctct atagaagtca tcacatctca agaaaaagaa 360 ataaccataa agaaacccaa tggagagacc accaagacaa ctgtgaggat ctggaatgaa 420 acagtttcta acctgacctt gatggccctg ggatcttctg ctcctgagat tctcctttca 480 gtaattgaag tgtgtggcca taacttcact gcaggagacc tcggtcctag caccatcgtg 540 ggaagtgctg cattcaatat gttcatcatt attgcactct gtgtttatgt ggtgcctgac 600 ggagagacaa ggaagattaa gcatttgcgt gtcttctttg tgacagcagc ctggagcatc 660 tttgcctaca cctggcttta cattattttg tctgtcatat ctcctggtgt tgtggaggtc 720 tgggaaggtt tgcttacttt cttcttcttt cccatctgtg ttgtgttcgc ttgggtagcg 780 gataggagac ttctgtttta caagtatgtc tacaagaggt atcgagctgg caagcagagg 840 gggatgatta ttgaacatga aggagacagg ccatcttcta agactgaaat tgaaatggac 900 gggaaagtgg tcaattctca tgttgaaaat ttcttagatg gtgctctggt tctggaggtg 960 gatgagaggg accaagatga tgaagaagct aggcgagaaa tggctaggat tctgaaggaa 1020 cttaagcaga agcatccaga taaagaaata gagcaattaa tagaattagc taactaccaa 1080 gtcctaagtc agcagcaaaa aagtagagca ttttatcgca ttcaagctac tcgcctcatg 1140 actggagctg gcaacatttt aaagaggcat gcagctgacc aagcaaggaa ggctgtcagc 1200 atgcacgagg tcaacactga agtgactgaa aatgaccctg ttagtaagat cttctttgaa 1260 caagggacat atcagtgtct ggagaactgt ggtactgtgg cccttaccat tatccgcaga 1320 ggtggtgatt tgactaacac tgtgtttgtt gacttcagaa cagaggatgg cacagcaaat 1380 gctgggtctg attatgaatt tactgaagga actgtggtgt ttaagcctgg tgatacccag 1440 aaggaaatca gagtgggtat catagatgat gatatctttg aggaggatga aaatttcctt 1500 gtgcatctca gcaatgtcaa agtatcttct gaagcttcag aagatggcat actggaagcc 1560 aatcatgttt ctacacttgc ttgcctcgga tctccctcca ctgccactgt aactattttt 1620 gatgatgacc acgcaggcat ttttactttt gaggaacctg tgactcatgt gagtgagagc 1680 attggcatca tggaggtgaa agtattgaga acatctggag ctcgaggaaa tgttatcgtt 1740 ccatataaaa ccatcgaagg gactgccaga ggtggagggg aggattttga ggacacttgt 1800 ggagagctcg aattccagaa tgatgaaatt gtcaaaacaa tatcagtcaa ggtaattgat 1860 gatgaggagt atgagaaaaa caagaccttc ttccttgaga ttggagagcc ccgcctggtg 1920 gagatgagtg agaagaaagc cctgttattg aatgagcttg gtggcttcac aataacagga 1980 aaatacctgt ttggccaacc tgtcttcagg aaggttcatg ctagagaaca tccgattctc 2040 tctactgtaa tcaccattgc agacgaatat gatgacaagc agccactgac cagcaaagag 2100 gaagaggaga ggcgcattgc agaaatgggg cgccccatcc tgggagagca caccaagttg 2160 gaagtgatca ttgaagaatc ctatgaattc aagagtactg tggacaaact cattaagaag 2220 acaaacctgg cccttgtggt tgggactaac agctggagag aacagttcat tgaagctatc 2280 actgtcagtg ctggggaaga tgatgacgac gatgaatgtg gggaagagaa gctgccctcc 2340 tgtttcgatt acgtgatgca ctttctgact gtgttctgga aggtcctgtt tgccttcgtc 2400 ccccctactg aatactggaa tggctgggcg tgtttcattg tctccatcct catgattggc 2460 ctactgacag ctttcattgg agacctggct tcccactttg gctgcaccat tggcctgaaa 2520 gattctgtga ctgcagtcgt gttcgtcgca cttggaacat cagtgccaga cacatttgcc 2580 agcaaagtgg cagccaccca ggaccagtat gcagacgcct ccataggtaa cgtcacgggc 2640 agcaacgcgg tgaatgtctt cctgggaatc ggtgtggcct ggtccatcgc tgccatctac 2700 cacgcagcca atggggaaca gttcaaagtg tcccctggca cactagcttt ctctgtcact 2760 ctcttcacca tttttgcttt catcaatgtg ggggtgctgc tgtatcggcg gaggccagaa 2820 atcggaggtg agctgggtgg gccccggact gccaagctcc tcacatcctg cctctttgtg 2880 ctcctatggc tcttgtacat tttcttctcc tccctggagg cctactgcca cataaaaggc 2940 ttctaaagga actatcagat atagtaaatt tatatatata catatatata cataaaaatt 3000 atgtataatg gacagaggaa actgacattt gtcatgttca cttacctgct gatggaatcc 3060 agcttcaaga gcatactctg tactagggcc gaagtaaaaa accatcacct cccattccca 3120 ggggcatcat catgttcaac aaggcatgga ggcagggcca tctttgcagc tcagtctaga 3180 agggctgcac tctctccagg ttgataaatc cttaaggctt tgatttgttt tgtttttggt 3240 tttgttttca gtggagctgg ggaggtagtt aatgtttggc tttatttttg ttattttgtt 3300 ttgttttgtt tttttgggag agtcagggtt gttgcttttc tttgtggaaa gtgaaaccat 3360 ccaaatgtaa atgggttttg gtaaaaattt aaatcattag tattccccct cacctccccc 3420 aatcacttta aaacttattt tggattaaga aaaaatctgg gcatggaaga agaaagaagc 3480 atgtcttcat cgtattacca aagttcatgc ttatctccgg aatgtgagtg gaggtgaagc 3540 tgcctccaag aagaagcata aaagtggaat ggagccagga aatccgatgg ttctagaaat 3600 agtctgatat ttaaacatgt gatacctggc agtctcgttt aacaggtaca aggaaaacgt 3660 gcctagattc ccaggaacgt gcaaaatcct ttctttctta tctctttagc tctggactgt 3720 gattggcaag gtccttcttc cagcattcag cccagctaag cccccaggtg ccccatccca 3780 accctgttcc tcctgtccac ctgccatccc ctatgcaaac agtaagaata accccattca 3840 aaaagcacat catcgttttc catttgcatt aacatgtgtc tcagtcccat gttgccgttg 3900 cttgggattg tctgtcagtt ttattttcaa aggcatccat ggcttgcaca atcctgttcc 3960 agtcatgact gaacatttgc tccttcttca tgtgccgttc ggaaatgttg ttgtgatacc 4020 tgttacacag tgcatggtga aaaacaaata aaacaaaaca aagagtatct gtatatagta 4080 gagtatagta catactgttc tcccatttgg caatgttgat tggacattga agacataagt 4140 gagttttctt ttcacctgag ttgttacttt tgtgctgtta ttgagtttga ttaattacta 4200 gggataaaag gagaaaatgg attattgttc acggttctgc acattcattt ctaagaagca 4260 ataactgtca tgtggggaga agttaaagct attgagagga tagcaggcaa actacaaaga 4320 tcttcatgga aaattagcca tgtggaacac atcagaggcc tctaaaaatc acccattaat 4380 tcaggaaggc caaggagaaa ggccttatag agacgttgat atgttggatg tgcctaggct 4440 ttcagagcca ccctttccac aacacccctc cctgcaaagt atttatttca catctgcact 4500 gtctggcaca gatggtagat agtgctggtt tgttcatttt atttttttac ttaaaaggct 4560 attttgagcc ctgtttcttt cactgtccag tctagtcctc tttgattata tcagtagttg 4620 ctgagtaaga aagaagccag ggtgaccaac gggcctttaa aagtgttgtc tcctctactt 4680 atgctgaaag agaaggcaat taaataagac tagtacctcc caggaggatt ggactgggat 4740 atttttaacc ctttaaaaag aatagctgtt tctatgttaa aataccaaag aacatggata 4800 aacccaacat tccaaagtag tgagtccact aatgagaaaa ataatagaat gactttggtc 4860 acctctcgga gacttctgtg tctataagga atcccaggct ggagacattc ctagccctct 4920 gtattgattc aaaaatactt aataaattaa agctgttgag acttattttt tcttctgtca 4980 ctcagtaacc atgatccttc ctcatttaat aaacatttgg tgactgaatg agtaattaaa 5040 tgctggttac ccacttaatg tgccaggtag tatgatactt tctggggact aagccatgaa 5100 caaaacagtc tagatccctg ccctcagaag ggttacagtt tatgtgatta ctattttcat 5160 gagtaaaagt gaagaaagcc atatggaaag atttttatct tgcaagaaaa aacaattatg 5220 aaactctttt aacataaaca cactgaaact gtatcaaagc aattgtccaa attgtattta 5280 tacccaagaa tttctttaac taagagagca taaggcatat gtttggaaaa ccaccctctt 5340 tatctttgac cgacttgcag ataaatatat ctctccattt taaaccaaga agggcaatca 5400 tgttggtgat ccagatcact gagaaagccc agtgtatccc atcttttatc tttgttggca 5460 atggaacttt tctatggccc acactttaca attctttgtc attctaaccc atccttccca 5520 tccttatttt tttttttttt gagaattgct aaatggaaag ctagcctaga agcaccaagt 5580 aaatatattc aaggaatata agttgtttaa acattagaaa aatttttgca ctcatttttt 5640 agctgtatta ggaatgtcaa taatcctgta gcaaattttc acagagaact ttaagaaatt 5700 cttgcattgg tcgatttcaa tttgaaagct ttttggtttg tttgcttttt aaattttcat 5760 gttctaggaa actatgattc tggttgttca ggattgttat tattatagtt gtgtaaaatt 5820 attttatttt gtgtgtattg tgcacagctt gggggggggg cgggaaatgc actaattgtg 5880 ctcttcctta taaatggtac atattactga cacagacaaa taaagtttct aattgtttct 5940 gatttaatca ctagtgatac agcatattct gtatgaaatg ttttctcctt tctcattgtc 6000 atctacttca ttttttgttt tcatgttttg aagaaataaa aaccaaaatg gta 6053 <210> 163 <211> 49009 <212> DNA <213> homo sapiens <400> 163 aaataatgag agacatagtg cattagaaaa taaagtaaac atttctgttt tctttctcag 60 aaaaatgaac tgtcatgtat gtttattttc tttcttttaa gggatgttac tggctggttt 120 tacaattagg aatgttccat tcatcaatga acatgtccat gttcctaacg catggtcttc 180 aattttaaga agcattgccc ttaacattat tctaatacga gctgggcttg gactcgatcc 240 acaggtagat ttacaattac aaatcgagta aggttatttc aaatattaga ggatggtgag 300 aaagaaaaag aagcaaaaat tttatttacc tgttccaagt ggagtctgta aacaaaccta 360 agataaagaa aaaaaggccg ggcatgatgg ctcatgcctg taatctacaa aaattagctg 420 ggcatggtgg catttacctg gtaatcccag ctactcgaga ggctgaggca agagaatcgc 480 ttgaacctga gtgacagagg ttgcagtgag ctgagataat gccactgcaa tccagcctgg 540 gggacagagt gagactctgt ctcaaaaaac aaaacaaaac aaaacaaaca aacaaaggtt 600 ttataagaaa aaccttatac aattcttttt cttttttagg gtgattaagg atttcagtaa 660 ttttttatga cgttttctct acaggattat gttcctgatt atctttgcat tattgtaaaa 720 tctaatcttt taaaacattt cttaaaatat tacattctag ggatcataaa ttccatctat 780 aagaagatga ctattcatga atatgacagc cactcaaata tatgtggcaa atgtggttta 840 atagaaatag ctcgagcaca aataattata gccaatgaga ttatattctc cagtagaaag 900 tatgaaccaa ggagaaaatt gaaaagttct cccttttaaa atgaattatg cagtttttaa 960 gttattttct ttggcatgtt agtattgtat ttatacttat taagttaatc aaacagttca 1020 tatcaaaaag ttaatgggaa aacactaata ggacactatt attatactat gtattaggaa 1080 agttcaggaa ggtagcatta actatttaat cacagtaaaa ttgatctttt aataattaaa 1140 atatacaata atattttata aaagatgaaa ttgtttataa tccaacctat gatgacatat 1200 aaaatataat agagttcaaa gtccagtggg acaatctgtt gaaatgagat tttgtttagt 1260 gaaagcttct tatgaaaaaa gactttatag accaacattt gttaaaataa ttttcttttt 1320 ggccattgta aatgtatcaa atgtgactgt tttgtgtttc aggctttgag gcatttgaag 1380 gtggtttgtt tcagattggc tataggtcca tgccttatgg aggcaagtgc agctgctgtt 1440 ttatcccact tcattatgaa attttcctgg caatgggcaa ttctattagg gtaatttctt 1500 tctcattttt tcttacgaaa atattcaatt aaagaggctt ggttaaaact gttaaaatat 1560 tcagaatatt gtatagaaaa gctctattaa aattcatttc acagtgttaa aatccttgga 1620 aagcacttga ttaaaagcag agcatgtccc aaattgcacg aaatttttta acaaacatta 1680 atagccccta aatgtttatc atcaagaaaa ttcgcgtgat caatttattc cttttcatct 1740 gtattataac atatctgtat gctttaatct atctaatggc ctcttcctca tggctatatg 1800 taaatacagt tgcacatttc atatatatgt atgtgtatat atatatatat atttgagaaa 1860 cattttatat agacagaaga aagcaagcaa acaaaatctc ttgccgtata tccaatgccc 1920 catccatctt tatctaccat ccatttgtct tatgtttgaa ttcctcaaaa taagtctata 1980 actactgtct ctagatccta actccttttc atttcttaat taatcaactt ttgtctctgc 2040 ttatccattc caatgacact catagcaaag ttcatccatt acatagttac tacaaaatcc 2100 agtgaatttt taaattaatg tttatgataa aatactcaaa tgcactttta ttttaaaaat 2160 tagaacttta taaataaagg aggaatgacc ttaaactatg ccttcaaatc ataatgccca 2220 taactctacc caaagtgaca actcttagga gtttttttct tctccaattt ttattttggc 2280 tcaaggggta cattagcagg cttgttatat ggataaattg catgtcacag gggtttggta 2340 tgcagagtga cgattgatcc cttctttctg tccatgtgta ctcagtgttt agctcccact 2400 tataagtgag aatatgggat atttggtttc ctgctcctgc gttaattaac tttgtgtatt 2460 attctatggt gtatatgtgc cacattttct ttatccagtt caccattgat ggacatttag 2520 gttgatctca tgtctttttt attttttttc attagttttt aaggaacagg tggtgtttgt 2580 ttacatggaa aatattttta gtggtaattt ctgagatttt ggtgcaccca tcaccagagc 2640 actgtacact gcacccaagg tgtagtcttt tatccctcac cctcctccta ctcttccccc 2700 taagtcccca aagtccattg tatcattctt gtgcttttgc atcctcatag cataactccc 2760 acttataagt cagaatatac aatgtttggt tttttcattc ctgaattact tcacttagaa 2820 taatggtgtc cgactccttc caggctgctg tgaatgccat tatttcattc ctttttatag 2880 ctgagtagta ttctgtccat ggtctgtgtg tgtatatata tacacacaca tacacatata 2940 tatacacata tatacacata tgtgtgtata tacacatata tacacatata tacacacata 3000 tatgtgtgta tatacacata tatatacaca tatatgtgta tatacacata tatacacata 3060 tatgtgtgta tatacacata tatatatgca ccacattttc tctatgcatt cattgattga 3120 tgggcatttg agctagttcc atatctttca caattgcaaa ttgtgctgca gtaaacgtgt 3180 gtccaagtat ttttttcata taaagacttc ttttcctctg ggtagatacc tagtagtggg 3240 attgctagat caaatggtag atctactttt aattatttaa gaaatcttca tactcttttc 3300 catagtggtt gtcctagttt acattccccc cagcagtgta aaggtgttcc ctttttacca 3360 cacccatggc aacatctatt tttttttaat tttttgatta tggctattct tggaggagtg 3420 agatggtatc gcattgtggt tttgtttgca tttccctgat aattagtgat attgaggatt 3480 ttttcatgtt tcttggccat ttatatcttc ttttgggaag tgtctattca tgtccttaac 3540 acactttttg atagggtagt ttgttttttt cttgctgatt tgtttgtgtt ccttatggat 3600 tctacatatt agcactttgt tggatgcata gtttgtaaag attttctccc actctatata 3660 ggttgtcttt ttactctgct gattaattct tttgctgtgt agaagcttct tagtttaatt 3720 aagtcccatc tacttatctt tgcttttgtt gcctttgctt ttgggttctt ggtcatgaag 3780 tctttgccta agcaaatgtc tagaagggta tttccaatgt taccttctag aatttttata 3840 gttttaggtg ttagatttaa gtctttgatc catcttgagt tgatttttgt ataaggtgag 3900 agatgaggat gcagtttcat tcttctacat atggcttgcc aattaaccca gcaccatttg 3960 ttgaatatgg tgtcctttcc caactttatg tttttgtttc ctttgttaaa gatcagttgg 4020 cttaagtatt tggctttatt tctcagttct ctattcgatt ccattagtct acgtgcctat 4080 ttttatagca gtattatgct gctttggtga ctatagactt atagtacagc ttgaagtcaa 4140 gcaatgtgat gcatccacat ttgttctttt tgcttagtct tgctttcgtt atgcgggcta 4200 tttttgagtt ccacatgaat tttaggaatg ctttttctag ttcagggaag aatgatgatc 4260 tatgatcatc agtgataact gtcctgaagt tttctttttt gttgtgtctc tgccaggttt 4320 tcatatctga atgatgctga cctcataaaa tgagttaggg agggatcctt cctcctcctt 4380 ttttcggaac aatttcagta gcattgatac cagctcttct ttacacttcc ggtagaattt 4440 gtctctgaat ctgttgggtc ctgggcttgc attttttttt ctttttttgg ctcagagact 4500 ttttattact cattcagttt caaaacacat tttttgcttt gttcaggatt tcaatttctt 4560 cctagttcaa tcttgggagg ttgtatgttt ccagaaattt acccatttct tttttttttt 4620 tttatatact ttaagtttta gggtacatgt gcacattgtg caggttagtt acatatgtat 4680 acatgtgcca tgctggtgcg ctgcacccac taactcgtca tctagcatta ggtatatctc 4740 ccaatgctat ccctcccccc tccccccacc ccaccacagt ccccagagtg tgatattccc 4800 cttcctgtgt ccatgtgatc tcattgttca attcccacct atgagtgaga atatgcggtg 4860 tttggttttt tgttcttgtg atagtttact gagaatgatg atttccaatt tcatccatat 4920 ccctacaaag gacatgaact catcattttt tatggctgca tagtattcca tggtgtatat 4980 gtgccacatt ttcttaatcc agtctatcat tgttggacat ttgggttggt tccaagtctt 5040 tgctattgtg aataatgcca caataaacat acgtgtgcat gtgtctttat agcagcatga 5100 tttatagtca tttgggtata tacccagtaa tgggatggct gggtcaaatg gtatttctag 5160 ttctagatcc ctgaggaatc gccacactga cttccacaat ggttgaacta gtttacagtc 5220 ccaccaacag tgtaaaagtg ttcctatttc tccacatcct ctccagcacc tgttgtttcc 5280 tgacttttta atgattgcca ttctaactgg tgtgagatgg tatctcattg tggttttgat 5340 ttgcatttct ctgatggcca gtgatgatga acattttgtc atgtgttttt tggctgcata 5400 aatgtcttct tttgagaagt gtctgttcat atccttcacc cactttttga tggggttgtt 5460 tgtttttttc ttgtaaattt gtttgagttc attgtagatt ctggatatta gccctttgtc 5520 agatgagtag gttgcgaaaa ttttctccca tgttgtaggt tgcctgttca ctctgatggt 5580 agtttctttt gctgtgcaga agctctttag tttaattaga tcccatttgt caattttggc 5640 ttttgttgcc attgcttttg gtgttttgga catgaattct ttgcccatgc ctatgtcctg 5700 aatggtaata cctaggttgt cttctagggt ttttatggtt ttaggtctaa cgtttaaatc 5760 tttaattcat cttgaattga tttttgtata aggtgtaagg aagggatcca gtttcagctt 5820 cctacatatg gctagccagt tttcccagca ccatttatta aatagggaat cctttcccca 5880 ttgcttgttt ttctcaggtt tgtcaaagat cagatagttg taggaatgcg gcgttatttc 5940 tgagggctct gttctgttcc attgatctat atctctgttt tggtaccagt accatgctgt 6000 tttggttact gtagcttgta gtatagtttg aagtcaggta gtgtgatgcc tccagcttta 6060 ttcttttggc ttaggattga cttggcaata cgggctcttt ttttggttcc atatgaactt 6120 taaagtagtt ttttccaatt ctgtgaagaa agtcattggt agcttgatgg ggatggcatt 6180 gaatctgtaa attaccttgg gcagtatggc cattttcacg atattgattc ttcctatcca 6240 tgagcatgga atgttcttcc atttgtttgt atcctctttt atttccttga gcagtggttt 6300 gtagttctcc ttgaagaggt ccttcacatc ccttgtaagt tggattccta ggtattttat 6360 actctttgaa gcaattgtga atgggagttc actcatgatt tggctctctg tttgtctgtt 6420 gttggtgtat aagaatgttt gtgatttttg tacattgatt ttgtatcctg agactttgct 6480 gaagttgctt atcagcttaa ggagattttg ggctgagaca atggggtttt ctagatatac 6540 aatcatgtca tctgcaaaca gggacaattt gacttcctct tttcctaatt gaataccctt 6600 tatttccttc tcctgcctaa ttgccctggc cagaacttcc aacgctatgt tgaataagag 6660 tggtgagaga gggcatccct gtcttgtgcc agttttcaaa gggaatgctt ccagtttttg 6720 cccattcagt atgatattgg ctgtgggttt gtcatagata gctcttatta ttttgaaata 6780 catcccatca atacctaatt tattgagagt ttttagcatg gaaggttgtt gaattttatc 6840 aaaggctttt tctgcatctg ttgagataat catgtggttt ttgtctttgg ctctgtttat 6900 atgctggatt acatttattg atttgcatat attgaaccag ccttgcatcc cagggatgaa 6960 gcccacttga tcgtcgtgga taagcttttt gatgtgctgc tggattcggt ttgccagtat 7020 tttattgagg atttttgcat caatgttcat caaggatatt ggtctaaaat tctctttttt 7080 ggttgtgtct ctgcccggct ttggtatcag aatgatgctg gcctcataaa atgagttagg 7140 gaggattccc tctttttcta ttgattggaa tagtttcaga aggaatggta ccagttcctc 7200 cttgtacctc tggtagaatt ccgctgtgaa tccatctggt cctggactct ttttggttgg 7260 taaactattg attattgcca caatttcagc tcctgttatt ggtctattca gagattcaac 7320 ttcttcctgg tttagtcttg ggagagtgta tgtgtcgagg aatttatcca tttcttctag 7380 attttctagt ttatttgcgt agaggtgttt gtagtattct ctgatggtag tttgtatttc 7440 tgtgggatcg gtggtgatat cccctttatc attttttatt gtgtctattt ggttcttctc 7500 tctttttttc tttattagtc ttgctagcgg tctatcaatt ttgttgatcc tttcaagaaa 7560 ccagctcctg gattcattga ttttttgaag ggttttttgt gtctctattt ccttcagttc 7620 tgctctgatt ttagttattt cttgccttct gctagctttt gaatgtgttt gttctttctt 7680 ttctagttct tttaattgtg atattagggt gtcaattttg gatctttcct gctttctctt 7740 gtgggcattt agtgctataa atttccctct acacactgct ttgaatgcat cccagagatt 7800 ctggtatgtt gtgtctttct tctcattggt ttcaaagaac atctttattt ctgccttaat 7860 ttcgttatgt acccagtagt cattcaggag caggttattc agtttccatg tagttgagca 7920 gctttgagtg ggattcttaa tcctgagttc tagtttgatt gcactgtggt ctgagagata 7980 gtttgttata atttctgttc ttttacattt gctgaggaga gctttacttc caactatgtg 8040 gtcaattttg gaataggtgt ggtgtggtgc tgaaaaaaat gtatattctg ttgatttggg 8100 gtggagagtt ctgtagatgt ctattaggtc cgcttggtgc agagctgagt tcaattcttg 8160 ggtatccttg ttgactttct gtctcgttga tctgtctaat gttgacagtg tggtgttaaa 8220 gtctcccatt attaatgtgt gggagtctac gtctctttgt aggtcactca ggacttgctt 8280 tatgaatctg ggtgctcccg tattgggtgc atatatattt aggatagtta gctcttcttg 8340 ttgaattgat ccctttacca ttatgtaatg gccttctttg tctcttttga tctttgttgg 8400 tttaaagtct gttttatcag agactaggat tgcaacccct gccttttttt gttttccatt 8460 tgcttggcag atcttcctcc atccttttat tttgagccta tgtgtgtctc tgcatatgag 8520 atgggtttcc tgaatacagc acactgatgg atcttgactc ttcatccaat ttgccagtct 8580 gtgtctttta attggagaat ttagtccatt tatatttaaa gttaatattg ttatgtgtga 8640 atttgatcct gtcattatga tattagctgg tgattttgct cgttagttga tgcagtttct 8700 tcctagtctc gatggtcttt acattttggc atgattttgc aggggctggt accggttgtt 8760 cctttccata tttagcactt ccttcaggag ctcttttagg gcaggcctgg tggtgacaaa 8820 atgagtcagc atttgcttgt ctgtagagta ttttatttcc ccttcactta tgaagcttag 8880 tttggctgga tatgaaattc tgggttgaaa attcttttct ttaagaatgt tgaatattgg 8940 cccccactct cttctggctt gtagggtttc tgccgagaga tccactgtta gtctgatggg 9000 cttccctttg agggtaaccc gacctttctc tctggctgtc cttaacattt tttccttcat 9060 ttcaactttg gtgaatctga caattttgtg tcttggagtt gctcttctcc aggagtatct 9120 ttgtggtgtt ctctgttttt cctgaatctg aatgttggcc tgccttgcta gattggggaa 9180 gttctcctgg attatgtcct gcagagtgtt ttccaacttg gttccattct ccccatcact 9240 ttcaggtaca ccaatcagac atagatttgg tcttttctca tagtcccata tttcttggag 9300 gctttgctca tttcttttta ttcttttttc tctaaacttc ccttctcact tcatttcatt 9360 catttcatct tccattgctg ataccctttc ttccagttga tcgcatcggc tcctgaggct 9420 tctgcattct tcacgtagtt ctcgagcctt ggttttcagc tccatcagct cctttaagca 9480 cttctctgta ttggttattc tagttataca ttcttctgaa ttttgttcaa agttttcaac 9540 ttctttgcct ttggtttgaa tgtcctcccg tagctcagag taatttgatc gtctgaagcc 9600 ttcttctctc agctcgtcaa agtcattctc catccagctt tgttctgttg ctagtgagga 9660 actgcgttcc tttggaggag gagagacgct ctgcgtttta gggtttccag tttttctgtt 9720 ctgttttttc tccatctttg tggttttatc tacttttggt ctttgatgat ggtgatgtac 9780 agatgggttt tcggtgtgga tgtcctttct gtttgttagt tttccttcta acagacagga 9840 ccctcagctg caggtctgtt ggaataccct gccgtgtgag gtgtcagtgt gcccctgctg 9900 gggggtgcct cccagttagg ctgctcgggg gtcaggggtc agggacccac ttgaggaggc 9960 agtctgccgg ttctcagatc tccagctgcg tgctgggaga accactgctc tcttcaaagc 10020 tgtcagacag ggacatttaa gtctgcagag gttgctgctg tctttttgtt tgtctgtgcc 10080 ctgcccccag aggtggagcc tacagaggca ggcaggcctc cttgtgctgt ggtgggctcc 10140 acccagttcg agcttcccag ctgctttgtt tacctaagca agcctgggca atggagggcg 10200 cccctccccc agcctcgctg cctccttgca gtttgatctc agactgctgt gctagcaatc 10260 agcgagattc cgtgggcgta ggaccctcca agccaggtgt ggcatatagt ctcgtggtgc 10320 gccgtttttt aagccagtct gaaaagcgca atattcgggt gggagtgacc cgattttcca 10380 ggtgcgtcca tcaccccttt ctttgactca gaaagagaac tccctgaccc cttgcgcttc 10440 ccaggtgagg caatgcctcg ccctgctttg gctcacgcac agtgagcaca cccactggcc 10500 tgtgcccact gtctggcact ccctagtgag atgcacccgg tacctcagat ggaaatgcag 10560 aaatcacccg tcttctgtgt tgctcacgct gggagctgta gaccggagat gttcctattc 10620 ggccatcttg gctcctcccc ccgaaattta cccatttctt gtaggtgttc tactttgttt 10680 gcataaacat gttcatcata gtctctgaga gttttttgta tttctgtgtg gttggcggta 10740 atgtccactt taccatttct gattgtgttt tttgtatctt ctcttttttt ttttccttat 10800 tggtctagct agtgacctat caaatttatt tattcttttg aagaaccagc ttttagtttc 10860 atttatcctt tgtatgcctt ttcatgactc aattttattc cattctgctc tgattttggt 10920 tatttattct cttctgctag ctttgggttg gtttcctctt gtttttctat ttcctttaag 10980 tatgatatta ggttgttaat ttaagatcct tctaactttt caatatgggc atttagcacg 11040 ataaactttt cccttaacac tgctttgcct gtgtcttaga gagcctagaa tgttgtatct 11100 ttgttttaat tagtttcaaa gaatttattg gtttctgcct taatttcatt gtttacccaa 11160 aagtcattca ggcacaggtt gtttaatttc catgtaattg tatggttttg agagttcttc 11220 ttagtgttga cttctatttt tgttacactg agcggtccaa gattgtggtt ggcatgattt 11280 caggggtttc ttttaattta ctgaaaataa ttttagactg atagtgtgat caattttaca 11340 atatatgcca tgtacagatg agaggaagat atattctgtt gttgttgggt ggagtgttct 11400 gtagatggct gttaggtcca tttagccaag tgttgacttc aagtcctgaa tatctttgtt 11460 cattttctgt ctctatgatc tgtctagtac cgtcagtgag atgttgaagt ctcccactat 11520 tctgtggtta tctaagtctc tctataggta tctatgaact tgttttacga atgtgaatgc 11580 tccagttttg agcacattta tctttcagac agttaagtct tcttgttgaa ttgaaccctt 11640 tatcattact tagtgccctt ctttgtcttt ttgattgttg ttggtttaaa gtctattttg 11700 tctgaattag aataacaatg cttacccttt tttgttttac atttgcttgg tagatttttt 11760 tccatccttt tacttcaagc gaatgggtat tgttgcatat gagctgggtc tcttgacaac 11820 agataaggtt gggctttgct tctttatcca acttgtcatt ctgtgagttt taagcggggc 11880 atttatactg tttacattca cagttaatat tggtatttat agctttggtc ctaccattat 11940 gttgttagct ggttattatg cagacttgat tgtgtagtta ctttacaacg tcaatggtct 12000 atgtacttaa atgtattttt gtggtggcca ttaacagtct ttcacttcca cgcttagcac 12060 tcccttaagg acctcttgta aggcatgtct ggtggtaaca gattccatta gcatttgctt 12120 gtctgaaaag gatcttactt ctccttcaca tatgaagttt agtttggctg gatattaagt 12180 tcttggttga attttttttt tttttttttt tttttttttt gtgacagagt cttgctctgt 12240 ccccaggctg gagtgtggtg gtgttatctc ggcttactgc aacctccacc tcctgggtta 12300 agtgattctc ttgcctcagc ctcccgagta gctgggacta cagacacgca ccaccatgcc 12360 cagataattt ttgtattttt attagagatg aggtttcacc atgttggcca ggatggtctt 12420 gatctcttga ccttgtgttc tgcctccctc agcctcccaa agtgctggga ttacaggcat 12480 gagccaccac acccagccaa gtattttttt tttaagaatg ctgaaggccg ggcatggtgg 12540 ctcacacctg taatcccagc actttgagag gccgaggtgg tcagatcatg aggtcaggaa 12600 tttgagacca ccctggccaa tatggtgaaa tcctgtctct actaaaatta caaaaaattg 12660 ctgggtgttg tggtgcacac ctgtagtccc agctacttgg aaggctgagg gggaagaatt 12720 gcttgaaccc gggaagtgga ggttgcagtg agccgagata gcaccagtgc actccagcct 12780 gggcaacaga gtgatactcc gtctcaaaaa aaaaaaaaaa gaatgctgaa tataggcccc 12840 caatttcttt tggattgtag agtatcttat agttccactg ttagcctgat gggattccct 12900 ttgtatgtga cctgcccctt cattttagct gcctttcata tttttttatt tcatgttgac 12960 cttggagaat ctgatgactc tctgtcttgg ggatggtcat cttgtatagt gtctcacagg 13020 attctctgca tttcctggat ttaaatggtg acttctctag caagatttgg gaaatttttg 13080 tgggcagtat cctcaaatat gttttccaac ttgcttgttc ttcctccctt tctttgagtg 13140 atgccttgag tcatatgttt ggtctcttta cataatctca tatttctcag aggttttgtt 13200 cattcttttt tgttctttat tttcatctga ctgagttgat tcaaagaagt ggtctttgag 13260 atctgagatt ctttcctcag cttggtccgt tctgctgtta gtacttgtta ttgtattatg 13320 aaattcttga ggtgcatttt tcagctctat cactttagtt tggttatttc ttaaaatgcc 13380 tgtttcatct ttaagctctt atgtcatctt attggattcc ttagattatt tggattggat 13440 tttgactttc ttctgaatct caatgatctt tgtttctatc cagattctga attctatgtc 13500 tgtcatttaa tcctggttaa caaccattgt tggagagtta gtatgattgc ttgaagacag 13560 gaagacattc tggattttta cattgccaga gttcttgcac tggttctttc acatctgtgt 13620 gagctaaggt tcctttaatg ttttgaatca ctgtcctttg gatggagttt tttccttttt 13680 tatattcttt aatgcccttg agggtttgac tgtggcacaa ggtagtttca gtcaaatggc 13740 ttcatttctg gaagatttca gggggtaaag gctcagctca gcactcctga actgcatact 13800 ctaactttgc aaggctggta ccataccaac agatttgttg tctggccctt caatgttaag 13860 cactgaggtg ttcccagtcc actggcaaca acactctgat ggggtgtgcc agccaaagtg 13920 cttcattgta gtgattgtag caaggtcccc actcacacat atgtgtcagc agcagcagca 13980 cacagcaggt atgcatgtgt tggcaggggt gcagtgctgg caggagtggg atgggggtgt 14040 tctgcatact tgcatgtgtc agccggggca atggtgttgt ggggtgcact catgtgctgc 14100 tggagacaga gtggcagcat cttcatgagt tttatgttat cattctaaat ctttaaaaat 14160 aatgttctag acttctaaca aatgtatttg tgaacccaga gaaaaaaaga gtattatttt 14220 gtgcattatt acttaatcat atccaagaaa attttacttt acaatttgtt cttttcactc 14280 aacaatagtg ttgaggttta tccatctcaa gatggataca catgtagttt attcctttta 14340 attgtataag attacattgt atgtcaacag cagattttat ttactatgtt ataacaaaaa 14400 tagcatttta tttgtctcat tttatataaa tataagtttg tctagaatag ttacctgggt 14460 tacatgaatt tttagtttga tgtatactgc caaaatcttt ttggtatggc cactttaatt 14520 tgccctaata ccaatagctt atgagcatac ctgttgttct tgaaaatcct tgcaaatcct 14580 tgatattatt aaattttata atgttttcca gtctgatcat tgaaaaaatg gcatattttt 14640 gttattttag tttgcatttc tgtgattatt cacaagcttg aatatctttt atatacgtgt 14700 tgtccttcag cttttcctta tctgtaacta gcctgttcat atcctttgtc catttttttg 14760 ttgagttggt cttctttatt aattatatct gttatatgca tttgtaaatt atatgtattg 14820 caaatatcag tagatattta attttgtttg tgatgatttt tttttcactc taagaagtgt 14880 attttgttat tttcaacaga cagaattgcc aatacacaac accgttcact tgactttgaa 14940 aatgaaaaag aaaaaggggg agaaagagca gaattgcttt tgaagtagta ctttattata 15000 gtacttttga agttgctttt gaagtactac tttaatataa ttgaatgtat tacaatctct 15060 ttttatgtct aatgtctttg tatgtatcat tcaaaaggtc ctttttacct catgatcaca 15120 aatatattat tctacatctt ttttttgttg ttcagagtct tgctgtcacc caggctatag 15180 tgcagtggca tgatctcagc tcactgcaac ttccacctcc caggttcaag tgattctcct 15240 gcctcaacct cccaagtagc tgggactaca ggcatgcacc actgcaccca gctattggtt 15300 tcaccatgtt ggccaggctg ttctcagatt cctgatctgt ccacctcagc ctcccaaagt 15360 gctgggatta caggtgtgag ccatcaggcc tagcccacta cattttctta ttactacttt 15420 tccttttgag cttttaacat ttattatatg taaggatcta tctatattcc tttccacata 15480 aatagttatc tcaacaccat ttgtgaaaga tttctttctt tctcccactg atttaaaata 15540 ccaattgtat gatgtaacaa atcccataga tttgtttcca cactttgtat tctcttttct 15600 tccaatttat tttgtctttt tatatgtcac tattattcag ttttaactat tttaccttta 15660 caaaaacagt atcttgtttt cttaagttta cttgatcttt cattctaaga ccttattctt 15720 ccaaatgaat tttataatca gcttgtcaag ctcagtataa atccctgcaa agattttgat 15780 tggtgtatct gattaattca tttgggggag agtttacatc tttatattat tgaggctttg 15840 gccaggcatg gtggctcaca cctataagcc aagcactttg ggaggccaag gcaggcatat 15900 cacttgaggt caggagttca agaccagcct ggccaaaatg atgaaacacc gtatctacta 15960 aaaacaccaa aactagccag gcgtggtgtt gagcgatggt aaaattgggg ctttttagtt 16020 cacacttgtg aaatgtctcc ctaagtattc aggtattatc ttaattatta tattattata 16080 ttcacaattt ttataaaagt atagactgtc ttcacagttt tgttcttaga tactttgtgt 16140 ttttaattga tgttgtggat taaattctct ttgatcactt attcctgggg aagccagctg 16200 ccatgtcctg aggcagccct gtggagaaaa ccccactgga aaaaactgaa gcctgcaatg 16260 gctacatgag taaacttgga agcagatctt ctccacccca ccctacctca tgggaaatct 16320 taagtcaagg catacaacta agccatgccc agattcctga cccacagaag tcataagaca 16380 ataaatattt gttgttttaa gctgctatgt ttggggatga cttgttaagc aaaataagaa 16440 aaataataca acaggtgatt acaatgtgca gcagagttca ggaaccactg aactagacca 16500 gtatgtggtt ttagagaagt ctagtctctt cttgagccca cagggaaatc tgtagcataa 16560 actgcgccat agagttgtac agccagaagc aaatctcaca tcagtacgtc attggcagat 16620 gctgtctgga gggaaagtag aggggtgcac aacctcccta gtattcccag gtaggtgctt 16680 gtcagcagga caaaggttct agaaacctgc agatattagc agccaacaag aagcactggg 16740 agatgtgttc atagacctgg taaatggatt ctggcaggag caccaaaagc atttctacac 16800 aggatatact tcacacttta taaagtaaat gtagaagaga tgaggtgaat ttctggataa 16860 gatatgccaa tagaaagtat tctgagcagg agcctcccca ttcctcatgg gtgtcatcaa 16920 ccactccaga aatgttctca tttgcctttg taacttaggt ggccacactt gttcttttgg 16980 gcagacaact ctgttccttc cttccttact tacttattta ctcaagaggt aggaaatgtg 17040 tggaaggtag atttgtctga ccattcttac agtggtactc caaataatca actatttggt 17100 ttccccagag gtctctcctg ctcccagcat ctgtcatttc agggcttgga ccacttttag 17160 aagcacatgt atcttttgag gcaattttat ttacacacat tttggtttat ggtttccttt 17220 tttcaatcct aaattgtctg tctcttatct ttctggcata tacttagtta cttgtccatt 17280 gatgattcac cttttgcttt ctagttaggt tatgaatttt tctattacct ttacatcttc 17340 acttctaagg atttaggaat agagggagag gctgcaacct gtgctcagcc caacatttta 17400 aacaacgtct gtataaaatt ttagccagca ctaaacaatg catggaaagt tttatcacca 17460 ttaaattgca ttcactcaaa tttgaaattc ttctaaacaa tgtttgttat aaatttatta 17520 taaactactt gtacttataa aacactactt gattaaaaag atgcttttaa attaattttc 17580 attcttcttt cagttttgtt ctaggtgctg tctctcctgc tgttgttgtt ctttacacga 17640 tggtgttgca agaaaatgga tatggtgttg aggaagacat tccaacctta ctaatggctg 17700 ctagcagtat ggatgacatt ctggctctca ctggattcaa tacatgcttg agcatagtct 17760 tctcctcggg taaacaagaa aatataacaa ccaccagatc attcatgacc ttttttgtta 17820 gttctttaaa cagggtttct ggctttgctt cttcatttat taaccaagac tgttcaattt 17880 aacatctttt taatctccat agaaagctca ttccagacca aggaagatat ttcagtggct 17940 taagatacca ctacttaaca cacatgatct cactttaata atcatatgac aattagtttg 18000 ataaaccata ttattactat ttatctgctt atgttgcttt tgaattttat cagttctcat 18060 tagaaaaaat taagcagcag tattatttgt actactaata ttttaatagg catttttgaa 18120 atgcgccttt ttggccatcc taataaacaa ctggttgctc tattataaga caacataaac 18180 atacagagct gggacagcca tatgcctttt tggtagtgtt aggacaaaat cctgcaccag 18240 ttctgattcc caaggtgata tctggtcttg aatatcacta cagaaattgt gaaactaaac 18300 atttccacat gtagtaatgc tttaattatc tgcaatgttt gagtcttctg tattattgaa 18360 gcgctaaact atttttaagt tgaaaagtaa tatatatagt tttatagttt ctcttaaaat 18420 aagaaaatat aaataaataa gaaaaagagg aaaagttaaa aataaaatct gcaatagtca 18480 catccagaag aaaagaatca tttccttctg aaccttttgg tataaatcca cccatattcc 18540 cttcccttcc cttcttccct tcttcccttc tcttcccttc ccctctcctc ccccttccct 18600 tcccttaccc ctctctctct gtcaaatatt cttataaaaa tcagtgaata tttaccaaca 18660 tgttctttta ttattttttt ttgaggcgga gtcttgctct gtcacccagg ttggagtgca 18720 gtggcacaat ctcggctcac tgcatgctct gcctcccggg ttcatgccat tctcctgcct 18780 caactgcaca agtagttggg actacaggcg cccgccacca cgcccggcta attttttttg 18840 tatttttagt agaaccaggg tttcaccatg ttagccagga tggtcttgat ctcctgacct 18900 cgtgatccgc ctgcctcagc ctcccaaagt gctgggatta caggcgtgag ccatcgcacc 18960 cggcctaata tgttcttata aactgaattg ttttacactt aactgtatat cacaaacatg 19020 tttctttaca gtaaatgtat ttgtatatca tttttaatag ttgtttagct taatgaaaga 19080 gtattcaatg tgctgcatca tgattactta tcctgttcaa aattaaagtt aactccaata 19140 tttactatta aaatgatacg tagttgtgtt gctataaaaa ttttttttaa attaaaaaat 19200 tggccgggca tggtggctca cacctataat cccagcactt tgggaggcca agaagggtgg 19260 atcacttgag gtcaggagtt caacaccagc ctggccaaca aacatggtga aaccctgtct 19320 ccactaaaaa tacaaaactt agccgggcat gttggtgggc atctgtaatc ccagctactc 19380 aggaggatga agcagaagaa tcacttgaac ccaggaggcg gaggctgtag tgagctatcc 19440 agcctgggca acagagcaag actctgtctc aaaaaaaatt ttttaattaa aaaatatact 19500 tagttgaaca tatagagaaa tatttgtacc taatcttcat attttcttaa gcttaaaagt 19560 gtaattgttg atctaaaatg tatatacatt tatgagtgtt ctgaaacata ttgccacaat 19620 atcatgtcct acccgggtac ataaacttgt catttcctct cacctctctt caaaacttgg 19680 tattactagc ctttttcatc tttgctaatt tgataggtga aggagggatc tctataaatg 19740 aagtactttg aatactagtg atgttaaata tccatgttta ttagtcattg gcattttgta 19800 aattgctttt cttgaaagtt ttttgcctat ttcttttagg tgggttcacc ttttattctt 19860 tttgatttgt caagattctg cattaaattg agaatgaaaa cctttgtttt atatacttta 19920 gttttttcaa tttgtaattt ggcttttaat tttctcactc tttttaccat tcagaagtta 19980 aagtttttta ttgtcaattg tgaaaatctt ttccttcatg attggtatct gtcattcttt 20040 caaaaaatat tgttatcagt catgtttcca aaaaatattt ccaggctggg cccaatggct 20100 cacgcctata atcccaacac tttgggaggc caaagcgggg ggatcactta aggacatgag 20160 ttcaagacca gcctggccaa catagcaaag ctccatctct actaaaaata caaaaagtta 20220 gctgggtgtg gtggcacagg cctctaatca cagctactca gggggctgag gcacaagaat 20280 cgcttgaacc caagaggcag aggttgcagt gagccaagat cacaccactg cactccagcc 20340 tgggtgacag agggatactg tctgaaaaaa agaaaaaaag tattcctctt ccttttgcca 20400 gctactatgc caaacactga gaataaacag taggcaacaa cattagcttt tattgaatac 20460 ttgcttgact cttgttctaa gttccatata tgtcaccact catttacagg taaggaaacc 20520 gagaaagatg ttaagtaatt ttctcaagga cagagatcca ataagtaggg gagccaagat 20580 gcaaatctga cagtctccct ccacacccac acatttaact cttctcttct ccactgcctc 20640 ccaacacaac agagagacaa gatcaaatgg tgcatgttct caaggagctt gtatattaaa 20700 gaaaaattac aaatgggatg aatattacat tgtgaaggtt aatattaagt aagtgtcaac 20760 ttgattggat tgaaggatcc aaagtattgt tcccggttgt gtctgtgagg gtgttgccaa 20820 aggagattaa catttattta gtggactggg aaaggcagat ccaccctcaa tgtgggtggg 20880 caccatacaa tcagctgcca gcatggctag aataaagcag gcagaagaag gtaaggagaa 20940 gctgacttgc tgagccttct ggccctcatc tttctcccat gctggatgct tcctgcactc 21000 aaatatcaga ctccaggttc tttggctttt ggactcttgg acttcctcca gttgttttcc 21060 aggggctctc aggccttcat ccagagactc aaagctggcc tgtctgtttc cctacttttg 21120 aggtgttggg actcagactg agccaatact agattccttg ctcctcaact tgcagacggc 21180 ctgttgtagg acttcacttt gtgatggtgt gattcaattc tccttaataa actccctttc 21240 atatatatat attctattag ttctatccct ctagagaacc atgactaata cagattttga 21300 tactgaggta atggagtatt gctataagat acctgagaat gtggaagtga ctttggaact 21360 gtgtaatgtg cagactttgg aacagttggg aggactcaga agaagatcag aagatgtggg 21420 aaagtttgga actgcctaga gacttgttga atggctttga ccaaactgct gatagtgact 21480 tggacagtga agtccaggct gaggaggtcc gagatggaga tgaacaactt gttgggaact 21540 gaagtaaagg tcactcttgc tatgctttag caaagagact ggtggcattt tgtccttgcc 21600 ctagagattt atggaacttt gaaattgaga gagatgactg aggacatctg gtagaagaaa 21660 cgtttgttgt tgttgttata ccttaagttc tagggtacat gtgcacaacg tgcatgtttg 21720 atacatagct atacatgtgc catgttggtt tgctgcaccc atcaactcat catttacatt 21780 aggtatttct cctaatgctc tccctccccc agccctccac cccccaacag gccccagtgt 21840 gtgatgttcc cagccctgtg tccaagtgat ctcattgttc aattcccatc tatgagtgag 21900 aacatgcgct gtttggtttt ctgtccttgt gatagttttg ctgagaatga tggtttccag 21960 cttcatctat ctccctgcaa aggacatgaa ctcatccttt tttatggctg catagtattc 22020 catggtgtat atgtgtcaca tgtcttaatc cagtccatca ttaatggaca tttgggttgg 22080 ttccaagtct ttgctattgt taatagtgcc gcaataaaca tacatgtgca tgtgtcttta 22140 tagtagcatg atttataatc ctttgggtat atacccagta acgggattgc tgggtcaaat 22200 ggtaattcta gttctagatc ctcgaggaat cgccacaatg tctttcacaa tggttgaact 22260 agtttacact cccaccaaca gtgtaaaagc tttcctattt ctccatatct tctccagcat 22320 ctgttgtttc ctgacttttt aatgattgcc attctaactg gggtgagatg gtatctcatt 22380 gtggttttga tttgcatttc tctgatgacc agtgatggtg agcttttttt cttgtgtctg 22440 ttagctgcat agatgtcttc tttggagaag tgtctattca tatctttgcc cactttttga 22500 tgggttgttt ttttcttgta aatttgtttg aattctttct ttgtcaaatg ggtagattgc 22560 aatttatctc ccgttctgta tgttgcctgg ttcactctga tggcagtttc ttttgctgga 22620 agctctttag tttaattaaa tcccatttgt caattttggc ttttgttgcc attgcttttg 22680 gtgttttagt catgaagtcc ttgctcatgc ctatggcctg aatggtattg cctaggtttt 22740 attctagggt ttttatggtt ttaggtctaa catttaagtc tttaatccat cttgaattaa 22800 tttttgtata agatgtaagg aagggatcca gtttcagctt tgtacatatg gctagctagt 22860 tttcccagca tcatttatta aataggcaat cctttcccca tttcttgttt ttgtcaggtt 22920 tgtcaaatat cagatggctg tagatgtgtg gttttacttc tgaggcctct gttctgttcc 22980 attggtctat atatctgttt tggcaccagt accatgctgt tttggttact gtagccttgt 23040 agtatagttt gaagtcaggt agtgtgatgc ctccagcttt gttctttttg cttaggactg 23100 tcttggcaat gcaggttctt ttttgtttcc atatgaactt taaagtagtt tttttccaat 23160 tctgtgaaga aagtcattag tagcttgatg gggatgatat tgaatctata aattactttg 23220 tgcagtatgg ccattttcat gatattgatt cttcctatcc atgagtgtgg aatattcttc 23280 catttgtttg tgtcctcttt taattcgttg agcagtggtt tgtagttctc cttgaagagg 23340 tccttcatgt cccttgtaag ttggattcct aggtatttta ttctctttgt agcaattgtg 23400 aatggaagtt cactcatgat ttggctctct gtttgtctat taatggtgta taggaatgct 23460 tgtgattttt acacattgat tttgtatcct gagactttgc tgaagttgct tatcagctta 23520 aggagatttt gggctgagaa ggtggggttt tctaaatata caaacatgtc atctgcaaac 23580 agggacaatt tgacttcatc ttttcctaac tgaataccat ttatttcttt ctcctacctg 23640 attccactgg tcagaacttc caacaccatg ttgaataaga gtggtgagag agggcatcct 23700 tgtcttgtgc tggttttcaa aaggaatgct tccagttttt gcccattcag tatgatattg 23760 tctgtgggtt tgtcataaat agctcttatt attttgagat acgtcccatc aatacctagt 23820 ttattgagag tttttagcat gaaggagtgt tgaattttgt caaaggcctt ttctgcatct 23880 attgagataa tcatgtggtt tttgtctttg gttctgttta tgtaatggat tatgtttatt 23940 gatttgcata tgttgaacca gccttgcatc ccagggatga agcccacttg gtcatggtga 24000 ataagctttt tgatgtgctg ctggattcag tttgccagta ttttattgag gatttttgca 24060 tcaatgttca tcaaggatat tggtctaaaa ttctcttttt ttgttgtgtc tctgccaggc 24120 tttggtacca ggatgatgct ggcctcataa aatgagttag ggaggattcc ctattgttct 24180 ttttttgttt tttggatgaa aaaagaactg tttaattttt ttgatgtttt caatgttgat 24240 attttttcca agaattagag aaatatctct ggatggttat ctaaaattta taattttttt 24300 accggtatgg tatgtaggag agtgtcatag tttttctatt attatacttt aagttctagg 24360 gtacatgtgc acaatgtgcc agtttgttac atatgtatac atgtgtcatg ttggtgtgct 24420 gcacccatta actcgtcatt tacattagat gtatctccta atgctatccc ccctcccccc 24480 actccatgac aggccccagt gtgtgatgtt ccccaccctg tgtccaagtg ttctcattgt 24540 tcaattccca cctatgagtg agaacatgtg gtgtttagtt ttctgtcctt gcgatagttt 24600 tttcagaatg atggtttcta gcttcatcca tgtccttaca aaggacatga actcatcctt 24660 tttatggctg catagtattc catggtgtat atgtgccaca ttttcttaat ccagtctatc 24720 attgatggac atttaggttg gctccaagtc tttgctattg tgaatagtgc cgcaataaac 24780 atacatgtgc atgtgtcttt atagcagcat gattcacaat cctttgggtg tatgcccagt 24840 aatgggatgg ctgggtgaaa tggtatttct agttctagat ccttgaggaa ttgccacact 24900 gccttctaca atgattgaac tagtttacac tcccactaac agtgtaaaag ccttcctatt 24960 tctccatatc ctctccagca cctgttgttt cctgaccttt taatgatcac cattctaatt 25020 ggtgtgagat ggtatctcat tgtggttttg atttgcattt ctctgatggc cagtgatgat 25080 gagcattttt tcatgtgtct gttggctgca tagatgtctt cttttgagaa gtcactgttc 25140 ataccctttg cccacttttt gatggggtag tttgattttt tcatataaat ttgtttaagt 25200 tctttgtaga ttctggatat tagccctttg tcagaggggt agattgtaaa aattttctcc 25260 cattctgtag gttgtctgtt cactctgatg gtagtttctt ttgctgtgca gaagctcttg 25320 aatttaattc gatctcattt gtcaattttg gcttttgttg ccattgctat tggtgtttta 25380 gtcatgaatt ccttgcccat gcctatgtcc tgaatggtat tgcctaggta ttcttctagg 25440 gtttttatgg ttttaggtct gatatttaag tctttaatcc atcttgaatt actttttata 25500 taaggtgtaa ggaagggatc cagtttcagc tttccacata tggctagcca gttttcccag 25560 caccatttat taaataggga atcctttccc cgtttcttgt ttatgtcagg tttgtcaaag 25620 atcagatggt tgtagatgtg tggtattatt tccgagggct ctattctgtt tcattggtct 25680 gtatctctgt tttggcacca gtaccatgct gttttggtta ctgtagcctt gtagtgtagt 25740 ttgaagtcag gtagtgtgat gcctccaggt ttgttctttt tgcttaggat tgacttggca 25800 atgcaggttc ttttttggtt ccatatgatc tttaaagttg ttttttccaa ttctgtgaag 25860 aaagccattg gtagcttgat ggggatgaca ttgaatttat aaattacctt tggctgtatg 25920 gccattttca cgatattgat tcttcctatc catgagcatg gaatgttcct ccatttgttt 25980 gtatcctctt ttattttgtt gagcagtggt ttgtagttct ccttgaagag gtccttcaca 26040 tcccttgtaa gttggattcc taggtatttt attctctttg aagcaattgt gaatgggagt 26100 tcactcatga tttggctctc tgtttgtctg ttatcagtgt ataggaatgc ttgtgatttt 26160 tgcacattga ttttgtatcc tgagactttg ctgaagttgc ttttcagctt aaggagattt 26220 tgggctgaga cggtggggtt ttctaaatat acaatcatgt catctgcaga cagggacaat 26280 ttgacttctt cttttcctaa ttgaataccc tttatttcat tctcttgcct gattgccctg 26340 gccagaactt ccaagacaat gttaaatagg agtggtgaga gagggaatcc ttgtcttgtg 26400 ccaggtttca aagggaatgc ttccagttat tgtccattca gtatgatatt ggctgtgggt 26460 ttgtcataaa tagctcttat tattttgaga tacgtcccat caatacctag tttattgaga 26520 gttcttagca tgaaggctgt tgaattttgt caaaggcctt ttctgcatct attaagataa 26580 tcatgtggtt tttgtctttg gttctgttta tatgatggat tacgtttatt gatttgcata 26640 tattgaacaa gtcttgcatc ctagggatgc caacttgatc atggtggata agctttttga 26700 tgtgctgctg gattcagttt gttagtatct tatcgaggat atttgcatca atgttcatca 26760 gggattttgg tctaaaattc tctttttttg ttgttgtgtc tctgtcaggc tttggtatca 26820 ggatgatgtt gccctcataa aatgaattag ggaggattct gtctttttct attgattgga 26880 aaagtttcag aaagaatggt accagctcct ctttgtacct ctggtagagc tcagctgtga 26940 atccatctgg tcctggactt ttttttgttg gtaggctatt aattattgcc tcaatttcag 27000 agcctgttat tggtctattc agagattcaa cttcttcctg gtttagtctt gcaagggtgt 27060 atgtgtccca gaatttatac atttcttcta gatgttcaag tttatttgtg tagaggtgtt 27120 catagtattc tctgatggta gttttatttc cctgggctca gtggtgatat cccctttatc 27180 atttttattg catctatttg attcctctct cttttcttct ttattagtct tgctagcagt 27240 ctatcaattt tgttgatcct ttcaaaaaac cagctcctgg attcattgct tttttgaagg 27300 gttttttgtg tctctgtctc cttcagcttt gctctgatct tattttttgc cttctgctag 27360 cttttgaata tgtttgctct tgcttctcta gttcttttaa ttgtgatgtt agggggtcaa 27420 ttttagatct ttcctgcttt ctcttgtggg catttagtgc tataaatttc cccctacaca 27480 ctgctttaaa tgtgtcccag agattctggt acattgtgtc tttgttctca ttggtttcaa 27540 agaacatctt tatttctgcc ttcattttgt tatttaccca gtagtcattc aggagcaaat 27600 tgttcagttt ccatgtagtt gttcagtttt gagtgagctt cttaatccta agttcgaatt 27660 tgattgcact gtggtctgag agacagtgtg ttgtgatttc tgttctttta catttggtga 27720 ggagtgcttt acttccagtt atgtggtcaa atttagaata agtgagattt ggtgctgaga 27780 agaatgtata ctctgttgat ttggggtgga gagttctgtg gatgtctatt gggtctgttt 27840 gttgcagagc tgatttcagg tcctggatat cttttttaac cttctgtctt gttgatcttt 27900 ctaatattga cagttgggtg ttaagtctcc ctttattatt gtgtgggagt ctaagtctct 27960 ttgtaagtct ctaaggactt gctttaagaa tctgggtgct cttgtattgg gtgcatatat 28020 atttaggata gttagctctt cttgttgcat tgatcccttt accattatgt aatggccttc 28080 tttgtctctt ttgatctttg ttggtttaaa gtctgtttta tcagagacaa ggattgcaaa 28140 ccctgccttt ttttgttttc cgttttcttg gtagatcttc ctccatccct ttattttgaa 28200 cctatgtgtg aatttgcgca tgagttgggt ctcctgaata cagcacactg atgggtcttg 28260 actctttatc caatttgcca gtctgtgtcc tttaatttgg gcatttagcc catttacatt 28320 tacagttaat attgttatgt gtgaatttga tcctgtcatt atgatattcg ctggttattt 28380 gcccgttaat tgatgcagtt tcttcctagc attgatggtc tttacaactt ggcatgtttt 28440 tgcagtggct ggtaccgggt gtttctttcc atgtttagtg cttccttcaa gagctcttgt 28500 aaggcaggcc tggtggtgac aaaatctctc agcatttgct tgtcagtaaa gaattttatt 28560 ttctccttca cttatgaagc ttagtttggc tggatatgaa actctggatt gaaaattatt 28620 ttctttaaga atgttgaata ttggctccca ctctcttctg gattgtaggg tttctgccaa 28680 gagatcagct gttagtctga tgggcttccc tttgtggcta acctgacctt tctctctggc 28740 tgcccttaac actttttcct acacttcaac cttggtgaat ctgacaatta tgtgtcttgg 28800 aatcgctctt ctcaaagagt atctttgtgt tgttctctgt atttcctgaa gttgaatgtt 28860 ggcctgccat gctaggttgg ggaaattctc ctggataata tcctgaagag tgttttacaa 28920 cttggttcca ttctcctcat cactttccag tgcaccaatc aaatatagat ttggtctttt 28980 cacatggtcc catatttctt ggaggctttc ttcatttctt tttactcttg tttctctaac 29040 cttgtcttct cactttattt catttatttg atcttcaatc actgataccc tttcttccac 29100 ttgattgaat cggctattga agattgtgca tgcatcacaa agttctggtg ccatggtttt 29160 cagctccttt gggtcactta aggtcttctc tacactgttt attcttgtat gccattcgtc 29220 aaatcttttt tcaaggtttt tagcttcctt gcaatgggtt ccaacatcct cctttagctc 29280 agagaagttt gttattacca accttctgaa gcctacttct gtcaactcgt caaagtcatt 29340 ctctgtccag ctttgttccg ttgctgacaa ggagctgtga tcctttggag gagaagaggt 29400 gctctgattt ttagagtttt cagcttttct gctctggttt atccctatcc ttctgatttt 29460 atctaccttt ggtctttgat attcttgacc tacagatggg gttttggtgt agatgatctt 29520 ctgttaatgt tgacactatt cctttctgtt ttttagtttt ccttctgaca gtcaggaccc 29580 tcagctgcag ttctgttgga gtttgctgga gttccactcc agacactgtt tgcctgggta 29640 tcaccagtgg aggctgcaga acagcaaata ttgcagaaca gcaaatattg ctgcctgatc 29700 cttcctctgg aagcttcgtc caagaggggt agccgtctat atgaggtgtc tgtcagcccc 29760 tactgggagg tgtgtcccag ttaggctaca caggggtcag ggacctactt gaggaggcag 29820 tctgtccatt ctcagaactc aaacgccatg ctggaaaaac cactgctctc ttcagagctg 29880 tcagacaggg atgtttaagt ctgcagaagt tgctgccttt tgttcagcta tccctgccca 29940 cagatgtgga gtctagaggc aatgggccct gttgagctgc ggtgggctcc acccagttca 30000 atcttccctg gccactttgt tcacctactt aagcctcagc aatggtggac gcccctcccc 30060 cagccaggct gccacctcac agatggattt cagactgttg tgcgtgtggg tgtgggaccc 30120 actgagccag gcacaggaga gaatcacgtt gtctgctagt tgctaagacc ttgggaaaag 30180 tgcagtattt gggtgggagt gccctgtttt tccaggtagt ctgtcacagc ttcccttggc 30240 aaggaaaggg aaatccccca accccttgtg cttcccgggt gaggcgatga cccaccctgc 30300 ttcagctcac cctctgtggg cctgcacgca ctctccaacc agtgctgatg agatgaacca 30360 ggtacctcag ttggaagtgc agaaatcacc tgtcttctgt gtcgatcgtt ctgggagctg 30420 cagaccggaa ctgttcctgt ttggccatct tggaacccat ccaggacatc tggtagaaga 30480 aatttgtaag cagcaaagtg ttcaatttat gacctgagtg ctcttaaaag tgttcagttt 30540 tatgcactca caaaaatatg gtttggaatt agaacttatg tttaaaaggg agcagagcat 30600 aaaaatttgg aagatttgca gcctgatgat gtgatagaaa agaaaaccca ttttctgggg 30660 agaaattcaa gctgactgca gaaatttgca aaattaacaa ggagccaaat gttaattgaa 30720 aagataatgg ggaaattgtc tccagggcat gtcagagttc ttcacgacag cccctcccat 30780 cacagggttg gaggcctagg agggaaaaaa tggttttgtg ggccaggccc agaactttgc 30840 tgctctgtgc agtcttggga cttggtgccg tgtgtcccag ccatggctaa aaggagccaa 30900 tgtacagctc aggctattgc ttcagagttc aatccccaag ccttggcatc ttccacatag 30960 tgttgggttg atatgctagt tggccatttg tatttttttt tagaaaaaat gtctattcaa 31020 gtctatctta gtccattcct gctgctataa caaaatacct taggctggta atttataaaa 31080 aacagaaatt tatttcttgc attctggaat gtgagaagtc caagatttag gctacagcag 31140 actcagtgac tggtgaggtc actatattca ctatacatag caccttctct gtgtcctcac 31200 gtgttcaaaa ggcaaaacaa actcccttaa gcctctttta taaaggccct agtcccattt 31260 ctgagggcta tgacttcatg aacttatcat ctccaaaatg ccccacctct taatattatc 31320 acattgaata ttagtctcca gcatatgaat attgggagaa catttggacc atagcaaagt 31380 caactgacca tttctcatat aggttgtttt gttattgagt tgttattctg catatatttt 31440 agatattaac cccttatcag gtatgtggtt tcctgggagg tttttgattc ctgattcagt 31500 tactagttat aggtttatta agatttttta ttttgtgact tagtcttggt aacttgcatg 31560 ttactaggaa tctgttcatt tctcctaggt tatccaactt gtcagtatat aatcattcat 31620 agtagactct tagaatcctt tttatttctg taatatctgt tgcagtgtct tctcttttgt 31680 tcctaaaaga agttgagtct tctttatttt ttttcttaaa tattctagct aatgatttgt 31740 caattttgtt gaactttaaa acaactacta gtttcattgg gttttttcta ttctctagcc 31800 ttttatttta ttttatttta ttttattttg agatggagtt ttgctcttat tgcctaggct 31860 gtagtgtaat ggcgtgatct ccgctcgctg caacctctgc ctcccagttc aagtgactct 31920 cctgcctcag cctccagagt agctgggatt acaggcatgc accaccatgc ccggctaatt 31980 ttgtattttt tagtagagac agatttctcc atgttgctga ggctggtctc aaactcccga 32040 cctcaggtga tccacctgcc tcggcctccc aaagtgctgg gattagagtc atgagccact 32100 gcaactgacc ttctgctcta gactttatta tttccttcct tttgctaaca ttgggttgag 32160 ttcttctttt tccagtttct tgaggtgtaa agctaagttg ctgattttag atctttcttc 32220 ttttttaagg taggtagtta gatacataaa ctgtcctctt cacattcatt ttgctgtatc 32280 ccacaagctt tggaatgttg tgtttccatt tttatttctc tcaagacatt ttataatttt 32340 ccttgtgact tattctttga ctatgtatta atcagagttc tccagagggt cagatccaat 32400 aggagatata gatatagata tagatataga tatagataat agatatagat acatatacat 32460 gtatctaaaa gagaatatat ttatatatat atgaaatata atttattaag gagaattggc 32520 tcacataatt acaaaggcaa agtcccacaa taggccatct ataagctgga aaatgagaga 32580 agcctacagc atggctccca aggaaggcag tgacatggct cagtccaaat ctggaagtct 32640 caaaaccagg gaagctgaca gtgcagccac tagtctgagg cccaaggcct gagagctccc 32700 aaaaggctgc tgatgcaagt cccagggtcc taagactcag gccaaagaac ctagagtttg 32760 atgtgcaagg gcaagaggag aaaaaggcat actgctctgg aagagagaga aagtgcataa 32820 aacagaaatc taagcaagct gaatgtttcc attcttctgc ctttttgttc tagtcacact 32880 tgcaaccaat tgcatgttgc ctacccacaa tgaggatgga tttttctctc tcagtccact 32940 aactcatcca tcattctcct gtggcagcac cctcacagat atacccacac acagtgcttc 33000 atcaggcatc taagcatccc tcaatcaaat tgacaattaa tattaaccac acaggccaat 33060 tggttaagag agtatatttt tgtaatttcc acgtatttat tacttttcct ttttccttct 33120 gctatgaatt tgtaatttca tttaatgtgg tcagaaaaga tatttggtat gagttcagtt 33180 ttcttaattt tttaaaaact tgtttgtgga ctagcatgcc atctatcctg gaaaatcttg 33240 gtatgtactt gagaagaaag catattttgc cattattggg tgaagtgttc tgtatatgtc 33300 agacaggtcc aattggtcta caatgttgct caagttctgt gttttccagt tgatctgtct 33360 ggttattgta tccataattg aaagtggaat attgaagttt tctgttatta tgatgttgtt 33420 atctatgtta cccctcaatt ctgtctatgt tagcttcata tatttagatg ctgcactgtt 33480 agttgcatat acatttataa ttgctatatc ttcttggtca attggccctt ttattattat 33540 gtaatatcct tgtctcttgt gctattattt gacttaaact ctattttgtc taagtatggc 33600 catccttgtt ctcttttggt taccaaatgc attgaatatc tttttccatc ctttcacttt 33660 caacctttgt gtgtgtttag atctaacata agtctcttgc atatagtata tgtttagatt 33720 tttttaatcc attcgggcaa ttctctgtct tttgattgga aaattagcct atttgcattt 33780 aaagtagtta ctgatagaga ggggcttact attgtcattt tgttcattgt tttatacatg 33840 tcttgcaggt atttttttcc acttttcctc tctttctgcc tccctttatg tttcactgat 33900 ttcttttttt ggtagggatg tgctttggtt cctttctcat ttttatttgt gtatcttctg 33960 taggtctttt ctttgtggtt actgtagaat tacatgaaaa catcttatag ttataataat 34020 ctattttaaa ttgacaacaa cttaagttta atcacataca aaaactctac ttatttacac 34080 ctccttctca ctttgttatc aatgtcacaa aatatatatt ttatattgtt tattcacata 34140 atttaataca gtaatattat gcttttacct tttaaattct atgcttcaat taaaagtgaa 34200 ttacaggcta ggtgttgtgt ctcacacctg tagtcccagc actttgagag gccaaaatgg 34260 gaggatcgct tgagcctagg agtttgagac cagcaaggcc ttatctctgc taaaaattta 34320 aaaatattat ctgagtgtgg tggtgcatgt ctgtagtccc agccactcgg gaggctgagg 34380 tgggaggata gctttagccc atgactgcaa ggctgcagtg agccatgatc aaaccactgc 34440 actccagcct gggcaacaga gcaagacttt gtctcaaaaa aaaaaagtaa aggaaaaaaa 34500 gtgttttgct taccaccatt agagtattaa aggattctat gttcactcat atatttacct 34560 ttaccaaaga agtttatatt ttatatgttt ttgtatttct atccaatgcc ttttcatttc 34620 cacttggagg actcccttta acattttttg taaggtaggt ctagtggtga tcaactccct 34680 caccttttac ttctctgggg aactctttgt ttgtccttca cttttgaagt agagttttac 34740 tggctataca gttcttggtt gacagttttt tttttctttc agccctttta atataccacc 34800 ccattctctt ctggcctgta gagtttttgc tgagaattcc attgattacc atatggcatc 34860 tcccttgtat gtgacaagtt gctttgatcc tgttcctttc aaaattctct ctttgtcttt 34920 gacttttgac agtttgattg taatgtgtct cattgtaggt cttttgcaaa ttatccaact 34980 tggagttctt tgagcctctt ggatttgtat gtccatttcc ttctttaagt ttgagaagtt 35040 tttggtcatt atttttttaa ctggctctct gccgctttat ttttctcttc tccttctggc 35100 actttcataa tgcatacatt ggtctgcttg atggcatcct gtaagtctct taggctgtct 35160 tcactcttca ctccttttcc cttttgctcc tctgactcta taatttcaga tgactagtct 35220 tccgtttcac tgattctttc ttctgcttga tgttattgaa actgcctttg caaaaattat 35280 aactgaagaa attatgacag caaaagacat cagacttaat caactccatc tcgcttctag 35340 catttaaact gtccttgttc attcctggca gtaggatgaa ctaattttgg gaaggtattc 35400 agttcatggt ttgactctga aacaaagttg ataataacca tttcccaaaa agatcccctt 35460 cttgcctgga accagtctgc ctttgcagga taaacacatt agctataaca ttagaaatta 35520 cagttgaggg gttatgcagc ctctggctcc aagagtctaa acctctccaa attgctcctg 35580 gggataacat cactattgta aaacctaaaa tcagtgcttg agatattttg cagaccctgc 35640 actggatgaa tcagctgaca ccacccagac tggtaatatg gctcaactag ttctgccacc 35700 ccacccacaa acagaagaca gcaagaaaac atcacttcaa ccccgtctga tttcatctcc 35760 aacctgatga ataagcagtc cccacttccc aagcccctac ctgccaaatt atctttaaaa 35820 gttctgatcc ccgaatgctc agggagactg atttgagtag taataaaatt ctgatctccc 35880 gcacagccag ctctgcctga attactcttt ctccattgca attcccctgt cttgataaat 35940 cagctctgtc taagcaggac acgaggtgaa cccattgggc agttacacag tctattggtg 36000 atttccgata gtgaattttt caattgagct attgtattcc ttagctccag attttctgta 36060 tgattccttt tttttttttt agtttctatc tctgttaata ttttcatttt gttcatgaat 36120 tatttcctgc tttcacttag ttgtctattt ctgttgtcac tgggcttcat taagagagtt 36180 aatttggatt ctttgtcagg taactgattt atctatttct ttagggttgg tttctggaga 36240 tttattttgc tcctttaatt tagtcatcag atttctctgt ttcttcttat gtcttgttat 36300 tttttatttt ttatttattt ttgccaagat ttgggcgttt gaaaaaactg ccacttctcc 36360 cagtttttat cagctggctt catacggaag aacttcatac ctgaatcagc atggctatag 36420 gttccagcag cctctcaaac tttttctggg aatgcatctt ctttgggttt atacattgca 36480 atatcccaag tagaggtttg ccagtttctt tttctggagc tgttgctccc tctggtatct 36540 gtctgtggta ctgcaggttc cctggtgctg catcatctct gacctctcct ttattcccag 36600 tggctcccat gcatccaagg tatgccagtt gggcgtcaag ttagagagag agagagagct 36660 tcaggtaacc tcataaaact attccgttcc agtcttctct ttccctgcta acggagaagc 36720 tgcaagttga gtgcttccca gccaaaccaa cctgttcgag cttggggaag gggtatcatg 36780 agtataatgc aacagctttt cttatttgtt caatgccact attcttggct ttgcacttgt 36840 ctgtgctact acaacttctt aatggtttat ggaactccat aaaggctttt agaccatata 36900 ttgtttttca gttgctatct ttatggagaa tcaaggtttg gagtcattcc accacctggc 36960 tgacatcact ctgtttatat tattttttac ttttattata ctttattttc ttgagacagg 37020 atcttgctct gtcagccagg ctagagtgca gcctcgaact cctgagctca agggacctcc 37080 tccctcaggc tactgagtac ttggactata ggcacacacc acataccggg ctaatttctt 37140 attttcttgt gaagatgggg tttcactatg ttgcccaagt tggtatcaac tcttgggctc 37200 aagcaatcct tctgccttgg cctcccaaag tgctaggatt aaaggtgtga gcccaccatg 37260 cgctgcctgt tatatttagt agaaaatata tctaaaaata tacttacgta ctctattgaa 37320 tccactaccc agagcttaac tgaactattt ttgtgactca ttctgttttt tttatttttt 37380 gctttttact tattacaatg aactacaagt atggatatat taatattaat taatataaaa 37440 tatactggaa tcttttgtat tttttttcct tttttcttca ccaaaagcag aaacttaaac 37500 atactgaaat cttaaatgac cattgaatgt ttctaggact gaccctggaa caaaattttt 37560 tatgttgtta ttacattgtt cttttcatgt ttaaatcatt tgtttctttt tcatgtagta 37620 catcaaagaa gaattgttga tatagccctt accagccata tgctaagtgc cacaagtgtt 37680 tcggtctctc tcaattcttg tacctcactt ggtctttttt ttttttcctt tgggggtgta 37740 gcctccgtct ttcacccagg ctggagtggg gtggcacgat ctcagctcac tgcaacctct 37800 gcctcccggg ttcaagtgat tctcctccct cagcctcctg agaacctggg accacagttg 37860 tgtgtcacca tgcccaccta atttttgtat ttttagtaga gatggggttt cattatgttg 37920 gtcaggctgg tcttgaactc ctgacctcaa gtaatccacc ctcctcagcc tcccaaagcg 37980 ctgggattac agacatgagc cactgcacct ggactacctc actctgtctt ttaaattggc 38040 tatgtaaggg gagcatcttg tgcttgttaa gtctttgttt tctggcctat ttatataatg 38100 gacatttctg agttgtgtgt atatattaaa ttatttgaga gtatatattt aatgtactaa 38160 atagagctaa gtgttttcat acatgtcact ataaaaggac catttgcata tatttgttct 38220 ataaaatgct tacttttctt catgaaccac ctagatttgc ttttctgatg tgtagtgtat 38280 gtgaaaatat ttctttgtgt ttttttttta ttgtgtgccc ctacaggtgg tatgcttaat 38340 aacgccatag cctctatagg gaacgtatgt attagtctgc tggcagtaat tgttttggga 38400 ctttttgttc gatattttcc aagtgaagac caggtaaata caaaatctat tttatagaag 38460 tatagtatta gacatttttt tcaaaatatt aaactttggt aagatccatg aaatttagta 38520 cttaactcta tttttctaaa actagcctcc aatgcctact ctgtatttaa aactgagcac 38580 agcagtgatt gatacaggtc aatggctttg attaaagtct ctgcttcctg atttggcaaa 38640 taaggaatgt caaaaaatat acttaatgca gagtatccct ctgaattata ctttcccttt 38700 ctctactaaa ttgtctattg atgtttgata atttccccca aattttccct taaacatttt 38760 agggggagat aggttcccat ttatttctgc atattttctg actgaaattc actcctgcta 38820 tcctttgaca aaggcaacac tcaaacttag ccatttcctg ccttaaagga aaacatgcca 38880 ttacttttgt atttctgtaa tttccatcca aatttagctg taacatattg accaaagaga 38940 tattcaaata ttttttaaga attcactgga tatgttatat gaaattggag attttatggg 39000 tctcttttct tcttcactta aagtaacact ttaaccattt tactgatact agtatcagag 39060 atgtggcaga agatgaaacg ttactaattg gaaattttgt tacttggtag taagtctgct 39120 aaaatgtatg gtgagaaaga aaatcaaaat tttagacatt taatataaca tttaaagaca 39180 taatatcaaa gggtcaaaca tatataatag ataatgtcaa atcttgtatt atatatttaa 39240 tataaactaa tttctaaata tctatctaat tctagaaaaa acttacattg aagagaggat 39300 tccttgtttt gactacgtgt gtttctgctg tcttaggcag ccaacatatt ggtttacatg 39360 gatctggagg attatgcaca ctagtgttga gtttcattgc agggacaaaa tggtcccaag 39420 aaaaggtgaa tatttttaat atgctatatt ttaaaagcta agacaactga attttttaca 39480 tatatttagg aaatcccctc attctggttg gaaaatattc caaaaggttt gctatcctca 39540 agaaagtgta tgaatcaatc gaggaaataa aatatttagg aaaagcagct ggaaatatac 39600 taatatggaa tcagaagttg agttaatcac atcaggcttc tctttttccc aagttttata 39660 taatattatt atattactta tatcaatcta attattgtat tcattgaaat tttaattata 39720 caattaatcc atgaagaatg tttgtaaaag gccaggcaca gtggctcatg cctgtaatcc 39780 cagaactttg ggaggtcgag gtggacagat cacctggggt caggagtttg agaccagcgt 39840 ggccaacatg gtgaaacccc atctctacta aaaatacaaa aattagctgg gcatggtggc 39900 gtggtggtgg gcacctgtaa ttccagccac tcaggaggct gaggcaggag cattgcttga 39960 acccaggagg tggaggctgc agtgagccga gatcatgcca ttgcactcca ggctgggcaa 40020 caagtgcaaa actccatcac acacaaaaaa aataataata aacaaataaa taataaaaat 40080 agaaatgctt gtaaaagaaa gatttcttta ttccccacca ctgtcaaata tctaaccccc 40140 ttacattttt ttaagtaacc agtattctat ttatagacat taagatcgtt tccactttta 40200 gttatttaca aacagtgctg tcataaacag tgttgttcat gtcttttttt tttttttttg 40260 agacacagtt tcactcttgt cacccaggct ggagtgcggt agcataatct tggctcactg 40320 caacctccac ctcctggatt caagtgattc ttctatttca gcctccctag tagctgggaa 40380 tacaggcgcg caccaccacg cccagcaaat ttttgtattt ttagtagaga cggggtttca 40440 ccatgttggc caggcaggtc ttgaactcct gacctcaggt gatactcttg cctcggcctc 40500 ccaaagtgtt gggattacag gttcatctgt aggaatagag tcctagaaat gatttttttt 40560 ttttttttga gacagagtct ctgtctatgt tgcccaggct ggtctcaaaa tcctgagctc 40620 aagggatcct cccatcttga cattgcaaag tgctaggatt acaagcatga gctaccacac 40680 ctggctggaa atgatctgtg ttttattttg atggacactg ctaaattatc ccttcaaaaa 40740 ttttggttat ttacactctg ccaacagtgc acaaaaatat ctaatacttt aactcatcaa 40800 cagcacttga tattatcact agttctattc tttttactat taaatgacct caccatccaa 40860 ttcttatagt ttcttacaat tatgtgatgt tgttattctt tatttacatt tctctgatta 40920 gtagtatagt aagcttctct tcatatattc tttttaaaat acctatgatc ttctttgacc 40980 atttttattg ggttatttat ttttttgttt ctaatttata gtttctctta gtgttagggc 41040 tactgatcct ttgttatgta tatattgcat ataatttttg cttatcttca actttgttta 41100 tggtttctgg tgtaggaaag taaaatttcc tatgaccaaa cctattgggt tttcctgttt 41160 tggttttgga ttctgcatct catttaagaa ggactttctc actgaagatt ataacgtata 41220 aacattacaa agatatacta ttttgtgtat tatcatttaa tattttggta gtttttgttt 41280 gtttaatttg tttttttatt tagtctttta atctatctgg aatttatctt tgtgaatgct 41340 gtgaggtaag gtaataatat atacatatgt gtatcttaca aactatatat atatatgtac 41400 acacacacat acagtttgta agttaactga acagagatag aactacatca tgcctgatgt 41460 gtgtgtgtgt atatatatat atatatacac acataaatat aaatgcatat tcagacacac 41520 atatatactt gcatgtgatg aatatgtaca tacagatata tgcacataaa ctagacagtc 41580 attttttgcc aaattgttta tttattgacc aattcattaa taattcagtt ttttaacatg 41640 aactaaattc tcccatatat attaattctg aagtctattt aatcctactt ctctatttct 41700 atgccaacac tactgtttta aatcactgca gttttatgtg tcaaaatcta atatagatta 41760 tacttctttt taaagtattt ttggctgttc ctacacatat tctttcttag ataaatttta 41820 gaatcagctt gagaagttcc ctaatcaaaa atcatagtgg cattttgctt agtattctta 41880 tataatcata attataaaag aaatgaaatg aatgaaatgc aaatcaataa ataaaattaa 41940 aactgctaga atttttttaa atggtaaaag aaacagaact aaaacaagtt ttaaagatta 42000 aaagtaacaa ataggataat tatactgtaa agagtagtaa catcgttttt ctttgttttt 42060 ctttttttaa actataataa gtggggatca gaaaacacag tcataaggga aatagttatg 42120 aagatagttt atgcctcaag gaagagacat caaagttctt atgtatcttc tgtttaaaaa 42180 aaaaaattaa acccagactg agactgaaat ctcttcatcc aaattcctgg agaagagcca 42240 gagtaatgta ggccaatagg ggactttcct gtaatctttt aattggggaa gtagcactgg 42300 gaggcattca tttccagaaa gggaagctgg gtaggcagct aaatgagaat ctaatatatg 42360 ttttggtttt gttttaagga aaaagtaact ttaaagtatt caacatgggt tttttggaag 42420 caggcctagc agacttccaa attgtttttc ctagtagtat acactatata tatcaggatt 42480 cactttaatg ggattgagtt ccaggatggt tgttagtgga aggcttccca acccccttct 42540 gagaacccaa atgtttgcat gaactgggta tgttctcatc aggcatgatg tagttctatc 42600 tctgttcagt taacttagag acaaaatctg gaactcatat gaaacatggc tagaacccta 42660 aggacatcac ttattctgtg acaaaatggc caaatagtat tattttattg ctttgtgagt 42720 ttcttttaat caaattctac ctaagtgttt gagtaaaact attgaagtgt tcagttttta 42780 ttaattaagt ttaacatttt tattaaaata aagtatctta aatttattaa ctgttaagtg 42840 actttaggtc aggcatggtg gctctttcta taatgccagt gctttgagag gccacagcca 42900 gagaccactt gaagacagga gttctagacc atcctgggca atatagcgag accccatctc 42960 tataaacaat ttaaaaatta gcccagcatg gtggtacaca cctgtagttc tacttgggag 43020 actgcgagag gattacttga gcccaggagt tcaaggctac agtgagctaa gattatgcca 43080 ctacactcca gcctgggcaa cagagcaaga ccgcatctct aaaatactta aaaagtgaaa 43140 aaaaaaaggt gagggagact ttaactttct gaaatttatt tatgtgccaa aataattata 43200 aatgtatttc tcttttctat agatgaaagt ccgaaagatt attacaaatg tatgggatat 43260 ttttcaacca cttctttttg gtttagttgg agcagaagta tctgtttcac tgcttgaatc 43320 aaatattgtt ggtaagaata attagagcac aaaaaatatg aaattcaaaa atatttaaga 43380 aaattataaa tacatttatt tttatttaca atatatcttt gaatggctac aaggaccttc 43440 ttcagaaaca catgttgata cactgtcata ttttcctatt gctcttcctt tacactgtgt 43500 gctctttttt tttaaaccaa ggacagccct gaatatcttc cctgagtttt ctaaggaaat 43560 aaatataaga tttctttcct gagggaacat atttgatatg atcagcactt tttgagtact 43620 ttcatttaaa actattggct gggtgtggtg gctcatgcct gtaatcttag cactctggga 43680 ggccgaagcg ggcggatttc ttaaagttag gagttcaaga cctgcctagc taacatgggg 43740 aaccccatct ctcctagaaa tacaaaaatt agccaggtgt ggtagtgcgc acctgtaatc 43800 ccagctactc aggaggctga ggcaggagaa tcacgtgaac ccgggagttg gaagttgcag 43860 tgagctgaga ttgtaccact gcactccagc ctgggtgaca gagcaagaat ccttctcaaa 43920 aagtaaatta ttattaataa taataaaagt attcaaaaaa agtctattag ttcagaattg 43980 tataaatgtc atctgtctta tttttcatgg tacctccacc gtcagatact gtcttgcatt 44040 ttacagagaa tcctccatca tattcatttt tattatcatt gttttatgta aaaattaaac 44100 acatgaagag acaatagcct taaaatgctt ttaaaagttt tagaaatcat attcctgggc 44160 ataaagaaca cttcttcaca aatattttgt tatttatgtt tgttttcatc tgttgtaggc 44220 atatctgttg ccactctgag tttggcatta tgtgttcgaa ttttaaccac atatctattg 44280 atgtgctttg ctggttttag ttttaaggag aaaatattta ttgctttagc atggatgccc 44340 aaatatgtac aggtaagaac atattaagcc tattgcttaa tgctttcgtt ttgatgcttt 44400 taaaatttaa aatgaaaaat gttactccaa tcacaaaata tgagctatta tccttacttt 44460 ttaaatgttt gattgatcat aactattcat taaaattaac gtaaccagtc ccagctactc 44520 aggaggctga gacgggagaa ttgcttgaac ccaggaggcg gaggtcacaa taagctgaga 44580 tggcaccact gtactccagt ctgggagaca gagcaagact caatctcaaa aaaataaata 44640 agtaaacaaa aacaaacaaa gaaactcaat gtaacctttt tctattttta ttttcatttt 44700 gggaccaggt ctcactctgt cacccaaact ggagtgcagt ggcatgatca tggctcactg 44760 cagcctcaac cacctgggct caaacaatcc tctcacatca gcctcctgag tagctaggat 44820 cacagtcacc tgccaccaca cccaactgct tttttttcag attttttttt ttttttgaga 44880 cagtcttact ctgttgccca ggctggagtg cagtggcatg atctcaggtc aatgcaacct 44940 ccacctccca ggttcaagcg attctcctgc ctcggcctcc tcagtagctg ggattacagg 45000 tgcacaccac catacccagc taattttttt attttttgtg gatatggggt ctcaccatgt 45060 tggccaggct agtctcaaac tcctgacctc aagtgatccg cctgcctcag cctcccaaag 45120 tgctgggatt acaggcatga gccacagtgc ctggtctttt ctttatgatt tttttgtaaa 45180 gaggaggtct tgctatgttg cccgggctga tcttgaactc ctaggttcaa gtgaccttcc 45240 tgtctcagcc tcctaaagtt ctgagattac aggcataacc cactgggccc agccaacgta 45300 accttttgaa atctcagttt taaaagcaat tattttgaaa tcaaaaagta ttctttcaat 45360 aagtacttcc taagtttatg aaaatatgtt ttttattttc ctaaaatata taataagaat 45420 atatctgaaa attggagttt ttatattttg ctgaatataa caaagctaaa tgttacaatt 45480 ttaaaaagta gagacacagg ccaggcattg tggctcatgc ctgtaatcct agcacttcag 45540 gaggctgagg caggcagatc acttgagctc aggagttcaa gaccagcctg ggcaacatgg 45600 taataccccc gtctctacaa aaaatacaaa aaaattagtc agatgtggtg acacgcatct 45660 gtagtcacat ctactggggg gctgagggag gaggattgct tgaacttggg aggttgaggc 45720 tgcagtgagc tgaggtcacg ccacatcact ccagcttggg tgacaaagtg agaccctgtc 45780 acaaaaaaaa gtaaagtaaa atagagaaac attgattttt taaaaaatac ttttcctacc 45840 tttccactca ctccatcaca caaatgcaca tatatttttt taattacaca tttatttgta 45900 tactatttgg ttaatggcta aatccctgcc cccgcccctt tgatagacta tgtaaggaca 45960 gggacagtgt ctggttgttg cagttgtttt tcattatttc tccctggcac ttaacacagt 46020 gcctgacatg caggaggcaa atacgtattg catgcctgca aggatgaatg aacggaaagg 46080 gaaaccttgt aattttgccc tgttattcaa ggagattctc ctcctactaa aatatattgc 46140 tacttcttgt cagactgttt aacttggcag cataatatag cttaatttcc tgtggctctt 46200 ttcttagttg ttattccaaa acagaagctc ctaaattttc atgcaaaaaa acctctatta 46260 tgttagaaaa gcaggctcag agggccagac tacctgtttt gaataccatg ttacttgcct 46320 ataacctcag gaaaattatt ttctagtctc tcagtccttc agtgttctca tcttacaatg 46380 aagtctatga ctgtatctgt ttcttagcag tgttgtcagg attcaatgag ataatccacg 46440 taaagtgctt aacactctct ctggcatatg gtggtgctca gttaacaaac aatgttgtta 46500 ttttatctta ccttcaagta atataaataa taacttttta tttttaatgt ctactgtagg 46560 gaataataaa tctacaaaag gagtaactgt tctctctcct tccaacaata ctcttgcaat 46620 tttgtttcat tatttcataa ttttcataaa gcagggaaaa aagaaaagca ggtaggagga 46680 aagagaccac tcactcgagt cctgcagtat tattctgctt ctgcctattc ctgtctgctg 46740 gctccaggct agcttctaca caaagaatat caagctggtt ccaggaactg gcaagacata 46800 aaaaattaat tagttataca agtagagtca caacagcaat aatagataac aataatgtca 46860 caagtaaata cgatcaacaa atatttaaat ttcaatttta aattattttc acctttatcc 46920 tcttctgccg ttctctgctg ctaaaataaa attggctaag gttcagcttt ctcttattcc 46980 ttagttttga gttactgata aaaattagac tggaaaaata gaagctatta ggagagtaaa 47040 taaataattt agtttacaaa tgtaagatca gcttggcaat tggatttttt taaagaaata 47100 atattaaatc tcagtcacta ggaggaaatc atttatcatc taataaaagt cctcacataa 47160 taaggttgtc ataaaaatta aatgaattga taaatggaaa gctttaagaa tgatacctga 47220 catatgatga atgccatata actataaaaa tattatttct agtttcacca ttatcgtcat 47280 catctcctaa aagtcaatgg gtttggtttt tgtttttttt tttttctgtt ggcagttctt 47340 ttatgttcaa atcctcttct aaactgtaag attctttcaa ggtggttttc tgcatgatta 47400 tttttttctc cctagcatcc tccagcacac tggatcatgt tcagtacatt aaaagttatg 47460 atataaaaat aataccattt taaattattg atttaggata tagaaattga tcttaaattg 47520 aggggttctt ttgccataat gttccatatc aaaggtaatg tttaatgttg ttactttgca 47580 actccataga aaatatgtta tatattggta tttaattccc ccaaatttta aggcaatttc 47640 atgcctagtt attaaacaca aggaaagaga gttagcaaga aatttgcttt atgttattaa 47700 aaataatgtg gtagaaggta actagggaaa aaaacttgtg acccagtaga gtcattctaa 47760 aacaaaaact tcaaaggaac tcattctctg acctggcagg ggatgaggag tgaaggagaa 47820 agaaacttac tactatctga atacctactc tgtgccaggt attcttcaca ttctcatatt 47880 taattttcac aaccgtccag taagagaagt attttgttct tcattttaca cgtaagtaag 47940 tagaaggtta gagagtgtga gtcatttgta caaggtcact agcctggttg cagcaaaaat 48000 agaattcaaa cccagtttgc tagattccaa gcctgctgtc agttctgcta taacccagtg 48060 ccccctgaat aaggagaaca atgagaagaa gggcaacaaa tcctagagaa ccataagaaa 48120 acttaatatt ttattatgtc ttcttgtagt caaaaaccac tggtacacga taaaggcaac 48180 taagcaaaac cggtttcctt agaactcctg gtgttatgag ggcaacactc aaaagagata 48240 tttgaataga ggaacactga gaggacaaga gtgcaaaatc agcccaaaaa tgtttgcatg 48300 ctgatttgtc actattgtac tcttcctcca catatatttt ctaggaagaa catggaactg 48360 atgagtaact tatgaaaatt actgagtact ttttttctaa tagtctagta ctagattttg 48420 tttattttaa cagagccatt tacattatat attaactcag tttaatattt ttctttatgc 48480 cccattttta cccctaattg tagactgtgt taggtcctct ggctctagaa acagcaagag 48540 tctccacacc ccacttggaa ccatatgcga aggatgagat gacagtagca tttttagcca 48600 tctcgatcgc agctccaaat ggagctctac ttatgggcat tctggggcct aaaatgctta 48660 cacaccatta tgatccaagt aaaataaaac tgcaattgtc aacattagaa catcattaaa 48720 aagtttacct gtcatcatct gcctgcttct tttaatgaat tatttcacat gacagaagaa 48780 ttttaaagta gaaatatgta gggactgtac agaaaatcca ggatttagta aacatgtgat 48840 ttcagtacag ggcttttctt ggacatttta ctccaaagtt aatttaataa aaataataat 48900 taaatggaat gctctcttgg tatttacata ctgtaagaac aaattaaatc tgtaaatccc 48960 taggaaagtt taaaataatc cctcaggctg aatttgatat cataataca 49009 <210> 164 <211> 5334 <212> DNA <213> homo sapiens <400> 164 cccacgccgc gccttccggt tggtccttga ggcgacgggt gaggcacagc tgagcgccaa 60 agccacaggc tggggcgcta acgcccccgc tcagcgctct gcgctccaga cagctgcgag 120 ctggagtagg aaggttcagg cggtggcgga gagtgcgctg gaggctggag ggccaggagg 180 cgggaagctt cccgcacggg ggcgctgtca cctgcctgtg ggaggagcca gagagggacc 240 tggctctgct gctctgaagc accggagtcg ggagaaccca tccagacatg aagagcgcca 300 aaggtattga gaacttggct tttgtcccct ccagcccaga catcctgcgc cgcttgtctg 360 cgtcgccctc ccaaatcgaa gtctctgcct tgtcctctga cccccaaaga gagaattctc 420 agccacagga gcttcagaag ccccaggagc cccagaagtc accagagcca tctctgcctt 480 cagcccctcc caatgtctcc gaagagaagc tccggtcact gtcgctgtcc gagtttgagg 540 aggggtctta cggctggagg aacttccatc ctcaatgtct ccagcgctgc aacacacctg 600 gaggctttct gcttcactac tgcctcttgg ccgtcacgca aggtattgta gttaatggcc 660 tagtaaatat tagcatttcc actgttgaga agcgttatga aatgaagagt tccctgactg 720 gcctgatttc atcaagctac gatatttcat tctgtttgtt gtctttattt gtatcattct 780 ttggtgaaag aggacataag ccgagatggc ttgcatttgc agcctttatg attggactgg 840 gagcacttgt attctcattg ccacaatttt tcagtggaga atataaattg gggtctcttt 900 ttgaagacac ttgtgtaaca acaaggaata gcaccagttg tacatcttca acttcttcac 960 tttctaacta cttgtatgtc ttcatcttgg gacaactatt gctgggggca ggaggaactc 1020 ctctttatac tctgggaaca gcctttcttg atgattctgt gcccacacac aagtcttctc 1080 tctatatagg aaccggttat gctatgtcaa tcttaggccc tgctattggc tatgtattgg 1140 gaggacaact gctaaccata tacattgatg ttgctatggg agaaagcact gatgtcactg 1200 aggatgatcc gcgatggttg ggagcttggt ggattgggtt tcttctatca tggatctttg 1260 cttggtcttt aataatacct ttttcttgct ttccaaaaca tttaccaggt acagcagaaa 1320 ttcaagctgg aaaaacttcc caggctcatc agagtaatag taatgcagat gtgaaatttg 1380 gaaaaagtat taaagatttt ccagctgctc taaagaattt gatgaagaat gctgtcttta 1440 tgtgtttagt tctatcaact tcttcagaag ccttaattac tactggattt gctacatttt 1500 tacctaaatt tatagaaaat caattcggat tgacatccag cttcgcagct actcttggag 1560 gggctgtttt aattcctgga gctgctctcg gtcaaatttt aggtggcttc cttgtttcaa 1620 aattcagaat gacatgtaaa aacacaatga agtttgcact gttcacatct ggagttgcac 1680 ttacgctgag ttttgtattt atgtatgcca aatgtgaaaa tgagccattt gctggtgtat 1740 ctgaatcata taatgggact ggagaattgg gaaacttgat agccccttgt aatgccaatt 1800 gtaactgttc gcgatcatat tattatcctg tctgtggaga tggagtccaa tatttttctc 1860 cctgctttgc aggctgttca aacccagttg cacacaggaa gccaaaggta tattacaact 1920 gttcctgtat tgaaaggaaa acagaaataa catccactgc agaaactttt ggttttgaag 1980 ctaaagctgg aaaatgtgaa actcattgtg cgaaactgcc catattcctt tgcattttct 2040 ttattgtaat tatttttacc tttatggccg gtactcctat aactgtgtct atcctaaggt 2100 gtgttaatca cagacaacgg tccctagcct tgggaataca atttatggtc cttcgattat 2160 tagggacaat tcctggacca attatatttg gtttcacaat agacagcaca tgtattcttt 2220 gggatataaa tgattgtgga attaaaggag cttgctggat ttatgataac atcaagatgg 2280 cccatatgct agtagccata agtgttactt gtaaagttat caccatgttc ttcaatggat 2340 ttgcaatctt tttgtataaa ccacctccat cagccacaga tgtgtcattt cataaagaga 2400 atgcagttgt gactaatgtt ttagcagaac aggatctcaa caaaatagta aaagaagggt 2460 gaaatgggaa aagagaagac tgttttacac ctggaaaatt tacctcgatt tttaagaaca 2520 cacattgcca tggcaggatt atctatccaa tatggacaat catatttaca aaattgatgt 2580 ttttataatc aaatgtattt ttttacttat gtagtttttg ttttatgcaa gaaacagacc 2640 tgtgccttca aagcccacgt aaagcctcaa aacacagcac acacacacac gagcacacac 2700 acacacacac acacgaacac acacacacac acacacacgc acacatacac acttatttcc 2760 tattcccatt gtctaggtat gaaatcctca agcaataaca agaaaaaagg cccacaatta 2820 gaaaaattta catttaaaaa aaatgttgtt tctatcccca ttacaacttg tttaatttta 2880 attttcattg tcaatatttt gagcttagaa catttatggt ataaaaattt aaactaatca 2940 aagttgtgtg atgatttccg ggaattatta ttgaaagcct atgaatttaa aaccaggttt 3000 accatgtaat ttgtttttaa atttatgtat actagcctgg cctttctcca agcaaattat 3060 tgaactatta gaatatgtta gttatcatcc ttgtgtctta gtatatagtg aatacagaaa 3120 catcagcatt gtatacacat attttcactt taactcaaga attccaggag gtaatttgtt 3180 gatattacaa tttttaacac atttatgatt ctgtgataat attattcaat tgcatatatt 3240 tcagaggaaa gtaccagtca gtaaagaaaa atgccaacta aacatgaaac tattgatcaa 3300 tacttatata cctttaattt ttcctatttg aaaagccaac cacttaacac attactcata 3360 gcacctaaga cagtgccttg catagtgtag tcatctatta ttattgttta attagaatat 3420 taaaccctac cctttaactc agcagtcccc aacctttttt gcatcaggga ccatttttgt 3480 ggaagacaat ttttccatgg gggaagaagg tatggttttg agatgaaact gctccacctc 3540 agaccatcag gcattagtta gattctcata aggagagtgc aacctagatc ccttgcatgt 3600 gcagttccca atggagtgtg cactcctatg agaatctaat gccactactg atctaacaag 3660 aggtggagct caggcagtaa tgctcactca cctgcctctc agctcaccaa ctgtgtggcc 3720 cgattcctaa caggccacac acagcccagg gctggggacc cctgctttaa ctgatgcatt 3780 gatttgataa agtattttac aagcctgata atgttataac cctgtttatt caggtcagat 3840 ttatgccaac tttgctgaga atatggaggg tatagatgag tgaacatcaa caaacataac 3900 ttctaccatg gttaagaatt ttacttagga aaagtattga agttcaaatc cagatagtat 3960 tacatttgaa attgttataa gggttattaa tttaataaaa ttcatcatca ggtttcccct 4020 ataagctttc tcctaggtta attttccaca agcattgttt tatatacact gtaatcagga 4080 taacacaagc ttagtgttag atcttgtagg aaaccaagat tagaaacatt agaaatttgc 4140 agaatttaag aaattatgtt ttgtggtaat ctatggccaa cgatgttaga acctagcgca 4200 attgtaaagt gaaattcaag gagaaggaat gaggagttag ggaagcagca tacttgaata 4260 ttagagaagg agaggagctg tgggtcagga atcagagaga cctgctaaaa ccagacagat 4320 ataaacacca aagacggaag ccaaataggt agccaaaaat ccagatattt gagaagcagg 4380 aaatttatag caaccaaaga aatagggcaa gagaggcagg tgaacacaca tgatacctca 4440 attgacaatc ttcctcccac caagccagac acgttgtaaa tgctgcttcc tattggagcc 4500 cagaaaaaag gaaaaggaaa gtttaggctt tctttgtcct ttgtgtggaa gcagggaatt 4560 ggattgaaga ctttcatagt tgtaacataa aggcaaatcc tgaggaactc actgatggag 4620 atgtgaaatg gcagtaagga agaaaacaga ataactgaac aaatatatta gtctagggcc 4680 acttaattta gaggaagaaa aaaaatcaac ccatccatag aaatagtttg ataaacaggt 4740 cactaaatca ttggcgttta taaagattct tagctatcaa gggctgcatt gtattttata 4800 tactcagttt tataaggtga tactttttaa ataagcgctt taatgaaaat ggttagactg 4860 aaaataattt tggtccttaa aaggagtcag gagcttttat atataaggta catattttaa 4920 aagaatacct cctttataac agggttttac agacactacc ataatttata atcattattt 4980 tttacttttg ggttcaccta gatcatatga gttgatgtga tacttctaga acaaaattat 5040 tcatagtgcg ttttttgtaa tttatgattg ttaagtaagc ttgacttata aattgacatt 5100 gtaattgtgt acataattgg atatatgtgt taaaatttaa catttagatt tacttaattg 5160 tagaaaatac aaatgtaaaa cttacacatg gaaagaactg tatgcagttg actttactat 5220 gtaaattgga gggaaacaaa gttttagatc cattttcttt caaaattttc tttattgtaa 5280 agtatgcaaa atatatattc ataccattta ttaaatcaga atgtttatac aaaa 5334 <210> 165 <211> 2043 <212> DNA <213> homo sapiens <400> 165 tctgtctttt cctccttcca gtgcccggcg ttcctccctt ccccctcgcc gccgaccgag 60 ttcttccttt tcagaccggg tcgccttgct gtcgtcgcgg tgattttcct gctactgcta 120 ctgctgctgc tgccaccgcc actaccactg ggctcatttg ccccgacccc ttcccgccgc 180 cccgccccca gccccacaca agatgtcaga ggatttagca aagcagctgg caagctacaa 240 agctcagctc cagcaagttg aagctgcatt atctggaaat ggagaaaatg aagatttgct 300 aaaattgaag aaagatttac aagaagttat agaactaacc aaagaccttc tgtcaactca 360 accttctgag acgcttgcaa gttcagacag ttttgcttct actcaaccta ctcattcatg 420 gaaagtagga gacaagtgta tggcagtctg gagtgaagat ggacagtgtt atgaagcgga 480 gattgaggag atagatgaag aaaatggcac cgctgcaatc acctttgctg gttatggcaa 540 tgctgaagtg actccactgt tgaacctcaa gcctgtagaa gaaggaagga aggcaaagga 600 ggacagtggc aacaaaccca tgtcaaaaaa agaaatgatt gcccagcagc gtgaatataa 660 aaagaagaaa gctttgaaaa aagctcagag aataaaagaa cttgagcagg aaagagagga 720 ccagaaagtg aaatggcaac aattcaacaa cagagcctat tctaaaaaca aaaaaggcca 780 ggtaaagagg agtatttttg cttcacctga gagtgtgact ggtaaagttg gagtaggaac 840 ctgtggaatt gctgataaac ctatgacaca atatcaagat acctctaaat acaatgtcag 900 gcatttgatg cctcaataat cagaaaaact gttggatttc atctctgcag ggctttacat 960 ttaccttttt atccttatat ttttctaaag gtaaattatt tgttagatga gtaagcaaga 1020 taccattgtc gtcattggtt ggcttcagta gaatgaaacg tgaagaaatt gcatttgata 1080 actgctattc atttaacttt tctcattatc agtaccacgg ttccctcaaa gtttgttgaa 1140 taaagcaact tttgtagatg ctgtttcata cagcacttag atgaattatt gatcttccta 1200 atatcaggcg cctacttaac ctatggtgtg tactttttgt aagttgtaac ttgaaatttt 1260 cagatgcttt gaacttgaca catactctag caattcattg gaacaccaag gcaaaaacac 1320 caacctgcta aaagagatct tttcattttt cttattttca gctttaaaac ttagctgtcg 1380 ttcagttaag cttaaagata ggttaatttg taaatggcaa agtttgtttt gaggtttttc 1440 ctcaataact tgtttcccag gcctattagg ccatctctaa aattgatcta gctgttttat 1500 ttttatgtac tcttagtttt atgtaagaaa ccttaggatg agctcccttt tctaaggtgt 1560 ttttgttttt tgtatgtttg cttttttcct gttttttgtt ttttccattt acggcagtgg 1620 taccatgttt tggatgtgtg atgtttatat gggagaacaa aaagctgatg tatagccctg 1680 tatacagtgt agatactatt tttgtaaaaa cacaaggcta aattaatgaa caagaatact 1740 gaatatttca tcattaaaaa tttcttgtat ttcttgtgca ttaatctgac gataatttcc 1800 ctgtatatta tgttcattta gctgtttgta atttttgtta attagatcag gttgtctgca 1860 tttgttggtg taagtgaaca tcatcacagt tatcctgagt tgagtttaag ccaaatacat 1920 gcatagaaaa gggtcttcct attaatggaa gaaggtaatt tttaggatgt gtattatttc 1980 agttttgtat gtttaacttt tattaaataa agtgttttta aaatctccaa aaaaaaaaaa 2040 aaa 2043 <210> 166 <211> 130 <212> DNA <213> homo sapiens <400> 166 tgcctcattc tagagaatgg gcactgttga tcatggtgtc caaaaatagt taatgtggct 60 aaattgagac aggttatgct tccatcacag tatgcatatt gcagtggtga caatgagacc 120 tgtaacattt 130 <210> 167 <211> 132 <212> DNA <213> homo sapiens <400> 167 ctgcgaatat tctcgctgtt ctgattttgt aatagtcagg acaggctaaa cattcgctat 60 attaagacca tgcatgtgtc cccaaaccta gttctttccc taggtctggt ttcataaatg 120 ctggtgataa ac 132 <210> 168 <211> 137 <212> DNA <213> homo sapiens <400> 168 gtcttctcat tgagctcctt tctgtctatc agtggcagtt tatggattcg cacgagaaga 60 agagagaatt cacagaacta gcattatttt accttctgtc tttacagagg tatatttagc 120 tgtattgtga gacattc 137 <210> 169 <211> 77 <212> DNA <213> homo sapiens <400> 169 gggaccaatg ataatgactg ttggggtatg agtcagtgag gttgaataac agtttgtatc 60 tggaaatctg aggtcca 77 <210> 170 <211> 81 <212> DNA <213> homo sapiens <400> 170 gggtcgatga tgagaacctt atattgtctg aagagaggtg atgacttaaa aatcatgctc 60 aataggatta cgctgaggcc c 81 <210> 171 <211> 94 <212> DNA <213> homo sapiens <400> 171 tggatcgatg atgacttcca tatatacatt ccttggaaag ctgaacaaaa tgagtgaaaa 60 ctctataccg tcatcctcgt cgaactgagg tcca 94 <210> 172 <211> 70 <212> DNA <213> homo sapiens <400> 172 cagtagtgat gaaattccac ttcattggtc cgtgtttctg aaccacatga ttttctcgga 60 tgttctgatg 70 <210> 173 <211> 217 <212> DNA <213> homo sapiens <400> 173 aagactatac tttcagggat catttctata gtgtgttact agagaagttt ctctgaacgt 60 gtagagcacc gaaaaccccg aggaagagag gtagcgtttt ctcctgagcg tgaagccggc 120 tttctggcgt tgcttggctg caactgccgt cagccattga tgatcgttct tctctccgta 180 ttggggagtg agagggagag aacgcggtct gagtggt 217 <210> 174 <211> 2980 <212> DNA <213> homo sapiens <400> 174 ggggggagcg cgccgggcgc agggagctga gtggacggct cgagacggcg gcgcgtgcag 60 cagctccaga aagcagcgag ttggcagagc agggctgcat ttccagcagg agctgcgagc 120 acagtgctgg ctcacaacaa gatgctcaag gtgtcagccg tactgtgtgt gtgtgcagcc 180 gcttggtgca gtcagtctct cgcagctgcc gcggcggtgg ctgcagccgg ggggcggtcg 240 gacggcggta attttctgga tgataaacaa tggctcacca caatctctca gtatgacaag 300 gaagtcggac agtggaacaa attccgagac gatgattatt tccgcacttg gagtccagga 360 aaacccttcg atcaggcttt agatccagct aaggatccat gcttaaagat gaaatgtagt 420 cgccataaag tatgcattgc tcaagattct cagactgcag tctgcattag tcaccggagg 480 cttacacaca ggatgaaaga agcaggagta gaccataggc agtggagggg tcccatatta 540 tccacctgca agcagtgccc agtggtctat cccagccctg tttgtggttc agatggtcat 600 acctactctt ttcagtgcaa actagaatat caggcatgtg tcttaggaaa acagatctca 660 gtcaaatgtg aaggacattg cccatgtcct tcagataagc ccaccagtac aagcagaaat 720 gttaagagag catgcagtga cctggagttc agggaagtgg caaacagatt gcgggactgg 780 ttcaaggccc ttcatgaaag tggaagtcaa aacaagaaga caaaaacatt gctgaggcct 840 gagagaagca gattcgatac cagcatcttg ccaatttgca aggactcact tggctggatg 900 tttaacagac ttgatacaaa ctatgacctg ctattggacc agtcagagct cagaagcatt 960 taccttgata agaatgaaca gtgtaccaag gcattcttca attcttgtga cacatacaag 1020 gacagtttaa tatctaataa tgagtggtgc tactgcttcc agagacagca agacccacct 1080 tgccagactg agctcagcaa tattcagaag cggcaagggg taaagaagct cctaggacag 1140 tatatccccc tgtgtgatga agatggttac tacaagccaa cacaatgtca tggcagtgtt 1200 ggacagtgct ggtgtgttga cagatatgga aatgaagtca tgggatccag aataaatggt 1260 gttgcagatt gtgctataga ttttgagatc tccggagatt ttgctagtgg cgattttcat 1320 gaatggactg atgatgagga tgatgaagac gatattatga atgatgaaga tgaaattgaa 1380 gatgatgatg aagatgaagg ggatgatgat gatggtggtg atgaccatga tgtatacatt 1440 tgattgatga cagttgaaat caataaattc tacatttcta atatttacaa aaatgatagc 1500 ctatttaaaa ttatcttctt ccccaataac aaaatgattc taaacctcac atatattttg 1560 tataattatt tgaaaaattg cagctaaagt tatagaactt tatgtttaaa taagaatcat 1620 ttgctttgag tttttatatt ccttacacaa aaagaaaata catatgcagt ctagtcagac 1680 aaaataaagt tttgaagtgc tactataata agtttttcac gagaacaaac tttgtaaatc 1740 ttccataagc aaaatgacag ctagtgcttg ggatcgtaca tgttaatttt ctgaaagata 1800 attctaagtg aaatttaaaa taaataaatt tttaatgacc tgggtcttaa ggatttagga 1860 aaaatatgca tgctttaatt gcatttccaa agtagcatct tgctagacct agttgagtca 1920 ggataacaga gagataccac atggcaagaa aaacaaagtg acaattgtag agtcctcaat 1980 tgtgtttaca ttaatagtgg tgtttttacc tatgaaatta ttctggatct aataggacat 2040 tttacaaaat ggcaagtatg gaaaaccatg gattctgaaa gttaaaaatt tagttgttct 2100 ccccaatgtg tattttaatt tggatggcag tctcatgcag attttttaaa agattcttta 2160 ataacatgat ttgtttgcct ttctagattt ctttatcttt ctgaccagca acttagggag 2220 cagaatttaa attaggaaga caaagggaaa gattcattta aaccatattt ttacaaagtt 2280 tgtcatttgc cccaaggtca aattttaaat tcttaatttt cattttattt cccattttag 2340 gtaaaagttt gcatttaatc ttagaattat gttatttttg ttagtagtgt ggaaacttag 2400 agaacttatt gtatggtgcc ttgcaaaaat agagatagaa agattttagc atgcatacca 2460 atatagtata ttacgcaata tataagcaca cctaattaac agattaatat cagtaaaggt 2520 attgctgctg gaatgaagaa aatgggatac gtttgtttct ttttttctat tgttacataa 2580 ttgccatgtg gacttgttta tgattattgt gtagagtagc atttaagatt taactgtagc 2640 aaaaattact ttaaccgctg tatttaagtt agcatgttaa ttaattgtgt agacattttg 2700 gcacaccatc acttttaact atatcatacc aatggttttg tgcccataat aaaaatggaa 2760 aaacctgttg aatgttacgt attggtatct ttaatttcaa cagtgggtaa actggtttcc 2820 cagtatacaa ttcattgaaa gcaaaattga ttaattattt ccatttaatt tatacacact 2880 caatacaaaa tttaatgttg actttacgta ataaagtata atgcattttc ttttttactg 2940 tttatgtata gtttacaaaa taaagaatct tgtaaccaaa 2980 <210> 175 <211> 4604 <212> DNA <213> homo sapiens <400> 175 gctcttcttc cttccttctc cagtcccttc cactgtgcgt cttctgtccc ccgttcttcc 60 ccagcggacc cctctttcga gactccctag tggggtcccc agctcccggg cgatcctgcc 120 cttgccgagc gcgttttctg gagtcacctg ggggagggga gtcctgggca gggccgggct 180 ggggaagacg cctggggcac tgcccggcgt taacaaaggg agccgatacc gaccggcgtg 240 ggcgcggagc gggcggccgc caccgagcgt gctgagcaac cgcagcctcc gcggccgaga 300 gtgcagcgag caaggggaga gccagttgcg cagagccctg caaccagcag tccagggaga 360 agtggtgaat gtcatggagc ccagctgaaa tggactggcc cccttgagcc tgtcccaagc 420 cctggtgcca ggtgtccatc cccgtgctga gatgagtttt gatcatcctg agaaaaatgg 480 gccttggcct gcagacccaa taaaccttcc ctcccatgga taatagtgct aattcctgag 540 gacctgaagg gcctgccgcc cctgggggat tagccagaag caggcttgtt ttcctgctca 600 gaacaaagtg acttccctga acacatcttc attatgattc acaccaacct gaagaaaaag 660 ttcagctgct gcgtcctggt ctttcttctg tttgcagtca tctgtgtgtg gaaggaaaag 720 aagaaaggga gttactatga ttcctttaaa ttgcaaacca aggaattcca ggtgttaaag 780 agtctgggga aattggccat ggggtctgat tcccagtctg tatcctcaag cagcacccag 840 gacccccaca ggggccgcca gaccctcggc agtctcagag gcctagccaa ggccaaacca 900 gaggcctcct tccaggtgtg gaacaaggac agctcttcca aaaaccttat ccctaggctg 960 caaaagatct ggaagaatta cctaagcatg aacaagtaca aagtgtccta caaggggcca 1020 ggaccaggca tcaagttcag tgcagaggcc ctgcgctgcc acctccggga ccatgtgaat 1080 gtatccatgg tagaggtcac agattttccc ttcaatacct ctgaatggga gggttatctg 1140 cccaaggaga gcattaggac caaggctggg ccttggggca ggtgtgctgt tgtgtcgtca 1200 gcgggatctc tgaagtcctc ccaactaggc agagaaatcg atgatcatga cgcagtcctg 1260 aggtttaatg gggcacccac agccaacttc caacaagatg tgggcacaaa aactaccatt 1320 cgcctgatga actctcagtt ggttaccaca gagaagcgct tcctcaaaga cagtttgtac 1380 aatgaaggaa tcctaattgt atgggaccca tctgtatacc actcagatat cccaaagtgg 1440 taccagaatc cggattataa tttctttaac aactacaaga cttatcgtaa gctgcacccc 1500 aatcagccct tttacatcct caagccccag atgccttggg agctatggga cattcttcaa 1560 gaaatctccc cagaagagat tcagccaaac cccccatcct ctgggatgct tggtatcatc 1620 atcatgatga cgctgtgtga ccaggtggat atttatgagt tcctcccatc caagcgcaag 1680 actgacgtgt gctactacta ccagaagttc ttcgatagtg cctgcacgat gggtgcctac 1740 cacccgctgc tctatgagaa gaatttggtg aagcatctca accagggcac agatgaggac 1800 atctacctgc ttggaaaagc cacactgcct ggcttccgga ccattcactg ctaagcacag 1860 gctcctcact cttctccatc aggcattaaa tgaatggtct cttggccacc ccagcctggg 1920 aagaacattt tcctgaacaa ttccagcctg ctccttttac tctaggggcc tctgtcagca 1980 agaccatggg gacttcaaga gcctgtggtc aggaaatcag gtccagcctt ccctgtagcc 2040 agacagttta tgagcccaga gcctcctgcc acacacatgc acacatatct agcattcttt 2100 ccagacagca tcctccccgc cttccacctt ggtagatgca aggtctatct ctcccatcag 2160 ggctgccaaa gctgggcttt gtttttccca gcagaatgat gccattctca caaaccaatg 2220 ctctatattg cttgaagtct gcatctaaat attgatttca cgttttaaag aaattctctt 2280 aaattacaat tgtgcccaat gcagggtggc tctggggggc aagtaggtgg tacaggggat 2340 tggaaacatg ctccgcgcct ccagagaaaa gttgctcccg aggtccatgc ccctggaacg 2400 tgttcctatc actctggctg gttgggctgg tccttagact gggtgcttat gattaaaggg 2460 tcttggttag cccactttcc ctctccatgt ggagatggaa ggtagagaag gatacagtgt 2520 ctatcctcaa gttgctacgg ttcagtgaga gaggcagaca tctgaacagg caggtaggat 2580 tcagtgtgct cagtgcactg gggatttgga gagagatggg cttgctctct ctgtgcaccc 2640 aggagggcca cgcacttaaa actgtgtttg tggatcagag aaggctttat agcacagggg 2700 gcattcagat gagtcttaga ggaagagaag aaacatggca agcagattac atctgagccg 2760 tttgaattgt gtttttcttt cttcccatgt ttattttcta agatctacct gaacttagag 2820 actcaagata tttttttagg aaacctccta cccatgtctg aggtagcaag tgcagcctca 2880 cgacagatac caggcaatcc agagccacaa aacgtgattc ctccaggctc tgcctggcct 2940 gaccctgtcc tgtcagctgg gtttacatac cagtcccatt cttccttttc aatacctacc 3000 cccaaatctt ctcctaacca ccatctgttt ttttttttta aagcattttt tgctttaaaa 3060 gcatcctgac cccaatttct ttgagctcac gggccttttg ctgaaggtct ctcagggtgt 3120 agtggtgtgg ctctctggac ttaacgtcac tctcagaggt cagaaccttg gagatcagaa 3180 ctgattctca ccaggtgtga gaggtgtggt agcagattgc aatgctctgc acctcttcct 3240 tgcaagtgag caacttcagg ctctctgggc agaggctggc ccactgtagt ttgcagacat 3300 gctctccaga tggttttact aagtcccctc tccctgatag ggaatcctgc tggaccagcg 3360 cagccctggt gtggagaggt taaaagactt gcacaggatc accaagtcat gctgtagagc 3420 caggattcct agacccaggg ctctgcactc tcaaggctgg ccccatgtgc tcaaggggat 3480 ctaatgtttg ggctccaaac taaccatctc ggagctgggc tcctcattta ctgccaaacc 3540 ctcagcttat gtagctagaa agggccctgg agtgagaaag cctggatttt caaattgatg 3600 ctcccctact gactagctgt gccactctgg gcaaatgctc ttccttgagc ctgtttccac 3660 acctgtaaag tggggatgat gatcctatct cactgctttt gtgaggatta caggaaagca 3720 cctgtcctgg ctctgtacct ggcacgtagt aggtgctcag ttcatgctgg tttccttcct 3780 gcctttagta gggacctgct ctgtgctcac acctcggctg catgcaccct gctgtgacgg 3840 aggctagtgt ggaagaggtc ctgtcctcag ggaattaact gtcttattgg gagacaacaa 3900 ctgtcctcct tggaacaccc aagaaaccat gcaaagcagt ggacaacaca gaacacgccc 3960 tcctcctcgc tgcctgcagc tccaatctga ttctgcttgg gaatgggcgg agcacgtggg 4020 ctgcttaact gctgtatagg acaagcccct tacccctctc tgggcccatg aattcctggc 4080 ttggtttatg ttctgatttg acacactgat tttaatcttc gaatcatgac actgagtgca 4140 gaggaggtgg cattccgaca gcaggacata catgttggtg tgaagactgg gacgacactg 4200 ggtagaatct agtttttaat tattattaat ataaaggatc aaattaattt aaatatgatt 4260 ctgaagtcta cagaactttt agttctgtgc tgtctatgtg gacactttgg taaaatgcaa 4320 attatgatat ggacgttatc attggtctgg tgagatgttt catatttgtg acagttaatt 4380 taaaaattat gagttaatgc tgcctgtgtc tatggggttc tgtcttcttt gatagccatc 4440 tattcatctg gatcatggga ccctctctaa tccttccacc aatcaaataa gctattgcta 4500 ttggtttgga gttgagatat cagtctcgga aacttctgaa aaatgctaat aattacccaa 4560 ggattatgtc aaattttaaa ataaatgtgt gtgtgtttct ttaa 4604 <210> 176 <211> 2094 <212> DNA <213> homo sapiens <400> 176 gcggaggcag aggcggaggc ggcacccagg ggccggggca ggggaggccg ggaccatcgc 60 agtgacaatt tattttcctg cagcagcggc agcagggacg gttgctgcag gttcggggtc 120 ggccggcctg cgcgtgggct tgcgaggacg ctgttcgtcc cctgcgctgg ggtgtccgac 180 agcgaggagg agaacgacgc acggagcccg cgcgactgga accagcaaag ctccatctgt 240 cggcagagga gaagggggag gaggcacggc cgaggcaaac gagcggacgc ctcgtcgccg 300 ggtgccggta tcaccccgct gcaacgcctt ccagcaaaag ccaccgcggc ccgggttgca 360 gcagccggac ggatgccaag gccacacggc agccacgggg gcagccgtcg cagtcgccgt 420 cccacacggg ctgcggacac caagggttgc taatgaagtg attgagaaga aacagtgaac 480 atcctcattt cacagataag acaacatgga tcagcctttt actgtgaatt ctctgaaaaa 540 gttagctgct atgcctgacc atacagatgt ttccctaagc ccagaagagc gagtccgtgc 600 cctaagcaag cttggttgta atatcaccat cagtgaagac atcactccac gacgttactt 660 taggtctgga gtagagatgg agaggatggc gtctgtgtat ttggaagaag gaaatttgga 720 aaatgccttt gttctttata ataaatttat aaccttattt gtagaaaagc ttcctaacca 780 tcgagattac cagcaatgtg cagtacctga aaagcaggat attatgaaga aactgaagga 840 gattgcattc ccaaggacag atgaattgaa aaacgacctt ttaaagaaat ataacgtaga 900 ataccaagaa tatttgcaaa gcaaaaacaa atataaagct gaaattctca aaaaattgga 960 gcatcagaga ttgatagagg cagaaaggaa gcggattgct cagatgcgcc agcagcagct 1020 agaatcggag cagtttctgt ttttcgaaga tcaactcaag aagcaagagt tagcccgagg 1080 tcaaatgcga agtcagcaaa cctcagggct gtcagagcag attgatggga gcgctttgtc 1140 ctgcttttcc acacaccaga acaattcctt gctgaatgta tttgcagatc aacctaataa 1200 aagtgatgca accaattatg ctagccactc tcctcctgta aacagggcct taacgccagc 1260 tgctactcta agtgctgttc agaatttagt ggttgaagga ctgcgatgtg tagttttgcc 1320 agaagatctt tgccacaaat ttctgcaact ggcagaatct aatacagtga gaggaataga 1380 aacctgtgga atactctgtg gaaaactgac acataatgaa tttactatta cccatgtaat 1440 tgtgccaaag cagtctgcgg gaccagacta ttgtgacatg gagaatgtag aggaattatt 1500 caatgttcag gatcaacatg atctcctcac tctaggatgg atccatacac atcccactca 1560 aactgcattt ttatccagcg ttgatcttca cactcactgt tcctatcaac tcatgttgcc 1620 agaggccatt gccattgttt gctcaccaaa gcataaagac actggcatct tcaggctcac 1680 caatgctggc atgcttgagg tttctgcttg taaaaaaaag ggctttcatc cacacaccaa 1740 ggagcccagg ctgttcagta tatgcaaaca tgtgttggta aaagacataa aaataattgt 1800 gttggatctg aggtgatatg ttctgaatgt aagcaccgtc aacatcagac acctactcat 1860 ggacatgtgg ttgccggatt ttcttaagat gtttccagaa atgactgata ttttatattt 1920 atacatttta gatgacaaag cttgatattt attgctgttg cacattttaa agttttcttt 1980 ttgggttgct ctgtgtcaag agaggttaca tggtgttaaa tcggtacctg ataatgtacc 2040 caaatactat ggccagataa taaattgtgc tgcaaacaac atgtcttgta ttta 2094 <210> 177 <211> 1323 <212> DNA <213> homo sapiens <400> 177 gatttcggcc tgactattac ttgggccacg gaaatagcca acccttttct tccgcacggt 60 tggaggaggt cggctggtta tcgggagttg gagggctgag gtcgggaggg tggtgtgtac 120 agagctctag gacaccaggc cagtcgcggg ttttgggccg aggcctgggt tacaagcagc 180 aagtgcgcgg ttggggccac tgcgaggccg ttttagaaaa ctgtttaaaa caaagagcaa 240 ttgatggata aatcaggaat agattctctt gaccatgtga catctgatgc tgtggaactt 300 gcaaatcgaa gtgataactc ttctgatagc agcttattta aaactcagtg tatcccttac 360 tcacctaaag gggagaaaag aaaccccatt cgaaaatttg ttcgtacacc tgaaagtgtt 420 cacgcaagtg attcatcaag tgactcatct tttgaaccaa taccattgac tataaaagct 480 atttttgaaa gattcaagaa caggaaaaag agatataaaa aaaagaaaaa gaggaggtac 540 cagccaacag gaagaccacg gggaagacca gaaggaagga gaaatcctat atactcacta 600 atagataaga agaaacaatt tagaagcaga ggatctggct tcccattttt agaatcagag 660 aatgaaaaaa acgcaccttg gagaaaaatt ttaacgtttg agcaagctgt tgcaagagga 720 ttttttaact atattgaaaa actgaagtat gaacaccacc tgaaagaatc attgaagcaa 780 atgaatgttg gtgaagattt agaaaatgaa gattttgaca gtcgtagata caaatttttg 840 gatgatgatg gatccatttc tcctattgag gagtcaacag cagaggatga ggatgcaaca 900 catcttgaag ataacgaatg tgatatcaaa ttggcagggg atagtttcat agtaagttct 960 gaattccctg taagactgag tgtatactta gaagaagagg atattactga agaagctgct 1020 ttgtctaaaa agagagctac aaaagccaaa aatactggac agagaggcct gaaaatgtga 1080 caggatcatg aatgtcaaag gtgaagcata tagaaaaaac gacttcatag aaatgaataa 1140 agataaatgt ggatatatgt accagtctgg tggtgaagaa attctgaaac ccagaacttt 1200 ataacaagaa aaaaaatttt taaccctgtg aagaagtttg tgaaagaaac ttgtgaagta 1260 gtaataatta gaaaaaaaac cattaaaaca ccagagaaaa tacatagaaa aaaaaaaaaa 1320 aaa 1323 <210> 178 <211> 954 <212> DNA <213> homo sapiens <400> 178 atgggtggtg tcataaagag catatttaca ttcgttttaa ttgtggaatt tataattgga 60 aatttaggaa atagtttcat agcactggtg aactgtattg actgggtcaa gggaagaaag 120 atctcttcgg ttgatcggat cctcactgct ttggcaatct ctcgaattag cctggtttgg 180 ttaatattcg gaagctggtg tgtgtctgtg tttttcccag ctttatttgc cactgaaaaa 240 atgttcagaa tgcttactaa tatctggaca gtgatcaatc attttagtgt ctggttagct 300 acaggcctcg gtacttttta ttttctcaag atagccaatt tttctaactc tatttttctc 360 tacctaaagt ggagggttaa aaaggtggtt ttggtgctgc ttcttgtgac ttcggtcttc 420 ttgtttttaa atattgcact gataaacatc catataaatg ccagtatcaa tggatacaga 480 agaaacaaga cttgcagttc tgattcaagt aactttacac gattttccag tcttattgta 540 ttaaccagca ctgtgttcat tttcataccc tttactttgt ccctggcaat gtttcttctc 600 ctcatcttct ccatgtggaa acatcgcaag aagatgcagc acactgtcaa aatatccgga 660 gacgccagca ccaaagccca cagaggagtt aaaagtgtga tcactttctt cctactctat 720 gccattttct ctctgtcttt tttcatatca gtttggacct ctgaaaggtt ggaggaaaat 780 ctaattattc tttcccaggt gatgggaatg gcttatcctt catgtcactc atgtgttctg 840 attcttggaa acaagaagct gagacaggcc tctctgtcag tgctactgtg gctgaggtac 900 atgttcaaag atggggagcc ctcaggtcac aaagaattta gagaatcatc ttga 954 <210> 179 <211> 3080 <212> DNA <213> homo sapiens <400> 179 acgtcagagg gtcgcgccgc tgcaggaacc cgctctgcct gagctaccgc gagtcgtaga 60 aaattacgta atgatagggg gccggtcaga gtgagggcac ctgaggtaca cgaaatccct 120 ccggcttgcc cacttcctcg gactttccac caatcaggag cttcctcccc agcaccaacc 180 aattgtggga gagaagtttt ctctgtgcta caagcccgga atttcattca tacccagcta 240 cgctccgaat gagggagcag aggtacagcg gccgaatgag cgggaacagt tattccacga 300 caggtgtaca tcagacgcat tgcttaggcc tcttatttta cgttctccaa gcaactccat 360 aagacaactg tctcggaaag gctacagtga tgacagaccg acttaagttc ggattcggct 420 tccaccgctt cttagtggta tgcaaagaag ccttttcacc ctgatgtcct tagagataat 480 atggatcagt ccagagttct cctctgggtg aaagcagaac cctttatagt gggtgccttg 540 caggtccccc ctccatccaa gtttagtctt cactatctca ggaagatatc cacctatgtg 600 caaatccggg ccacagaagg agcttacccg cgcctctact ggtctacatg gaggcacatc 660 gcttgtggga agctgcagtt ggccaaggac ctggcgtggc tttacttcga aatatttgat 720 agtctttcaa tgaagacacc tgaggagcgc ctggaatggt ctgaggttct gtccaactgc 780 atgtctgagg aggaagttga aaagcagaga aatcagcttt cagtggacac gctacagttt 840 ctgctcttct tatacattca acagttgaac aaggtctccc taaggacatc tttgattggc 900 gaagagtggc ccagtcccag aaacaaatct cagtctcctg acctgactga aaaatctaat 960 tgtcataata agaactggaa tgattacagt caccaagctt ttgtctatga tcatctgtct 1020 gatctcctcg agctgctttt agatccaaaa caactcactg catcatttca ttcaacccat 1080 agtagtctag tgtctcgaga agctgttgtg gcgctcagct tccttattga aggtacaata 1140 agtagagcca ggaagatcta tccacttcat gaacttgcac tgtggcaacc actgcatgca 1200 gatagtggct tctcaaagat ctctaagact ttctctttct acaaactgga aacctggttg 1260 aggtcctgtt tgactgggaa tccatttggt acatcagctt gcctcaagtc tggaaagaaa 1320 ttggcttggg ctcatcaagt tgaagggacc accaaaagag ctaagattgc ttgtaatact 1380 catgtggccc ctaggatgca ccgactggta gtgatgagcc aggtttacaa gcagacactg 1440 gctaagagct cagacactct ggcgggggca catgtaaaga ttcatcgttg caacgaatct 1500 tttatatatc tgctctctcc cttacgatct gtgacaattg agaagtgcag gaatagcatc 1560 tttgtcttgg gccctgtagg gactacactt cacctccaca gttgtgacaa tgttaaagtc 1620 attgctgttt gccatcgttt gtccatctct tctacaacag gttgcatctt tcacgttctt 1680 acgcctacac gcccacttat tctctctggg aaccagacag taacttttgc cccttttcat 1740 acacattacc caatgctaga ggaccatatg gccaggactg gccttgctac agtgcctaac 1800 tattgggata atccaatggt tgtgtgcaga gagaacagcg acacaagagt cttccagctt 1860 ttaccacctt gtgaattcta tgtatttatt attccctttg aaatggaagg ggacacaaca 1920 gagatacccg ggggtcttcc atctgtatat cagaaagcac tgggtcaaag agaacagaag 1980 atacagatct ggcagaaaac tgtgaaggag gctcatttga caaaggatca aaggaagcag 2040 ttccaggtac tggtagagaa caagttttat gaatggttga ttaatacagg acatcgccaa 2100 cagctggaca gccttgtacc ccctgcagca ggctccaaac aagcagctgg ataaggatct 2160 tacatgcaga cactgggccc tggaaataca aggataaatg gaggatggtg ctcatcttga 2220 aacttgaaac taaattggga aggtgctatt gctgcttaag agacattggg acttttctgt 2280 cttttttttt tttttttttt gaggcagagt cttgttctgt cgcccaggct ggagtgcagt 2340 ggcgcgatct cggctcactg caagctctgc ctcccgggtt cacgccattc tcctgcctca 2400 gcctcctgag tagctgggac tacaggcgcc cgccaccacg cccggccaat tttttttgta 2460 tttttagtag agacggggtt tcaccgtgtt agtcaggatg gtctcgattt cctgacctcg 2520 tgatccgccc atctcggcct cccaaagtgc tgggattaca ggcgtgagcc accgtgccca 2580 gccttctgtt ctatttaaga actttgattt ccattccatt ttcatttatt actgtttagg 2640 ccgaattttc gctaaacttc tgactttcat ataaacatat tgcttataga acatcagaag 2700 actcgtcttt gtgatgccca aatgaaaaag ttggtgaagg tagtaccatt gtatgtatgt 2760 taatattaaa gcaactgagt gtagatttgc aactatagtg tgtatcttca tttgtgtgat 2820 gaaagagttt tattctttct agagttaaat aagagtttta tagttctttg taactattta 2880 aaaggaaatt gctactcctt ttaaaaaata attggaaagg aagtatgatt tgttggtata 2940 tagacataga aatagtttta tactatattt tagtccttaa agtatggaac ttaatgaaat 3000 tgtttaaaaa aatctttatt tttcacttcc tgcttcaaat tttcaataaa caaactctaa 3060 agaaaaaaaa aaaaaaaaaa 3080 <210> 180 <211> 3062 <212> DNA <213> homo sapiens <400> 180 gggtcagggc tagagccgtg agtgtcagcc tgggatgggc tacataaggc ccagctctgg 60 caccagagct tcattctttg ttgcacagca aactgcagag gtcactccag gctgtggctc 120 cacatcccga ggaacaaaag cgggcctgct cagctgtctg caaggacggc cgttccagac 180 caagtggcct gctgctccga ggacccagct cgctccaggc tgtgactcca catcccgagg 240 tcgctgcctg gcgaccgggc agcgaggacc ggccacccca gacttcctgt cccgcagccc 300 caaagacaga gctgcgaccg ccgggacagc gacgcctgca cagctctggt gagatggcgg 360 cagggtccac tacgctgcac gcagtggaga agctgcaggt gcgtctggcc actaagacgg 420 agccgaaaaa gctagagaaa tatttgcaga aactctccgc cttgcccatg acggcagaca 480 tcctggcgga gactggaatc agaaagacgg tgaagcgcct gcggaagcac cagcacgtgg 540 gcgactttgc cagagactta gcggcccggt ggaagaagct ggtgctcgtg gaccgaaaca 600 cccggcctgg cccacaggac cctgaggaga gcgcttcccg acagcgcttc ggggaggctc 660 ttcaggacca ggaaaaggcc tggggcttcc cagaaaacgc gacggccccc aggagcccat 720 ctcacagccc tgagcacaga cggacagcac gcagaacacc tccggggcaa cagagacctc 780 acccgaggtc tcacagtcgc gagcccagag ctgagagaaa gtgccccaga atagccccag 840 ctgattccgg ccgctatcgg gcctctccaa cgcgcacagc tcccctccgg atgcccgagg 900 gccctgagcc cgctgcgccc gggaagcaac ccggaagagg ccacactcac gcggctcagg 960 gcgggcctct gctgtgtcca ggctgccagg gccaacccca ggggaaagcc gttgtgagcc 1020 acagcaaggg gcacaaatcg tctcgccagg aaaaacgccc cttgtgtgcc cagggagatt 1080 ggcactcccc tactttgatc agggagaaat catgcggggc ctgcttaaga gaggaaaccc 1140 caaggatgcc ctcctgggca agtgccaggg acaggcagcc ttcggacttc aagacagaca 1200 aggaaggggg gcaagctggc agcggccagc gtgtccctgc cttggaggag gctccagaca 1260 gtcaccagaa gaggcctcag cacagtcact cgaacaagaa gaggcccagt ctagacggcc 1320 gggacccagg aaatgggaca cacggcctgt cgcccgagga gaaagagcag ctttccaacg 1380 accgagagac tcaagagggg aagccaccga ctgctcattt ggacagaacg tccgtgagct 1440 ccctctctga ggtggaggag gtagatatgg ctgaggaatt cgagcagccc actctgtcat 1500 gtgaaaaata cctcacctac gatcagttgc ggaagcaaaa gaaaaagact ggaaaatctg 1560 ccaccactgc acttggagat aaacaaagga aagcaaacga atccaagggc actcgtgagt 1620 cctgggattc ggctaagaaa ttgcctcctg tccaggaaag ccagtcagag aggctgcagg 1680 cggccggcgc tgattccgcc gggccgaaaa cggtgcccag ccatgtcttc tcagagctct 1740 gggacctctc agaggcctgg atgcaggcca actacgatcc gctttcggat tctgactcca 1800 tgacctccca ggcaaagcca gaagcactct cttcaccaaa gttccgggag gaagctgctt 1860 tccctggacg cagagtgaat gctaagatgc cggtgtactc gggctccagg cctgcctgcc 1920 agctccaggt gccgacgctg cgccagcagt gtgcccaggt gcttagaaac aatccggacg 1980 ccctcagcga cgtgggagag gtcccctact gggttcttga acctgttctg gaagggtgga 2040 ggcccgatca gctgtatcgc agaaagaaag acaatcacgc actcgttaga gagacagacg 2100 aattacggag gaatcattgt ttccaggact tcaaggaaga aaagccacag gaaaacaaaa 2160 cttggaggga gcagtacctg cggcttccgg acgccccaga gcagcggctg agagtaatga 2220 caacgaatat ccgatctgca cgtggaaaca accccaacgg cagagaggca aagatgatct 2280 gtttcaaatc tgtggccaag acgccttatg atacttcaag gaggcaagag aagtctgcag 2340 gagacgctga ccccgaaaat ggggagatca agccagcctc caagcccgcg ggaagcagcc 2400 acactccctc cagccagagc agcagcggcg gtggcagaga cagcagcagc agcatccttc 2460 gctggctccc tgagaagcgg gccaacccct gcctgagcag cagcaatgag cacgcggcgc 2520 ccgcggccaa aacccggaaa caggctgcca agaaagtggc cccgctgatg gccaaggcaa 2580 ttcgagacta caagagaaga ttctcccgac gataaactca ggacttgcct tgcagataaa 2640 atctgggggg atttttgcat tggcaaagtc aatgcgggtt ggggaacgaa acttccaatg 2700 gacaccagaa cctttaactt ggtgcaaagt tgagcctttg aattctgcag gtgtcatgtg 2760 ctggccctgt gattttgcct cccacaccca gccactacct cccagcttgg agaacacctc 2820 agaattcaga agatatgaac gcattgggaa caattctatt ttggatgttc actgataatt 2880 tttaaaaaca ccctagttgt aatcataaat aaggaaaaag atgtgagatt tcctttttcc 2940 tttctttttt ttttcgaaat caagtagata agaacttctt agacaaaaac acacaagcca 3000 ttagttgaca ctgataactc cgaatacata aaatgtttgc tgttgcaaaa aaaaaaaaaa 3060 aa 3062 <210> 181 <211> 2269 <212> DNA <213> homo sapiens <400> 181 cagttgcttc tacaaaaccc gtgaaagttc tctgtccaaa agccttgttg gtcccgcggt 60 acatgcttcc tgttcccaga gagattcacc cttgggcttt cctatcagtc ttccctaaag 120 ttggctgctc ctgtgtcctg tcacataaaa ctgtgaaccg aggtctccga cttacgtcat 180 gtcagtcaca gcagggtgag gctccacaag tgtgagttct ggcccctgct gctttccttt 240 caaatgcagt ttacagttta ttatggtatt ggacacccca tgctccttac tgcattggct 300 ttgggtaaga aggagtgaaa attagtgtgc gaacctgaaa acctagaatt tctgattggg 360 actgaagaaa acctttgtgc tgcagtcagt ccccgagcca gacgcctgtg actctcttca 420 catggaaata gatgactatc cacagtaaaa gcaaaattaa aaagtgactt gtgaaaaata 480 tcctccatgc tcctcttacc aagcctgcaa cttaaaacct atggtttaaa ctgtgctttc 540 aattatctgg aggaggccag cactgatgag cccatcctga gccagtcatt ttaaggccag 600 tgctacctaa ctgagacaag gctaatctgg tcgccttgct gttagaggct ctttcccaga 660 agttggacga agaggctcag gcgttgctgt ttcttgtctt ccaagtcaag tggttactct 720 ggtaatggat tgcctctctc cgagctttca ccctggtgag actgtccaga tctagtctgt 780 aaacccagct tagaagcact gttgtaaaaa tgactgaaga gcccatcaag gagatcctgg 840 gagccccaaa ggctcacatg gcagcgacga tggagaagag ccccaagagt gaagttgtga 900 tcaccacagt ccctctggtc agtgagattc agttgatggc tgctacaggg ggtaccgagc 960 tctcctgcta ccgctgcatc atcccctttg ctgtggttgt cttcatcgcc ggcatcgtgg 1020 tcaccgcggt ggcttacagc ttcaattccc atgggtctat tatctccatc tttggcctgg 1080 ttgttctgtc atctggactt tttttactag cctccagtgc cttgtgctgg aaagtgagac 1140 aaaggagcaa gaaagccaag agacgggaga gtcaaacagc tctcgtggca aatcagagaa 1200 gcttgtttgc ttgagactga atacgaccaa atgggccatt gggcctggaa aacgtgctct 1260 gactttgtca cccaattcac ccagaaccat ggtgggagag aacagacttg gcgttggagc 1320 agactggaag aatgggggtg ggagggtgga ggggcttctc ctttgtgagg aatgactcat 1380 gtcttcttta acgacaaact taaccctaag ggctacttct gagactgaaa aatcagcttt 1440 ctatttacat gaaacacttt gggggtcatg ggagtgcaca gcattagaca gtatttggtt 1500 caccctgtaa agtagccaag aaaagatgag aaaaatcaag ataggcctgg cacactagac 1560 atttgcctcc aaaagaaata acctacagtc ttaagatgta tcataaaaat gttctgccaa 1620 ggatctaaat taccttgggt ttcgcatatg tctatgaaat tctgtgataa tttttttcaa 1680 tacattgatt cactggcgtc tgttttcatt ttatactttt aataactcat cactggtggt 1740 actttatctt gaaaagtaat attttttata ttttaacatt ggacagtgtt agccagttgt 1800 aatgatgtat cagaagtaaa gaaaaaccca ttaaagttat agctaataga tgctgttggg 1860 ggttaaatta atagtaaaat aatccaatat agcacttttg atgattttta tataaaagtc 1920 aactgtacat ttcattcaga ataataaata cttattgctg ctaaaacttc ttaaatggtt 1980 gtttctgcta tagttatttc tattgcagtt ccaaattgcc atcttccctt gtctcatttg 2040 caagttctca attgtatttc tctcaaatgg acaggttcct tctttactgg aggatttttg 2100 tttttatcat attggttttt cattacttct gaatagtctt aattacgttt actaaattct 2160 aaaggatttc tgtgctatta taattaggaa atcaacgtct ttggtcagga actttataat 2220 gtgctattaa atgtatatta catttttgtg gaaaaaaaaa aaaaaaaaa 2269 <210> 182 <211> 1213 <212> DNA <213> homo sapiens <400> 182 ttagggtttt caggcagagg aacagttggc caaggaagtc agcttctcag agctcaagag 60 tagatctgag tttaactcat taaagatggc atggaagagc agtgtcataa tgcaaatggg 120 aagatttctt ctcttagtaa ttttatttct gccacgtgag atgacaagtt ctgttttaac 180 tgtgaatggt aaaactgaga actatatcct ggatactaca cctggctccc aagcatctct 240 gatatgtgct gttcaaaacc acaccagaga ggaagaactg ctctggtacc gagaggaggg 300 gagagtggat ttgaaatctg gaaacaaaat caattccagc tctgtctgtg tctcttccat 360 cagtgaaaat gacaacggaa tcagctttac ctgcaggctg gggagggatc agtccgtgtc 420 cgtttcggtg gtgctgaatg ttacttttcc tcctctccta agtggaaacg acttccaaac 480 agttgaggaa ggcagtaatg tgaagttggt ttgcaatgtg aaagccaacc cccaggctca 540 aatgatgtgg tacaaaaaca gtagtctcct cgatttagag aaaagccgtc accaaatcca 600 acagacaagt gagtcttttc agctgtcaat caccaaagtc gagaagcctg acaacggaac 660 ctacagttgt attgcaaagt catctctgaa aacggagagc ttggactttc acctgattgt 720 taaagataaa actgtgggtg taccaataga gcccattatt gctgcatgtg ttgtgatctt 780 tctgacattg tgctttggac tgattgctag aagaaagaaa ataatgaagc tctgcatgaa 840 ggataaagac cctcacagtg aaacagctct atgagaaagc tgagatgcca tcgaatacag 900 agagagtttt gcatcaggac ctccacaatt tatgtagtcc catctgtatt tattgctatt 960 attaaattca ctcctgtcac tcctgtttca ttaatcactt aacagtagtt gttaggacta 1020 atttgataca cttgtggaac atttttatgg aaagagctat taagaatgaa aagtaagatt 1080 ttgttaagtc ttctccttga agtatatgtt aattaattga gatttgttcc aaataggttg 1140 gtaatcattt actgtttagt gtgttttttt tctaggtagg agatacttgg gtctcacaaa 1200 ttggtgcaaa gcc 1213 <210> 183 <211> 4575 <212> DNA <213> homo sapiens <400> 183 cagggagggg aagacgggga gccggacgca cgaccggcga gcacagaagg gcacaggagc 60 tgctccgcga gataccagcg agctgaggcg cggggctggc tgggaagtag tcccggccgg 120 gccctggccc cgcccctgca gggcggaggg acgcatcacg caggggtggg gaagccggat 180 ccgtgcgcag ggttgctaag ggtgaaactt ttcattgact ttgctcactt cgggccgggg 240 cgcgggaagg tgcgggttgt tggctgaggc aagccgtggc tcgggcgacg cggggccagg 300 agggcaggac cgtctgccgg cgacagccca taccgtctgc cgttgcgcga cacgaaccac 360 cctccgatcc gccatccccg cgtcgtcgcc gctagtccgc ccgcccgccc tcgggccccc 420 cgctgccgag cccgacctcc taagagctga aagaaattat tgagagtcat agtccatagc 480 cccctgcttc gtcccccaac cctcaacgac gaaaaggact tcggtcccct ggcccggcga 540 cgcccgggaa ggaaaggaga gcgacctccg ccccgcgctc aggccaccct ggagggagaa 600 gccgccccgc ggccggtaga gcgccccgcc gccgcggaga cccgaagccg cctggagccc 660 aaggctgtac acgtgccctg tgctgattct ctgcctagga aaggaccatg cagctagaga 720 tcaaagtggc cctgaacttc atcatctcct acttgtacaa caagctgccc cggcgccggg 780 cagacctgtt tggggaggag ctagagcggc ttttgaaaaa gaaatatgaa ggccactggt 840 accctgagaa gccactgaaa ggctctggct tccgctgtgt tcacattggg gagatggtgg 900 accccgtggt ggagctggcc gccaagcgga gtggcctggc ggtggaagat gtgcgggcca 960 atgtgcctga ggagctgagt gtctggattg atccctttga ggtgtcctac cagattggtg 1020 agaagggagc tgtgaaagtg ctgtacctgg atgacagtga gggttgcggt gccccagagc 1080 tggacaagga gatcaagagc agcttcaacc ctgacgccca ggtgttcgtg cccattggca 1140 gccaggacag ctccctgtcc aactccccat cgccatcctt tggccagtca cccagcccta 1200 ccttcattcc ccgctccgct cagcccatca ccttcaccac cgcctccttc gctgccacca 1260 aatttggctc cactaagatg aagaaggggg gcggggcagc aagtggtggg ggtgtagcca 1320 gcagtggggc gggtggccag cagccaccac agcagcctcg catggcccgc tcacccacca 1380 acagcctgct gaagcacaag agcctctctc tgtctatgca ttcactgaac ttcatcacgg 1440 ccaacccggc ccctcagtcc cagctctcac ccaatgccaa ggagttcgtg tacaacggtg 1500 gtggctcacc cagcctcttc tttgatgcgg ccgatggcca gggcagcggc accccaggcc 1560 cgtttggagg cagtggggct ggcacctgca acagcagcag ctttgacatg gcccaggtat 1620 ttggaggtgg tgccaacagc ctcttcctgg agaagacacc ctttgtggaa ggcctcagct 1680 acaacctgaa caccatgcag tatcccagcc agcagttcca gcccgtggtg ctggccaact 1740 gaccatctac ctgcccgtgg ggccaggagc acccaagacc acagaaaaga gaaaggaaag 1800 gccaaaaaaa agaggaaaag aaaaatgtac aaaaagattt tcgatcttct cactcttact 1860 tctagaaaaa agatccagcc caggcacgga atgggagggc cctgcaaagc acccaagtgt 1920 gtttcactca ccccttaccg ctcgcccacc ggcctgtgat ttatttggtt ggtttgggtt 1980 ttatatttct ttttcttttt tttttttctt acatgtagtt ttctatataa catctttaat 2040 gagtggcttc ctgtgctaag aatggtccag atgtgaactg ctgctccctg ctcctccctt 2100 cctccttcac actcctagtt taggattgat gtgtccaagc tcatagggaa gaaagagctg 2160 cagctggagc ctgaccctcc ctggaacagg gagaggctgg cccgtgtcac tgcctctgtc 2220 acccagctat cctcgcactc aaagccatcc aacctcagca ggccttctcg ggccctgcca 2280 cctgaatagg tctgacccca gtccccactc cctttcaggc tgggccacag ggagttgctg 2340 gctggccact tgacaccctc cccctggagc tgatgtctgt gactacaggg agattagcac 2400 ttcgtctagt gaaactcctt tcatctctgt cctatggccc caccccacca ttccctctag 2460 gcccagacca tcatcatggc cctggccatt gatgtgtatg ggctttcttt ccctcatgca 2520 gccccttctt ccccaggctg gatgttgtgg gtagggaggg gtgtgtgtgt gtgtatttgg 2580 tttgctgtcc ttttttaaag gattccaagc catgtgaaac ttcccttctg gatgtgattc 2640 tgggtcgcaa gtccttattt atatgtgagg ctggggaatg ggctgggggt attggcagtc 2700 cttttgcagg gcagtgtgtg tggtggggtg acaccgctgt ggcttagccc aagacactcc 2760 cagaggaaaa cactgcagaa ggaactggtt tgcagactgt ggaaggatct gcagttttgt 2820 ttttgaccaa aaaaataata ataagttagc tctgaagggc agagggaata cccaagcccc 2880 tgatgcctat gagaagtccc tggacttcaa ccctcctgtt gtttggcctt agcccagagg 2940 gagctgctca cctgagcacc cttgggggtg ggcagagagg cagggtggga ttttagagtt 3000 agtgtctgtg cgggggcagc cctgagcctg gagttgagac tttggggtct cttagtttgg 3060 aggtgttgag tgcatttgtg cccctgcctg gttgagagct tcttggtacc tcttgccacc 3120 ccttctcact gccctgaccc aaccccactg gaccttgatg ctgcgaggag tggtgtcctg 3180 acggactcag cactcccgcc tgatgtattg gatcatagga gagcacttgc tctcctgcct 3240 ctgccaggag agggcttgtt cctccaactc taggaggcca ggcaagcatg gacaggagcc 3300 aagggagcag ggtcattaac tttttcttct ttgcaaagtg ggcacttggc atcagggtcc 3360 caatcaccag aaagcaccaa agcccctggc accccaccca ctccatccta cccagggacc 3420 ccaagtaggc aactgttatg gcagtgggtc cagcccaggc cagcactgcc agcctcctct 3480 ccctgcagta ggcaccagct ctacctcccc cggcaggcaa tgtcctggct tctcagccca 3540 gcaccatctg ttcccctaga cttctcaggg gccagcccag tctgggccac cctttgtttc 3600 cctcatcctc ggctcccaca caggtgacag acccagcaga tagcttctct ctgggaaagg 3660 ttggatgctg ccttacatcc ccttctagcc ctcctcccat ccacacacac aggcacccac 3720 ccacaccagg tcggcttgtt tctcacatgt agggagagag gggagaccaa cccctttgtg 3780 tcttttgaaa tacgaagaaa aatgtgtgtt caggagcatg actccagtgc tgcgctcttg 3840 ggcccagttc agtctgtctt gtctcaaatc taggcatttt tgcttcaatt ttattttttt 3900 taagaataca aaaacagaaa tctgcactaa tttacctggt ttcgtaggaa aacttttttt 3960 tattttttac attttttggt gtccgtttgt attgaataat ttgctacatt tgtaaaatgt 4020 aagaggtata taatatatgt atatttctaa cgtaaaaaac ataatttttt tcttttcaag 4080 attttttctt aaaaagatga gagaaacata ttttttcagg aaaaacaaac tttaaaaaaa 4140 aaagaggaga aataaaacct tttctcccct ttccccatcc tctatctatc cctctttccc 4200 aggaacaaat caaaaggtgg attatcttct gaagaatgga aactgttagt ccagaatgat 4260 gtgtttttct caatgcagtg agttatagat tctctagttt tctccctagg gatgggaagg 4320 gggcattgag gcaagcctgg agaggagccc ggggagcagg gtcatgaact tttttcttta 4380 gtgaaggagg aatacaatca agggttttgt attcagaatg ttgtgcaata ttttggaatg 4440 ggacattggt gtgtttagag attttagttt aaaaacaaaa caaaaagatt gatcaaatct 4500 gtacagtttc tattgttcca gattttttta agtttgtatt aaaagcatga tacataatag 4560 ccttcaaaaa aaaaa 4575 <210> 184 <211> 1504 <212> DNA <213> homo sapiens <400> 184 atgagggaga tcgtgctcac gcagatcggg cagtgcggga atcagatcgg cgccaagttc 60 tgggaggtga tctctgatga acatgccatc gactccgctg gcacctacca cggggacagc 120 cacctgcagc tggagcgcat caacgtgtac tacaacgagg ccagcggtgg caggtacgtg 180 ccccgcgctg tgctcgtgga tctggagccg ggcaccatgg actctgtgcg ctcggggccc 240 ttcgggcagg tcttcaggcc agacaacttc atcttcggtc agtgtggggc cggaaacaac 300 tgggccaagg gacactacac cgaaggcgcg gagctgatgg agtcagtgat ggacgttgtc 360 agaaaggagg ctgagagctg tgactgcctg cagggtttcc agctgaccca ctccctgggt 420 ggggggactg ggtctgggat gggtaccctt ctgctcagta agatccggga ggagtaccca 480 gacaggatca taaacacatt cagcatcctg ccctcgccca aggtgtcgga caccgtggtg 540 gagccctaca acgccaccct ctcagtccac cagctcatag aaaacgcaga tgagaccttt 600 tgcatagata acgaagctct gtatgacata tgttccaaga ccctaaaact gcccacaccc 660 acctatggtg acctgaacca cctggtgtct gctaccatga gtggggtcac cacgtgcctg 720 cgcttcccgg gccagctgaa tgctgacctg cggaagctgg ccgtgaacat ggtcccgttt 780 ccccggctgc atttcttcat gcccggcttt gccccactga ccagccgggg cagccagcag 840 taccgggcct tgactgtggc tgagcttacc cagcagatgt ttgatgctaa gaacatgatg 900 gctgcctgtg acccccgtca cggccgctac ctaacggcgg ctgccatttt caggggtcgc 960 atgcccatga gggaggtgga tgaacaaatg ttcaacattc aagataagaa cagcagttac 1020 tttgctgact ggctccccaa caacgtaaaa acagccgtct gtgacatccc accccggggg 1080 ctaaaaatgt cagccacctt cattgggaat aatacggcca tccaggaact cttcaagcgt 1140 gtctcagagc agtttacagc aatgttcagg cgcaaggcct tcctccactg gtacacgggc 1200 gagggcatgg atgagatgga attcaccgag gccgagagca acatgaacga cctggtgtct 1260 gaatatcagc aatatcagga tgccacggcc gaggaggagg aggatgagga gtatgccgag 1320 gaggaggtgg cctagaactc tccttttcta ggtaaagggg ggaagcagtg tggattcttt 1380 actgtgttct gacagccatg tgtcactata cgcttgttaa tttgtgtctt cacatctcct 1440 gctgcgtttt aaagcatttt tatagtatgc ggttttgact aataaagtat tctcacagca 1500 tctg 1504 <210> 185 <211> 1006 <212> DNA <213> homo sapiens <400> 185 gattgcttga ggagagaagt atgtgatcag aaagcattct ttgtctatta actcctgccc 60 agcaaaagtg aaagaaaatt catgggagca tgcaagaaca aagagcacag caaagctgga 120 caaacacagc aatccaggca ggggatttcc aactcaactc tggtatataa gctgcatgca 180 aagtcctttt tctgtctctg gtttctggcc ccttgtctgc agagatggct cccaatgctt 240 cctgcctctg tgtgcatgtc cgttccgagg aatgggattt aatgaccttt gatgccaacc 300 catatgacag cgtgaaaaaa atcaaagaac atgtccggtc taagaccaag gttcctgtgc 360 aggaccaggt tcttttgctg ggctccaaga tcttaaagcc acggagaagc ctctcatctt 420 atggcattga caaagagaag accatccacc ttaccctgaa agtggtgaag cccagtgatg 480 aggagctgcc cttgtttctt gtggagtcag gtgatgaggc aaagaggcac ctcctccagg 540 tgcgaaggtc cagctcagtg gcacaagtga aagcaatgat cgagactaag acgggtataa 600 tccctgagac ccagattgtg acttgcaatg gaaagagact ggaagatggg aagatgatgg 660 cagattacgg catcagaaag ggcaacttac tcttcctggc atgttattgt attggagggt 720 gaccaccctg ggcatggggt gttggcaggg gtcaaaaagc ttatttcttt taatctctta 780 ctcaacgaac acatcttctg atgatttccc aaaattaatg agaatgagat gagtagagta 840 agatttgggt gggatgggta ggatgaagta tattgcccaa ctctatgttt ctttgattct 900 aacacaatta attaagtgac atgattttta ctaatgtatt actgagacta gtaaataaat 960 ttttaaggca aaatagagca ttcaaagcca aaaaaaaaaa aaaaaa 1006 <210> 186 <211> 2099 <212> DNA <213> homo sapiens <400> 186 gaaagaaaca acaactggaa aagaagcact gcataagacc aggatgtctc tgaaatggat 60 gtcagtcttt ctgctgatgc agctcagttg ttactttagc tctgggagtt gtggaaaggt 120 gctggtgtgg cccacagaat acagccattg gataaatatg aagacaatcc tggaagagct 180 tgttcagagg ggtcatgagg tgattgtgtt gacatcttcg gcttctattc ttgtcaatgc 240 cagtaaatca tctgctatta aattagaagt ttatcctaca tctttaacta aaaatgattt 300 ggaagatttt tttatgaaaa tgttcgatag atggacatat agtatttcaa aaaatacatt 360 ttggtcatat ttttcacaac tacaagaatt gtgttgggaa tattctgact ataatataaa 420 gctctgtgaa gatgcagttt tgaacaagaa acttatgaga aaactacaag agtcaaaatt 480 tgatgtcctt ctggcagatg ccgttaatcc ctgtggtgag ctgctggctg agctacttaa 540 catacccttt ctgtacagtc tccgcttctc tgttggctac acagttgaga agaatggtgg 600 aggatttctg ttccctcctt cctatgtacc tgttgttatg tcagaattaa gtgatcaaat 660 gattttcatg gagaggataa aaaatatgat atatatgctt tattttgact tttggtttca 720 agcatatgat ctgaagaagt gggaccagtt ttatagtgaa gttctaggaa gacccactac 780 attatttgag acaatgggga aagctgaaat gtggctcatt cgaacctatt gggattttga 840 atttcctcgc ccattcttac caaatgttga ttttgttgga ggacttcact gtaaaccagc 900 caaacccttg cctaaggaaa tggaagagtt tgtgcagagc tctggagaaa atggtattgt 960 ggtgttttct ctggggtcga tgatcagtaa catgtcagaa gaaagtgcca acatgattgc 1020 atcagccctt gcccagatcc cacaaaaggt tctatggaga tttgatggca agaagccaaa 1080 tactttaggt tccaatactc gactgtataa gtggttaccc cagaatgacc ttcttggtca 1140 tcccaaaacc aaagctttta taactcatgg tggaaccaat ggcatctatg aggcaatcta 1200 ccatgggatc cctatggtgg gcattccctt gtttgcggat caacatgata acattgctca 1260 catgaaagcc aagggagcag ccctcagtgt ggacatcagg accatgtcaa gtagagattt 1320 gctcaatgca ttgaagtcag tcattaatga ccctatctat aaagagaata tcatgaaatt 1380 atcaagaatt catcatgatc aaccggtgaa gcccctggat cgagcagtct tctggattga 1440 gtttgtcatg cgccataaag gagccaagca ccttcgggtc gcagcccaca acctcacctg 1500 gatccagtac cactctttgg atgtgatagc attcctgctg gcctgcgtgg caactatgat 1560 atttatgatc acaaaatgtt gcctgttttg tttccgaaag cttgccaaaa caggaaagaa 1620 gaagaaaagg gattagttat atcaaaagcc tgaagtggaa tgaccaaaag atgggactcc 1680 tcctttattc cagcatggag ggttttaaat ggaggatttc ctttttcctg cgacaaaacg 1740 tcttttcaca acttaccctg ttaagtcaaa atttattttc caggaattta atatgtactt 1800 tagttggaat tattctatgt caatgatttt taagctatga aaaataataa tataaaacct 1860 tatgggctta tattgaaatt tattattcta atccaaaagt taccccacac aaaagttact 1920 gagcttcctt atgtttcaca cattgtattt gaacacaaaa cattaacaac tccactcata 1980 gtatcaacat tgttttgcaa atactcagaa tattttggct tcattttgag cagaattttt 2040 gtttttaatt ttgccaatga aatcttcaat aattaaaaaa aaaaaaaaaa aaaaaaaaa 2099 <210> 187 <211> 1224 <212> DNA <213> homo sapiens <400> 187 atttcctttc cggcggcgcg ctgtcgtcac gcgtcccgcg cctcctcgcg cctgcgccgt 60 ggttggaagg tcgtccctgt gaccggcttg gcggttggag cggctgtcgc catgttgtcg 120 gtagcatccc gctcaggccc gttcgcgccc gtcctgtcgg ccacgtcccg cggggtggcg 180 ggcgcgctgc ggcccttggt gcaggccacg gtgcccgcca ccccggagca gcctgtgttg 240 gacctgaagc ggcccttcct cagccgggag tcgctgagcg gccaggccgt gcgccggcct 300 ttggtcgcct ccgtgggcct caatgtccct gcttctgttt gttattccca cacagacatc 360 aaggtgcctg acttctctga ataccgccgc cttgaagttt tagatagtac gaagtcttca 420 agagaaagca gcgaggctag gaaaggtttc tcctatttgg taactggagt aactactgtg 480 ggtgtcgcat atgctgccaa gaatgccgtc acccagttcg tttccagcat gagtgcttct 540 gctgatgtgt tggccctggc gaaaatcgaa atcaagttat ccgatattcc agaaggcaag 600 aacatggctt tcaaatggag aggcaaaccc ctgtttgtgc gtcatagaac ccagaaggaa 660 attgagcagg aagctgcagt tgaattatca cagttgaggg acccacagca tgatctagat 720 cgagtaaaga aacctgaatg ggttatcctg ataggtgttt gcactcatct tggctgtgta 780 cccattgcaa atgcaggaga ttttggtggt tattactgcc cttgccatgg gtcacactat 840 gatgcatctg gcaggatcag attgggtcct gctcctctca accttgaagt ccccacgtat 900 gagttcacca gtgacgatat ggtgattgtt ggttaagaga cttggactca agtcataggc 960 ttctttcagt ctttatgtca cctcaggaga cttatttgag aggaagcctt ctgtacttga 1020 agttgatttg aaatatgtaa gaattgatga tgtatttgca aacattaatg tgaaataaat 1080 tgaatttaat gttgaatact ttcaggcatt cacttaataa agacactgtt aagcactgtt 1140 atgctcagtc atacacgcga aaggtacaat gtcttttagc taattctaat taaaaattac 1200 agactggtgt acaagatact tgtg 1224 <210> 188 <211> 3844 <212> DNA <213> homo sapiens <400> 188 agcactcatt ggacttcagc atgactactc agttgccagc ttacgtggca attttgcttt 60 tctatgtctc aagagccagc tgccaggaca ctttcactgc agctgtttat gagcatgcag 120 cgatattgcc caatgccacc ctaacaccag tgtctcgtga ggaggctttg gcattaatga 180 atcggaatct ggacattttg gaaggagcga tcacatcagc agcagatcag ggtgcgcata 240 ttattgtgac tccagaagat gctatttatg gctggaactt caacagggac tctctctacc 300 catatttgga ggacatccca gaccctgaag taaactggat cccctgtaat aatcgtaaca 360 gatttggcca gaccccagta caagaaagac tcagctgcct ggccaagaac aactctatct 420 atgttgtggc aaatattggg gacaagaagc catgcgatac cagtgatcct cagtgtcccc 480 ctgatggccg ttaccaatac aacactgatg tggtatttga ttctcaagga aaactggtgg 540 cacgctacca taagcaaaac cttttcatgg gtgaaaatca attcaatgta cccaaggagc 600 ctgagattgt gactttcaat accacctttg gaagttttgg cattttcaca tgctttgata 660 tactcttcca tgatcctgct gttaccttgg tgaaagattt ccacgtggac accatagtat 720 tcccaacagc ttggatgaat gttttgccac atttgtcagc tgttgaattc cactcagctt 780 gggctatggg catgagggtc aatttccttg catccaacat acattacccc tcaaagaaaa 840 tgacaggaag tggcatctat gcacccaatt cttcaagagc atttcattat gatatgaaga 900 cagaagaggg aaaactcctc ctctcgcaac tggattccca cccatcccat tctgcagtgg 960 tgaactggac ttcctatgcc agcagtatag aagcgctctc atcaggaaac aaggaattta 1020 aaggcactgt ctttttcgat gaattcactt ttgtgaagct cacaggagtt gcaggaaatt 1080 atacagtttg tcagaaagat ctctgctgtc atttaagcta caaaatgtct gagaacatac 1140 caaatgaagt gtacgctcta ggggcatttg acggactgca cactgtggaa gggcgctatt 1200 atctacagat ttgtaccctg ttgaaatgta aaacgactaa tttaaacact tgcggtgact 1260 cagctgaaac agcttctacc aggtttgaaa tgttctccct cagtggcact ttcggaaccc 1320 agtatgtctt tcctgaggtg ttgctgagtg aaaatcagct tgcacctgga gaatttcagg 1380 tgtcaactga cggacgcttg tttagtctga agccaacatc cggacctgtc ttaacagtaa 1440 ctctgtttgg gaggttgtat gagaaggact gggcatcaaa tgcttcatca ggcctcacag 1500 cacaagcaag aataataatg ctaatagtta tagcacctat tgtatgctca ttaagttggt 1560 agaatattga ctttttctct tttttatttg ggataattta aaaaatgatg gatgagaaaa 1620 gaaagattgg tccgggttaa tattatcctc tagtataagt gaattactag tttctcttta 1680 tttagacaaa cacacacaca ccagataata taaacttaat aaattatctg ttaatgtaga 1740 ttttatttaa aaaactatat ttgaacattg gtctttcttg gacgtgagct aattatatca 1800 aataagtatc acaaatcttt tacgcagaag aaataaaaac tacgggtaga aaacataaga 1860 actatcataa aatttactta caaggaggct gctcttgtta ccacttttat tatattacgt 1920 atcacttatt cagctctgct gaaaatttcc aatgactttg tttgtttgct ctttttgttt 1980 tttacctaaa caatacattt tgattctctt gtgggttgat aatgtctccc caaaatttac 2040 atgttgaagc acctcagaat gtgactgtat ttggagacag ggtctttaaa gaggtaaaat 2100 aaggtcatta ggatagaccc taattcaata tgactgatga tcataaaaga agaggcgagt 2160 agggcacaac aggcacaaag ggagaccata aggagacaca gaggaaggac aactctttac 2220 aagctaagaa gagagggcct cagaagaaac caaccctgcc aacaccttga tcttggactt 2280 ccagcctcca aaactatgag aaataaattt ctattgttta agtcacccag tccatggtac 2340 tttgttaggc agccctggca aatgaatcaa agacccattc ctgttcctct ccccaccact 2400 actgttttct actgtaatct gaagcttcaa caaaaggctt acctggtaag aatattcagc 2460 tggtctgggt cctcaagact ccaatagaca ctcttagaga aggattgctg atggattgat 2520 agtgaaacca ttagatcatt gaattcctct ggaattagaa aaccagagag tcccatttta 2580 agaaattaga tatttaatat agcattgtgt gttctatttt agtaacagca gaatctcttg 2640 acattacaca actcagtgaa acaacatcat ttaagccaaa atatctccca actgactgat 2700 agactctgag cactaatatc atagtgctgt gatgatggac aattacatag taccgataac 2760 agccatgcac tgtgcaaagc atgcccttct gcacaggaga gcaaggcact tgcagtagtg 2820 atctatgcca gcaaaacatc attttgagac aaacattttt gtggcagatg tttttcctaa 2880 aaagtactat atcatccaag aaatatttga gtaaaatccc ttgttctttt gggtgacatt 2940 aactgacatt tgcttttttt caagacctaa tagaaaataa gaaagcccat aatgtattta 3000 gaaacaggaa tcctcagagc aattctctgt attctcatat aatttcaatg taaaacagaa 3060 aacatattga tgtgttggtg ataggcttga attattaaaa acttcaaaaa catcctaagt 3120 gtttcttttt tgctcaacgt tgtcaactat agtaggtctc ccttgtggtg taatgaattg 3180 cccccaaact attatcttaa aacaacaaac atttattatc ttatagcatt tctgagggtc 3240 aggatctggg actggcttag tggagttgtt ctggatcagg gcctttggaa agttgtagtt 3300 aacttgtccc cagggctgcc atcatctcaa ggctcgggtg gggctggaga aaatctgctt 3360 ctcagctcac tcacggcggt tgccaggcct ccattcttta ggatgctaga aaaactttca 3420 taaaatgtca tctggcttct cctagagcaa tgatactgag agagaaagca catgagagaa 3480 agagcgaggg aacttggatg taagccacag tctttgaaaa cctaatcaca gaagtgacat 3540 ctcttcttcc acatgatgtt ggtcacatgg accaacaatg gcacaacgtg gacagaatca 3600 aacagagttg agaatatcag gaggtggggc ttcatggggg ccattttgga tgctatcata 3660 gtgaatatat gtatttatat ttatatctgt atatattgca atgtaattta aaaaatagga 3720 ttgttttcct tttctttttg ctatatgtga tatgtatttc aaaatacact cccaatagtt 3780 acgtctgaaa agcactacac taaaaaactt tctatacatt gaataattaa attaaataat 3840 ctaa 3844 <210> 189 <211> 2003 <212> DNA <213> homo sapiens <400> 189 gcctcaagag gcggatatta acctcccagg acggaagttc cggagccttc aaactctcgg 60 ggaagcaact cggcagcgga ccaagatggc ggcgccctgt gagggacaag cgtttgccgt 120 aggggttgaa aagaattggg gtgcagtagt tcgctcccca gaagggaccc cccagaaaat 180 ccggcagctg atagatgagg ggattgcccc ggaagaggga ggcgtggacg cgaaggacac 240 gtctgccaca tcccagtcag ttaatggatc accccaagcg gaacaacctt cattggaatc 300 tacaagcaaa gaagccttct ttagcagagt ggaaacattt tcttctttga aatgggcagg 360 taagcccttt gagctgtctc cactcgtctg tgcaaaatat ggctgggtca cagtggaatg 420 tgatatgctc aagtgctcta gctgtcaagc ttttctctgt gccagtttac aaccagcttt 480 tgactttgac agatataagc aacgatgtgc tgagctgaag aaagccttgt gtactgccca 540 tgagaagttc tgtttctggc cagacagccc atccccagac cgatttggga tgttgcccct 600 ggatgagcct gctattcttg ttagtgaatt cctagatcgt tttcaaagcc tttgtcactt 660 ggacctccag cttccttccc taaggccgga ggacttgaaa actatgtgct tgacagaaga 720 caagatcagt cttctcctac acttgcttga agatgaactt gatcaccgaa ctgatgagag 780 aaaaactaca atcaaattag gctcagacat ccaagtccac gtcactgcct gtattctctc 840 tgtgtgtggc tgggcgtgta gttcctcttt ggaatccatg cagctctccc tgataacatg 900 ttcgcaatgt atgaggaagg tggggctctg gggcttccag cagattgaat cgtccatgac 960 tgacctggat gcatcctttg gcctgaccag ctccccaatc ccaggccttg aggggcgacc 1020 agagcgctta cctctggtgc ctgaatctcc tcggaggatg atgacccgga gccaggatgc 1080 cactttctcc ccaggctcag agcaggctga aaagagccct ggtcccattg tctctcgaac 1140 tcggagctgg gactcttcca gtcctgttga ccgtcctgag ccagaggctg ctagccccac 1200 caccagaact cgcccagtga cccgaagcat gggaacagga gacacccctg gcctggaggt 1260 accatctagc cctctgcgga aagccaagcg agctcgcctc tgctcctcca gcagttcgga 1320 cacatcttcc cgaagcttct ttgatcccac ctctcagcat agagactggt gcccttgggt 1380 gaatatcaca cttggcaaag aaagcaggga gaatggtgga actgaaccag atgccagcgc 1440 cccagcagag ccaggctgga aagcagtgct gaccatcctc ttggcgcaca aacagtctag 1500 ccagccagct gaaacggact ccatgagtct ctctgagaaa tcaaggaaag tattccgaat 1560 atttcggcag tgggaatctc tgtgctcatg ctgaagatac tccagcgcct tcctggagat 1620 agctggaatg agagtgactt tttgaaaaat taaggctgag ttcctttcgg tcagctgaca 1680 ctaagttttt cctgttctgg gttaatcata aggagccccc tgccatagca aaggcagtga 1740 gtgtcaacta tctgcatctg gctgagagag acccgtttcc tttcagggat gtggacaggg 1800 taagggcagc aagcatggtt ctgttaaagg agtgtgggat taacagacta gaaggaagac 1860 taaggacctg accacccatt tcagcatctt caatgtggag cagtgttctg aggactcttc 1920 tatcctagga ctatgacagt gtgtattaat aaaatatttg ctaagattct caaaaaaaaa 1980 aaaaaaaaaa aaaaaaaaaa aaa 2003 <210> 190 <211> 2296 <212> DNA <213> homo sapiens <400> 190 gattggccgc actagcccgc tcgtcacgct cttttgtctc agctggcaga ggataaaagc 60 cgccgcggct gccttaggaa cggcgctgcc tcgtctctgc tacccctggt tgggcggccc 120 tgcgaagcag ctccttcggg cagccccggg tcgcttagcg gccaaggagg cttcagttct 180 ttgccgcctg caaggcggag accagaaggc ggaatccaca gctggcgacg cgggagcatc 240 tgctgtccac cagcggagca caggccatca aagccgcatc tgaacttgaa ttctgtgcag 300 ctgattgcag agctggaccc ggatctgcga ccccctgtgg acagaggttg accgtacccc 360 ggagaggagc tttctcacgg agggcactgg ttgcagaggc tggaagtgaa ataaagacgc 420 gctcttgttt cagagttcgt cccctgctga gataggaagg cagagccacc tcctctcctc 480 tcccacctgc agattaagct tttctaaaaa gcctaggcat cttcttatat tcagataccc 540 tatcgtcgtc agtcatggct agcatcattg cacgtgtcgg taacagccgg cggctgaatg 600 cacccttgcc gccttgggcc cattccatgc tgaggtccct ggggagaagt ctcggtccta 660 taatggccag catggcagac agaaacatga agttgttctc ggggagggtg gtgccagccc 720 aaggggaaga aacctttgaa aactggctga cccaagtcaa tggcgtcctg ccagattgga 780 atatgtctga ggaggaaaag ctcaagcgct tgatgaaaac ccttaggggc cctgcccgcg 840 aggtcatgcg tgtgcttcag gcgaccaacc ctaacctaag tgtggcagat ttcttgcgag 900 ccatgaaatt ggtgtttggg gagtctgaaa gcagtgtgac tgcccatggt aaatttttta 960 acaccctaca agctcaaggg gagaaagcct ccctttatgt gatccgttta gaggtgcagc 1020 tccagaacgc tattcaggca ggcattatag ctgagaaaga tgcaaaccgg actcgcttgc 1080 agcagctcct tttaggcggt gagctgagta gggacctccg actcagactt aaggattttc 1140 tcaggatgta tgcaaatgag caggagcggc ttcccaactt tctggagtta atcagaatgg 1200 taagggagga agaggattgg gatgatgctt ttattaaacg gaagcgtcca aaaaggtctg 1260 agtcaatggt ggagagggca gtcagccctg tggcatttca gggctcccca ccgatagtga 1320 tcggcagtgc tgactgcaat gtgatagaga tagatgatac cctcgacgac tccgatgagg 1380 atgtgatcct ggtggagtct caggaccctc cacttccatc ctggggtgcc cctcccctca 1440 gagacagggc cagacctcag gatgaagtgc tggtcattga ttccccccac aattccaggg 1500 ctcagtttcc ttccaccagt ggtggttctg gctataagaa taacggtcct ggggagatgc 1560 gtagagccag gaagcgaaaa cacacaatcc gctgttcgta ttgtggtgag gaaggccact 1620 caaaagaaac ctgtgacaac gagagtgaca aggcccaggt ttttgagaat ttgatcatca 1680 ctctccagga gctgacccat actgagatgg agaggtcaag agtggcccct ggcgaataca 1740 atgacttctc tgagccactg taagggacca cccccaggtt tcagtgaacc cttacctata 1800 ttcagcatcc agtagtggga aaactggggt gggggtgggg gtgggacttc taactgcatg 1860 aattaatcca caaagcggct atcttttggg gtggagtaga aagggtcttg gataccagca 1920 cattggaggg agatagcctg acctctgtcc ttgctccttc tccctgcagc ctacgggtct 1980 gttttctgtg tgtgcccatt tccttgacag ctttattctt tgtgaaagtg gtataattta 2040 ttgttaaata tttgaacaat aaaaaaggta caaaaagtga agtacaaatt acccaaatct 2100 ctccaccctt atataatcat tgtcaaccct ttgatgagtg atatttccct atacctatgt 2160 acccagatag atatatgcat agataaaagt gatgaaatat aagtgctgtt ctatctgtat 2220 tttttcacca aacaatatat gttgtgagct tctatgtcaa taaatatata tatcagcatc 2280 tgcaaaaaaa aaaaaa 2296 <210> 191 <211> 1680 <212> DNA <213> homo sapiens <400> 191 gttgctattt catttaccac agtagtttga gtcatttcca catcttgcga gtccttccga 60 acgagtctcc tttccttggg gctcgcaacc acccaatgat cgattcagga gaaaagaagc 120 ctgggcggag agcagaggag gcagtgacct tcaaggatgt ggctgtgatc ttcactgagg 180 aggagctggg gctgctggac cctgcccaga ggaagctgta ccgagatgtg atgcttgaga 240 acttcaggaa cctgctctca gtggggcatc aaccattcca tggagatact ttccacttcc 300 taagggaaga aaagttttgg gtgatgggga caacaagcca aagagaaggg aatttgggag 360 gcaagatcca aactgagatg gagactgttc cagaagcagg aacacatgaa gaattttcct 420 gcaagcaaat ttgggaacaa attgcaagtg acttaaccag gtctcaagat accaccataa 480 gtaactctca gttatttgaa caagatgaca acccctccca gattaaagca agactatcta 540 cagttcacac aagagaaaaa cctttccagg gtgaaaattg taaacagttc ttcagtgatg 600 tttccttctt tgatcttcct cagcagttat attcaggaga gaagtctcat acctgtgatg 660 agtgtggaaa aagcttctgt tacatctcag cccttcatat tcatcagagg gtccacatgg 720 gagtgaaatg ctataagtgt gatgtgtgtg gtaaggaatt tagtcagagc tcacgtctgc 780 aaactcatca aagagtccac actggagaga aaccattcaa atgtgagcag tgtgggaaag 840 gcttcagatg tagatcagca cttaaagttc attgcaaatt acacatgaga gagaaacctt 900 ataattgtga gaaatgtggg aaggctttca tgcacaattt ccagcttcag aaacatcaca 960 gaattcatac tggggagaag ccattcaaat gtgaaatatg tggtaagagc ttctgtctta 1020 ggtcaagtct taataggcat tgcatggtcc acacagcaga gaaactgtac aaatctgaaa 1080 agtatggaag aggtttcatt gataggctag atttgcataa gcatcagatg attcatatgg 1140 gacagaaacc atataattgt aaagaatgtg ggaagagctt caaatggtcc tcatatcttt 1200 tggtccatca acgagtccac actggagaaa agccatacaa atgtgaggag tgtgggaagg 1260 gctacattag taagtcaggt cttgacttcc accatagaac ccacacggga gagagatctt 1320 ataactgtga taactgcggg aagagcttta gacatgcttc tagtattttg aatcataaga 1380 aactccactg ccaaagaaag ccattgaaat gtgaagactg tggaaagagg cttgtatgcc 1440 ggtcatactg taaagaccaa caaagagacc acagtggaga aaacccatcc aaatgtgagg 1500 actgtgggaa gcgctacaag aggcgcttga atctggatat aattttatca ttatttttaa 1560 atgacatata agttatacat atttatggag tgtgaaattt gatacatgta tataatgtgt 1620 gctgattaaa tcagtttaat ttcacctgaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1680 <210> 192 <211> 2181 <212> DNA <213> homo sapiens <400> 192 gagagcggcg gaagtaggaa gccgaggtct gaattgcgcg tggtggccat ggcggccagc 60 ggggctgtgg aaccagggcc cccgggggct gccgtcgccc cgtcgcccgc cccggccccg 120 ccgcctgccc ctgatcacct gttccggccc atcagcgccg aggacgagga gcagcagccc 180 accgagatcg agtcgctatg catgaactgt tactgcaatg gcatgacgcg cctcctgctc 240 accaagattc ccttcttcag agaaataata gtgagctcct tttcctgcga gcactgtggc 300 tggaacaaca cggagatcca gtcggcaggc aggatccagg accagggagt gcgctacact 360 ttgtctgtca gggctctgga ggacatgaac agagaagtgg tgaagactga ctctgctgcc 420 acaaggattc ctgagctaga ttttgaaatt cctgccttta gccagaaagg agctctgacc 480 actgttgaag gattgatcac ccgtgctatc tctggcctgg agcaggacca gcctgcacga 540 agggcaaaca aagatgctac agctgaaaga attgatgagt tcattgtcaa actgaaggag 600 ctaaagcaag tagcctcccc tttcactctg atcattgatg atccctcagg gaacagtttt 660 gtggaaaacc cacatgctcc tcagaaagat gatgccctgg tgatcacaca ctacaaccgg 720 acccgacagc aggaagagat gctggggctt caagaagaag caccagcaga gaagccagaa 780 gaggaagatc tcagaaatga agtgctccag ttcagcacaa actgcccaga atgcaatgcc 840 cccgctcaga ccaacatgaa gctagtacaa atccctcact ttaaggaggt tatcatcatg 900 gctaccaact gcgagaactg tgggcatcgg accaatgagg tgaaatctgg aggagcagta 960 gaacccttgg gcaccaggat caccctccac atcacagatg cctcagatat gaccagagac 1020 ctcctcaagt ctgagacttg cagtgtggaa atcccagagc tagaatttga actgggaatg 1080 gcagtcctcg ggggcaagtt caccacactg gaagggctgc tgaaagacat ccgggaactg 1140 gtgaccaaaa atcctttcac actgggcgac agttccaatc ctggacagac ggagagacta 1200 caggagttta gccagaagat ggaccagatc atcgaaggta acatgaaggc ccactttatt 1260 atggatgatc cagcaggaaa cagttacttg cagaatgtgt atgcgcctga agatgatcct 1320 gagatgaagg tggagcgtta caagcgcacc tttgaccaaa atgaggagct agggctcaat 1380 gacatgaaga cagagggcta tgaggcaggc ctggctccgc aacggtagca gtgggtggct 1440 caagggccag cctccagcgc tgctctttct gtaggttatt tattagtatt ggatgaaggc 1500 gaaggctggg agtgtctttc ccaccagccc ttgcccatgg tggggaggac atctggtctg 1560 agtcagagat ctgtgcacac tttctaaaca gcttgtgatg caagtgtgag cctattgtgt 1620 tacttgacct tattttggaa gttttgaatt ggcctaggag gaaacccaga aatgaaccag 1680 gggtatgtca tcactttttt catatcaagt cctcaccctc cttccacata atgctctatc 1740 ctctaaggtt ggaactctga agttggagaa ggtggaataa agttacacct ggagtttgtt 1800 gttggttttg agtatataaa atactgactt tgaacaggaa aggagtctcc tgaggggaga 1860 ccgagtccag cacaagtgaa ggagttacca ttgaaatgat gactttcaaa cagcactggc 1920 ctctgtattg accctatcct tgtttgatat catgctgtta gaattcagcc tcctaaagaa 1980 aattttcccg tgtatctact gtaatttggg gattgcagct ggcatttaat tcattccttc 2040 agcagatgct tgcttatcta ctttatgcca agcacaccac agaacagagg acaaaataaa 2100 tctctttcat ggaacttgaa gtctagtggg gaaaaatgac aataaacaga tcaggaaaac 2160 agtaaaaaaa aaaaaaaaaa a 2181 <210> 193 <211> 2566 <212> DNA <213> homo sapiens <400> 193 aaaaaattgc tttatggaag aaagtaagta tagacagaga gaaagggatc tgatgaccaa 60 agcagggaat aaatgtttgg agtccacggc atcctgagaa cttcttggga atagagtcta 120 ggcccccaat gctgtcactc tcacccatcc tcctctacac atgtgagatg tttcaggacc 180 cagtggcttt taaggatgtg gctgtgaact tcacccagga ggagtgggct ttgctggata 240 tttcccagaa gaatctctac agggaagtga tgctggaaac tttctggaac ctgacctcta 300 taggaaaaaa gtggaaagac cagaacattg aatatgagta ccaaaacccc aggagaaact 360 tcaggagtgt cacagaagag aaagtcaatg aaattaaaga agacagtcat tgtggagaaa 420 cttttacccc agttccagat gacaggctga acttccagaa gaagaaagct tctcctgaag 480 taaaatcatg tgacagcttt gtgtgtgaag ttggcctagg taactcatct tctaatatga 540 acatcagagg tgacactgga cacaaggcat gtgaatgtca ggaatatgga ccaaagccat 600 ggaagagtca acaacctaaa aaagccttca gatatcaccc ctccttgaga acacaagaaa 660 gggatcacac tggaaagaaa ccctatgctt gtaaagaatg tggaaaaaac attatttacc 720 attcaagcat tcaaagacac atggtagtgc acagtgggga tggaccttat aaatgtaagt 780 tttgtgggaa agcattccat tgtctcagtt tatatcttat ccatgaaaga actcacactg 840 gagagaaacc gtatgaatgt aaacaatgtg gtaaatcttt tagttattct gctacccatc 900 gaatacatga aagaactcac attggagaaa agccttatga atgtcaggaa tgtgggaaag 960 cattccatag tcccagatcc tgtcacagac atgaaaggag tcacatggga gagaaggctt 1020 atcaatgtaa ggaatgtgga aaagcattca tgtgtccccg ttatgttcgt agacatgaaa 1080 ggacccactc taggaaaaaa ctttatgaat gtaagcagtg tgggaaagca ttatcctctc 1140 ttacaagttt tcaaacacac ataagaatgc actctggaga aagaccttat gaatgtaaga 1200 catgtgggaa aggcttttat tctgccaagt catttcaaag acatgaaaaa actcacagtg 1260 gagagaaacc gtataaatgc aagcaatgtg gtaaagcctt cactcgttcc ggttcctttc 1320 gatatcatga aaggactcac actggagaga aaccctatga gtgtaagcaa tgtgggaaag 1380 ccttcagatc tgccccaaat cttcaattgc atggtaggac tcacactgga gagaaaccgt 1440 atcaatgtaa ggaatgtggg aaagctttca gatctgcctc acaacttcga atccatcgta 1500 ggattcacac tggagagaaa ccctatgaat gtaagaaatg tgggaaagcc ttcagatatg 1560 tccagaactt tcgatttcat gaaaggacac aaacacataa gaatgcactc tggagaaaga 1620 ccttataaat ataagatata tgggaaacac ttttattctg ccaagttatt tcaaacacat 1680 gaaaaaattc acactggaga gaaaccctat aaatgcaagc aatgtggtaa agccttaatt 1740 gttccagttc ctttcgatat ctaaaaggac tcacagtgga gaaaaactct atgagtgtaa 1800 gcaatgtggg aaagtcttca gatctgtcaa gaacctttca atttatgaaa ggacacacac 1860 tggagagaaa ccctatgaat gtaagaaatg tggaaaagcg ttccataatt tctcttcttt 1920 tcaaatacat gaaagttgca cagaggagag gcgccctaag aatgtaagca ttgtgggaaa 1980 gcattcatat ctgccaagat cgtttgaata catgcaaaac acacactgga gagaaaccta 2040 tgaatgtaag gaatgcaaac aagcattcaa ttatttttct tccttgcata tacatgaaag 2100 gactcatacg agagagaatc cgtatgaatg taaggattgt gggaaagcat tcagcttgct 2160 taattgcttt catagacatg taaagacaca ccagaaggaa accctatgaa tgtaagcaat 2220 gtggcaaaag ctttcacttc ttccagttct tttcaatatc atgaaaggac tcacactggg 2280 gagaaaccgt atcaatgtaa gcaatgtggg aaagccgtca gatcagcctc aagacttcaa 2340 atgcatggaa gcactcacac ttggcagaaa ctctatgaat gtaagcagta tgggaaagcc 2400 ttcagatcgg ctaggattct ttgaatacaa ataatgaatg taaacaatta actgtttata 2460 ataactgtat actaacaaat gttattcttt ttaaataatt aagaagctat aataaaatat 2520 ccattggtgt catgtattag atcaagctta aaaaaaaaaa aaaaaa 2566 <210> 194 <211> 1491 <212> DNA <213> homo sapiens <400> 194 agtttccatg gtgagatggt caacaagcct gtaagttcct cagctacgac taccaggtac 60 ctcgggttcc tccctcctcc gagagaccgc cgaggtgcgg gctgtgagag ggggagcgtg 120 gagcctccga ggccgaggga tcagtgtcct tcagtgatgt ggctgtgggc ttcacccagg 180 aggagtggca gcatctggac tctgctcaga ggaccccgta cagagacatg atgctggaga 240 actacagcct cctcctctca gtgggatatt gcattaccaa accagaggtg gtttgcaagt 300 tggagcatgg acaggtgctg tggatattag aggaagagtc cccaagtcag agccacctag 360 actgctgcat agatgatgac ctgatggaga agagacagga aaatcaagac cagcatttgc 420 agaaagttga ttttgtcaac aataaaacac tgactatgga cagaaatggt gtattaggaa 480 aaacattttc tcttgacaca aaccccattc tatcaagaaa aatacgtggc aactgtgact 540 catctggaat gaatttgaat aatatttcag aattaattat tagtaataga agctcctttg 600 taaggaaccc tgctgagtgt aatgtacgtg ggaaatttct cctctgtatg aagcgtgaga 660 atccttatgc cagagggaaa cctttggaat atgatggaaa tgggaaagcc gtctctcaga 720 atgaggactt atttaggcat cagtatattc aaactcttaa gcagtgtttt gaatacaatc 780 agtgtgggaa ggcttttcat gaagaggcag cctgcagtac ccataagaga gtgtgctcat 840 gggagaccct gtgaatataa tgaacatgtg agagcctttt ccgatagacc aatattcatt 900 gttcatcaga gaactcacat aaggaagagt caccatgaat tcaatgaatg tgagaggagg 960 tctggtgaga ggccacctgt aaataaacac cacagggtta tggagatgaa atactatgag 1020 tgtaatgcga gtgagaatag ttttggcaag aaatcactcc tcattctaca aagttacaga 1080 ggagagaaaa cttgactgta gtagacattt ggaagtattc tgcaagaagc caaatttcac 1140 tcaacatcaa gaaacacata taggaaagaa tgcctataaa attaatcagt atgctagtac 1200 attttgctgt aagccaaagc attctgtata tcagaaaaca gatacagaag aaaaactcta 1260 tgaatgtagt gaatgtggga aaaccttcag ccataaatcc tcttttatcc tacagcagag 1320 gatacacaga ggagagaaac cctatgaatg cactgaatgt gggaaaactt ttggatatag 1380 gtcatgcctt gcagtacatc aaagaacaca cacgggacaa aacctatgaa tgtaatgaat 1440 gtggaaaaaa cttctgtgag aagtcaaatc ttcatgtaca tcagagaaca c 1491 <210> 195 <211> 4071 <212> DNA <213> homo sapiens <400> 195 gcagcggaac gattcgattc ttctcagcac caagttgcgc tcccaatctc tcagagctgg 60 gctcgcggga ggccgctcgt gcaaaaccta ggctgagctc ccctgcgcgg agctgtgagc 120 cctggaacac cgtggtctgc ttctcaggac gcgcaaacag tgaagccagt cccgcccggg 180 tgagccgcgg gggcctctgg gaagcgtcgc ccctggtgta acggaccgag acttgtggcg 240 ctctcagcca ccgacagcgc cggcctcagt gccgcctctg tcccagcccg cgccggctct 300 gccactttgg cagcgttaag tgtggaatcg gggcctgtgt ccgcgggctt ggtgagttct 360 tcatatatta aggattcatt cattcataga ctcatttatt gaaggctgtc tgtgtaacag 420 gcacaatcct aggtgcttgg gatatagcag tgaacaagag acaaaccccc tactatcatg 480 gtacttacat ttttgtgggc tggataataa acaagctcta cttctgcagg ccccatccct 540 tcccagaaag aagaggaaat gactgagtcc cagggaacag taacattcaa agatgtggct 600 atcgacttca ctcaggagga gtggaagaga ttggatcctg ctcagagaaa actgtaccgg 660 aatgtgatgc tagaaaacta taacaactta atcacagtag gctatccgtt caccaaacct 720 gatgtgattt tcaaattgga gcaagaagaa gaaccatggg tgatggagga agaagtatta 780 aggagacact ggcaaggaga aatatgggga gttgatgagc atcagaaaaa ccaggacaga 840 cttttgagac aagttgaagt taaattccag aaaacactga ctgaagaaaa aggcaatgaa 900 tgtcaaaaga aatttgcaaa tgtatttcct ctgaactctg attttttccc ttccagacac 960 aatctctatg agtatgactt atttggaaag tgtttagaac ataattttga ctgtcataat 1020 aatgtgaaat gccttatgag aaaggagcat tgtgaatata atgaacctgt gaaatcatat 1080 ggtaatagct catcccattt tgtcattacc ccctttaagt gtaatcattg tggaaaaggc 1140 ttcaatcaga ctttggacct catcagacat ctgagaattc atactggaga gaagccctat 1200 gaatgtagta actgtagaaa agccttcagt cacaaggaaa aacttattaa acattataaa 1260 attcacagta gggagcagtc ttacaaatgt aatgaatgtg gtaaagcttt cattaaaatg 1320 tcaaatctca ttagacatca aagaattcat actggagaga agccctatgc atgtaaggaa 1380 tgtgagaagt ccttcagcca gaaatcaaat cttattgatc atgaaaaaat tcatactgga 1440 gagaaacctt atgaatgtaa tgagtgtgga aaagcattca gccagaagca aagcctcatt 1500 gcacatcaga aagttcatac tggggagaaa ccttatgcat gtaatgaatg tggtaaagcc 1560 ttccctcgaa ttgcatccct tgctcttcat atgagaagtc atacaggaga aaaaccttat 1620 aaatgtgata aatgtggtaa agccttctct cagttttcca tgcttattat acatgttaga 1680 attcatacag gtgaaaaacc ctatgaatgt aatgagtgtg gaaaagcctt ctctcaaagc 1740 tcagccctta ctgtacatat gagaagtcac actggtgaga aaccctatga atgtaaggaa 1800 tgcagaaaag ccttcagcca caagaaaaac ttcattacac accagaaaat tcatactaga 1860 gagaaacctt atgagtgtaa tgaatgtggg aaagctttta tacagatgtc aaatcttgtt 1920 agacaccaga gaattcatac tggggaaaaa ccctatatat gtaaggaatg tgggaaagcc 1980 tttagccaga aatcaaatct cattgctcat gaaaaaattc attctggaga gaaaccctat 2040 gaatgcaatg aatgtggtaa agccttcagc caaaagcaaa acttcattac acatcaaaaa 2100 gttcatactg gagagaaacc ttatgattgt aatgaatgtg gtaaagcctt ctctcaaatt 2160 gcatccctta cccttcattt gagaagtcat acaggggaaa agccttatga atgtgataaa 2220 tgtggtaaag ccttctctca gtgctcactg cttaatttac atatgagaag tcacacaggt 2280 gagaagccct atgtatgtaa tgaatgtggg aaagccttct ctcaaagaac ttcccttatt 2340 gtgcacatga gaggccatac aggtgaaaaa ccctatgaat gtaataaatg tggaaaagcc 2400 ttctcccaaa gctcatccct tactatacat atacgaggac atacaggtga gaaacccttc 2460 gactgtagta aatgtggaaa agccttctct caaatctcat ctcttaccct tcatatgaga 2520 aaacatacag gtgagaagcc ctatcactgt attgagtgtg gcaaggcttt cagccaaaag 2580 tcgcaccttg ttagacacca gagaattcat actcattaga aaccctatga atattgtgaa 2640 tatggcaagg ccatctgaag gaattaacac ctcattgcac attacatgat cacttccaga 2700 gtagaaaact atgaatgtgg gatagccttc tgaaaaagcc acaaatttat gaaacattag 2760 agaattcttc caaggtgaca aattatataa tgaaaaagct gttaccagaa actttcagca 2820 gacatcttat tgataatatt taatcagcat tctcattgaa atctgaaaca aggtatcttc 2880 catcagcata acaacacaac acttgagctc ctagccaatg tattaagtaa ggaaaacaag 2940 tatcaacgaa gaactataaa aataactttt atacaagaaa taattagaaa atgtgttgat 3000 agaaaaccta agaataaaca caacaatgag ttaggtcttt atcaagttat aaaatatgtt 3060 gaaaggcaca aaagaacacc tgaaaaatga tattttgtct gaaaagactt gacattgtaa 3120 aaatataatt tctctcccaa atcactaagt ttaatatact tctgaagttt acatcagttt 3180 tattttaagg aacttcacaa acttatccaa aaattttatg tggaaaagta aagaaacaca 3240 aatagctgaa acaaacttga caaagcaagt agagaagaca cactctatta ttagatatat 3300 catgtactta tttaaagctg ctgtcattta aacaatgtat taccaagtga ataaatcaag 3360 cagtagtaag atagtgagca ttcatacaaa aatccaagaa gatacaggaa ttctgtgtat 3420 gacagtgcta ttgaaatcac tggggaatga atggcttatt taataaatgg aaggttcata 3480 ggagaaaaat tttagctttc tactttatat catatacaaa aataaaatcc aactaaagac 3540 cagaatataa aaagcaaaat tttaaaacta tgatgaaagt agaatccgtt actttagggt 3600 aacaagattt ctttaaaaaa catgtaaaca tggaatagtc tgttgaattt tggtgtattg 3660 gcctcacagg cacccacaaa tgtacacaaa gagatatata tcactgtgtt cctgaatcat 3720 ggtttgtatt gcccaaaatt ggatataaca aatttttatc aattgtggaa tagatgaata 3780 agtgtgatca tttctgtgat aaaatacaga atttagaaac aaaatctacc tatagttata 3840 tggatagatt acaatatata atattgagag aaaaaattaa aatgcacaaa ggaacacagt 3900 ataacatttg tataatttaa taagatcttg caaagaacag tactgtgtat tggtcatgga 3960 tccatatatg acttggttgc cttttgggat gtgggaaagg tttggtggga gttgttatat 4020 ttatctgtaa tatttcttta ataaaagagt gaaagcaaaa aaaaaaaaaa a 4071 <210> 196 <211> 8565 <212> DNA <213> homo sapiens <400> 196 ttgagaggcg gagggggttt ccgggatctg gcggggcctt tgtcttgtgc tccagctgga 60 gctttggtcc cgtattctcg gctatttatc cccagctgcg ggaggccctg gtgactctgc 120 tgctgcagtg tctggtttcc ctgtgacctg caggtactgg gagttacata gctaagatgc 180 caggacaccc cgaaagccgg aaaacgagac gcattctcac tatgttgccc aggctggtct 240 tgaactcctt ccctcaagtg attcttctgc ctaatcctcc caaagttctt agattacagg 300 gactactggc attcagtgat gtggtcatag aattctctcc agaggagtgg gcatgcctgg 360 accctgccca gcgaaatttg tatagggatg tgatgttcga gaactacaga aacctggtct 420 ccctggctat tttatcttat tccattcaag accttttgcc agagcaggat atgaaagatt 480 tatgccaaaa agtgacactg acaagacata gaagctgggg ccttgacaat ttgcacttag 540 tgaaagactg gagaactgtg aatgaaggta aggggcagaa agaatattgc aatagactta 600 ctcaatgttc atcaactaaa agcaaaatct ttcaatgtat tgaatgtggc agaaatttta 660 gctggaggtc aatccttact gaacataaga gaattcatac tggagagaag ccatacaaat 720 gtgaagaatg tggcaaagtt ttcaatcgat gttcaaacct aacaaaacat aaaagaattc 780 atactggaga gaaaccctac aaatgtgacg aatgtggcaa agtttttaat tggtggtcac 840 aactaactaa ccataagaaa attcatactg gagagaaacc ctacaaatgt gatgaatgtg 900 acaaagtttt taattggtgg tcacaactaa ctagccataa gaaaattcat agtggagaga 960 aaccataccc atgtgaagaa tgtggcaaag cctttaccca gttctcaaac cttacacaac 1020 ataagagaat tcatactgga gagaaaccct acaaatgcaa agaatgttgc aaagccttta 1080 acaagttctc aaaccttact caacataaga gaattcatac tggagagaaa ccttacaagt 1140 gtgaagaatg tggcaacgtt tttaatgagt gctcacacct aactagacat aggagaattc 1200 atactggaga gaaaccctac aaatgtgaag aatgtggcaa agcctttaca cagtttgcaa 1260 gccttactcg tcataaaaga attcatactg gagaaaaacc ctaccaatgt gaagaatgtg 1320 gcaaaacttt taatcggtgt tcacacctaa gtagccataa gagaattcat actggagaga 1380 aaccctacaa atgtgaagaa tgtggcagaa cctttactca attctcaaac ctcactcagc 1440 ataaaagaat tcatactgga gagaaaccct acaaatgcaa agaatgtggc aaagcgttta 1500 acaagttctc aagccttact caacatagga gaattcatac tggagtgaaa ccctacaaat 1560 gtgaagaatg tgggaaagtt tttaaacagt gctctcacct aactagccat aagagaattc 1620 atactggaga gaaaccctac aaatgtaaag aatgtggcaa agctttttac caatcctcaa 1680 tccttagtaa gcataagaga attcatactg aagagaaacc ctacaaatgt gaagaatgtg 1740 gcaaagcctt taaccagttc tcaagcctta ctcgtcataa aagaattcat actggagaga 1800 aacgctacaa atgtaaagaa tgtggaaaag gtttttacca atcctcaatc catagtaagt 1860 ataagagaat ttatactgga gaggaacctg acaaatgtaa aaaatgtggc agtctttaaa 1920 aactgcttca ttatacatgg cttcactaat ttcatactga ataaaagtgg tatgagcata 1980 atgactgttt aaggatgttt cacaaaatgt aagcttcaga gtgcacaaca ctatactgaa 2040 tgaaatttat aaatataaaa gattacaata tctttatttc aaagatcttc ctgtaaacag 2100 aatctgtact agaggaaaaa cccttaaaca attattcaga ctttattcaa ctttagagga 2160 ttttacgggg gcaaaaaacc tcctacaaat gtggaaaaac attttttcaa gatatatgcc 2220 ttagaaaaca ccagagttta tagtatagta gaatatattt tacagataca gtgaatacaa 2280 acaaatgtcc aaaattaagt ctaaataaaa cattacataa tttactgtag aaagtactaa 2340 ggcactaaca gtttcagatg ttactttaaa gcagtgttga ttgtcgagaa taattcaaag 2400 ttaaaataga taatttagtt gtatgtaaat ttaaatgaat caagagatga tgtctttttg 2460 aagcacagtt acattcatgt tatacttttt tgcattaaaa gtttttatat ttttgattat 2520 atattttaat attgatataa ttcatatctc aaataacttg atttttatta tatttattgt 2580 ttatgttaaa gtatgtggtc agttgttgct gcataagagc tatgagaagt tcttctatat 2640 tagatgacca tcatttatat gctttttcat gaatgattaa gggcaccgaa atgtaacatt 2700 tataaggaaa atctaagtag aaatgctttt tgttgatgta taacagtgtt ttaagtaaca 2760 cattaggtat tcagagaagt attttgcatt atagtaatag ggaaacattt tgaatttcag 2820 tagtaaattg ttttatgagt tgcacattaa gataatacag tagcttttga aatgttattt 2880 ttagaatgca atttcttttc ataaaacaaa attattttta atgtgttaag aatattttgc 2940 attgaatgaa gtatatcttg ccacaataat taacctatac caccttaccc aaagttgtag 3000 gtaacagata gtaacaatac actactgggt aacagtgaaa ggacacctct agtaatctct 3060 tttcccagtg gcttttaatt tcaaacaact tggggaggtt ttttttatgt gatatgcttt 3120 ggtttttttg tgccttacct catgttgaaa tgtgttcccc catgttggag gcggggtcta 3180 gtggaaggtg tttaggtcat gggtgtagat tactcatgaa tggattggtg ttcttaccac 3240 tgcagttagt gtgttctctg ttagttcatg tgaaagctgg ttgttaaaaa caaaaacaaa 3300 caaacaaaaa actgatattc ctcttgcttt gtcttttgcc atgatacccc tttgcctttt 3360 attatgcata aaagcttcct gaggcctcat cagaagttaa gcagatgttg atgtcatgct 3420 tgtatagcca acagaactga ggctaataaa cctcttttct gtattaattt gccagtgtta 3480 agtattccct tctagcagca caaaatggac taacatccca taggttatat ttttattttt 3540 ttcttttgta aatactggac aatgatactc ttatataatc ttcagtataa ccattataat 3600 tgcccactat aaaggagtat aatgaaaggc catgtatttt gaatcacgaa tgactattta 3660 caaaatgtca tactacgttt ttctttgagc ctgtgacccc tctggcctgt aaaaacacat 3720 acatacattt agttttgatt aacatggagt taattttata agtctgtcac tctaaacata 3780 agtgttagct ttaagagaat tacagagcat gtaattgtgt ttgagtgtag gtgtgtactt 3840 ttttgagaag aaaacaaaaa tattggaaca aaatataatt taaaaagtat tggtaattta 3900 ctagcaaact aggaatctca aagattctga aagtaaatat ttattctctg ctttgtattg 3960 aatttacttc tgtaaaatct tatggctgct ggctcagaat cttctcatgc aaatcctgtt 4020 tttttcttgt ctgttgatca tactaaacct aatgtatagt tttctcattc caaagttcat 4080 gaaattttct ctatattcct gagaaattct aagaataact ttcataaaat gtattgatgt 4140 tcacaagata attttaagat gtaattctac aatatgtgtg ttactacatt ttatttaatt 4200 agtatatttt atttttgtat ttcaattgga gaaccctatt ttggccaatt tttacttggt 4260 ttttgtttcc attttaatat tttacataat tgaatttttt tcactttatt gagccatttt 4320 gtttagatgt acactgggaa ggcttcataa ttcacaaagt tgttttgaca tataaatgag 4380 gtgaacaaac acaggaaagt gctaggtttc ctgggggtat aatagatgct ctataattag 4440 cagtaaatat tcttgtttaa gtcacttttt ggctacaagt aagagattag aaatattcag 4500 cataaagaga tggcattaac tctgcatgta aagaaaacac atgtataccc aggctgtaca 4560 actgcctctg aaattaagag gaattgtgtt tatttcatag ttatctctgg tacttcactg 4620 ttattttatt ttcaccccca actatgcgtc aatcatagcc ctttcccttc tttgcttatt 4680 atggctacag atttctcact gttctctgca gcccatgtaa tttcatacag tattttgtag 4740 gttgtgataa ggaatttgaa atttttaata tagtgaaaaa ttggatttaa ctggagagtt 4800 tgaggacatt tttaagttag aaatgcacca tttgaatcat ttaattggca taattgggat 4860 gtactctaca cagtttatag gattaaatta ctgagttagt aatgtttgta tgaaagaaat 4920 gttattagat tctaccacaa aatatagtaa acatgaaatc agttagaata ggtaaagcat 4980 taataatggt aggctatata tcataatcac tatataaaga aacatcagaa tttggaaacc 5040 ccttaagcaa aaatatatct tagaaatctt aaggacactt aatggcaagc aaaaaagttt 5100 aaatttagtt ttttataaat tacatatagc acaatttatg tgtacatgta gaatctttta 5160 gtttttagtg tttatgtaat atattagaca ataataaaca tttacattta tgtttacatt 5220 tatatttaat ttttcaaatt taatttaaat ttctaaatgc ttctgtggat ttaaattttg 5280 gaataatctt ttcttcccca ttgatactgg aatcttggga agtttcttac tcatatcaca 5340 atatgtttta tttaaatgga tgcagcttac attgcagagt ttatataaat aatcacataa 5400 caagccaatt ccttagtcat tttctgtatt aaaaaactca gagatctaga gagcttttgg 5460 attgaaatat ttccttggtg attttggatg caaacctgat ttctgtgttc acaccatggc 5520 cagagatggg actgttagca ccacctgctt ctttaatgtc gtccatatga tcagcatcag 5580 caccagaaac tccaggtgtc ccaaacttaa agtgaaagcc atagagtcct ttggtgactc 5640 ccatgttctg tgctggttct agaacatgct ggtaaatatc agagtttcta tgcttatggc 5700 tgataagtag acatttttaa aaatcataaa aactgtattt tctatatagt tcagctaagt 5760 ttatgaaaaa gatgcagact cagtatttgg agcattgcta tcgctccatg atgtgtttaa 5820 aaattatttt taaattgaca aaattttata tctacatata tatatatctt gtaacacatg 5880 atgtttgaaa tgcttaattc tagccaatta aaaatgcttt acctcaatag ttatttttat 5940 tgtgagaaag gtcaacatgg tcttggcact taaaaaaaaa aaaacaatat attctcaata 6000 actgtattca ctctgcacta caataggtct cttgaactaa ttcctcctag ctaacaggca 6060 ttgtttatca tttaacagat aattctctaa gcccccttct cctaaaactt cagcatctct 6120 taaccttctt tctagtctct acttttatga gatcaacttg tttagattcc acgtgagtga 6180 gaccatgagg tattcatctt tctgtgttct gctccattgg tctatttatc tgtttttaat 6240 gccagtattg gactgtttca gttactgtag ctttgcagta tatttgactg tcaagtagtg 6300 cagtgcttcc aaccttcaga gtcttttact gtactatatg aatttttgtg ttttttttgt 6360 gaaaaatttt attgatattt tgatagacat tatgttaaat atatacatca ttttgtgtaa 6420 catagacttt ttagcaatat taatttggcc aatttatgaa taagggataa cttttcattt 6480 atttatgttt aattttatac ctcagttttc tttagctttt aatgtagaga tctttaacat 6540 ttttgaataa ttttatttgg aagtaaactt tctgtaacta ttgcaggtgt caattgtttt 6600 ctttatttct ttttcagata gtttgttgtt agtgtataga aatgctactg acccttatat 6660 cttgattttg tatcctgcaa ctttagtgaa tttattctaa gtatttttaa agttttctat 6720 ttataagact atgatatctg caaacaggga caattatttt ctttctttcc aatttggttg 6780 tctttggttt tgttttctaa tttctctggc ctggaaattc agtagcatgt taaataagag 6840 tgatgaagtt agatatattt gccttactat aactcttaga aaaaaggctt acaacttttg 6900 aaggtttagc atgatgtcag atgtccattt gtcatatatg gcctttattg gcttgaggta 6960 tgtatgttct atatgtaatt tgttttgaga ttttgtcata aagtaatgtt gaattttcta 7020 aaattctttt tctgcattca cttaaaagtt ataattggtt ctgagatcct tcatctttct 7080 cagaatctag gaggatgcat ctgtacctag aggaggacac aaaggcatca tatgttacat 7140 tctcgtgaca tataatgtct actgcttata atgtctactg tgagtttctg actccccaaa 7200 tgaaattgag gcccagaaac tttcaactgc tttgttcgtt gaataatgcc aagtgtctgg 7260 aaatgtgact attcagatta aatgcttaat gtgtgtgtgt tgactaaata aatctcaacc 7320 agaaccttct cagatatttt gttgaacgtg ggacctttgt ttttttttgt tgttttgttt 7380 tgttttgttt ttgttgttgt tgttgttgtt gtttaccagc aggggacccc tgttttgtct 7440 atgtcaagaa caaagaccag gcaaaagaaa tgtcaagccg catttacaaa tgcaaaaatg 7500 gacttgtttt tgatatgctt ttcccaacaa taagggacat gagtcattgg ggcatgttac 7560 agagagtttc agtaaaattc agaaaaaaat aataaatatg aacagccaca gcatgcccag 7620 aagccttttt atggagccag gcatggttga cctgctttcc atgtctcaaa acattagtcc 7680 ctacaagaac cctatgaggt ttatcttctt ttcacccatt ttgagagaag aaaagttcag 7740 ctcagagagc tgcaggaaca ttggggacat ctccaagtca cagccaatag gtggcagtca 7800 tcagtgtgtc ttggaaggga caaacattga gcttctgaac agctactcca gaaactatgg 7860 tgctgtggtg aagtcctggt taggagccta ggaaaatggt gaaggaaaag atggtcccag 7920 cctgcaaagc tgaagtcagg aacccaccag gatctccctt ctccctagcc tggtggtcca 7980 catcatgcag atttactcta gattcagctt agactcattt ttatactact cgggggacaa 8040 ggagggaact acagtcagta acagcagcat gagcctcagg tgctttgggg attgaaattc 8100 agaccaggaa attccaatac atcagtgcat gtggaggaca tgagtattta aggagaaggt 8160 tctaggcttc cgaagtaaaa ttggatgtgg aggttgggga ttgattcaaa cattaatact 8220 ttcaagcgtt tctatggtat ttgtcagctg tggagcaaca gcacacatct gtattaatag 8280 cctgtgttaa gagattactg tgaatcctga aaaacatcct cattgtagag atgagaaaac 8340 acaggctttt gcacatccaa tgtctcctta aagcatgtgg ttcagaattg agaacgtgca 8400 gagtgagagt ggtatgaatt ttcctgtaag ctacctgaag ttctgtttgc tgtcatgtgg 8460 aagaaaagag ccttggagaa gttttatttt tttctgtttg gaaagaatac acagagcaag 8520 atgatttaca ataaaccttt tgacctaacg cacaaaaaaa aaaaa 8565 <210> 197 <211> 2108 <212> DNA <213> homo sapiens <400> 197 atgggaaatg tggtctccga cggatggcct acacccggga ggagtccagg aactctaggt 60 ggacagttac ttccgcacac gcgtagtagg acggtagccg gtattcaatc ttcaaatcag 120 cgccgcggga agtgcgggcg ggtgttgctc ccctgtctct ggacgacgct gtgactgatc 180 ccaggcttgg agccggagct gcgagcgagg cagtgaaagg gtggcagatt tctgtgtaag 240 agctgcagaa aatgatcagc ttccaggaat cagtgacatt ccaggatgtg gctgtggatt 300 tcactgcaga ggagtggcag ctgcttgatt gtgctgagag aaccctgtat tgggatgtga 360 tgttggagaa ctatagaaac ctcatctcag tgggatgtcc aattaccaaa acaaaagtga 420 tcctcaaggt agagcaagga caagagccat ggatggtgga gggagcgaat ccacacgaga 480 gctctccaga atctgactac ccacttgttg atgaaccagg gaagcatcgg gaaagcaaag 540 acaatttttt gaagtcagtt ttgctcacat tcaataaaat tctgactatg gagagaatcc 600 accattataa tatgagcaca agtcttaatc caatgagaaa aaaatcatat aaatcgtttg 660 agaagtgttt gccacctaat ttagacttac ttaaatataa tagaagttat actgtagaaa 720 acgcttatga atgcagtgaa tgcgggaaag ccttcaaaaa gaagtttcat ttcattagac 780 atgaaaaaaa tcatacaagg aaaaaacctt ttgaatgcaa tgactgtgga aaagcctata 840 gcaggaaggc acaccttgca actcatcaga aaattcataa tggagagaga ccctttgtgt 900 gcaatgattg tgggaaggcg tttatgcata aagcccaact cgtggtccac cagagacttc 960 acactggaga gaagccttat gagtgcagtc aatgtgggaa aacattcact tggaactcct 1020 catttaatca acacgtgaaa tctcatacac ttgagaagtc atttgaatgt aaggaatgtg 1080 ggaaaacctt caggtatagt tcatcccttt ataaacattc cagatttcat acaggagaga 1140 aaccctacca gtgtatcata tgtggcaaag cttttggcaa cacatccgtg cttgttacac 1200 accaaagaat tcatacagga gagaaacctt acagttgtat tgaatgtggc aaagccttca 1260 tcaagaagtc ccatctcctc agacatcaga taactcatac aggagagaag ccctatgaat 1320 gtaacagatg tgggaaagca ttttcccaga agtcaaatct tattgtacat cagaaaattc 1380 atacataata ttcactttat gaatatgaga aggccttatt aaatatttgc taaatcttat 1440 taaatactaa agaattcatg gtgagaagtc tacaatttaa atgaatttgg aagagtagat 1500 tcccataaaa aacaaccaat gccaatcatg ttctggaagt gataataaac tttttacaga 1560 aaatatgaca gaaaacaact ataaataata gagcataaag cttggaaagt aagcataact 1620 taaaaaatca aagaaccagt gaaaactaca tttgccattc ctgactttta atttttataa 1680 taaaataatt atgcaagtgt gagtttaaaa tatatgctta tacattatat taaagtatgc 1740 ctattaacag tttctgcagt aaataacatt ttttcttcca gtctcaacat acataattaa 1800 tcaagtgaga aaatgtgttt taatatgtca tatgaatttc agtgatattt tcatccattt 1860 gctggcactt ttaatgggca tgacagtgtt tctgaatctg agtctccttt aattatacaa 1920 gtgaagactt cttattaaaa ttaatataaa gatattttcc tatgtatgta aataccagaa 1980 caaaaaacaa gacactaatt gaggagagaa aggcacttgt attctgtatt acagtaagta 2040 ttcagttgag gaaaagaatt atttaaatat gtaaataaat aatttgcact tcaaataaaa 2100 aaaaaaaa 2108 <210> 198 <211> 5210 <212> DNA <213> homo sapiens <400> 198 ctttttgctt ctctgcgccc agagctccag tccttctctt cactgctctg cgtcctctgc 60 tcctggaggc caagcctctg tggccttgtg tcctgcaagt attcgcagat ttatggctaa 120 aagaccggga ccccctggaa gccgagaaat gggactgttg acattcagag acatagctat 180 agaattttct ctggcggaat ggcaatgcct ggatcatgct cagcagaatt tatatagaga 240 tgtgatgtta gagaactaca gaaacctggt ctccctgggt attgctgtct ctaagccaga 300 cttgatcacc tgtctggagc aaaataaaga gccccagaat ataaagagaa atgagatggt 360 agccaaacac ccagttacat gttctcattt cacccaagac cttcagtcag agcagggcat 420 aaaagattca ctccaaaaag tgatactgag aagatatgga aaatgtggac aggaggattt 480 acaagtaaaa aaatgctgta aaagtgtagg tgagtgtgag gtgcacaaag gaggttataa 540 ttatgttaac caatgtttgt cagctaccca aaacaaaaca tttcagactc ataaatgcgt 600 caaagtcttt ggtaaatttt caaattccaa tagacacaag acaagacata ctggaaagaa 660 acatttcaaa tgtaaaaacg atggcaaatc attttgcatg ctttcacgcc taaatcaaca 720 tcagataatt catactaggg agaagtctta caaatgtgaa gaatgtggca aatcctttaa 780 ctgctcttca acccttacta gacataaaag aattcatact ggagagaaac cctacagatg 840 tgaggaatgt ggcaaagctt ttagctggtc tgcatccctt actaaacata agagaattca 900 tactggagag aaaccttaca catgtgaaga acgtggcaaa gtctttagcc gctcaacact 960 tactaactac aagagaattc atactggaga gaaaccctac acatgtgaag aatgtggcaa 1020 agcctttagc cgctcttcaa cacttactaa ccacaagaga attcatactg gagagagacc 1080 ctacaaatgt gaagaatgtg gcaaagcctt tagcttatcc tcaaccctta agaaacataa 1140 gatagttcat actggggaga aactctacac atgtgaagaa tgtgggaaag cctttacctt 1200 ctcctcaact ctaaatactc ataagaggat tcatactgga gagaaaccct acacttgtga 1260 agaatgtggc aaagccttta gcttaccctc aaccttcact taccacaaga gaactcatac 1320 tggagagaaa ccctacaaat gtgaagaatg tggcaaagcc tttaactgct cctcaaccct 1380 taagaaacat aagataattc atactggaga gaaactctac aaatgtaaag aatgtgggaa 1440 agcctttacc ttctcctcaa ctctaaatac tcataagagg attcatactg gagagaaacc 1500 ctacaaatgt gaagaatgtg accaaacttt taagtggcat tcaagtcttg ctaatcataa 1560 gaatatgcat actggagaga aaccctacaa atatgaataa tgtggtaaag tccagccctc 1620 aggccttata atacataaaa taatttatac tggaaaaaat cactacaagt gtggagaatg 1680 tggccaattc tttaaccagt tccaaaccac tgctgtccat aagataattc atattggaca 1740 aaagtcttat aaatgtaaaa aaaaaagtaa cagcctttaa ccacccctca aaccttaatg 1800 aacccaagag aatttattta aaaaaatttt tttgagacag agtctcactt tgtcacccag 1860 gctggagtgc agtggcacga tgtcagctca ctgcaacctc tgcctcctgg gttcaagcga 1920 ttctcctgcc tcagcctcct gagtagctgg aattacaggc acgtgcaacc acactggctg 1980 agttttgtat ttttagtaga gatggggttt caccattttg accaggctgg tctcaaactc 2040 ctgacttcag gtgaaccacc tgcctcagcc tcccaaagcc taagagaatt tatattagag 2100 agactctaca aaggtcaaaa atgtgacaaa acatttaagc acatctcagg ccttacacaa 2160 tatcagataa ttcattctag agacaaaccc tacaaaaaca atgtggtaaa gcttttacct 2220 agtcttgaac ccttattata cactaaaaga attgatactg aagaaaaacc ctacaataag 2280 gaatatggaa atgtctttta aaagtcctca aactttttgt ttgaataaat gtaaaataat 2340 tgatactgga gagaacccct gcaattgtaa aaaaaaaaaa aaatgtggca aagcttttaa 2400 ctggttctcc atctttatta attaaaatat tttatactgg agagaaactc tacatacata 2460 aaaaatgtga cagcatttaa ccacacctga catttttcta aaatagagaa atcatactgg 2520 tgaaaaactc tagaaatgtg ttaaatgagg taagtccttt aaatggtagt tgcatgttat 2580 ggtaggtaag ataatttata ctgaagaaaa ctcaggcaaa tatgaaaaat gtggcaaaac 2640 ttttaacaaa ttttcccatc ttattgcaca ggaagccttt tatactagag aaaaattgta 2700 aaaatataaa gaatgtgaaa agccattaat gtctgttcac atcttactca atatcagaaa 2760 gtttatactt aacaaaagca ttataggcta gatgtggtgg ctcatgcctg taatcccagc 2820 actttgggag ctcatggcag gtggatcatg aggtcaggag ttcaagacca gcctggctaa 2880 catggtgaat ccccatctct actaaaaaca caaaaattag acaggcatgg tggtgtgcac 2940 ctgtaatccc agctactcag gaggctgaag caggagaatt gcttgaaccc aggtggtgga 3000 ggttgcagtg agtcaagatc accccaccat actccagcct gggtgacaga gcaagaatcc 3060 atcttaaaaa aaaaaaaaaa gcgtaaatgt gattactgta aaaagacctt tcagaaaaca 3120 taggccttta aagcaaagac tatttattct aaagacaaac attaaaacat aaagaggatt 3180 gtgtagtacc tttatttgta ttacggattt tattgtacac attttatatc aaaggaaaac 3240 cctgaaacag atgctcaaac tttgttgaac atcggagaat ttatattgga gagaaagtgt 3300 aaatgaatgt caaaaaatat ttgttcaaaa actacagttt agaaaacact agtttatact 3360 aaaaaaatat ttttgcagat gcagtaaatg gggaaaatat gtttaatcaa aaattaagtc 3420 tacataaaca tttgaggatt cacagtagaa agaatgaagg tgctgaaact tcagacatta 3480 cactaaatca gagtgttgag tgtaaaaaag atataaatct aacaatataa atttaaagaa 3540 gtagatttat ttggagattt ataattacat tcgaggtatg cttctttctt tgtaaaaaaa 3600 aatatagatt ttctgaaaag caaatagtaa tgtaactcac atttcaaatt acttcatgtt 3660 gatcctttct tcccattgtt tctgtgaaag tattggacca attgttgaat cagagatatg 3720 agattgtttt ttataggtgt ccattattca tgaactttcc tatggatgag taaggacatt 3780 aagttgtaag atgcataatg aaaatctaaa tggagaggtt ctttgtggtt gacttataac 3840 attgttttag tgatgtataa ggcgagcgtt cagagtaata ttctaaattc tagtgaggaa 3900 aacctttgaa cgtcagtagt aaattatttt atcaattgta cctttatgta aacaaagttg 3960 tttttaatga gctaaaacta ttgtgctttg aaagaagtat taagctgcca ttgactctat 4020 cgtgtctcat cttaaggttc tgcgtaaaag atggtgacaa tatactattt gttaatgtag 4080 gggaatgaca tcactagtag tctctttttt gccagtgttt ttgtttgttt gttttgagac 4140 taagtcttac tctgtcaccc agactggggt gcagtggtgc gatctcagct cactgcaacc 4200 tccacctcct gggtccaagt gattctcctg cttcagcctc acaagtagct ggaactagag 4260 gcaggcacca ccactcctgg ctaatttttg tatttttagt agagatgagg tttccccatg 4320 ttggccaggc tggtctcaaa ctcctgacct caggtgatac acccacctcg gtgtaccgaa 4380 gtgctgggat tacaggcatg agccaccatg cctggcctac tagaggtttt acacagcaaa 4440 caagttgaag aattttgttc ccataggaca aatttgtact tttttacctt atttaatttt 4500 tttttaattt ttgtgggtag tgtgcataca cacttatggc atatatgaga tatgttaaca 4560 catgcacata atatttaatg atcacaacag agtaaatgag gcattcatca ccttgagcat 4620 gtatttatcc tttgtattac aaacaatccc attatacagt tttagttatt tcaatatgtg 4680 caattgaatt actattaacc acagggtcat tttatgatca taaaaattac atgagtataa 4740 ttaataccca tacatttctg agtcttgatt aaatattttt aaaattttgt tttataaatt 4800 ttttgcacat gtggcatctc tgctgacaaa caaaaacaga cttttagttt caatttacat 4860 agagttacat atacaaatat attactctaa agatatacca gccgagcaca gtggctccca 4920 gcattttggg agcctgaggt gggaggatca tttgaggtta ggagttcaag accagcctgg 4980 ccaacatggt gaaaccccat ctctactaaa aatacaaaaa attagctggg catggtggtg 5040 catgcccatg gtcccagtta ctcaggaggc tgaggcagga gaattgcttg aacctcggag 5100 gtggaggtag cagtgagctg agatggtgct actgcactcc agcctgggtg aaagagcgag 5160 aaaccatctc aaaaaaaaaa ataaataaat aaaagatata ccttaagcat 5210 <210> 199 <211> 3669 <212> DNA <213> homo sapiens <400> 199 gggtgcggca tccgggatct ggcgcggctt ttgcttgtag ctccagccag agctcggtta 60 gggcctcatc gctctgctcc cgctccttag ggaagcctcg gtgattctgc cacagcctca 120 gcctctgtgg ctctgtgacc tgccggtatt ggatgattcg tatctaagac tctgggacac 180 tcctgaagtc gggaaatgga actcttaaca ttcaaggatg tggccataga attctctcca 240 gaagagtgga aatgtctgga cacttcccag cagaatttat atagagatgt gatgttggag 300 aactacagaa acctggtctc cctgggtgtt agtatctcta acccagacct ggtcaccagt 360 ctggagcaaa gaaaagagcc ctacaatttg aagatacatg aaacagcagc cagaccccca 420 gctgtgtgtt ctcatttcac ccaaaacctt tggacagtgc agggcataga agattcattc 480 cacaaactta taccaaaagg acatgagaaa cgtggacatg agaatttaag aaaaacttgt 540 aaaagtataa atgagtgtaa ggtgcagaaa ggtggttata atagaattaa ccaatgctta 600 ttaactaccc agaaaaaaac aattcaatct aatatatgtg tcaaagtttt tcataaattt 660 tcaaattcaa acaaagataa gataagatat actggagata aaacctttaa atgtaaagaa 720 tgtggcaaat catttcacgt gctctcacgc ctaactcaac acaaaagaat tcatactgga 780 gagaacccct acacatgtga agaatgtggc aaagccttta attggtcctc aattcttact 840 aaacataaga gaattcatgc cagagagaaa ttctacaagt gtgaagaatg tggtaaaggc 900 tttactcggt cctcacacct tactaaacat aagagaattc atactggaga gaaaccctac 960 atatgtgaaa aatgtggtaa agcttttaac caatcctcaa cccttaattt acataagaga 1020 attcattctg cacaaaaata ctacaaatgt gaagaatgtg gtaaagcctt taagtggtcc 1080 tcatccctta atgaacataa gagaattcat gctggagaga aacccttctc atgcgaagaa 1140 tgtggcaatg tctttaccac atcctcagac tttgctaaac ataagagaat tcatacagga 1200 gagaaaccct acaaatgtga agaatgtgga aaatccttta ataggtccac aactcttacg 1260 acacataaga gaatccatac tggagagaaa ccctacacat gtgaagaatg tggaaaagcc 1320 tttaattggt cctcaaccct taatgtacac aagagaattc actctggaaa aaatccctac 1380 aaatgtgaag attgtggcaa agcctttaaa gtgtttgcaa acctgcataa tcataagaaa 1440 attcatactg gagagaaacc ctacatatgt aaacaatgtg gcaaagcctt taaacagtcc 1500 tcacacttga ataaacataa gaaaattcac actgtagata aaccctacaa atgtaaagaa 1560 tgcgggaaag cttttaagca gtactccaac cttcctcaac ataagagaac tcatactgga 1620 ggaaaatttt agaaatgtga agaatgtggg agcctttaag tcttcctcag tcttttctaa 1680 tcataattca tactggagag aaactctaca catgaaaaaa ttgacaaagc ttttaaccgc 1740 aactcaatct gttctaaaca taagagaaat ggtattggtg agaagccata aaaatatgaa 1800 aaatgtggaa aagccttcaa atgcttgtca catattactg aatataattc ttactgcaga 1860 aaacccctag gaatattaaa agtgtggcaa aacctttaac caatgctcat atctctttgc 1920 acatgatagc atttatactt gagaaaaatt gtacaaatat agaaaatgta gaaaagccat 1980 taatgcctac tcatgtgtta ctaaatatca gagagtttgt acttaataaa aggattataa 2040 atgtagtatt tgttgaaaga cctattagaa aatacaggtc ttaaaagtga agaagagtat 2100 tctgaagata gacaatagaa atagtaagag ggttgtagta cctgtacttg catcatgggt 2160 cttattgtgc atatttcata ctagaagaaa accctgaagc agttgcccaa actttctttg 2220 acattagaga atttatattg gaaagaaatt ttacaaatgt aataaatttg gaaaagcatt 2280 tgttcaaaaa ctatagctta aaaaaaacca gtttatacta gaagatattt tgtagatgcg 2340 gtaagtatga aaagatagtc tgaaattaag actaaatgtc agaatattta cagtagaaag 2400 aaaaaggcat taacacttga aacattacag tatatcagag tgtaaagtat aaaaaaattc 2460 caaagctgaa actgttagat aatttctttc tatataagtt gaaaaggagt agctttttga 2520 aattattcca ttgaaattat acttttttta cctgaaaaaa ttatagattt tttgaaaagc 2580 aaattcaact ctaaaattac ttcatactga ttcaacttat tgtttatatg aaagcatgtg 2640 atgaattgtt gcatcagagg tatgagtgat tctttttagg tgggcatcat tcatgaactt 2700 tttttttttt tttgagacgg agtctcgctc tgtcgcccag gctggagtgc agtggcggga 2760 tctcggctca ctgcaagctc tgcctccccc tgggttcacg ccattctcct gcctcagcct 2820 cccaagtagc tgggactaca ggcgcccgcc actacgcccg gctaattttt tgtattttta 2880 gtagagacgg ggtttcaccg ttttagccgg gatggtctcg atctcctgac ctcgtgatcc 2940 gcccgcctcg gcctcccaaa gtgctgggat tacaggcgta ttcatgaact tttacatgaa 3000 tgagtaagga cattgaaaga tgcatgagat gatgcataca tctttgtggt tgacttatca 3060 ttgcatgatg catgacgtac atgttcagag taatattctt ctgcattata gtgagagaaa 3120 aatcttgaat tttagtaata aattgctttt accagttgca catttatgta ataaaataca 3180 gtaaatttta aaattctctt ttaagattgt gtgtgaacct tactcaaggg tgtaggtaaa 3240 aaatggtaac agtatacttt tagtaacata gtttaatgac atttctagta atttcttttt 3300 ccagtggctt taaacagcaa ataagttgaa gaatattgtt ctcatgttaa atttttatta 3360 ttttttatat ttaaatttat ttttaaaaat ttatgtgggt acatggtatg tgtatacatt 3420 catggcatag atgggttact ttgatacaga catgcaacat gtaatcacat cagagtaaat 3480 gagttattca tcacctcaag catttatcct ttgtattaca aacaatccaa ttatacactt 3540 catttttaaa tgtacaatta aattattttt tattacaggt aattttatga ttgtatttag 3600 aattatatca gaatataatt ataatttaga catttctgtg tcctgaataa atatgttttt 3660 aaatgttcc 3669 <210> 200 <211> 6696 <212> DNA <213> homo sapiens <400> 200 atgaggccgc gctcgggcgg gcgcccaggg gccacgggcc gccgccgccg ccgcctgcgc 60 cgccgccccc gcggcctccg gtgcagccgc ctgccgccgc cgccgccgct gccgctgctg 120 ctcgggctgc tgctggcggc cgcggggccc ggcgcggcgc gggccaagga gacggcgttc 180 gtggaggtgg tgctgttcga gtcgagccca agcggcgatt acaccaccta caccaccggc 240 ctcacgggcc gcttctcgcg ggccggggcc acgctcagcg ccgagggcga gatcgtgcag 300 atgcacccac tgggcctatg taataacaat gacgaagagg acttgtatga atatggctgg 360 gtaggagtgg tgaagctgga acagccagaa ttggacccga aaccatgcct cactgtccta 420 ggcaaggcca agcgagcagt acagcgggga gctactgcag tcatctttga tgtgtctgaa 480 aacccagaag ctattgatca gctgaaccag ggctctgaag acccgctcaa gaggccggtg 540 gtgtatgtga agggtgcaga tgccattaag ctgatgaaca tcgtcaacaa gcagaaagtg 600 gctcgagcaa ggatccagca ccgccctcct cgacaaccca ctgaatactt tgacatgggg 660 attttcctgg ctttcttcgt cgtggtctcc ttggtctgcc tcatcctcct tgtcaaaatc 720 aagctgaagc agcgacgcag tcagaattcc atgaacaggc tggctgtgca ggctctagag 780 aagatggaaa ccagaaagtt caactccaag agcaaggggc gccgggaggg gagctgtggg 840 gccctggaca cactcagcag cagctccacg tccgactgtg ccatctgtct ggagaagtac 900 attgatggag aggagctgcg ggtcatcccc tgtactcacc ggtttcacag gaagtgcgtg 960 gacccctggc tgctgcagca ccacacctgc ccccactgtc ggcacaacat catagaacaa 1020 aagggaaacc caagcgcggt gtgtgtggag accagcaacc tctcacgtgg tcggcagcag 1080 agggtgaccc tgccggtgca ttaccccggc cgcgtgcaca ggaccaacgc catcccagcc 1140 taccctacga ggacaagcat ggactcccac ggcaaccccg tcaccttgct gaccatggac 1200 cggcacgggg agcagagcct ctattccccg cagacccccg cctacatccg cagctaccca 1260 cccctccacc tggaccacag cctggccgct caccgctgcg gcctggagca ccgggcctac 1320 tccccagccc accccttccg caggcccaag ttgagtggcc gcagcttctc caaggcagct 1380 tgcttctccc agtatgagac catgtaccag cactactact tccagggcct cagctacccg 1440 gagcaggagg ggcagtcccc acctagcctc gcaccccggg gcccggcccg tgcctttcct 1500 ccgagcggca gtggcagcct gctcttcccc accgtggtgc acgtggcccc gccctcccac 1560 ctggagagcg gcagcacgtc cagcttcagc tgctatcacg gccaccgctc ggtgtgcagt 1620 ggctacctgg ccgactgccc aggcagcgac agcagcagca gcagcagctc cggccagtgc 1680 cactgttcct ccagtgactc tgtggtagac tgcactgagg tcagcaacca gggcgtgtac 1740 gggagctgct ccaccttccg cagctccctc agcagcgact atgacccctt catctaccgc 1800 agccggagcc cctgtcgtgc cagtgaggcg gggggctcgg gcagctcggg ccggggacct 1860 gccctgtgct tcgagggctc cccgcctccc gaggagctcc cggcggtgca cagtcatggt 1920 gctgggcggg gcgagccttg gccgggccct gcctctccct cgggggatca ggtgtccacc 1980 tgcagcctgg agatgaacta cagcagcaac tcctccctgg agcacagggg gcccaatagc 2040 tctacctcag aagtggggct cgaggcttct cctggggccg cccctgacct caggaggacc 2100 tggaaggggg gccacgagtt gccgtcgtgt gcctgctgct gcgagcccca gccctcccca 2160 gccgggccta gcgccggagc agctggcagc agcaccttgt tcctggggcc ccacctctac 2220 gagggctctg gcccggcggg tggggagccc cagtcaggaa gctcccaggg cttgtacggc 2280 cttcaccccg accatttgcc caggacagat ggggtgaaat acgagggtct gccctgctgc 2340 ttctatgaag agaagcaggt ggcccgcggg ggcggagggg gcagcggctg ctacactgag 2400 gactactcgg tgagtgtgca gtacacgctc accgaggaac caccgcccgg ctgctacccc 2460 ggggcccggg acctgagcca gcgcatcccc atcattccag aggatgtgga ctgtgatctg 2520 ggcctgccct cggactgcca agggacccac agcctcggct cctggggtgg gacgcgaggc 2580 ccggataccc cacggcccca caggggcctg ggagcaaccc gggaagagga gcgggctctg 2640 tgctgccagg ctagggccct actgcggcct ggctgccctc cggaggaggc gggtgctgtc 2700 agggccaact tccctagtgc cctccaggac actcaggagt ccagcaccac tgccactgag 2760 gctgcaggac cgagatctca ctcagcagac agcagcagcc cgggagcctg agctcaggag 2820 gaactcttac ctggaaattg ggaactgtat ggagactcca aactgacttc tttcaaaaaa 2880 caaaaacaaa aaattttttt agctttgaca aacacacaaa agtggtaata aagagagccc 2940 tccttgtcaa cccaaaatgt gagccccctg tggcaaaacc accccctacc ccattaacaa 3000 atcaacagac aaaattctcc gagtcctttg cctcttttga taacatgttg ttctgttttg 3060 taaagtgtgt gtgcttgggg ttccgaggtg tgggattgag ttctctgctt tgtttttttt 3120 taagatattg tatgtaaatg taaaaagtta tttaaatata tattttaaag aaccctaact 3180 gccaactttt gctgaaaaag aaaaaaaaat cactgctgca ttaaatgaac cacatcatgt 3240 gtagatactg ttgtctccct gaagggagct caggcctttg aaaagctcag ggcttcacct 3300 gccttagaaa atgaaccaga aacttgaagt aaagctagtt gataggggta caggctctga 3360 ggagcagtgc aaaactgcct ctttctttct cgtggcaaat cccaatgtac acgatttcag 3420 gtctcagacg ccatgcctct ccagcccacg cctttaggca ggtgatggca gcagctagga 3480 atagggtgta catgatccac agccctgcgg agccaggtca agccgctgct atgaaagctc 3540 cagggtgatg gggacgattc tgcccagtgt cctcagtctg tcccctcagg tcatggtccc 3600 aagtgaaatg acagagttca cagccctggt cttggctgag gtccaggtca tagtaagggc 3660 atgttcttgg ggccctcgac ctgaactctg accctccggg cagggaagag gaggttgtcc 3720 cctttggttg tcctggcttt ggagtccttt gcaaaaatat tttgggcccc ctgccactgg 3780 ctgcagaaat ggctcgacgg ggtgtgtggg gacagacacc cagaaggaat gtacttttgt 3840 ggccttggtg tccgatgggg ctgggggaga gtgctctcca ctgacccagc agcacaccca 3900 tgtgcagtgc gcctgcatct gtgtgggggc agccacaccc cttggctgct gcttccttgg 3960 gctgcctttc tgggggcatg tgactggacc tacgaggtct gcactgagct ccatttgaat 4020 gatacctttc ctatcccatt tcccccacgg aagcaccgct tcagggttat tcagtcctct 4080 gcctcatggc tgaaattgct catctcgtct gcagatgtct actatcctgt ctacctaatg 4140 cactattatg tattgattct ccatgagaca gagagagaga gagactatca gatagtttac 4200 acccaaaggg taggtttttg tatatttttc cagccttttt tattaagggg aaggggagag 4260 tttaaaaacc caaaccgttg tggttttaag gtgtttcatt tttaaaaggg agagagaatc 4320 tatttaaagc tatttcagat cagggattgt catccttttt tgtccaatgt attccttgtt 4380 ctttaaaaaa atttttttta gaggaaacta atattagtct ttgtgttcac taactcttct 4440 ggtcacttgt atttatttat tcattcattc atcagatatt tgttgccatc tgaaagaact 4500 ggcccagtgg gtctgaaagc tcgcttgaga ataggaaact tgagacctgg ccccctgtgg 4560 gtaggagaac aaggaccacc tgggttctcc agtcttgaac gagaatctca ctcttatcag 4620 aatgtttttc ttaacctcag cgtatgatga ggaaatttac ttatctctag ctaggatttg 4680 acaaattcca acatcaaatg atcaaaacat ttgccactga ggcttcactg gtgagatccg 4740 ttctccgtcc tcgggtgcag tcccttgggg gctgctcctc ggactgcgcc ccgcacacct 4800 gttatcgagg gtgtgagaag cgcctaagct ggtgacatgt gatctgggac gccttcattt 4860 ctcgggccag gagtagcagc tgctaaggac agcagcttgc attgcgtggt tttagggaag 4920 cagggtctgg cttttaatat gaactgcaaa aagcagcttc tcactgatat ttttttgttg 4980 ttgtttctgg ggggtttttt tgttttgttt ttaatgcctt tgagtgcata ttttcttcct 5040 cgtctgaaac cgaactccca aagtggcttt ctttagccct ggctggaaaa ccacctctca 5100 atagccttaa gcaataaata gatgagtaga gaatgtggct tcaactgggc ttattaaagt 5160 aagtgtgtct agttttcact tgaacaagtg atagctgcag atggcgaaag aaacccattt 5220 aatttttgta gcttacaggt ggtagaaaca aaaatgcaat tttaaaacct taaataccaa 5280 ataccaacca ttgccttttt tttttttgag atggaatttt gctcttgtca cccaggctgg 5340 agtgcaatgg cgcgatctca cctcactgca acctctgcct cccgggtcca agtgattctc 5400 ctgcctcagc ctcccaagta gctgggatta caggcatgcg ccaccacacc cagctaattt 5460 tgtatttttg gtagagacag ggtatctcca tgttggtcag gctggtcttg gattcccgac 5520 ctcaggtgat ccgcccacct cggcctccca aagtgctggg attacaggcg tgagccacca 5580 tgcctgccca gcaataccaa ccattgtctt ttaaattcgt gttggcttct cagacaggga 5640 gatcactgga ataaaataac cgatggtctt attttgtcac acgtaaatca aaagaaatgt 5700 cctctttgaa gttgtaagac tccaccaatg acagacaccc ttttcggtgg actctgagtg 5760 gtgtgtagtg gttttatagc catggaaact aggagtatct cactttccac tgagaacccc 5820 tgcccccaat ccctctaagt tggggtgtgg cagttgggca gggtcaagtg acccagccct 5880 ggctgtagga cagccatata cagtgaagag ttctagaacc agctaaaaat ggaagtttgg 5940 gtgtttacca acaaggtacc tctttatgga tgcagcccca gtaagctggc tttaactctc 6000 agctccttcc ctgtctcctc ctaatccaag cccttttata aaataaagcc ccttctgtcc 6060 cactgctcac atacttatgt gctgctagtc tctactcgaa gttcgtgcag gactaatgct 6120 tttaaaatga ggtctaaaaa ataattacta gtcgagacta ttattcttta aacagaactg 6180 cctttttcta ctctttatgt aaactctttc tattgtgttg gtctaacaag gcactatttt 6240 aaaatttttt aatttttccc atagcactta aaagagattt tgtaaagacc ttgctgtaaa 6300 gattttgtaa taaaatggtc taagggctct ttttccaaca ttaccatttt taaaaaatgt 6360 tttaaaagct agaagacaac ttatgtatat tctgtatatg tatagcagca catttcattt 6420 atggaaatat gttctcagaa tatttattta ctaatatatt tatcttaagc catgtcttat 6480 gttgagagtg tgacattgtt ggaataatca ttgaaaatga ctaacacaag accctgtaaa 6540 tacatgataa ttgcacacag attttacata tttgcagacc aaaaatgatt taaaacaagt 6600 tgtagtcttc tatggttttg taacaaattg tacacatgac tgtaaaaaaa aaatacaatt 6660 ttatcaagta tgtgttaaaa aaaaaaaaaa aaaaaa 6696 <210> 201 <211> 5607 <212> DNA <213> homo sapiens <400> 201 attccttctg atagtgccat ctttctctgc cctaggaaga aacacctctt acagtcatct 60 gcaggggatt ctccaaggac atgggaagat agatgtaagc cctggaaccc agactcctaa 120 gcgaagggaa gctgcattct gctattaatg atggccaaat cagctctaag agagaatggc 180 actaactctg agaccttccg acagcgtttc aggagattcc attaccagga ggtggctggg 240 ccgcgggagg ctttcagcca actctgggaa ctttgctgtc ggtggctaag gccggaggtg 300 cgcaccaagg agcagattgt agaactgttg gtgctagagc agttcctgac cgtcttacct 360 ggggagatcc agaattgggt acaggaacaa tgtccagaaa atggagagga ggcagtgact 420 ctcgtggaag atttagaaag agagcctgga agacctagat cttcggtcac agtctctgtg 480 aaggggcagg aagtgcgctt ggagaagatg acacccccga aatcatcaca agagttatta 540 agtgttcggc aggagtcagt ggaaccccag cccaggggtg tacccaagaa agagagggca 600 agaagcccag acctgggacc acaggagcag atgaacccaa aggagaagct caaacctttt 660 caaaggagcg gattgccatt tcctaaatcc ggtgtggtct ccaggttgga gcaaggagag 720 ccatggatcc cagatctgct gggctctaag gagaaagaac ttccaagtgg cagccacata 780 ggagacagac gagtgcatgc tgatctgtta ccatccaaga aagatagaag aagctgggtg 840 gaacaggatc actggagctt tgaagatgag aaggtggcag gtgtgcactg gggctatgaa 900 gagaccagaa cgctcctcgc aattctcagc cagactgagt tttatgaggc tctcagaaac 960 tgccatagga acagccaagt gtatggggct gtggctgagc ggctcaggga atatggcttc 1020 ctccggaccc tggaacagtg tcggaccaag ttcaaaggtc tccagaagag ctatcggaaa 1080 gtcaagagcg gccacccacc tgagacctgc cccttctttg aagagatgga agccctgatg 1140 agtgctcagg tcattgccct gcccagtaat ggcctggaag cagcagcctc tcactctggc 1200 ctggtaggca gcgatgctga gactgaagag ccagggcaga ggggctggca gcatgaggag 1260 ggagcagaag aggctgtggc tcaggagtct gacagtgatg acatggatct agaggcgacc 1320 ccccaggacc ccaactcagc tgcacctgtt gtgttcagaa gcccaggtgg tgtacactgg 1380 ggctatgaag agaccaagac ttaccttgca attcttagtg agacccagtt ttatgaagcc 1440 ctccggaact gtcaccgcaa cagccagctg tatggagcag tggctgagag gttatgggaa 1500 tatggctttc ttaggacccc agaacagtgt cggaccaagt ttaaaagcct gcaaaccagc 1560 tatcggaaag ttaagaatgg ccaggcacca gagacctgtc ccttctttga agagatggat 1620 gctttggtga gtgtccgggt tgctgcccca cccaatgatg gccaggaaga gactgcttct 1680 tgccccgtcc aggggaccag tgaggctgaa gctcagaagc aagctgagga agcagacgag 1740 gccacagagg aagattctga tgatgatgaa gaggatactg agataccccc aggggctgtc 1800 ataacccgtg ctccagtgtt attccaaagc ccccgtggtt ttgaagctgg atttgagaat 1860 gaagataatt caaaacggga tatttctgag gaagtacaac tgcataggac attacttgca 1920 agatctgaaa ggaaaattcc ccggtatctt catcagggta aaggcaatga gagtgactgt 1980 agatcaggaa gacagtgggc aaagacctca ggggagaaaa gaggaaaact gacactcccg 2040 gagaagagct taagtgaagt cctaagtcaa cagagacctt gcttgggaga gagaccctat 2100 aaatatctca aatacagcaa aagctttggt ccaaactccc ttctcatgca tcaggtatcc 2160 caccaggtgg aaaatccata taaatgtgct gattgtggga aaagcttcag tcggagtgca 2220 cgactcatta gacaccggag aatccacact ggagagaaac cttataaatg tcttgactgt 2280 ggaaaaagtt tccgtgacag ttcaaatttc atcacccata ggagaatcca cacaggagag 2340 aaaccttatc aatgtggtga gtgtgggaaa tgcttcaatc agagctcaag ccttatcatt 2400 caccagagaa cccacacagg agaaaagccc tatcaatgtg aagagtgtgg aaaaagcttc 2460 aataacagtt ctcattttag tgcacatcgg aggatacaca caggagagag accccatgtg 2520 tgtcctgact gtggaaagag tttcagtaag agttctgact tacgtgcaca tcatagaacc 2580 cacacaggag agaaacccta tgggtgtcat gactgtggta agtgcttcag taaaagctct 2640 gcccttaata agcacggaga aatccatgca cgggaaaagc ttctgacaca gtcagctccc 2700 aagtaagccc ctgaggatat ataacggaaa gaggctcaat aaatgtattg tttagaaagt 2760 cttccaatag tgagattcat ctactattct gtgtccagtt agcttaggaa attcacttta 2820 ggatttatgc cactgtttgt tccttgtttt tcctgatcta gactcaaatc cccaaggcag 2880 tctaaagaat gaaaggaaga tttcagtccc tctctttgcc tgcatctgaa ttgatggata 2940 acatcttttc cctctcagtg cctatggtgt tcccttaata taagcacaga ggacaaggta 3000 atagatccta tgaatttgat aagcatcctt ctttactcat tctgtcattc agctgcattt 3060 tgacaggaaa aacccattac atttcgagaa gaagttatga gactttgccc attaggtggg 3120 tctagctctt tttttttttt ttggagacgg agttttgctc ttgttgccca ggctggagtg 3180 caatggcacg atctcagctc actgcaacct ctgcttcccg ggttcaagtg attctcctgc 3240 ctcagcctcc caagtggctg gaattacaag catgcgccac catgcccagc taattttata 3300 tttttagtag agatggggtt tctccatgtt gggcaggctg gtctcaaact cccgacctca 3360 ggtgatctgc ctgcctcggc ctcccaaagt gctgggatta caggcatgag ccactgcgcc 3420 gggctttttt ttttcgagat ggagtctcac tctgtcgtcc aggctggagt gcagtggcat 3480 gatctcagct cactgcaacc tctgccttct gggttcaaac aattttcctg cctcagcctc 3540 ctgagtagct gggattacag ccacctgcca ccataccagg ctaaattttg catttttagt 3600 agagatgggg tttcaccatg ttggccaggc tggttttgaa ttgacctcat gatctgcctg 3660 cctaggtctc ccaaagtgct gggattacag gtgtgagcca ctgcacccgg cccagctctt 3720 ctttatacaa taatggaaat gctaaaatga atgactcttc ctgctcactt aaacctgtgc 3780 tcaaaatgac atatttgtca ggcaccctct tcatttacct taaagaagga gagtttaatg 3840 tccatcttgg ttctgcccta tgaatcatct tgtcaagaac aggtgttctt atgcagaaac 3900 aatgaaaacc ttatactgaa gtgtgaaccc tggatttctt agtttcttct gagtcctaga 3960 agaagggttg gaatagaata atacatttac aggatttagg ttggttttct ttctgtccag 4020 tctcatctga atttcgtctg tctcttgtgg tccagaagtt ccacagagca acgcagctgc 4080 atgtggtgac aggtagagca gttaaagctg ccaataggaa ctcgtccata ttccacacac 4140 ctggtatagt gttatgccct ccatgggcac ttacctgcaa taagcagaag ccactgccac 4200 attcccgtgt attgggaaaa tggactactg tgtgcgaaca ggccctttac cctaatggca 4260 gggaagatgg attatctttg gccagtggag ctgccaatct agacatacac attcaactga 4320 atacaattaa aagcagttct ttaaatgcaa atataattac tcatctttat aatacaatag 4380 tattaactgc ccatatgctc atagtatgat gagccctgta tagcacaagg tcaacaggtc 4440 ctctccttgt ccttacaatc taaagcagat gacactgaca tggacaaaca agtgcacatg 4500 catagttgcg gcagttttag agaaatctag aaagctaggt agcaacacta tgcataaatg 4560 ttgtggtcca atgcattagt ttgctttaac aaaaatctgg gaggtatttt ttctctttat 4620 tcaggaaggc ttcatgaagc aggaagtggt caaaggaggg aaggttactg gttaaattat 4680 gataggaaga actttccata actagttgca aaattgagtg ctgggtgggt tgaggaatgg 4740 gaaaaagggg gagcaaggtg ttttgtgtag atggaacaaa gggcaaagga tagactgtaa 4800 ggaaggccag ataaagcttg gagtagcatg agaacttgag gaatagtatg atatgggctg 4860 tgcagcaggc agagagaatc accttagctg aaacatgggt gttaggagca gaccatgagg 4920 tggtagaacc atcatctata gtaaatcagg tactacgcta taactattga taaggaaaca 4980 gctgactgcc actgaaagaa taagcagttt taggggacta gctcctatgg gagataaagg 5040 tcagaaatcg tagtatctga tgaagatatt ttgatgagca ggtgagaaga aagataaaca 5100 tggccagatg gccaaggact gggataagta gccgtttcac attcaattag aattctgtgg 5160 ctggaataag atcagggaga gcagtaggaa gatatagtat tctataattc atagcttgtt 5220 gtgttagaga ttaattagga ttctgctgtt gaatcttagt acaaaaaaat ctaatattta 5280 ttaggaatta agggaagatg gtacttctgt tatgttgcct aagcagacag gaagctacaa 5340 gaaacaccag tctgaagcag tgcctcagga tctcagatga tttaggaagt gtgctgtaat 5400 gtcaaaaaaa aaaaaaagta ttgtctttag tatatctatg tatagtctcg tgggaaaagc 5460 attggttgtg gtatcaacag atattctggt tccagatgtc ttgtaagtta acctgcctcc 5520 atttcccttt ctgtaaagca aaataatgtt tacacctaat ctgtctctca gggataccat 5580 attaataaaa atcatgtcta taaagtg 5607 <210> 202 <211> 626 <212> PRT <213> homo sapiens <400> 202 Met Ala Asp Gln Arg Met Asp Ile Ser Ser Thr Ile Ser Asp Phe Met 1 5 10 15 Ser Pro Gly Pro Thr Asp Leu Leu Ser Ser Ser Leu Gly Thr Ser Gly 20 25 30 Val Asp Cys Asn Arg Lys Arg Lys Gly Ser Ser Thr Asp Tyr Gln Glu 35 40 45 Ser Met Asp Thr Asp Lys Asp Asp Pro His Gly Arg Leu Glu Tyr Thr 50 55 60 Glu His Gln Gly Arg Ile Lys Asn Ala Arg Glu Ala His Ser Gln Ile 65 70 75 80 Glu Lys Arg Arg Arg Asp Lys Met Asn Ser Phe Ile Asp Glu Leu Ala 85 90 95 Ser Leu Val Pro Thr Cys Asn Ala Met Ser Arg Lys Leu Asp Lys Leu 100 105 110 Thr Val Leu Arg Met Ala Val Gln His Met Lys Thr Leu Arg Gly Ala 115 120 125 Thr Asn Pro Tyr Thr Glu Ala Asn Tyr Lys Pro Thr Phe Leu Ser Asp 130 135 140 Asp Glu Leu Lys His Leu Ile Leu Arg Ala Ala Asp Gly Phe Leu Phe 145 150 155 160 Val Val Gly Cys Asp Arg Gly Lys Ile Leu Phe Val Ser Glu Ser Val 165 170 175 Phe Lys Ile Leu Asn Tyr Ser Gln Asn Asp Leu Ile Gly Gln Ser Leu 180 185 190 Phe Asp Tyr Leu His Pro Lys Asp Ile Ala Lys Val Lys Glu Gln Leu 195 200 205 Ser Ser Ser Asp Thr Ala Pro Arg Glu Arg Leu Ile Asp Ala Lys Thr 210 215 220 Gly Leu Pro Val Lys Thr Asp Ile Thr Pro Gly Pro Ser Arg Leu Cys 225 230 235 240 Ser Gly Ala Arg Arg Ser Phe Phe Cys Arg Met Lys Cys Asn Arg Pro 245 250 255 Ser Val Lys Val Glu Asp Lys Asp Phe Pro Ser Thr Cys Ser Lys Lys 260 265 270 Lys Ala Asp Arg Lys Ser Phe Cys Thr Ile His Ser Thr Gly Tyr Leu 275 280 285 Lys Ser Trp Pro Pro Thr Lys Met Gly Leu Asp Glu Asp Asn Glu Pro 290 295 300 Asp Asn Glu Gly Cys Asn Leu Ser Cys Leu Val Ala Ile Gly Arg Leu 305 310 315 320 His Ser His Val Val Pro Gln Pro Val Asn Gly Glu Ile Arg Val Lys 325 330 335 Ser Met Glu Tyr Val Ser Arg His Ala Ile Asp Gly Lys Phe Val Phe 340 345 350 Val Asp Gln Arg Ala Thr Ala Ile Leu Ala Tyr Leu Pro Gln Glu Leu 355 360 365 Leu Gly Thr Ser Cys Tyr Glu Tyr Phe His Gln Asp Asp Ile Gly His 370 375 380 Leu Ala Glu Cys His Arg Gln Val Leu Gln Thr Arg Glu Lys Ile Thr 385 390 395 400 Thr Asn Cys Tyr Lys Phe Lys Ile Lys Asp Gly Ser Phe Ile Thr Leu 405 410 415 Arg Ser Arg Trp Phe Ser Phe Met Asn Pro Trp Thr Lys Glu Val Glu 420 425 430 Tyr Ile Val Ser Thr Asn Thr Val Val Leu Ala Asn Val Leu Glu Gly 435 440 445 Gly Asp Pro Thr Phe Pro Gln Leu Thr Ala Ser Pro His Ser Met Asp 450 455 460 Ser Met Leu Pro Ser Gly Glu Gly Gly Pro Lys Arg Thr His Pro Thr 465 470 475 480 Val Pro Gly Ile Pro Gly Gly Thr Arg Ala Gly Ala Gly Lys Ile Gly 485 490 495 Arg Met Ile Ala Glu Glu Ile Met Glu Ile His Arg Ile Arg Gly Ser 500 505 510 Ser Pro Ser Ser Cys Gly Ser Ser Pro Leu Asn Ile Thr Ser Thr Pro 515 520 525 Pro Pro Asp Ala Ser Ser Pro Gly Gly Lys Lys Ile Leu Asn Gly Gly 530 535 540 Thr Pro Asp Ile Pro Ser Ser Gly Leu Leu Ser Gly Gln Ala Gln Glu 545 550 555 560 Asn Pro Gly Tyr Pro Tyr Ser Asp Ser Ser Ser Ile Leu Gly Glu Asn 565 570 575 Pro His Ile Gly Ile Asp Met Ile Asp Asn Asp Gln Gly Ser Ser Ser 580 585 590 Pro Ser Asn Asp Glu Ala Ala Met Ala Val Ile Met Ser Leu Leu Glu 595 600 605 Ala Asp Ala Gly Leu Gly Gly Pro Val Asp Phe Ser Asp Leu Pro Trp 610 615 620 Pro Leu 625 <210> 203 <211> 333 <212> PRT <213> homo sapiens <400> 203 Met Leu Phe Leu Gln Phe Leu Leu Leu Ala Leu Leu Leu Pro Gly Gly 1 5 10 15 Asp Asn Ala Asp Ala Ser Gln Glu His Val Ser Phe His Val Ile Gln 20 25 30 Ile Phe Ser Phe Val Asn Gln Ser Trp Ala Arg Gly Gln Gly Ser Gly 35 40 45 Trp Leu Asp Glu Leu Gln Thr His Gly Trp Asp Ser Glu Ser Gly Thr 50 55 60 Ile Ile Phe Leu His Asn Trp Ser Lys Gly Asn Phe Ser Asn Glu Glu 65 70 75 80 Leu Ser Asp Leu Glu Leu Leu Phe Arg Phe Tyr Leu Phe Gly Leu Thr 85 90 95 Arg Glu Ile Gln Asp His Ala Ser Gln Asp Tyr Ser Lys Tyr Pro Phe 100 105 110 Glu Val Gln Val Lys Ala Gly Cys Glu Leu His Ser Gly Lys Ser Pro 115 120 125 Glu Gly Phe Phe Gln Val Ala Phe Asn Gly Leu Asp Leu Leu Ser Phe 130 135 140 Gln Asn Thr Thr Trp Val Pro Ser Pro Gly Cys Gly Ser Leu Ala Gln 145 150 155 160 Ser Val Cys His Leu Leu Asn His Gln Tyr Glu Gly Val Thr Glu Thr 165 170 175 Val Tyr Asn Leu Ile Arg Ser Thr Cys Pro Arg Phe Leu Leu Gly Leu 180 185 190 Leu Asp Ala Gly Lys Met Tyr Val His Arg Gln Val Arg Pro Glu Ala 195 200 205 Trp Leu Ser Ser Arg Pro Ser Leu Gly Ser Gly Gln Leu Leu Leu Val 210 215 220 Cys His Ala Ser Gly Phe Tyr Pro Lys Pro Val Trp Val Thr Trp Met 225 230 235 240 Arg Asn Glu Gln Glu Gln Leu Gly Thr Lys His Gly Asp Ile Leu Pro 245 250 255 Asn Ala Asp Gly Thr Trp Tyr Leu Gln Val Ile Leu Glu Val Ala Ser 260 265 270 Glu Glu Pro Ala Gly Leu Ser Cys Arg Val Arg His Ser Ser Leu Gly 275 280 285 Gly Gln Asp Ile Ile Leu Tyr Trp Gly His His Phe Ser Met Asn Trp 290 295 300 Ile Ala Leu Val Val Ile Val Pro Leu Val Ile Leu Ile Val Leu Val 305 310 315 320 Leu Trp Phe Lys Lys His Cys Ser Tyr Gln Asp Ile Leu 325 330 <210> 204 <211> 270 <212> PRT <213> homo sapiens <400> 204 Met Gln Tyr Pro His Pro Gly Pro Ala Ala Gly Ala Val Gly Val Pro 1 5 10 15 Leu Tyr Ala Pro Thr Pro Leu Leu Gln Pro Ala His Pro Thr Pro Phe 20 25 30 Tyr Ile Glu Asp Ile Leu Gly Arg Gly Pro Ala Ala Pro Thr Pro Ala 35 40 45 Pro Thr Leu Pro Ser Pro Asn Ser Ser Phe Thr Ser Leu Val Ser Pro 50 55 60 Tyr Arg Thr Pro Val Tyr Glu Pro Thr Pro Ile His Pro Ala Phe Ser 65 70 75 80 His His Ser Ala Ala Ala Leu Ala Ala Ala Tyr Gly Pro Gly Gly Phe 85 90 95 Gly Gly Pro Leu Tyr Pro Phe Pro Arg Thr Val Asn Asp Tyr Thr His 100 105 110 Ala Leu Leu Arg His Asp Pro Leu Gly Lys Pro Leu Leu Trp Ser Pro 115 120 125 Phe Leu Gln Arg Pro Leu His Lys Arg Lys Gly Gly Gln Val Arg Phe 130 135 140 Ser Asn Asp Gln Thr Ile Glu Leu Glu Lys Lys Phe Glu Thr Gln Lys 145 150 155 160 Tyr Leu Ser Pro Pro Glu Arg Lys Arg Leu Ala Lys Met Leu Gln Leu 165 170 175 Ser Glu Arg Gln Val Lys Thr Trp Phe Gln Asn Arg Arg Ala Lys Trp 180 185 190 Arg Arg Leu Lys Gln Glu Asn Pro Gln Ser Asn Lys Lys Glu Glu Leu 195 200 205 Glu Ser Leu Asp Ser Ser Cys Asp Gln Arg Gln Asp Leu Pro Ser Glu 210 215 220 Gln Asn Lys Gly Ala Ser Leu Asp Ser Ser Gln Cys Ser Pro Ser Pro 225 230 235 240 Ala Ser Gln Glu Asp Leu Glu Ser Glu Ile Ser Glu Asp Ser Asp Gln 245 250 255 Glu Val Asp Ile Glu Gly Asp Lys Ser Tyr Phe Asn Ala Gly 260 265 270 <210> 205 <211> 195 <212> PRT <213> homo sapiens <400> 205 Met Thr Asp Ser Val Ile Tyr Ser Met Leu Glu Leu Pro Thr Ala Thr 1 5 10 15 Gln Ala Gln Asn Asp Tyr Gly Pro Gln Gln Lys Ser Ser Ser Ser Arg 20 25 30 Pro Ser Cys Ser Cys Leu Val Ala Ile Ala Leu Gly Leu Leu Thr Ala 35 40 45 Val Leu Leu Ser Val Leu Leu Tyr Gln Trp Ile Leu Cys Gln Gly Ser 50 55 60 Asn Tyr Ser Thr Cys Ala Ser Cys Pro Ser Cys Pro Asp Arg Trp Met 65 70 75 80 Lys Tyr Gly Asn His Cys Tyr Tyr Phe Ser Val Glu Glu Lys Asp Trp 85 90 95 Asn Ser Ser Leu Glu Phe Cys Leu Ala Arg Asp Ser His Leu Leu Val 100 105 110 Ile Thr Asp Asn Gln Glu Met Ser Leu Leu Gln Val Phe Leu Ser Glu 115 120 125 Ala Phe Cys Trp Ile Gly Leu Arg Asn Asn Ser Gly Trp Arg Trp Glu 130 135 140 Asp Gly Ser Pro Leu Asn Phe Ser Arg Ile Ser Ser Asn Ser Phe Val 145 150 155 160 Gln Thr Cys Gly Ala Ile Asn Lys Asn Gly Leu Gln Ala Ser Ser Cys 165 170 175 Glu Val Pro Leu His Trp Val Cys Lys Lys Cys Pro Phe Ala Asp Gln 180 185 190 Ala Leu Phe 195 <210> 206 <211> 607 <212> PRT <213> homo sapiens <400> 206 Met Ile Leu Leu Thr Phe Ser Thr Gly Arg Arg Leu Asp Phe Val His 1 5 10 15 His Ser Gly Val Phe Phe Leu Gln Thr Leu Leu Trp Ile Leu Cys Ala 20 25 30 Thr Val Cys Gly Thr Glu Gln Tyr Phe Asn Val Glu Val Trp Leu Gln 35 40 45 Lys Tyr Gly Tyr Leu Pro Pro Thr Asp Pro Arg Met Ser Val Leu Arg 50 55 60 Ser Ala Glu Thr Met Gln Ser Ala Leu Ala Ala Met Gln Gln Phe Tyr 65 70 75 80 Gly Ile Asn Met Thr Gly Lys Val Asp Arg Asn Thr Ile Asp Trp Met 85 90 95 Lys Lys Pro Arg Cys Gly Val Pro Asp Gln Thr Arg Gly Ser Ser Lys 100 105 110 Phe His Ile Arg Arg Lys Arg Tyr Ala Leu Thr Gly Gln Lys Trp Gln 115 120 125 His Lys His Ile Thr Tyr Ser Ile Lys Asn Val Thr Pro Lys Val Gly 130 135 140 Asp Pro Glu Thr Arg Lys Ala Ile Arg Arg Ala Phe Asp Val Trp Gln 145 150 155 160 Asn Val Thr Pro Leu Thr Phe Glu Glu Val Pro Tyr Ser Glu Leu Glu 165 170 175 Asn Gly Lys Arg Asp Val Asp Ile Thr Ile Ile Phe Ala Ser Gly Phe 180 185 190 His Gly Asp Ser Ser Pro Phe Asp Gly Glu Gly Gly Phe Leu Ala His 195 200 205 Ala Tyr Phe Pro Gly Pro Gly Ile Gly Gly Asp Thr His Phe Asp Ser 210 215 220 Asp Glu Pro Trp Thr Leu Gly Asn Pro Asn His Asp Gly Asn Asp Leu 225 230 235 240 Phe Leu Val Ala Val His Glu Leu Gly His Ala Leu Gly Leu Glu His 245 250 255 Ser Asn Asp Pro Thr Ala Ile Met Ala Pro Phe Tyr Gln Tyr Met Glu 260 265 270 Thr Asp Asn Phe Lys Leu Pro Asn Asp Asp Leu Gln Gly Ile Gln Lys 275 280 285 Ile Tyr Gly Pro Pro Asp Lys Ile Pro Pro Pro Thr Arg Pro Leu Pro 290 295 300 Thr Val Pro Pro His Arg Ser Ile Pro Pro Ala Asp Pro Arg Lys Asn 305 310 315 320 Asp Arg Pro Lys Pro Pro Arg Pro Pro Thr Gly Arg Pro Ser Tyr Pro 325 330 335 Gly Ala Lys Pro Asn Ile Cys Asp Gly Asn Phe Asn Thr Leu Ala Ile 340 345 350 Leu Arg Arg Glu Met Phe Val Phe Lys Asp Gln Trp Phe Trp Arg Val 355 360 365 Arg Asn Asn Arg Val Met Asp Gly Tyr Pro Met Gln Ile Thr Tyr Phe 370 375 380 Trp Arg Gly Leu Pro Pro Ser Ile Asp Ala Val Tyr Glu Asn Ser Asp 385 390 395 400 Gly Asn Phe Val Phe Phe Lys Gly Asn Lys Tyr Trp Val Phe Lys Asp 405 410 415 Thr Thr Leu Gln Pro Gly Tyr Pro His Asp Leu Ile Thr Leu Gly Ser 420 425 430 Gly Ile Pro Pro His Gly Ile Asp Ser Ala Ile Trp Trp Glu Asp Val 435 440 445 Gly Lys Thr Tyr Phe Phe Lys Gly Asp Arg Tyr Trp Arg Tyr Ser Glu 450 455 460 Glu Met Lys Thr Met Asp Pro Gly Tyr Pro Lys Pro Ile Thr Val Trp 465 470 475 480 Lys Gly Ile Pro Glu Ser Pro Gln Gly Ala Phe Val His Lys Glu Asn 485 490 495 Gly Phe Thr Tyr Phe Tyr Lys Gly Lys Glu Tyr Trp Lys Phe Asn Asn 500 505 510 Gln Ile Leu Lys Val Glu Pro Gly Tyr Pro Arg Ser Ile Leu Lys Asp 515 520 525 Phe Met Gly Cys Asp Gly Pro Thr Asp Arg Val Lys Glu Gly His Ser 530 535 540 Pro Pro Asp Asp Val Asp Ile Val Ile Lys Leu Asp Asn Thr Ala Ser 545 550 555 560 Thr Val Lys Ala Ile Ala Ile Val Ile Pro Cys Ile Leu Ala Leu Cys 565 570 575 Leu Leu Val Leu Val Tyr Thr Val Phe Gln Phe Lys Arg Lys Gly Thr 580 585 590 Pro Arg His Ile Leu Tyr Cys Lys Arg Ser Met Gln Glu Trp Val 595 600 605 <210> 207 <211> 821 <212> PRT <213> homo sapiens <400> 207 Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 1 5 10 15 Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 20 25 30 Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 35 40 45 Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 50 55 60 Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 65 70 75 80 Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 85 90 95 Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 100 105 110 Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 115 120 125 Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 130 135 140 Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 145 150 155 160 Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 165 170 175 Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 180 185 190 Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 195 200 205 Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 210 215 220 Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 225 230 235 240 Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 245 250 255 Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 260 265 270 Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 275 280 285 Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 290 295 300 Gly Leu Pro Tyr Leu Lys Val Leu Lys Ala Ala Gly Val Asn Thr Thr 305 310 315 320 Asp Lys Glu Ile Glu Val Leu Tyr Ile Arg Asn Val Thr Phe Glu Asp 325 330 335 Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Ile Ser Phe 340 345 350 His Ser Ala Trp Leu Thr Val Leu Pro Ala Pro Gly Arg Glu Lys Glu 355 360 365 Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile Gly 370 375 380 Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg Met 385 390 395 400 Lys Asn Thr Thr Lys Lys Pro Asp Phe Ser Ser Gln Pro Ala Val His 405 410 415 Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala 420 425 430 Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile Thr 435 440 445 Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val Ser 450 455 460 Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp Lys 465 470 475 480 Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val 485 490 495 Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala Val 500 505 510 Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp Leu 515 520 525 Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys His 530 535 540 Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu 545 550 555 560 Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu 565 570 575 Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn Arg 580 585 590 Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr Tyr 595 600 605 Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile His 610 615 620 Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val Met 625 630 635 640 Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp Tyr 645 650 655 Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro 660 665 670 Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp Ser 675 680 685 Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr 690 695 700 Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His 705 710 715 720 Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met Met 725 730 735 Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln 740 745 750 Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu Glu 755 760 765 Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr Pro 770 775 780 Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser Pro 785 790 795 800 Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile Asn 805 810 815 Gly Ser Val Lys Thr 820 <210> 208 <211> 480 <212> PRT <213> homo sapiens <400> 208 Met Glu Val Ala Pro Glu Gln Pro Arg Trp Met Ala His Pro Ala Val 1 5 10 15 Leu Asn Ala Gln His Pro Asp Ser His His Pro Gly Leu Ala His Asn 20 25 30 Tyr Met Glu Pro Ala Gln Leu Leu Pro Pro Asp Glu Val Asp Val Phe 35 40 45 Phe Asn His Leu Asp Ser Gln Gly Asn Pro Tyr Tyr Ala Asn Pro Ala 50 55 60 His Ala Arg Ala Arg Val Ser Tyr Ser Pro Ala His Ala Arg Leu Thr 65 70 75 80 Gly Gly Gln Met Cys Arg Pro His Leu Leu His Ser Pro Gly Leu Pro 85 90 95 Trp Leu Asp Gly Gly Lys Ala Ala Leu Ser Ala Ala Ala Ala His His 100 105 110 His Asn Pro Trp Thr Val Ser Pro Phe Ser Lys Thr Pro Leu His Pro 115 120 125 Ser Ala Ala Gly Gly Pro Gly Gly Pro Leu Ser Val Tyr Pro Gly Ala 130 135 140 Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Ser Val Ala Ser Leu Thr 145 150 155 160 Pro Thr Ala Ala His Ser Gly Ser His Leu Phe Gly Phe Pro Pro Thr 165 170 175 Pro Pro Lys Glu Val Ser Pro Asp Pro Ser Thr Thr Gly Ala Ala Ser 180 185 190 Pro Ala Ser Ser Ser Ala Gly Gly Ser Ala Ala Arg Gly Glu Asp Lys 195 200 205 Asp Gly Val Lys Tyr Gln Val Ser Leu Thr Glu Ser Met Lys Met Glu 210 215 220 Ser Gly Ser Pro Leu Arg Pro Gly Leu Ala Thr Met Gly Thr Gln Pro 225 230 235 240 Ala Thr His His Pro Ile Pro Thr Tyr Pro Ser Tyr Val Pro Ala Ala 245 250 255 Ala His Asp Tyr Ser Ser Gly Leu Phe His Pro Gly Gly Phe Leu Gly 260 265 270 Gly Pro Ala Ser Ser Phe Thr Pro Lys Gln Arg Ser Lys Ala Arg Ser 275 280 285 Cys Ser Glu Gly Arg Glu Cys Val Asn Cys Gly Ala Thr Ala Thr Pro 290 295 300 Leu Trp Arg Arg Asp Gly Thr Gly His Tyr Leu Cys Asn Ala Cys Gly 305 310 315 320 Leu Tyr His Lys Met Asn Gly Gln Asn Arg Pro Leu Ile Lys Pro Lys 325 330 335 Arg Arg Leu Ser Ala Ala Arg Arg Ala Gly Thr Cys Cys Ala Asn Cys 340 345 350 Gln Thr Thr Thr Thr Thr Leu Trp Arg Arg Asn Ala Asn Gly Asp Pro 355 360 365 Val Cys Asn Ala Cys Gly Leu Tyr Tyr Lys Leu His Asn Val Asn Arg 370 375 380 Pro Leu Thr Met Lys Lys Glu Gly Ile Gln Thr Arg Asn Arg Lys Met 385 390 395 400 Ser Asn Lys Ser Lys Lys Ser Lys Lys Gly Ala Glu Cys Phe Glu Glu 405 410 415 Leu Ser Lys Cys Met Gln Glu Lys Ser Ser Pro Phe Ser Ala Ala Ala 420 425 430 Leu Ala Gly His Met Ala Pro Val Gly His Leu Pro Pro Phe Ser His 435 440 445 Ser Gly His Ile Leu Pro Thr Pro Thr Pro Ile His Pro Ser Ser Ser 450 455 460 Leu Ser Phe Gly His Pro His Pro Ser Ser Met Val Thr Ala Met Gly 465 470 475 480 <210> 209 <211> 265 <212> PRT <213> homo sapiens <400> 209 Met Gly Ser Pro Ser Ala Cys Pro Tyr Arg Val Cys Ile Pro Trp Gln 1 5 10 15 Gly Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Leu Pro Asn 20 25 30 Ser Ala Gln Thr Asn Ile Asp Val Val Pro Phe Asn Val Ala Glu Gly 35 40 45 Lys Glu Val Leu Leu Val Val His Asn Glu Ser Gln Asn Leu Tyr Gly 50 55 60 Tyr Asn Trp Tyr Lys Gly Glu Arg Val His Ala Asn Tyr Arg Ile Ile 65 70 75 80 Gly Tyr Val Lys Asn Ile Ser Gln Glu Asn Ala Pro Gly Pro Ala His 85 90 95 Asn Gly Arg Glu Thr Ile Tyr Pro Asn Gly Thr Leu Leu Ile Gln Asn 100 105 110 Val Thr His Asn Asp Ala Gly Phe Tyr Thr Leu His Val Ile Lys Glu 115 120 125 Asn Leu Val Asn Glu Glu Val Thr Arg Gln Phe Tyr Val Phe Ser Glu 130 135 140 Pro Pro Lys Pro Ser Ile Thr Ser Asn Asn Phe Asn Pro Val Glu Asn 145 150 155 160 Lys Asp Ile Val Val Leu Thr Cys Gln Pro Glu Thr Gln Asn Thr Thr 165 170 175 Tyr Leu Trp Trp Val Asn Asn Gln Ser Leu Leu Val Ser Pro Arg Leu 180 185 190 Leu Leu Ser Thr Asp Asn Arg Thr Leu Val Leu Leu Ser Ala Thr Lys 195 200 205 Asn Asp Ile Gly Pro Tyr Glu Cys Glu Ile Gln Asn Pro Val Gly Ala 210 215 220 Ser Arg Ser Asp Pro Val Thr Leu Asn Val Arg Tyr Glu Ser Val Gln 225 230 235 240 Ala Ser Ser Pro Asp Leu Ser Ala Gly Thr Ala Val Ser Ile Met Ile 245 250 255 Gly Val Leu Ala Gly Met Ala Leu Ile 260 265 <210> 210 <211> 298 <212> PRT <213> homo sapiens <400> 210 Met Lys Thr Leu Gln Ser Thr Leu Leu Leu Leu Leu Leu Val Pro Leu 1 5 10 15 Ile Lys Pro Ala Pro Pro Thr Gln Gln Asp Ser Arg Ile Ile Tyr Asp 20 25 30 Tyr Gly Thr Asp Asn Phe Glu Glu Ser Ile Phe Ser Gln Asp Tyr Glu 35 40 45 Asp Lys Tyr Leu Asp Gly Lys Asn Ile Lys Glu Lys Glu Thr Val Ile 50 55 60 Ile Pro Asn Glu Lys Ser Leu Gln Leu Gln Lys Asp Glu Ala Ile Thr 65 70 75 80 Pro Leu Pro Pro Lys Lys Glu Asn Asp Glu Met Pro Thr Cys Leu Leu 85 90 95 Cys Val Cys Leu Ser Gly Ser Val Tyr Cys Glu Glu Val Asp Ile Asp 100 105 110 Ala Val Pro Pro Leu Pro Lys Glu Ser Ala Tyr Leu Tyr Ala Arg Phe 115 120 125 Asn Lys Ile Lys Lys Leu Thr Ala Lys Asp Phe Ala Asp Ile Pro Asn 130 135 140 Leu Arg Arg Leu Asp Phe Thr Gly Asn Leu Ile Glu Asp Ile Glu Asp 145 150 155 160 Gly Thr Phe Ser Lys Leu Ser Leu Leu Glu Glu Leu Ser Leu Ala Glu 165 170 175 Asn Gln Leu Leu Lys Leu Pro Val Leu Pro Pro Lys Leu Thr Leu Phe 180 185 190 Asn Ala Lys Tyr Asn Lys Ile Lys Ser Arg Gly Ile Lys Ala Asn Ala 195 200 205 Phe Lys Lys Leu Asn Asn Leu Thr Phe Leu Tyr Leu Asp His Asn Ala 210 215 220 Leu Glu Ser Val Pro Leu Asn Leu Pro Glu Ser Leu Arg Val Ile His 225 230 235 240 Leu Gln Phe Asn Asn Ile Ala Ser Ile Thr Asp Asp Thr Phe Cys Lys 245 250 255 Ala Asn Asp Thr Ser Tyr Ile Arg Asp Arg Ile Glu Glu Ile Arg Leu 260 265 270 Glu Gly Asn Pro Ile Val Leu Gly Lys His Pro Asn Ser Phe Ile Cys 275 280 285 Leu Lys Arg Leu Pro Ile Gly Ser Tyr Phe 290 295 <210> 211 <211> 359 <212> PRT <213> homo sapiens <400> 211 Met Ile Leu Asn Ser Ser Thr Glu Asp Gly Ile Lys Arg Ile Gln Asp 1 5 10 15 Asp Cys Pro Lys Ala Gly Arg His Asn Tyr Ile Phe Val Met Ile Pro 20 25 30 Thr Leu Tyr Ser Ile Ile Phe Val Val Gly Ile Phe Gly Asn Ser Leu 35 40 45 Val Val Ile Val Ile Tyr Phe Tyr Met Lys Leu Lys Thr Val Ala Ser 50 55 60 Val Phe Leu Leu Asn Leu Ala Leu Ala Asp Leu Cys Phe Leu Leu Thr 65 70 75 80 Leu Pro Leu Trp Ala Val Tyr Thr Ala Met Glu Tyr Arg Trp Pro Phe 85 90 95 Gly Asn Tyr Leu Cys Lys Ile Ala Ser Ala Ser Val Ser Phe Asn Leu 100 105 110 Tyr Ala Ser Val Phe Leu Leu Thr Cys Leu Ser Ile Asp Arg Tyr Leu 115 120 125 Ala Ile Val His Pro Met Lys Ser Arg Leu Arg Arg Thr Met Leu Val 130 135 140 Ala Lys Val Thr Cys Ile Ile Ile Trp Leu Leu Ala Gly Leu Ala Ser 145 150 155 160 Leu Pro Ala Ile Ile His Arg Asn Val Phe Phe Ile Glu Asn Thr Asn 165 170 175 Ile Thr Val Cys Ala Phe His Tyr Glu Ser Gln Asn Ser Thr Leu Pro 180 185 190 Ile Gly Leu Gly Leu Thr Lys Asn Ile Leu Gly Phe Leu Phe Pro Phe 195 200 205 Leu Ile Ile Leu Thr Ser Tyr Thr Leu Ile Trp Lys Ala Leu Lys Lys 210 215 220 Ala Tyr Glu Ile Gln Lys Asn Lys Pro Arg Asn Asp Asp Ile Phe Lys 225 230 235 240 Ile Ile Met Ala Ile Val Leu Phe Phe Phe Phe Ser Trp Ile Pro His 245 250 255 Gln Ile Phe Thr Phe Leu Asp Val Leu Ile Gln Leu Gly Ile Ile Arg 260 265 270 Asp Cys Arg Ile Ala Asp Ile Val Asp Thr Ala Met Pro Ile Thr Ile 275 280 285 Cys Ile Ala Tyr Phe Asn Asn Cys Leu Asn Pro Leu Phe Tyr Gly Phe 290 295 300 Leu Gly Lys Lys Phe Lys Arg Tyr Phe Leu Gln Leu Leu Lys Tyr Ile 305 310 315 320 Pro Pro Lys Ala Lys Ser His Ser Asn Leu Ser Thr Lys Met Ser Thr 325 330 335 Leu Ser Tyr Arg Pro Ser Asp Asn Val Ser Ser Ser Thr Lys Lys Pro 340 345 350 Ala Pro Cys Phe Glu Val Glu 355 <210> 212 <211> 453 <212> PRT <213> homo sapiens <400> 212 Met Gly Arg Thr Arg Glu Ala Gly Cys Val Ala Ala Gly Val Val Ile 1 5 10 15 Gly Ala Gly Ala Cys Tyr Cys Val Tyr Arg Leu Ala Trp Gly Arg Asp 20 25 30 Glu Asn Glu Lys Ile Trp Asp Glu Asp Glu Glu Ser Thr Asp Thr Ser 35 40 45 Glu Ile Gly Val Glu Thr Val Lys Gly Ala Lys Thr Asn Ala Gly Ala 50 55 60 Gly Ser Gly Ala Lys Leu Gln Gly Asp Ser Glu Val Lys Pro Glu Val 65 70 75 80 Ser Leu Gly Leu Glu Asp Cys Pro Gly Val Lys Glu Lys Ala His Ser 85 90 95 Gly Ser His Ser Gly Gly Gly Leu Glu Ala Lys Ala Lys Ala Leu Phe 100 105 110 Asn Thr Leu Lys Glu Gln Ala Ser Ala Lys Ala Gly Lys Gly Ala Arg 115 120 125 Val Gly Thr Ile Ser Gly Asn Arg Thr Leu Ala Pro Ser Leu Pro Cys 130 135 140 Pro Gly Gly Arg Gly Gly Gly Cys His Pro Thr Arg Ser Gly Ser Arg 145 150 155 160 Ala Gly Gly Arg Ala Ser Gly Lys Ser Lys Gly Lys Ala Arg Ser Lys 165 170 175 Ser Thr Arg Ala Pro Ala Thr Thr Trp Pro Val Arg Arg Gly Lys Phe 180 185 190 Asn Phe Pro Tyr Lys Ile Asp Asp Ile Leu Ser Ala Pro Asp Leu Gln 195 200 205 Lys Val Leu Asn Ile Leu Glu Arg Thr Asn Asp Pro Phe Ile Gln Glu 210 215 220 Val Ala Leu Val Thr Leu Gly Asn Asn Ala Ala Tyr Ser Phe Asn Gln 225 230 235 240 Asn Ala Ile Arg Glu Leu Gly Gly Val Pro Ile Ile Ala Lys Leu Ile 245 250 255 Lys Thr Lys Asp Pro Ile Ile Arg Glu Lys Thr Tyr Asn Ala Leu Asn 260 265 270 Asn Leu Ser Val Asn Ala Glu Asn Gln Gly Lys Ile Lys Thr Tyr Ile 275 280 285 Ser Gln Val Cys Asp Asp Thr Met Val Cys Arg Leu Asp Ser Ala Val 290 295 300 Gln Met Ala Gly Leu Arg Leu Leu Thr Asn Met Thr Val Thr Asn His 305 310 315 320 Tyr Gln His Leu Leu Ser Tyr Ser Phe Pro Asp Phe Phe Ala Leu Leu 325 330 335 Phe Leu Gly Asn His Phe Thr Lys Ile Gln Ile Met Lys Leu Ile Ile 340 345 350 Asn Phe Thr Glu Asn Pro Ala Met Thr Arg Glu Leu Val Ser Cys Lys 355 360 365 Val Pro Ser Glu Leu Ile Ser Leu Phe Asn Lys Glu Trp Asp Arg Glu 370 375 380 Ile Leu Leu Asn Ile Leu Thr Leu Phe Glu Asn Ile Asn Asp Asn Ile 385 390 395 400 Lys Asn Glu Gly Leu Ala Ser Ser Arg Lys Glu Phe Ser Arg Ser Ser 405 410 415 Leu Phe Phe Leu Phe Lys Glu Ser Gly Val Cys Val Lys Lys Ile Lys 420 425 430 Ala Leu Ala Asn His Asn Asp Leu Val Val Lys Val Lys Val Leu Lys 435 440 445 Val Leu Thr Lys Leu 450 <210> 213 <211> 122 <212> PRT <213> homo sapiens <400> 213 Met Val Pro Gly Pro Pro Glu Ser Val Val Arg Phe Phe Leu Trp Phe 1 5 10 15 Cys Phe Leu Leu Pro Pro Thr Arg Lys Ala Ser Cys Asp Pro Arg Asp 20 25 30 Leu Lys Ser Cys Asn Arg Pro Cys Val Trp Ser Arg Leu Leu Lys Pro 35 40 45 Asn Ser Ser Leu Ser Asn Leu Glu Thr Ala Tyr Phe Pro Gln Ile Leu 50 55 60 Arg Phe Leu Arg Pro Trp Tyr Phe Ser Arg Ser His Leu Asn Tyr His 65 70 75 80 Gln Lys Ala Pro Ala Arg Trp Glu Trp Leu Tyr Ser Ile Tyr Arg Lys 85 90 95 Gly Thr Lys Ala Gln Arg Arg Asn Val Leu Arg Ser Pro Cys Ala Pro 100 105 110 Pro Gln Pro Ser Trp Pro Cys Ser Val Ile 115 120 <210> 214 <211> 641 <212> PRT <213> homo sapiens <400> 214 Met Asp Gly Leu Gln Ala Ser Ala Gly Pro Leu Arg Arg Gly Arg Pro 1 5 10 15 Lys Arg Arg Arg Lys Pro Gln Pro His Ser Gly Ser Val Leu Ala Leu 20 25 30 Pro Leu Arg Ser Arg Lys Ile Arg Lys Gln Leu Arg Ser Val Val Ser 35 40 45 Arg Met Ala Ala Leu Arg Thr Gln Thr Leu Pro Ser Glu Asn Ser Glu 50 55 60 Glu Ser Arg Val Glu Ser Thr Ala Asp Asp Leu Gly Asp Ala Leu Pro 65 70 75 80 Gly Gly Ala Ala Val Ala Ala Val Pro Asp Ala Ala Arg Arg Glu Pro 85 90 95 Tyr Gly His Leu Gly Pro Ala Glu Leu Leu Glu Ala Ser Pro Ala Ala 100 105 110 Arg Ser Leu Gln Thr Pro Ser Ala Arg Leu Val Pro Ala Ser Ala Pro 115 120 125 Pro Ala Arg Leu Val Glu Val Pro Ala Ala Pro Val Arg Val Val Glu 130 135 140 Thr Ser Ala Leu Leu Cys Thr Ala Gln His Leu Ala Ala Val Gln Ser 145 150 155 160 Ser Gly Ala Pro Ala Thr Ala Ser Gly Pro Gln Val Asp Asn Thr Gly 165 170 175 Gly Glu Pro Ala Trp Asp Ser Pro Leu Arg Arg Val Leu Ala Glu Leu 180 185 190 Asn Arg Ile Pro Ser Ser Arg Arg Arg Ala Ala Arg Leu Phe Glu Trp 195 200 205 Leu Ile Ala Pro Met Pro Pro Asp His Phe Tyr Arg Arg Leu Trp Glu 210 215 220 Arg Glu Ala Val Leu Val Arg Arg Gln Asp His Thr Tyr Tyr Gln Gly 225 230 235 240 Leu Phe Ser Thr Ala Asp Leu Asp Ser Met Leu Arg Asn Glu Glu Val 245 250 255 Gln Phe Gly Gln His Leu Asp Ala Ala Arg Tyr Ile Asn Gly Arg Arg 260 265 270 Glu Thr Leu Asn Pro Pro Gly Arg Ala Leu Pro Ala Ala Ala Trp Ser 275 280 285 Leu Tyr Gln Ala Gly Cys Ser Leu Arg Leu Leu Cys Pro Gln Ala Phe 290 295 300 Ser Thr Thr Val Trp Gln Phe Leu Ala Val Leu Gln Glu Gln Phe Gly 305 310 315 320 Ser Met Ala Gly Ser Asn Val Tyr Leu Thr Pro Pro Asn Ser Gln Gly 325 330 335 Phe Ala Pro His Tyr Asp Asp Ile Glu Ala Phe Val Leu Gln Leu Glu 340 345 350 Gly Arg Lys Leu Trp Arg Val Tyr Arg Pro Arg Val Pro Thr Glu Glu 355 360 365 Leu Ala Leu Thr Ser Ser Pro Asn Phe Ser Gln Asp Asp Leu Gly Glu 370 375 380 Pro Val Leu Gln Thr Val Leu Glu Pro Gly Asp Leu Leu Tyr Phe Pro 385 390 395 400 Arg Gly Phe Ile His Gln Ala Glu Cys Gln Asp Gly Val His Ser Leu 405 410 415 His Leu Thr Leu Ser Thr Tyr Gln Arg Asn Thr Trp Gly Asp Phe Leu 420 425 430 Glu Ala Ile Leu Pro Leu Ala Val Gln Ala Ala Met Glu Glu Asn Val 435 440 445 Glu Phe Arg Arg Gly Leu Pro Arg Asp Phe Met Asp Tyr Met Gly Ala 450 455 460 Gln His Ser Asp Ser Lys Asp Pro Arg Arg Thr Ala Phe Met Glu Lys 465 470 475 480 Val Arg Val Leu Val Ala Arg Leu Gly His Phe Ala Pro Val Asp Ala 485 490 495 Val Ala Asp Gln Arg Ala Lys Asp Phe Ile His Asp Ser Leu Pro Pro 500 505 510 Val Leu Thr Asp Arg Glu Arg Ala Leu Ser Val Tyr Gly Leu Pro Ile 515 520 525 Arg Trp Glu Ala Gly Glu Pro Val Asn Val Gly Ala Gln Leu Thr Thr 530 535 540 Glu Thr Glu Val His Met Leu Gln Asp Gly Ile Ala Arg Leu Val Gly 545 550 555 560 Glu Gly Gly His Leu Phe Leu Tyr Tyr Thr Val Glu Asn Ser Arg Val 565 570 575 Tyr His Leu Glu Glu Pro Lys Cys Leu Glu Ile Tyr Pro Gln Gln Ala 580 585 590 Asp Ala Met Glu Leu Leu Leu Gly Ser Tyr Pro Glu Phe Val Arg Val 595 600 605 Gly Asp Leu Pro Cys Asp Ser Val Glu Asp Gln Leu Ser Leu Ala Thr 610 615 620 Thr Leu Tyr Asp Lys Gly Leu Leu Leu Thr Lys Met Pro Leu Ala Leu 625 630 635 640 Asn <210> 215 <211> 867 <212> PRT <213> homo sapiens <400> 215 Met Thr Glu Asn Lys Thr Val Ser Ser Ser Ser Thr Arg Asp Asp Gln 1 5 10 15 Thr Asn Ile Gly Leu Thr Cys Gln Glu Val Lys Ala Leu Arg Glu Lys 20 25 30 Ala Trp Ser Arg Thr Asn Glu Gly Asn Ala Met Ser Gln Ser Leu Val 35 40 45 Leu Tyr Gly Ala Ser Lys Glu Asn Ser Glu Gly Phe His Glu Ser Lys 50 55 60 Met Thr Asn Thr Glu Gly Val Asn Lys Gly Ile Tyr Phe Ser Tyr Pro 65 70 75 80 Cys Arg Arg His Ser Cys Ala Val Val Asn Ile Pro Ala Pro Cys Val 85 90 95 Asn Lys Met Ile Ser His Ile Gln Asp Val Glu Ser Lys Ile Gln Glu 100 105 110 His Leu Lys Arg Phe Glu Thr Ser Phe Glu Glu Trp Ser Arg Thr Ser 115 120 125 Ser Thr Lys Asp Leu Lys Glu Asp Trp Ser Val Thr Thr Pro Val Lys 130 135 140 Glu Val Lys Pro Gly Glu Lys Arg Asp Glu Lys Cys Pro Glu Leu Lys 145 150 155 160 Gln Glu Met Glu Thr Leu Leu Ser Glu Ala Ile Arg Leu Ile Lys Ser 165 170 175 Leu Glu Thr Asp Arg Ala Asp Ala Glu Glu Ala Leu Lys Gln Gln Arg 180 185 190 Ser Arg Lys Asn Met Ile Asn Met Lys Ile Asp Ser Trp Ser Val Trp 195 200 205 Lys Leu Gln Glu Leu Pro Leu Ala Val Gln Lys Glu His Glu Ala Tyr 210 215 220 Leu Ser Asp Val Ile Glu Leu Gln Trp His Leu Glu Asp Lys Ala Asn 225 230 235 240 Gln Leu Gln His Phe Glu Lys Gln Lys Thr Glu Leu Glu Glu Ala Asn 245 250 255 Ala Lys Ile Gln Ala Asp Ile Asp Tyr Met Asn Glu His Gly Pro Leu 260 265 270 Leu Asp Ser Lys Gln Asn Gln Glu Leu Gln Asp Leu Lys Asn His Tyr 275 280 285 Lys Lys Lys Met Glu Val Met Asp Leu His Arg Lys Val Asn Glu Glu 290 295 300 Leu Glu Glu Ala Leu Glu Ala Cys Glu Asn Ala Arg Leu Lys Ala Gln 305 310 315 320 Gln Ile Lys Glu Glu Ile Asp Lys Asp Ile Tyr Gln Asp Glu Lys Thr 325 330 335 Ile Glu Ala Tyr Lys Arg Glu Ile Tyr Gln Leu Asn Ser Leu Phe Asp 340 345 350 His Tyr Ser Ser Ser Val Ile Asn Val Asn Thr Asn Ile Glu Glu Lys 355 360 365 Glu Glu Glu Val Thr Glu Ala Ile Arg Glu Thr Lys Ser Ser Lys Asn 370 375 380 Glu Leu His Ser Leu Ser Lys Met Leu Glu Asp Leu Arg Arg Val Tyr 385 390 395 400 Asp Gln Leu Thr Trp Lys Gln Lys Ser His Glu Asn Gln Tyr Leu Glu 405 410 415 Ala Val Asn Asp Phe Tyr Ala Ala Lys Lys Thr Trp Asp Ile Glu Leu 420 425 430 Ser Asp Val Ala Lys Asp Phe Ser Ala Ile Ser Leu Ala Cys Thr Lys 435 440 445 Leu Thr Glu Asp Asn Lys Lys Leu Glu Ile Asp Ile Asn Lys Ile Thr 450 455 460 Val Lys Thr Asn Glu Ser Ile Arg Lys Lys Ser Lys Tyr Glu Ser Glu 465 470 475 480 Ile Lys Tyr Leu Thr Ile Met Lys Leu Lys Asn Asp Lys His Leu Lys 485 490 495 Asn Ile Tyr Lys Glu Ala Tyr Arg Ile Gly Thr Leu Phe His Leu Thr 500 505 510 Lys His Lys Thr Asp Glu Met Glu Asp Lys Ile Ala Glu Val Arg Arg 515 520 525 Lys Phe Lys Gly Arg Glu Glu Phe Leu Lys Lys Leu Thr Gln Gly Glu 530 535 540 Val Ala Ala Gly Met Val Leu Gln Lys Lys Leu Tyr Ser Ile Tyr Glu 545 550 555 560 Val Gln Ala Leu Glu Arg Lys Glu Leu Ile Lys Asn Arg Ala Ile Cys 565 570 575 Ala Met Ser Leu Ala Glu Leu Gln Glu Pro Leu Leu Gln Leu Glu Asp 580 585 590 Glu Ala Glu Arg Ile Arg Ser Leu Asp Lys Glu His Ser Val Met Leu 595 600 605 Asn Asn Ile Ile Asp Gln Lys Asp Leu Ile Arg Arg Lys Val Gly Lys 610 615 620 Val Lys Lys Lys Leu Arg Lys Lys Gly Lys Lys Thr Leu Asp Ala Leu 625 630 635 640 Ile Glu Thr Glu Ser Lys Arg Ser Ala Ile Phe Lys Asp Leu Glu Ala 645 650 655 Thr Lys Ser Lys Thr Met Ile Phe Tyr Ala Lys Ile Asn Glu Leu Asn 660 665 670 Glu Glu Leu Lys Ala Lys Glu Glu Glu Lys Lys Ser Phe Asp Gln Thr 675 680 685 Leu Glu Ile Leu Lys Asn Lys Phe Ile Thr Met Arg Phe Lys Arg Glu 690 695 700 His Ala Gln Thr Val Phe Asp His Tyr Met Gln Glu Lys Lys Asp Cys 705 710 715 720 Glu Glu Arg Ile Phe Glu Glu Asp Gln Arg Phe Arg Val Leu Leu Ala 725 730 735 Val Arg Gln Lys Thr Leu Gln Asp Thr Gln Lys Ile Ile Ala Asp Ser 740 745 750 Leu Glu Glu Asn Leu Arg Leu Ala Gln Glu Tyr Gln Gln Leu Gln Ile 755 760 765 Thr Phe Leu Lys Glu Lys Asp Asn Tyr Phe Asn Ile Tyr Asp Lys Gln 770 775 780 Leu Ser Leu Asp Thr Ser Ile Arg Asp Lys Lys Gln Leu Cys Gln Leu 785 790 795 800 Gln Arg Arg Met His Thr Leu Trp Gln Glu His Phe Lys Leu Val Val 805 810 815 Leu Phe Ser Gln Met Arg Leu Ala Asn Phe Gln Thr Asp Ser Gln Glu 820 825 830 Ser Ile Gln Lys Ile Leu Ala Val Gln Glu Glu Ser Ser Asn Leu Met 835 840 845 Gln His Ile Leu Gly Phe Phe Gln Thr Leu Thr Asp Gly Thr Cys Glu 850 855 860 Asn Asp Gly 865 <210> 216 <211> 101 <212> PRT <213> homo sapiens <400> 216 Met Asp Gln Tyr Val Ser Thr Ala Pro Pro Arg Phe Pro Ile Ala Gln 1 5 10 15 Leu Gly Thr Phe Lys Gln Asp Ser Ala Gly Met Gly Arg Ile Phe Lys 20 25 30 Gly Asn Leu Leu Gln Lys Lys Ala Leu Thr Thr Phe Glu Asn Glu His 35 40 45 His Ile Arg Phe Phe Thr Leu Leu Val Leu Phe His Val Met Val Leu 50 55 60 Leu Arg Asn His Ser Arg Ile Gln Gly Val Ser Glu Asp Trp Lys Arg 65 70 75 80 Ala Asn Ser Ile Phe Arg Asn Phe Leu Arg Leu Lys Ser Ser Arg Asn 85 90 95 Thr Ala Glu Ala Glu 100 <210> 217 <211> 333 <212> PRT <213> homo sapiens <400> 217 Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn 1 5 10 15 Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly 20 25 30 Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala 35 40 45 Lys Gly Asp Lys Gly Asp Ala Gly Glu Pro Gly Arg Pro Gly Ser Pro 50 55 60 Gly Lys Asp Gly Thr Ser Gly Glu Lys Gly Glu Arg Gly Ala Asp Gly 65 70 75 80 Lys Val Glu Ala Lys Gly Ile Lys Gly Asp Gln Gly Ser Arg Gly Ser 85 90 95 Pro Gly Lys His Gly Pro Lys Gly Leu Ala Gly Pro Met Gly Glu Lys 100 105 110 Gly Leu Arg Gly Glu Thr Gly Pro Gln Gly Gln Lys Gly Asn Lys Gly 115 120 125 Asp Val Gly Pro Thr Gly Pro Glu Gly Pro Arg Gly Asn Ile Gly Pro 130 135 140 Leu Gly Pro Thr Gly Leu Pro Gly Pro Met Gly Pro Ile Gly Lys Pro 145 150 155 160 Gly Pro Lys Gly Glu Ala Gly Pro Thr Gly Pro Gln Gly Glu Pro Gly 165 170 175 Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly Glu Lys Gly Lys 180 185 190 Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe Thr Val Gly Leu 195 200 205 Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Met Pro Ile Lys Phe Asp 210 215 220 Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr Ala Ala Gly Lys 225 230 235 240 Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr Tyr His Ile Thr 245 250 255 Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys Asn Gly Val Lys 260 265 270 Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu Asp Gln Ala Ser 275 280 285 Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu Val Trp Leu Gln 290 295 300 Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala Asp Glu Asp Asp 305 310 315 320 Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser Pro 325 330 <210> 218 <211> 126 <212> PRT <213> homo sapiens <400> 218 Met Ala Pro Gly Glu Val Thr Ile Thr Val Arg Leu Ile Arg Ser Phe 1 5 10 15 Glu His Arg Asn Phe Lys Pro Val Val Tyr His Gly Val Asn Leu Asp 20 25 30 Gln Thr Val Lys Glu Phe Ile Val Phe Leu Lys Gln Asp Ile Pro Leu 35 40 45 Arg Thr Asn Leu Pro Pro Pro Phe Arg Asn Tyr Lys Tyr Asp Ala Leu 50 55 60 Lys Ile Ile His Gln Ala His Lys Ser Lys Thr Asn Glu Leu Val Leu 65 70 75 80 Ser Leu Glu Asp Asp Glu Arg Leu Leu Leu Lys Glu Asp Ser Thr Leu 85 90 95 Lys Ala Ala Gly Ile Ala Ser Glu Thr Glu Ile Ala Phe Phe Cys Glu 100 105 110 Glu Asp Tyr Lys Asn Tyr Lys Ala Asn Pro Ile Ser Ser Trp 115 120 125 <210> 219 <211> 622 <212> PRT <213> homo sapiens <400> 219 Met Pro Pro Thr Gln Ala Glu Ser Val Ile Arg Ser Ile Ile Arg Glu 1 5 10 15 Ile Gly Gln Glu Cys Ala Ala His Gly Glu Ile Val Ser Glu Thr Leu 20 25 30 Ile Ala Phe Met Val Lys Ala Val Val Leu Asp Pro Ser Asn Gly Phe 35 40 45 Asn Met Asp Arg Thr Leu Met Lys Ser Asp Val Gln Asn Leu Val Lys 50 55 60 Leu Cys Met Thr Arg Leu Leu Asp Thr Lys Asn Pro Ser Leu Asp Thr 65 70 75 80 Ile Lys Met Gln Val Tyr Phe Asp Met Asn Tyr Thr Asn Arg Val Glu 85 90 95 Phe Leu Glu Glu His His Arg Val Leu Glu Ser Arg Leu Gly Ser Val 100 105 110 Thr Arg Glu Ile Thr Asp Asn Arg Ala Cys Ala Lys Glu Glu Leu Glu 115 120 125 Ser Leu Tyr Arg Lys Ile Ile Ser Tyr Val Leu Leu Arg Ser Gly Leu 130 135 140 Gly Ser Pro Thr Asp Ile Lys Thr Val Arg Glu Val Thr Ala Ala Leu 145 150 155 160 Gln Ser Val Phe Pro Gln Ala Glu Leu Gly Thr Phe Leu Thr Leu Ser 165 170 175 Lys Lys Asp Lys Glu Arg Gln Leu Lys Glu Leu Thr Met Ile Val Thr 180 185 190 Gly Ile Arg Leu Phe Asn Arg Asp Cys Gly Lys Gly Gly Glu Gly Ile 195 200 205 Asp Asp Leu Pro Ala Val Leu His Val Ala Ile Pro Ala Thr Met Gln 210 215 220 His Ile Asp Tyr Gln Leu Glu Thr Ala Arg Ser Gln Val Tyr Arg Tyr 225 230 235 240 Thr Ala Ile Leu Glu Lys Ala Ala Asn Asp Pro Leu Met Arg Ala Glu 245 250 255 Leu Gln Pro Tyr Met Leu Lys Glu Ala Leu Tyr Asn Ile Arg Gln Tyr 260 265 270 Glu Val Phe Leu Gln Ile Ile Leu Ser Asp Ile Ile Thr Gly Ala Gln 275 280 285 Glu Val Glu Met Met Thr Lys Gln Leu Gly Ala His Leu Glu Gln Leu 290 295 300 Lys Met Thr Ile Lys Ser Lys Ile Ala Val Pro Thr Ser Gln Val Phe 305 310 315 320 Pro Ile Phe Ile Ala Leu Ser Thr Leu Trp Thr Ser Leu Gln Asp Glu 325 330 335 Thr Ile Val Val Gly Val Leu Ser Asn Leu Phe Thr His Ile Gln Pro 340 345 350 Phe Leu Gly Ala His Glu Leu Tyr Phe Pro Glu Arg Val Met Gln Cys 355 360 365 His Leu Asn Gly Ala Thr Val Lys Thr Asp Val Cys Arg Met Lys Glu 370 375 380 His Met Glu Asp Arg Val Asn Val Ala Asp Phe Arg Lys Leu Glu Trp 385 390 395 400 Leu Phe Pro Glu Thr Thr Ala Asn Phe Asp Lys Leu Leu Ile Gln Tyr 405 410 415 Arg Gly Phe Cys Ala Tyr Thr Phe Ala Ala Thr Asp Gly Leu Leu Leu 420 425 430 Pro Gly Asn Pro Ala Ile Gly Ile Leu Lys Tyr Lys Glu Lys Tyr Tyr 435 440 445 Thr Phe Asn Ser Lys Asp Ala Ala Tyr Ser Phe Ala Glu Asn Pro Glu 450 455 460 His Tyr Ile Asp Ile Val Arg Glu Lys Ala Lys Lys Asn Thr Glu Leu 465 470 475 480 Ile Gln Leu Leu Glu Leu His Gln Gln Phe Glu Thr Phe Ile Pro Tyr 485 490 495 Ser Gln Met Arg Asp Ala Asp Lys His Tyr Ile Lys Pro Ile Thr Lys 500 505 510 Cys Glu Ser Ser Thr Gln Thr Asn Thr His Ile Leu Pro Pro Thr Ile 515 520 525 Val Arg Ser Tyr Glu Trp Asn Glu Trp Glu Leu Arg Arg Lys Ala Ile 530 535 540 Lys Leu Ala Asn Leu Arg Gln Lys Val Thr His Ser Val Gln Thr Asp 545 550 555 560 Leu Ser His Leu Arg Arg Glu Asn Cys Ser Gln Val Tyr Pro Pro Lys 565 570 575 Asp Thr Ser Thr Gln Ser Met Arg Glu Asp Ser Thr Gly Val Pro Arg 580 585 590 Pro Gln Ile Tyr Leu Ala Gly Leu Arg Gly Gly Lys Ser Glu Ile Thr 595 600 605 Asp Glu Val Lys Val Asn Leu Thr Arg Asp Val Asp Glu Thr 610 615 620 <210> 220 <211> 244 <212> PRT <213> homo sapiens <400> 220 Met Gly Asp Leu Phe Ser Leu Phe Trp Glu Val Asp Pro Pro Pro Ile 1 5 10 15 Pro Val Asn Cys Ala Ile Pro Asn Gln Asp Tyr Glu Cys Trp Lys Asp 20 25 30 Asp Ser Cys Gly Thr Ile Gly Ser Phe Leu Leu Trp Tyr Phe Val Ile 35 40 45 Val Phe Val Leu Met Phe Phe Ser Arg Ala Ser Val Trp Met Ser Glu 50 55 60 Asp Lys Lys Asp Glu Gly Ser Gly Thr Ser Thr Ser Val Arg Lys Ala 65 70 75 80 Ser Lys Glu Thr Ser Cys Lys Arg Gln Ser Lys Asp Ser Ala Trp Asp 85 90 95 Pro Ser Gln Thr Met Lys Lys Pro Lys Gln Asn Gln Leu Thr Pro Val 100 105 110 Thr Asn Ser Glu Val Ala Leu Val Asn Ala Tyr Pro Glu Gln Arg Arg 115 120 125 Ala Arg Arg Gln Ser Gln Phe Asn Glu Val Asn Gln Asn Gln His Asp 130 135 140 Ser Asp Thr Thr Glu Tyr Gly Ser Glu Glu Ser Asn Ser Glu Ala Ser 145 150 155 160 Ser Trp Lys Glu Ser Glu Ser Glu His His Pro Ser Pro Asp Ser Ile 165 170 175 Lys Arg Arg Lys Met Ala Gln Arg Gln Arg Asn Leu Gly Ser Tyr Gln 180 185 190 Met Ser Glu Arg His Cys Leu His Cys Lys Ala Leu Arg Thr Asn Glu 195 200 205 Trp Leu Ala His His Ser Arg Gln Lys Pro Ser Val Thr Pro Pro Met 210 215 220 Lys Arg Asp Ser Gln Glu Glu Ser Ser Ile Ser Asp Ile Asn Lys Lys 225 230 235 240 Phe Ser Lys Phe <210> 221 <211> 253 <212> PRT <213> homo sapiens <400> 221 Met Ser Phe Ser Val His Asn Gln Lys Gly Ser Lys Arg Pro Leu Pro 1 5 10 15 Leu Glu Pro Leu Leu Phe Leu Gln Val Pro Arg Ser Asn Tyr Leu His 20 25 30 Phe Gln Glu Glu Lys Gln Arg Leu His Leu Lys Lys Phe Leu Leu Asp 35 40 45 Arg Met Phe Leu Val Ala Lys Ile Gln Ala Asn Val Glu Arg Lys Asp 50 55 60 Val Ala Asp Tyr Tyr Glu Gln Met Phe Gln Ser Val Leu Lys His His 65 70 75 80 Leu Gly Glu Ala Val Thr Gly Leu Leu Leu Ile Tyr Pro Thr Ser Ile 85 90 95 Leu His Ile Leu Glu Ser Ser Ser Asp Thr Leu Tyr Lys Val Leu Leu 100 105 110 Asp Tyr Ile Gly His Val Lys Asp Glu Thr Val Phe Phe Ile Gln Gln 115 120 125 Met Lys Ile Ile Val Ile Ser His Asn Ile Pro Met Arg Leu Phe Met 130 135 140 Gln Trp His Val Ser Val Ile Lys Val Pro Val Met Tyr Leu Asp Asp 145 150 155 160 Val Thr Gln Ser Gln Ser Leu Lys Glu Val Ile Thr Asp Phe Leu Thr 165 170 175 Gln Thr His Lys Leu Ser Leu Tyr Leu Cys Gln Thr Met Lys Val Gly 180 185 190 Thr Lys Gly Pro Gly Asp Asn Leu His Gln Val Ala Pro Asp Leu Leu 195 200 205 Leu Pro Glu Gln Ile Ile Lys Tyr Leu Cys Lys Ser Glu Glu Phe Met 210 215 220 Asp Pro Ala Thr Phe Ile Asn Met Tyr Asn Arg Pro Ile His Ile Thr 225 230 235 240 Leu Asp Ser Glu Val Val Trp Pro Ala Pro Ser Arg Phe 245 250 <210> 222 <211> 1079 <212> PRT <213> homo sapiens <400> 222 Met Glu Trp Leu Leu Glu Asp Leu Leu Gly Ala Lys Gly Asp Met Gly 1 5 10 15 Leu Leu Trp Gly Gln Leu Thr His Ala Leu Ala Cys Arg His Cys Gly 20 25 30 Ser Ser Cys Phe Gln Ser Pro Gly Asn Leu Val Thr Leu Phe Leu Phe 35 40 45 Val Val Trp Gln Ile Gln Arg Trp Trp Gln Leu Gly Arg Leu Arg Gln 50 55 60 Leu His Pro Trp Cys Ser Gly Asn Met Val Gln Gly Lys Glu Leu Pro 65 70 75 80 Leu Leu His Arg Val Ala Phe Leu Asp His Leu Cys Lys Gln Lys Ser 85 90 95 Glu Val Glu Glu Glu Gly Glu Glu Glu Glu Glu Gly Glu Asp Glu Ala 100 105 110 Ser Leu Asp Pro Leu Lys Pro Cys Ser Pro Thr Lys Glu Ala Pro Thr 115 120 125 Gly Glu Gln Ala Thr Pro Ala Pro Pro Gln Pro Ser Cys Gly Ser Glu 130 135 140 Gly Leu Leu Lys Ala Ile Gly Ile Pro Glu Gln Thr Val Met Gln Pro 145 150 155 160 Val Ser Pro Ser Arg Ser Phe Pro Ile Phe Gln Ile Leu Thr Ser Phe 165 170 175 Pro Val Arg His Lys Ile Ala Ser Gly Asn Arg Gln Gln Gln Arg Lys 180 185 190 Ser Gln Leu Phe Trp Gly Leu Pro Ser Leu His Ser Glu Ser Leu Glu 195 200 205 Ala Ile Phe Leu Ser Ser Gly Gly Pro Ser Pro Leu Lys Trp Ser Val 210 215 220 Cys Ser Ser Val Phe Phe Asn Lys Leu Ala Phe Leu Pro Arg Ser Asn 225 230 235 240 Leu Leu Leu Pro Gln Tyr His Ser Ser Ala Gln Phe Ser Thr His Gly 245 250 255 Ala His Thr Met Glu Asp Leu Glu Gly Met Ala Pro Asp Pro Gln Leu 260 265 270 Leu Pro Pro Pro Ser Ser Pro Ser Val Ser Ser Leu Leu Leu His Leu 275 280 285 Arg Pro Phe Pro Val Asp His Lys Gly Val Leu Ser Gly Ala Glu Ala 290 295 300 Pro Thr Gln Ser Pro Gly Thr Ser Pro Leu Glu Val Leu Pro Gly Tyr 305 310 315 320 Glu Thr His Leu Glu Thr Thr Gly His Lys Lys Met Pro Gln Ala Phe 325 330 335 Glu Pro Pro Met Pro Pro Pro Cys Gln Ser Pro Ala Ser Leu Ser Glu 340 345 350 Pro Arg Lys Val Ser Pro Glu Gly Gly Leu Ala Ile Ser Lys Asp Phe 355 360 365 Trp Gly Thr Val Gly Tyr Arg Glu Lys Pro Gln Ala Ser Glu Ser Ser 370 375 380 Met Pro Val Pro Cys Pro Pro Leu Asp Ser Leu Pro Glu Leu Gln Arg 385 390 395 400 Glu Ser Ser Leu Glu Asp Pro Ser Arg Tyr Lys Pro Gln Trp Glu Cys 405 410 415 Arg Glu Asn Ser Gly Asn Leu Trp Ala Phe Glu Ser Pro Val Leu Asp 420 425 430 Leu Asn Pro Glu Leu Ser Gly Thr Ser Pro Glu Cys Val Pro Pro Ala 435 440 445 Ser Glu Thr Pro Trp Lys Gly Met Gln Ser Arg Glu Asn Ile Trp Val 450 455 460 Pro Ala Asp Pro Val Ser Pro Pro Ser Leu Pro Ser Val Pro Leu Leu 465 470 475 480 Glu Ser Leu Val Met Gly Pro Gln Gly Val Leu Ser Glu Ser Lys Ala 485 490 495 Leu Trp Glu Thr Met Gly Gln Lys Glu Asn Leu Trp Ala Ser Asp Ser 500 505 510 Pro Asp Pro Val His Ser Thr Pro Pro Thr Thr Leu Met Glu Pro His 515 520 525 Arg Ile Asn Pro Gly Glu Cys Leu Ala Thr Ser Glu Ala Thr Trp Lys 530 535 540 Asp Thr Glu His Ser Arg Asn Ser Ser Ala Ser Arg Ser Pro Ser Leu 545 550 555 560 Ala Leu Ser Pro Pro Pro Ala Leu Ala Pro Glu Leu Leu Arg Val Arg 565 570 575 Ser Met Gly Val Leu Ser Asp Ser Glu Ala Arg Cys Gly Asp Ile Gln 580 585 590 Lys Thr Lys Asn Ser Trp Ala Ser Lys His Pro Ala Cys Asn Leu Pro 595 600 605 Gln Asp Leu His Gly Ala Ser Pro Leu Gly Val Leu Ser Asp Ser Gln 610 615 620 Ser Ile Val Gly Glu Met Glu Gln Lys Glu Asn Cys Val Pro Val Phe 625 630 635 640 Pro Gly Arg Gly Ser Ser Pro Ser Ser Asn Ser Val Ser Lys Ser His 645 650 655 Val Ser Glu Pro Ile Ala Asp Gln Ser Asn Tyr Lys Pro Asp Gly Glu 660 665 670 Ala Val Glu Gln Arg Lys Asn His Trp Ala Thr Glu Leu Pro Ala Pro 675 680 685 Ser Ser Leu Ser Thr Pro Leu Pro Glu Pro His Ile Asp Leu Glu Leu 690 695 700 Val Trp Arg Asn Val Gln Gln Arg Glu Val Pro Gln Gly Pro Ser Pro 705 710 715 720 Leu Ala Val Asp Pro Leu His Pro Val Pro Gln Pro Pro Thr Leu Ala 725 730 735 Glu Ala Val Lys Ile Glu Arg Thr His Pro Gly Leu Pro Lys Gly Val 740 745 750 Thr Cys Pro Gly Val Lys Ala Glu Ala Pro Leu Ser Gln Arg Trp Thr 755 760 765 Val Pro Glu Leu Leu Thr His Pro Gly Ile His Ala Trp Gln Trp Ser 770 775 780 Arg Glu Leu Lys Leu Arg Leu Lys Lys Leu Arg Gln Ser Pro Ala Ser 785 790 795 800 Arg Ala Pro Gly Pro Ser Gln Ser Phe Cys Ser Ser Pro Ile Leu Ser 805 810 815 Ser Thr Ile Pro Asp Phe Trp Gly Leu Pro Ser Cys Pro Pro Gln Gln 820 825 830 Ile Tyr Pro Pro Asn Pro Cys Pro His Ser Ser Ser Cys His Pro Gln 835 840 845 Glu Val Gln Arg Thr Val Pro Gln Pro Val Gln Ser Ser His Cys His 850 855 860 His Phe Gln Ser Ser Ser Gln Leu Gln Pro Gln Glu Ser Gly Arg Ala 865 870 875 880 Glu Gln Gly Ser Gln Arg Gly Glu Lys Met Lys Gly Lys Met Val Ser 885 890 895 Gln Val Pro Ser Gln Gly Pro Cys Val His Met Glu Ala Gly Val Asp 900 905 910 Tyr Leu Ser Pro Gly Pro Gly Glu Pro Ser Asn Ser Lys Val Leu Val 915 920 925 Ser Gly Lys Arg Lys Asp Lys Ala Ser Ala Ser Ser Ser Ala Lys Lys 930 935 940 Arg Glu His Pro Arg Lys Pro Lys Ala Gly Asp His Arg Arg Gly Thr 945 950 955 960 Ala Arg Leu Gly Leu Ser Thr Val Thr Gly Lys Asn His Pro Ala Gln 965 970 975 Ala Arg Ser Leu Val Glu Ala Pro Val Ser Thr Phe Pro Gln Arg Ser 980 985 990 Gln His Arg Gly Gln Ser Ser Gln His Thr Ala Leu Pro Gln Leu Leu 995 1000 1005 Leu Pro Lys Ala Ser Gly Pro Gln Asp Gln Pro Glu Ala Gly Arg 1010 1015 1020 Arg Ala Ser Asp Ile Leu Thr Pro Arg His Cys Lys His Cys Pro 1025 1030 1035 Trp Ala His Met Glu Lys Tyr Leu Ser Phe Pro Thr Leu Lys Ala 1040 1045 1050 Ser Leu Thr Arg Gly Leu Gln Lys Val Leu Ala Lys Cys Leu Asp 1055 1060 1065 Asn His Arg Pro Leu Pro Thr Lys Ser Ser Gln 1070 1075 <210> 223 <211> 179 <212> PRT <213> homo sapiens <400> 223 Met Ser Ser Gln Lys Gly Asn Val Ala Arg Ser Arg Pro Gln Lys His 1 5 10 15 Gln Asn Thr Phe Ser Phe Lys Asn Asp Lys Phe Asp Lys Ser Val Gln 20 25 30 Thr Lys Lys Ile Asn Ala Lys Leu His Asp Gly Val Cys Gln Arg Cys 35 40 45 Lys Glu Val Leu Glu Trp Arg Val Lys Tyr Ser Lys Tyr Lys Pro Leu 50 55 60 Ser Lys Pro Lys Lys Cys Val Lys Cys Leu Gln Lys Thr Val Lys Asp 65 70 75 80 Ser Tyr His Ile Met Cys Arg Pro Cys Ala Cys Glu Leu Glu Val Cys 85 90 95 Ala Lys Cys Gly Lys Lys Glu Asp Ile Val Ile Pro Trp Ser Leu Pro 100 105 110 Leu Leu Pro Arg Leu Glu Cys Ser Gly Arg Ile Leu Ala His His Asn 115 120 125 Leu Arg Leu Pro Cys Ser Ser Asp Ser Pro Ala Ser Ala Ser Arg Val 130 135 140 Ala Gly Thr Thr Gly Ala His His His Ala Gln Leu Ile Phe Val Phe 145 150 155 160 Leu Val Glu Met Gly Phe His Tyr Val Gly Gln Ala Gly Leu Glu Leu 165 170 175 Leu Thr Ser <210> 224 <211> 328 <212> PRT <213> homo sapiens <400> 224 Met Glu Ile Val Trp Glu Val Leu Phe Leu Leu Gln Ala Asn Phe Ile 1 5 10 15 Val Cys Ile Ser Ala Gln Gln Asn Ser Pro Lys Ile His Glu Gly Trp 20 25 30 Trp Ala Tyr Lys Glu Val Val Gln Gly Ser Phe Val Pro Val Pro Ser 35 40 45 Phe Trp Gly Leu Val Asn Ser Ala Trp Asn Leu Cys Ser Val Gly Lys 50 55 60 Arg Gln Ser Pro Val Asn Ile Glu Thr Ser His Met Ile Phe Asp Pro 65 70 75 80 Phe Leu Thr Pro Leu Arg Ile Asn Thr Gly Gly Arg Lys Val Ser Gly 85 90 95 Thr Met Tyr Asn Thr Gly Arg His Val Ser Leu Arg Leu Asp Lys Glu 100 105 110 His Leu Val Asn Ile Ser Gly Gly Pro Met Thr Tyr Ser His Arg Leu 115 120 125 Glu Glu Ile Arg Leu His Phe Gly Ser Glu Asp Ser Gln Gly Ser Glu 130 135 140 His Leu Leu Asn Gly Gln Ala Phe Ser Gly Glu Val Gln Leu Ile His 145 150 155 160 Tyr Asn His Glu Leu Tyr Thr Asn Val Thr Glu Ala Ala Lys Ser Pro 165 170 175 Asn Gly Leu Val Val Val Ser Ile Phe Ile Lys Val Ser Asp Ser Ser 180 185 190 Asn Pro Phe Leu Asn Arg Met Leu Asn Arg Asp Thr Ile Thr Arg Ile 195 200 205 Thr Tyr Lys Asn Asp Ala Tyr Leu Leu Gln Gly Leu Asn Ile Glu Glu 210 215 220 Leu Tyr Pro Glu Thr Ser Ser Phe Ile Thr Tyr Asp Gly Ser Met Thr 225 230 235 240 Ile Pro Pro Cys Tyr Glu Thr Ala Ser Trp Ile Ile Met Asn Lys Pro 245 250 255 Val Tyr Ile Thr Arg Met Gln Met His Ser Leu Arg Leu Leu Ser Gln 260 265 270 Asn Gln Pro Ser Gln Ile Phe Leu Ser Met Ser Asp Asn Phe Arg Pro 275 280 285 Val Gln Pro Leu Asn Asn Arg Cys Ile Arg Thr Asn Ile Asn Phe Ser 290 295 300 Leu Gln Gly Lys Asp Cys Pro Asn Asn Arg Ala Gln Lys Leu Gln Tyr 305 310 315 320 Arg Val Asn Glu Trp Leu Leu Lys 325 <210> 225 <211> 248 <212> PRT <213> homo sapiens <400> 225 Met Phe Leu Ala Lys Ala Leu Leu Glu Gly Ala Asp Arg Gly Leu Gly 1 5 10 15 Glu Ala Leu Gly Gly Leu Phe Gly Gly Gly Gly Gln Arg Arg Glu Gly 20 25 30 Gly Gly Arg Asn Ile Gly Gly Ile Val Gly Gly Ile Val Asn Phe Ile 35 40 45 Ser Glu Ala Ala Ala Ala Gln Tyr Thr Pro Glu Pro Pro Pro Thr Gln 50 55 60 Gln His Phe Thr Ser Val Glu Ala Ser Glu Ser Glu Glu Val Arg Arg 65 70 75 80 Phe Arg Gln Gln Phe Thr Gln Leu Ala Gly Pro Asp Met Glu Val Gly 85 90 95 Ala Thr Asp Leu Met Asn Ile Leu Asn Lys Val Leu Ser Lys His Lys 100 105 110 Asp Leu Lys Thr Asp Gly Phe Ser Leu Asp Thr Cys Arg Ser Ile Val 115 120 125 Ser Val Met Asp Ser Asp Thr Thr Gly Lys Leu Gly Phe Glu Glu Phe 130 135 140 Lys Tyr Leu Trp Asn Asn Ile Lys Lys Trp Gln Cys Val Tyr Lys Gln 145 150 155 160 Tyr Asp Arg Asp His Ser Gly Ser Leu Gly Ser Ser Gln Leu Arg Gly 165 170 175 Ala Leu Gln Ala Ala Gly Phe Gln Leu Asn Glu Gln Leu Tyr Gln Met 180 185 190 Ile Val Arg Arg Tyr Ala Asn Glu Asp Gly Asp Met Asp Phe Asn Asn 195 200 205 Phe Ile Ser Cys Leu Val Arg Leu Asp Ala Met Phe Arg Ala Phe Lys 210 215 220 Ser Leu Asp Arg Asp Arg Asp Gly Leu Ile Gln Val Ser Ile Lys Glu 225 230 235 240 Trp Leu Gln Leu Thr Met Tyr Ser 245 <210> 226 <211> 278 <212> PRT <213> homo sapiens <400> 226 Met Thr Asp Leu Asn Lys His Ile Lys Gln Ala Gln Thr Gln Arg Lys 1 5 10 15 Gln Leu Leu Glu Glu Ser Arg Glu Leu His Arg Glu Lys Leu Leu Val 20 25 30 Gln Ala Glu Asn Arg Phe Phe Leu Glu Tyr Leu Thr Asn Lys Thr Glu 35 40 45 Glu Tyr Thr Glu Gln Pro Glu Lys Val Trp Asn Ser Tyr Leu Gln Lys 50 55 60 Ser Gly Glu Ile Glu Arg Arg Arg Gln Glu Ser Ala Ser Arg Tyr Ala 65 70 75 80 Glu Gln Ile Ser Val Leu Lys Thr Ala Leu Leu Gln Lys Glu Asn Ile 85 90 95 Gln Ser Ser Leu Lys Arg Lys Leu Gln Ala Met Arg Asp Ile Ala Ile 100 105 110 Leu Lys Glu Lys Gln Glu Lys Glu Ile Gln Thr Leu Gln Glu Glu Thr 115 120 125 Lys Lys Val Gln Ala Glu Thr Ala Ser Lys Thr Arg Glu Val Gln Ala 130 135 140 Gln Leu Leu Gln Glu Lys Arg Leu Leu Glu Lys Gln Leu Ser Glu Pro 145 150 155 160 Asp Arg Arg Leu Leu Gly Lys Arg Lys Arg Arg Glu Leu Asn Met Lys 165 170 175 Ala Gln Ala Leu Lys Leu Ala Ala Lys Arg Phe Ile Phe Glu Tyr Ser 180 185 190 Cys Gly Ile Asn Arg Glu Asn Gln Gln Phe Lys Lys Glu Leu Leu Gln 195 200 205 Leu Ile Glu Gln Ala Gln Lys Leu Thr Ala Thr Gln Ser His Leu Glu 210 215 220 Asn Arg Lys Gln Gln Leu Gln Gln Glu Gln Trp Tyr Leu Glu Ser Leu 225 230 235 240 Ile Gln Ala Arg Gln Arg Leu Gln Gly Ser His Asn Gln Cys Leu Asn 245 250 255 Arg Gln Asp Val Pro Lys Thr Thr Pro Ser Leu Pro Gln Gly Thr Lys 260 265 270 Ser Arg Ile Asn Pro Lys 275 <210> 227 <211> 1450 <212> PRT <213> homo sapiens <400> 227 Met Ser Ser Gln Gly Ser Pro Ser Val Ala Leu Ser Thr Thr Thr Val 1 5 10 15 Ser Ser Val Ala Val Gln Ala Gly Asp Ser Lys Ile Val Ile Ala Val 20 25 30 Ile Lys Cys Gly Lys Trp Val Gln Leu Gln Leu Ala Glu Ser Gln Pro 35 40 45 Asn Leu Leu Glu Ile Gly Ser Ser Gln Asp Glu Thr Lys Lys Leu Leu 50 55 60 His Asp His Glu Leu Leu Leu Ala Lys Leu Lys Ala Leu Glu Asp Arg 65 70 75 80 Val Trp Glu Leu Leu Gln Glu Ala Asp Lys Thr Ala Glu Glu Asn Lys 85 90 95 Asp Gln Ser Gln Val Tyr Asp Ala Met Ala Glu Thr Leu Gly Glu Ala 100 105 110 Trp Ala Ala Leu Val Ser Met Leu Glu Arg Arg Thr Glu Leu Leu Arg 115 120 125 Leu Thr Ser Glu Phe Phe Glu Asn Ala Leu Glu Phe Ala Ile Lys Ile 130 135 140 Asp Gln Ala Glu Asp Phe Leu Gln Asn Thr His Glu Phe Glu Ser Ala 145 150 155 160 Glu Ser Leu Lys Ser Leu Leu Gln Leu His Glu His His Thr Lys Glu 165 170 175 Leu Leu Glu Arg Ser Leu Ala Leu Leu Asn Lys Ser Gln Gln Leu Thr 180 185 190 Asp Phe Ile Glu Lys Phe Lys Cys Glu Gly Pro Asn Val Asn Pro Glu 195 200 205 Leu Thr Gln Gly Ala His Ser Ser Cys Leu Lys Val Asp Arg Leu Leu 210 215 220 Glu Leu Leu Gln Asp Arg Arg Arg Gln Leu Asp Lys Tyr Leu Lys Gln 225 230 235 240 Gln Trp Gln Glu Leu Ser Gln Val Leu Gln Ile Cys Gln Trp Asp Gln 245 250 255 Gln Glu Asn Gln Val Thr Cys Trp Phe Gln Lys Thr Ile Arg Asn Leu 260 265 270 Gln Glu Gln Ser Leu Gly Ser Ser Leu Ser Asp Asn Glu Asp Arg Ile 275 280 285 His Lys Gln Glu Glu Leu Ile Ile Lys Ala Lys Glu Trp Asn Ser Ala 290 295 300 Val Glu Lys Leu Lys Ser Glu Ala Leu Arg Ile Leu Leu Ser Lys Asp 305 310 315 320 Tyr Val Glu Lys Glu His Leu Gln Leu Ser His Gln Lys Leu Ser Gln 325 330 335 Leu Gln Glu Glu Phe Gly Gln Leu Met Val Glu Arg Asn Thr Trp Leu 340 345 350 Lys Lys Ala Asn Glu Phe Phe Asn Ser Ala Asn Lys Ala Phe Asp Val 355 360 365 Leu Gly Arg Val Glu Ala Tyr Leu Lys Leu Leu Lys Ser Glu Gly Leu 370 375 380 Ser Leu Ala Val Leu Ala Val Arg His Glu Glu Leu His Arg Lys Ile 385 390 395 400 Lys Asp Cys Thr Thr Asp Ala Leu Gln Lys Gly Gln Thr Leu Ile Ser 405 410 415 Gln Val Asp Ser Cys Ser Ser Gln Val Ser Gly Ile His Glu Met Met 420 425 430 Gly Cys Ile Lys Arg Arg Val Asp His Leu Thr Glu Gln Cys Ser Ala 435 440 445 His Lys Glu Tyr Ala Leu Lys Lys Gln Gln Leu Thr Ala Ser Val Glu 450 455 460 Gly Tyr Leu Arg Lys Val Glu Met Ser Ile Gln Lys Ile Ser Pro Val 465 470 475 480 Leu Ser Asn Ala Met Asp Val Gly Ser Thr Arg Ser Glu Ser Glu Lys 485 490 495 Ile Leu Asn Lys Tyr Leu Glu Leu Asp Ile Gln Ala Lys Glu Thr Ser 500 505 510 His Glu Leu Glu Ala Ala Ala Lys Thr Met Met Glu Lys Asn Glu Phe 515 520 525 Val Ser Asp Glu Met Val Ser Leu Ser Ser Lys Ala Arg Trp Leu Ala 530 535 540 Glu Glu Leu Asn Leu Phe Gly Gln Ser Ile Asp Tyr Arg Ser Gln Val 545 550 555 560 Leu Gln Thr Tyr Val Ala Phe Leu Lys Ser Ser Glu Glu Val Glu Met 565 570 575 Gln Phe Gln Ser Leu Lys Glu Phe Tyr Glu Thr Glu Ile Pro Gln Lys 580 585 590 Glu Gln Asp Asp Ala Lys Ala Lys His Cys Ser Asp Ser Ala Glu Lys 595 600 605 Gln Trp Gln Leu Phe Leu Lys Lys Ser Phe Ile Thr Gln Asp Leu Gly 610 615 620 Leu Glu Phe Leu Asn Leu Ile Asn Met Ala Lys Glu Asn Glu Ile Leu 625 630 635 640 Asp Val Lys Asn Glu Val Tyr Leu Met Lys Asn Thr Met Glu Asn Gln 645 650 655 Lys Ala Glu Arg Glu Glu Leu Ser Leu Leu Arg Leu Ala Trp Gln Leu 660 665 670 Lys Ala Thr Glu Ser Lys Pro Gly Lys Gln Gln Trp Ala Ala Phe Lys 675 680 685 Glu Gln Leu Lys Lys Thr Ser His Asn Leu Lys Leu Leu Gln Glu Ala 690 695 700 Leu Met Pro Val Ser Ala Leu Asp Leu Gly Gly Ser Leu Gln Phe Ile 705 710 715 720 Leu Asp Leu Arg Gln Lys Trp Asn Asp Met Lys Pro Gln Phe Gln Gln 725 730 735 Leu Asn Asp Glu Val Gln Tyr Ile Met Lys Glu Ser Glu Glu Leu Thr 740 745 750 Gly Arg Gly Ala Pro Val Lys Glu Lys Ser Gln Gln Leu Lys Asp Leu 755 760 765 Ile His Phe His Gln Lys Gln Lys Glu Arg Ile Gln Asp Tyr Glu Asp 770 775 780 Ile Leu Tyr Lys Val Val Gln Phe His Gln Val Lys Glu Glu Leu Gly 785 790 795 800 Arg Leu Ile Lys Ser Arg Glu Leu Glu Phe Val Glu Gln Pro Lys Glu 805 810 815 Leu Gly Asp Ala His Asp Val Gln Ile His Leu Arg Cys Ser Gln Glu 820 825 830 Lys Gln Ala Arg Val Asp His Leu His Arg Leu Ala Leu Ser Leu Gly 835 840 845 Val Asp Ile Ile Ser Ser Val Gln Arg Pro His Cys Ser Asn Val Ser 850 855 860 Ala Lys Asn Leu Gln Gln Gln Leu Glu Leu Leu Glu Glu Asp Ser Met 865 870 875 880 Lys Trp Arg Ala Lys Ala Glu Glu Tyr Gly Arg Thr Leu Ser Arg Ser 885 890 895 Val Glu Tyr Cys Ala Met Arg Asp Glu Ile Asn Glu Leu Lys Asp Ser 900 905 910 Phe Lys Asp Ile Lys Lys Lys Phe Asn Asn Leu Lys Phe Asn Tyr Thr 915 920 925 Lys Lys Asn Glu Lys Ser Arg Asn Leu Lys Ala Leu Lys Tyr Gln Ile 930 935 940 Gln Gln Val Asp Met Tyr Ala Glu Lys Met Gln Ala Leu Lys Arg Lys 945 950 955 960 Met Glu Lys Val Ser Asn Lys Thr Ser Asp Ser Phe Leu Asn Tyr Pro 965 970 975 Ser Asp Lys Val Asn Val Leu Leu Glu Val Met Lys Asp Leu Gln Lys 980 985 990 His Val Asp Asp Phe Asp Lys Val Val Thr Asp Tyr Lys Lys Asn Leu 995 1000 1005 Asp Leu Thr Glu His Phe Gln Glu Val Ile Glu Glu Cys His Phe 1010 1015 1020 Trp Tyr Glu Asp Ala Ser Ala Thr Val Val Arg Val Gly Lys Tyr 1025 1030 1035 Ser Thr Glu Cys Lys Thr Lys Glu Ala Val Lys Ile Leu His Gln 1040 1045 1050 Gln Phe Asn Lys Phe Ile Ala Pro Ser Val Pro Gln Gln Glu Glu 1055 1060 1065 Arg Ile Gln Glu Ala Thr Asp Leu Ala Gln His Leu Tyr Gly Leu 1070 1075 1080 Glu Glu Gly Gln Lys Tyr Ile Glu Lys Ile Val Thr Lys His Lys 1085 1090 1095 Glu Val Leu Glu Ser Val Thr Glu Leu Cys Glu Ser Leu Thr Glu 1100 1105 1110 Leu Glu Glu Lys Leu Lys Gln Gly Asp Val Leu Lys Met Asn Pro 1115 1120 1125 Asn Leu Glu Asp Phe His Tyr Asp Tyr Ile Asp Leu Leu Lys Glu 1130 1135 1140 Pro Ala Lys Asn Lys Gln Thr Ile Phe Asn Glu Glu Arg Asn Lys 1145 1150 1155 Gly Gln Val Gln Val Ala Asp Leu Leu Gly Ile Asn Gly Thr Gly 1160 1165 1170 Glu Glu Arg Leu Pro Gln Asp Leu Lys Val Ser Thr Asp Lys Glu 1175 1180 1185 Gly Gly Val Gln Asp Leu Leu Leu Pro Glu Asp Met Leu Ser Gly 1190 1195 1200 Glu Glu Tyr Glu Cys Val Ser Pro Asp Asp Ile Ser Leu Pro Pro 1205 1210 1215 Leu Pro Gly Ser Pro Glu Ser Pro Leu Ala Pro Ser Asp Met Glu 1220 1225 1230 Val Glu Glu Pro Val Ser Ser Ser Leu Ser Leu His Ile Ser Ser 1235 1240 1245 Tyr Gly Val Gln Ala Gly Thr Ser Ser Pro Gly Asp Ala Gln Glu 1250 1255 1260 Ser Val Leu Pro Pro Pro Val Ala Phe Ala Asp Ala Cys Asn Asp 1265 1270 1275 Lys Arg Glu Thr Phe Ser Ser His Phe Glu Arg Pro Tyr Leu Gln 1280 1285 1290 Phe Lys Ala Glu Pro Pro Leu Thr Ser Arg Gly Phe Val Glu Lys 1295 1300 1305 Ser Thr Ala Leu His Arg Ile Ser Ala Glu His Pro Glu Ser Met 1310 1315 1320 Met Ser Glu Val His Glu Arg Ala Leu Gln Gln His Pro Gln Ala 1325 1330 1335 Gln Gly Gly Leu Leu Glu Thr Arg Glu Lys Met His Ala Asp Asn 1340 1345 1350 Asn Phe Thr Lys Thr Gln Asp Arg Leu His Ala Ser Ser Asp Ala 1355 1360 1365 Phe Ser Gly Leu Arg Phe Gln Ser Gly Thr Ser Arg Gly Tyr Gln 1370 1375 1380 Arg Gln Met Val Pro Arg Glu Glu Ile Lys Ser Thr Ser Ala Lys 1385 1390 1395 Ser Ser Val Val Ser Leu Ala Asp Gln Ala Pro Asn Phe Ser Arg 1400 1405 1410 Leu Leu Ser Asn Val Thr Val Met Glu Gly Ser Pro Val Thr Leu 1415 1420 1425 Glu Val Glu Val Thr Gly Phe Pro Glu Pro Thr Leu Thr Trp Trp 1430 1435 1440 Val Ala Tyr Asn Asp Lys Pro 1445 1450 <210> 228 <211> 788 <212> PRT <213> homo sapiens <400> 228 Met Thr Ile His Gln Phe Leu Leu Leu Phe Leu Phe Trp Val Cys Leu 1 5 10 15 Pro His Phe Cys Ser Pro Glu Ile Met Phe Arg Arg Thr Pro Val Pro 20 25 30 Gln Gln Arg Ile Leu Ser Ser Arg Val Pro Arg Ser Asp Gly Lys Ile 35 40 45 Leu His Arg Gln Lys Arg Gly Trp Met Trp Asn Gln Phe Phe Leu Leu 50 55 60 Glu Glu Tyr Thr Gly Ser Asp Tyr Gln Tyr Val Gly Lys Leu His Ser 65 70 75 80 Asp Gln Asp Lys Gly Asp Gly Ser Leu Lys Tyr Ile Leu Ser Gly Asp 85 90 95 Gly Ala Gly Thr Leu Phe Ile Ile Asp Glu Lys Thr Gly Asp Ile His 100 105 110 Ala Thr Arg Arg Ile Asp Arg Glu Glu Lys Ala Phe Tyr Thr Leu Arg 115 120 125 Ala Gln Ala Ile Asn Arg Arg Thr Leu Arg Pro Val Glu Pro Glu Ser 130 135 140 Glu Phe Val Ile Lys Ile His Asp Ile Asn Asp Asn Glu Pro Thr Phe 145 150 155 160 Pro Glu Glu Ile Tyr Thr Ala Ser Val Pro Glu Met Ser Val Val Gly 165 170 175 Thr Ser Val Val Gln Val Thr Ala Thr Asp Ala Asp Asp Pro Ser Tyr 180 185 190 Gly Asn Ser Ala Arg Val Ile Tyr Ser Ile Leu Gln Gly Gln Pro Tyr 195 200 205 Phe Ser Val Glu Pro Glu Thr Gly Ile Ile Arg Thr Ala Leu Pro Asn 210 215 220 Met Asn Arg Glu Asn Arg Glu Gln Tyr Gln Val Val Ile Gln Ala Lys 225 230 235 240 Asp Met Gly Gly Gln Met Gly Gly Leu Ser Gly Thr Thr Thr Val Asn 245 250 255 Ile Thr Leu Thr Asp Val Asn Asp Asn Pro Pro Arg Phe Pro Gln Asn 260 265 270 Thr Ile His Leu Arg Val Leu Glu Ser Ser Pro Val Gly Thr Ala Ile 275 280 285 Gly Ser Val Lys Ala Thr Asp Ala Asp Thr Gly Lys Asn Ala Glu Val 290 295 300 Glu Tyr Arg Ile Ile Asp Gly Asp Gly Thr Asp Met Phe Asp Ile Val 305 310 315 320 Thr Glu Lys Asp Thr Gln Glu Gly Ile Ile Thr Val Lys Lys Pro Leu 325 330 335 Asp Tyr Glu Ser Arg Arg Leu Tyr Thr Leu Lys Val Glu Ala Glu Asn 340 345 350 Thr His Val Asp Pro Arg Phe Tyr Tyr Leu Gly Pro Phe Lys Asp Thr 355 360 365 Thr Ile Val Lys Ile Ser Ile Glu Asp Val Asp Glu Pro Pro Val Phe 370 375 380 Ser Arg Ser Ser Tyr Leu Phe Glu Val His Glu Asp Ile Glu Val Gly 385 390 395 400 Thr Ile Ile Gly Thr Val Met Ala Arg Asp Pro Asp Ser Ile Ser Ser 405 410 415 Pro Ile Arg Phe Ser Leu Asp Arg His Thr Asp Leu Asp Arg Ile Phe 420 425 430 Asn Ile His Ser Gly Asn Gly Ser Leu Tyr Thr Ser Lys Pro Leu Asp 435 440 445 Arg Glu Leu Ser Gln Trp His Asn Leu Thr Val Ile Ala Ala Glu Ile 450 455 460 Asn Asn Pro Lys Glu Thr Thr Arg Val Ala Val Phe Val Arg Ile Leu 465 470 475 480 Asp Val Asn Asp Asn Ala Pro Gln Phe Ala Val Phe Tyr Asp Thr Phe 485 490 495 Val Cys Glu Asn Ala Arg Pro Gly Gln Leu Ile Gln Thr Ile Ser Ala 500 505 510 Val Asp Lys Asp Asp Pro Leu Gly Gly Gln Lys Phe Phe Phe Ser Leu 515 520 525 Ala Ala Val Asn Pro Asn Phe Thr Val Gln Asp Asn Glu Asp Asn Thr 530 535 540 Ala Arg Ile Leu Thr Arg Lys Asn Gly Phe Asn Arg His Glu Ile Ser 545 550 555 560 Thr Tyr Leu Leu Pro Val Val Ile Ser Asp Asn Asp Tyr Pro Ile Gln 565 570 575 Ser Ser Thr Gly Thr Leu Thr Ile Arg Val Cys Ala Cys Asp Ser Gln 580 585 590 Gly Asn Met Gln Ser Cys Ser Ala Glu Ala Leu Leu Leu Pro Ala Gly 595 600 605 Leu Ser Thr Gly Ala Leu Ile Ala Ile Leu Leu Cys Ile Ile Ile Leu 610 615 620 Leu Val Ile Val Val Leu Phe Ala Ala Leu Lys Arg Gln Arg Lys Lys 625 630 635 640 Glu Pro Leu Ile Leu Ser Lys Glu Asp Ile Arg Asp Asn Ile Val Ser 645 650 655 Tyr Asn Asp Glu Gly Gly Gly Glu Glu Asp Thr Gln Ala Phe Asp Ile 660 665 670 Gly Thr Leu Arg Asn Pro Ala Ala Ile Glu Glu Lys Lys Leu Arg Arg 675 680 685 Asp Ile Ile Pro Glu Thr Leu Phe Ile Pro Arg Arg Thr Pro Thr Ala 690 695 700 Pro Asp Asn Thr Asp Val Arg Asp Phe Ile Asn Glu Arg Leu Lys Glu 705 710 715 720 His Asp Leu Asp Pro Thr Ala Pro Pro Tyr Asp Ser Leu Ala Thr Tyr 725 730 735 Ala Tyr Glu Gly Asn Asp Ser Ile Ala Glu Ser Leu Ser Ser Leu Glu 740 745 750 Ser Gly Thr Thr Glu Gly Asp Gln Asn Tyr Asp Tyr Leu Arg Glu Trp 755 760 765 Gly Pro Arg Phe Asn Lys Leu Ala Glu Met Tyr Gly Gly Gly Glu Ser 770 775 780 Asp Lys Asp Ser 785 <210> 229 <211> 796 <212> PRT <213> homo sapiens <400> 229 Met Lys Glu Asn Tyr Cys Leu Gln Ala Ala Leu Val Cys Leu Gly Met 1 5 10 15 Leu Cys His Ser His Ala Phe Ala Pro Glu Arg Arg Gly His Leu Arg 20 25 30 Pro Ser Phe His Gly His His Glu Lys Gly Lys Glu Gly Gln Val Leu 35 40 45 Gln Arg Ser Lys Arg Gly Trp Val Trp Asn Gln Phe Phe Val Ile Glu 50 55 60 Glu Tyr Thr Gly Pro Asp Pro Val Leu Val Gly Arg Leu His Ser Asp 65 70 75 80 Ile Asp Ser Gly Asp Gly Asn Ile Lys Tyr Ile Leu Ser Gly Glu Gly 85 90 95 Ala Gly Thr Ile Phe Val Ile Asp Asp Lys Ser Gly Asn Ile His Ala 100 105 110 Thr Lys Thr Leu Asp Arg Glu Glu Arg Ala Gln Tyr Thr Leu Met Ala 115 120 125 Gln Ala Val Asp Arg Asp Thr Asn Arg Pro Leu Glu Pro Pro Ser Glu 130 135 140 Phe Ile Val Lys Val Gln Asp Ile Asn Asp Asn Pro Pro Glu Phe Leu 145 150 155 160 His Glu Thr Tyr His Ala Asn Val Pro Glu Arg Ser Asn Val Gly Thr 165 170 175 Ser Val Ile Gln Val Thr Ala Ser Asp Ala Asp Asp Pro Thr Tyr Gly 180 185 190 Asn Ser Ala Lys Leu Val Tyr Ser Ile Leu Glu Gly Gln Pro Tyr Phe 195 200 205 Ser Val Glu Ala Gln Thr Gly Ile Ile Arg Thr Ala Leu Pro Asn Met 210 215 220 Asp Arg Glu Ala Lys Glu Glu Tyr His Val Val Ile Gln Ala Lys Asp 225 230 235 240 Met Gly Gly His Met Gly Gly Leu Ser Gly Thr Thr Lys Val Thr Ile 245 250 255 Thr Leu Thr Asp Val Asn Asp Asn Pro Pro Lys Phe Pro Gln Ser Val 260 265 270 Tyr Gln Met Ser Val Ser Glu Ala Ala Val Pro Gly Glu Glu Val Gly 275 280 285 Arg Val Lys Ala Lys Asp Pro Asp Ile Gly Glu Asn Gly Leu Val Thr 290 295 300 Tyr Asn Ile Val Asp Gly Asp Gly Met Glu Ser Phe Glu Ile Thr Thr 305 310 315 320 Asp Tyr Glu Thr Gln Glu Gly Val Ile Lys Leu Lys Lys Pro Val Asp 325 330 335 Phe Glu Thr Lys Arg Ala Tyr Ser Leu Lys Val Glu Ala Ala Asn Val 340 345 350 His Ile Asp Pro Lys Phe Ile Ser Asn Gly Pro Phe Lys Asp Thr Val 355 360 365 Thr Val Lys Ile Ser Val Glu Asp Ala Asp Glu Pro Pro Met Phe Leu 370 375 380 Ala Pro Ser Tyr Ile His Glu Val Gln Glu Asn Ala Ala Ala Gly Thr 385 390 395 400 Val Val Gly Arg Val His Ala Lys Asp Pro Asp Ala Ala Asn Ser Pro 405 410 415 Ile Arg Tyr Ser Ile Asp Arg His Thr Asp Leu Asp Arg Phe Phe Thr 420 425 430 Ile Asn Pro Glu Asp Gly Phe Ile Lys Thr Thr Lys Pro Leu Asp Arg 435 440 445 Glu Glu Thr Ala Trp Leu Asn Ile Thr Val Phe Ala Ala Glu Ile His 450 455 460 Asn Arg His Gln Glu Ala Lys Val Pro Val Ala Ile Arg Val Leu Asp 465 470 475 480 Val Asn Asp Asn Ala Pro Lys Phe Ala Ala Pro Tyr Glu Gly Phe Ile 485 490 495 Cys Glu Ser Asp Gln Thr Lys Pro Leu Ser Asn Gln Pro Ile Val Thr 500 505 510 Ile Ser Ala Asp Asp Lys Asp Asp Thr Ala Asn Gly Pro Arg Phe Ile 515 520 525 Phe Ser Leu Pro Pro Glu Ile Ile His Asn Pro Asn Phe Thr Val Arg 530 535 540 Asp Asn Arg Asp Asn Thr Ala Gly Val Tyr Ala Arg Arg Gly Gly Phe 545 550 555 560 Ser Arg Gln Lys Gln Asp Leu Tyr Leu Leu Pro Ile Val Ile Ser Asp 565 570 575 Gly Gly Ile Pro Pro Met Ser Ser Thr Asn Thr Leu Thr Ile Lys Val 580 585 590 Cys Gly Cys Asp Val Asn Gly Ala Leu Leu Ser Cys Asn Ala Glu Ala 595 600 605 Tyr Ile Leu Asn Ala Gly Leu Ser Thr Gly Ala Leu Ile Ala Ile Leu 610 615 620 Ala Cys Ile Val Ile Leu Leu Val Ile Val Val Leu Phe Val Thr Leu 625 630 635 640 Arg Arg Gln Lys Lys Glu Pro Leu Ile Val Phe Glu Glu Glu Asp Val 645 650 655 Arg Glu Asn Ile Ile Thr Tyr Asp Asp Glu Gly Gly Gly Glu Glu Asp 660 665 670 Thr Glu Ala Phe Asp Ile Ala Thr Leu Gln Asn Pro Asp Gly Ile Asn 675 680 685 Gly Phe Ile Pro Arg Lys Asp Ile Lys Pro Glu Tyr Gln Tyr Met Pro 690 695 700 Arg Pro Gly Leu Arg Pro Ala Pro Asn Ser Val Asp Val Asp Asp Phe 705 710 715 720 Ile Asn Thr Arg Ile Gln Glu Ala Asp Asn Asp Pro Thr Ala Pro Pro 725 730 735 Tyr Asp Ser Ile Gln Ile Tyr Gly Tyr Glu Gly Arg Gly Ser Val Ala 740 745 750 Gly Ser Leu Ser Ser Leu Glu Ser Ala Thr Thr Asp Ser Asp Leu Asp 755 760 765 Tyr Asp Tyr Leu Gln Asn Trp Gly Pro Arg Phe Lys Lys Leu Ala Asp 770 775 780 Leu Tyr Gly Ser Lys Asp Thr Phe Asp Asp Asp Ser 785 790 795 <210> 230 <211> 291 <212> PRT <213> homo sapiens <400> 230 Met Pro Thr Ser Ser Ser Phe Lys His Arg Ile Lys Glu Gln Glu Asp 1 5 10 15 Tyr Ile Arg Asp Trp Thr Ala His Arg Glu Glu Ile Ala Arg Ile Ser 20 25 30 Gln Asp Leu Ala Leu Ile Ala Arg Glu Ile Asn Asp Val Ala Gly Glu 35 40 45 Ile Asp Ser Val Thr Ser Ser Gly Thr Ala Pro Ser Thr Thr Leu Val 50 55 60 Asp Arg Val Phe Asp Glu Ser Leu Asn Phe Gln Lys Ile Pro Pro Leu 65 70 75 80 Val His Ser Lys Thr Pro Glu Gly Asn Asn Gly Arg Ser Gly Asp Pro 85 90 95 Arg Pro Gln Ala Ala Glu Pro Pro Asp His Leu Thr Ile Thr Arg Arg 100 105 110 Arg Thr Trp Ser Arg Asp Glu Val Met Gly Asp Asn Leu Leu Leu Ser 115 120 125 Ser Val Phe Gln Phe Ser Lys Lys Ile Arg Gln Ser Ile Asp Lys Thr 130 135 140 Ala Gly Lys Ile Arg Ile Leu Phe Lys Asp Lys Asp Arg Asn Trp Asp 145 150 155 160 Asp Ile Glu Ser Lys Leu Arg Ala Glu Ser Glu Val Pro Ile Val Lys 165 170 175 Thr Ser Ser Met Glu Ile Ser Ser Ile Leu Gln Glu Leu Lys Arg Val 180 185 190 Glu Lys Gln Leu Gln Ala Ile Asn Ala Met Ile Asp Pro Asp Gly Thr 195 200 205 Leu Glu Ala Leu Asn Asn Met Gly Phe Pro Ser Ala Met Leu Pro Ser 210 215 220 Pro Pro Lys Gln Lys Ser Ser Pro Val Asn Asn His His Ser Pro Gly 225 230 235 240 Gln Thr Pro Thr Leu Gly Gln Pro Glu Ala Arg Ala Leu His Pro Ala 245 250 255 Ala Val Ser Ala Ala Ala Glu Phe Glu Asn Ala Glu Ser Glu Ala Asp 260 265 270 Phe Ser Ile His Phe Asn Arg Val Asn Pro Asp Gly Glu Glu Glu Asp 275 280 285 Val Thr Val 290 <210> 231 <211> 359 <212> PRT <213> homo sapiens <400> 231 Met Ser Leu Gln Arg Leu Leu Gln His Ser Ser Asn Gly Asn Leu Ala 1 5 10 15 Asp Phe Cys Ala Gly Pro Ala Tyr Ser Ser Tyr Ser Thr Leu Thr Gly 20 25 30 Ser Leu Thr Met Asp Asp Asn Arg Arg Ile Gln Met Leu Ala Asp Thr 35 40 45 Val Ala Thr Leu Pro Arg Gly Arg Lys Gln Leu Ala Leu Thr Arg Ser 50 55 60 Ser Ser Leu Ser Asp Phe Ser Trp Ser Gln Arg Lys Leu Val Thr Val 65 70 75 80 Glu Lys Gln Asp Asn Glu Thr Phe Gly Phe Glu Ile Gln Ser Tyr Arg 85 90 95 Pro Gln Asn Gln Asn Ala Cys Ser Ser Glu Met Phe Thr Leu Ile Cys 100 105 110 Lys Ile Gln Glu Asp Ser Pro Ala His Cys Ala Gly Leu Gln Ala Gly 115 120 125 Asp Val Leu Ala Asn Ile Asn Gly Val Ser Thr Glu Gly Phe Thr Tyr 130 135 140 Lys Gln Val Val Asp Leu Ile Arg Ser Ser Gly Asn Leu Leu Thr Ile 145 150 155 160 Glu Thr Leu Asn Gly Thr Met Ile Leu Lys Arg Thr Glu Leu Glu Ala 165 170 175 Lys Leu Gln Val Leu Lys Gln Thr Leu Lys Gln Lys Trp Val Glu Tyr 180 185 190 Arg Ser Leu Gln Leu Gln Glu His Arg Leu Leu His Gly Asp Ala Ala 195 200 205 Asn Cys Pro Ser Leu Glu Asn Met Asp Leu Asp Glu Leu Ser Leu Phe 210 215 220 Gly Pro Leu Pro Gly Pro Gly Pro Ala Leu Val Asp Arg Asn Arg Leu 225 230 235 240 Ser Ser Glu Ser Ser Cys Lys Ser Trp Leu Ser Ser Met Thr Met Asp 245 250 255 Ser Glu Asp Gly Tyr Gln Thr Cys Val Ser Glu Asp Ser Ser Arg Gly 260 265 270 Ala Phe Ser Arg Gln Thr Ser Thr Asp Asp Glu Cys Phe Ile Pro Lys 275 280 285 Glu Gly Asp Asp Phe Leu Arg Arg Ser Ser Ser Arg Arg Asn Arg Ser 290 295 300 Ile Ser Asn Thr Ser Ser Gly Ser Met Ser Pro Leu Trp Glu Gly Asn 305 310 315 320 Leu Ser Ser Met Phe Gly Thr Leu Pro Arg Lys Ser Arg Lys Gly Ser 325 330 335 Val Arg Lys Gln Leu Leu Lys Phe Ile Pro Gly Leu His Arg Ala Val 340 345 350 Glu Glu Glu Glu Ser Arg Phe 355 <210> 232 <211> 704 <212> PRT <213> homo sapiens <400> 232 Met Val Ser Pro Thr Lys Met Ile Ile Arg Ser Pro Leu Lys Glu Thr 1 5 10 15 Asp Thr Asn Leu Lys His Asn Asn Gly Ile Ala Ala Ser Thr Thr Ala 20 25 30 Ala Gly His Leu Asn Val Phe Ser Asn Asp Asn Asn Cys Asn Asn Asn 35 40 45 Asn Thr Thr Glu Ser Phe Pro Lys Lys Arg Ser Leu Glu Arg Leu Glu 50 55 60 Leu Gln Gln Gln Gln His Leu His Glu Lys Lys Arg Ala Arg Ile Glu 65 70 75 80 Arg Ala Arg Ser Ile Glu Gly Ala Val Gln Val Ser Lys Gly Thr Gly 85 90 95 Leu Lys Asn Val Glu Pro Arg Val Thr Pro Lys Glu Leu Leu Glu Trp 100 105 110 Gln Thr Asn Trp Lys Lys Ile Met Lys Arg Asp Ser Arg Ile Tyr Phe 115 120 125 Asp Ile Thr Asp Asp Val Glu Met Asn Thr Tyr Asn Lys Ser Lys Met 130 135 140 Asp Lys Arg Arg Asp Leu Leu Lys Arg Gly Phe Leu Thr Leu Gly Ala 145 150 155 160 Gln Ile Thr Gln Phe Phe Asp Thr Thr Val Thr Ile Val Ile Thr Arg 165 170 175 Arg Ser Val Glu Asn Ile Tyr Leu Leu Lys Asp Thr Asp Ile Leu Ser 180 185 190 Arg Ala Lys Lys Asn Tyr Met Lys Val Trp Ser Tyr Glu Lys Ala Ala 195 200 205 Arg Phe Leu Lys Asn Leu Asp Val Asp Leu Asp His Leu Ser Lys Thr 210 215 220 Lys Ser Ala Ser Leu Ala Ala Pro Thr Leu Ser Asn Leu Leu His Asn 225 230 235 240 Glu Lys Leu Tyr Gly Pro Thr Asp Arg Asp Pro Arg Thr Lys Arg Asp 245 250 255 Asp Ile His Tyr Phe Lys Tyr Pro His Val Tyr Leu Tyr Asp Leu Trp 260 265 270 Gln Thr Trp Ala Pro Ile Ile Thr Leu Glu Trp Lys Pro Gln Glu Leu 275 280 285 Thr Asn Leu Asp Glu Leu Pro Tyr Pro Ile Leu Lys Ile Gly Ser Phe 290 295 300 Gly Arg Cys Pro Phe Ile Gly Asp Arg Asn Tyr Asp Glu Ser Ser Tyr 305 310 315 320 Lys Arg Val Val Lys Arg Tyr Ser Arg Asp Lys Ala Asn Lys Lys Tyr 325 330 335 Ala Leu Gln Leu Arg Ala Leu Phe Gln Tyr His Ala Asp Thr Leu Leu 340 345 350 Asn Thr Ser Ser Val Asn Asp Gln Thr Lys Asn Leu Ile Phe Ile Pro 355 360 365 His Thr Cys Asn Asp Ser Thr Lys Ser Phe Lys Lys Trp Met Gln Glu 370 375 380 Lys Ala Lys Asn Phe Glu Lys Thr Glu Leu Lys Lys Thr Asp Asp Ser 385 390 395 400 Ala Val Gln Asp Val Arg Asn Glu His Ala Asp Gln Thr Asp Glu Lys 405 410 415 Asn Ser Ile Leu Leu Asn Glu Thr Glu Thr Lys Glu Pro Pro Leu Lys 420 425 430 Glu Glu Lys Glu Asn Lys Gln Ser Ile Ala Glu Glu Ser Asn Lys Tyr 435 440 445 Pro Gln Arg Lys Glu Leu Ala Ala Thr Pro Lys Leu Asn His Pro Val 450 455 460 Leu Ala Thr Phe Ala Arg Gln Glu Thr Glu Glu Val Pro Asp Asp Leu 465 470 475 480 Cys Thr Leu Lys Thr Lys Ser Arg Gln Ala Phe Glu Ile Lys Ala Ser 485 490 495 Gly Ala His Gln Ser Asn Asp Val Ala Thr Ser Phe Gly Asn Gly Leu 500 505 510 Gly Pro Thr Arg Ala Ser Val Met Ser Lys Asn Met Lys Ser Leu Ser 515 520 525 Arg Leu Met Val Asp Arg Lys Leu Gly Val Lys Gln Thr Asn Gly Asn 530 535 540 Asn Lys Asn Tyr Thr Ala Thr Ile Ala Thr Thr Ala Glu Thr Ser Lys 545 550 555 560 Glu Asn Arg His Arg Leu Asp Phe Asn Ala Leu Lys Lys Asp Glu Ala 565 570 575 Pro Ser Lys Glu Thr Gly Lys Asp Ser Ala Val His Leu Glu Thr Asn 580 585 590 Arg Lys Pro Gln Asn Phe Pro Lys Val Ala Thr Lys Ser Val Ser Ala 595 600 605 Asp Ser Lys Val His Asn Asp Ile Lys Ile Thr Thr Thr Glu Ser Pro 610 615 620 Thr Ala Ser Lys Lys Ser Thr Ser Thr Asn Val Thr Leu His Phe Asn 625 630 635 640 Ala Gln Thr Ala Gln Thr Ala Gln Pro Val Lys Lys Glu Thr Val Lys 645 650 655 Asn Ser Gly Tyr Cys Glu Asn Cys Arg Val Lys Tyr Glu Ser Leu Glu 660 665 670 Gln His Ile Val Ser Glu Lys His Leu Ser Phe Ala Glu Asn Asp Leu 675 680 685 Asn Phe Glu Ala Ile Asp Ser Leu Ile Glu Asn Leu Arg Phe Gln Ile 690 695 700 <210> 233 <211> 547 <212> PRT <213> homo sapiens <400> 233 Met Glu Asp Ser Glu Ala Leu Gly Phe Glu His Met Gly Leu Asp Pro 1 5 10 15 Arg Leu Leu Gln Ala Val Thr Asp Leu Gly Trp Ser Arg Pro Thr Leu 20 25 30 Ile Gln Glu Lys Ala Ile Pro Leu Ala Leu Glu Gly Lys Asp Leu Leu 35 40 45 Ala Arg Ala Arg Thr Gly Ser Gly Lys Thr Ala Ala Tyr Ala Ile Pro 50 55 60 Met Leu Gln Leu Leu Leu His Arg Lys Ala Thr Gly Pro Val Val Glu 65 70 75 80 Gln Ala Val Arg Gly Leu Val Leu Val Pro Thr Lys Glu Leu Ala Arg 85 90 95 Gln Ala Gln Ser Met Ile Gln Gln Leu Ala Thr Tyr Cys Ala Arg Asp 100 105 110 Val Arg Val Ala Asn Val Ser Ala Ala Glu Asp Ser Val Ser Gln Arg 115 120 125 Ala Val Leu Met Glu Lys Pro Asp Val Val Val Gly Thr Pro Ser Arg 130 135 140 Ile Leu Ser His Leu Gln Gln Asp Ser Leu Lys Leu Arg Asp Ser Leu 145 150 155 160 Glu Leu Leu Val Val Asp Glu Ala Asp Leu Leu Phe Ser Phe Gly Phe 165 170 175 Glu Glu Glu Leu Lys Ser Leu Leu Cys His Leu Pro Arg Ile Tyr Gln 180 185 190 Ala Phe Leu Met Ser Ala Thr Phe Asn Glu Asp Val Gln Ala Leu Lys 195 200 205 Glu Leu Ile Leu His Asn Pro Val Thr Leu Lys Leu Gln Glu Ser Gln 210 215 220 Leu Pro Gly Pro Asp Gln Leu Gln Gln Phe Gln Val Val Cys Glu Thr 225 230 235 240 Glu Glu Asp Lys Phe Leu Leu Leu Tyr Ala Leu Leu Lys Leu Ser Leu 245 250 255 Ile Arg Gly Lys Ser Leu Leu Phe Val Asn Thr Leu Glu Arg Ser Tyr 260 265 270 Arg Leu Arg Leu Phe Leu Glu Gln Phe Ser Ile Pro Thr Cys Val Leu 275 280 285 Asn Gly Glu Leu Pro Leu Arg Ser Arg Cys His Ile Ile Ser Gln Phe 290 295 300 Asn Gln Gly Phe Tyr Asp Cys Val Ile Ala Thr Asp Ala Glu Val Leu 305 310 315 320 Gly Ala Pro Val Lys Gly Lys Arg Arg Gly Arg Gly Pro Lys Gly Asp 325 330 335 Lys Ala Ser Asp Pro Glu Ala Gly Val Ala Arg Gly Ile Asp Phe His 340 345 350 His Val Ser Ala Val Leu Asn Phe Asp Leu Pro Pro Thr Pro Glu Ala 355 360 365 Tyr Ile His Arg Ala Gly Arg Thr Ala Arg Ala Asn Asn Pro Gly Ile 370 375 380 Val Leu Thr Phe Val Leu Pro Thr Glu Gln Phe His Leu Gly Lys Ile 385 390 395 400 Glu Glu Leu Leu Ser Gly Glu Asn Arg Gly Pro Ile Leu Leu Pro Tyr 405 410 415 Gln Phe Arg Met Glu Glu Ile Glu Gly Phe Arg Tyr Arg Cys Arg Asp 420 425 430 Ala Met Arg Ser Val Thr Lys Gln Ala Ile Arg Glu Ala Arg Leu Lys 435 440 445 Glu Ile Lys Glu Glu Leu Leu His Ser Glu Lys Leu Lys Thr Tyr Phe 450 455 460 Glu Asp Asn Pro Arg Asp Leu Gln Leu Leu Arg His Asp Leu Pro Leu 465 470 475 480 His Pro Ala Val Val Lys Pro His Leu Gly His Val Pro Asp Tyr Leu 485 490 495 Val Pro Pro Ala Leu Arg Gly Leu Val Arg Pro His Lys Lys Arg Lys 500 505 510 Lys Leu Ser Ser Ser Cys Arg Lys Ala Lys Arg Ala Lys Ser Gln Asn 515 520 525 Pro Leu Arg Ser Phe Lys His Lys Gly Lys Lys Phe Arg Pro Thr Ala 530 535 540 Lys Pro Ser 545 <210> 234 <211> 298 <212> PRT <213> homo sapiens <400> 234 Met Ser Asp Ala Asn Leu Asp Ser Ser Lys Lys Asn Phe Leu Glu Gly 1 5 10 15 Glu Val Asp Asp Glu Glu Ser Val Ile Leu Thr Leu Val Pro Val Lys 20 25 30 Asp Asp Ala Asn Met Glu Gln Met Glu Pro Ser Val Ser Ser Thr Ser 35 40 45 Asp Val Lys Leu Glu Lys Pro Lys Lys Tyr Asn Pro Gly His Leu Leu 50 55 60 Gln Thr Asn Glu Gln Phe Thr Ala Pro Gln Lys Ala Arg Cys Lys Ile 65 70 75 80 Pro Ala Leu Pro Leu Pro Thr Ile Leu Pro Pro Ile Asn Lys Val Cys 85 90 95 Arg Asp Thr Leu Arg Asp Trp Cys Gln Gln Leu Gly Leu Ser Thr Asn 100 105 110 Gly Lys Lys Ile Glu Val Tyr Leu Arg Leu His Arg His Ala Tyr Pro 115 120 125 Glu Gln Arg Gln Asp Met Pro Glu Met Ser Gln Glu Thr Arg Leu Gln 130 135 140 Arg Cys Ser Arg Lys Arg Lys Ala Val Thr Lys Arg Ala Arg Leu Gln 145 150 155 160 Arg Ser Tyr Glu Met Asn Glu Arg Ala Glu Glu Thr Asn Thr Val Glu 165 170 175 Val Ile Thr Ser Ala Pro Gly Ala Met Leu Ala Ser Trp Ala Arg Ile 180 185 190 Ala Ala Arg Ala Val Gln Pro Lys Ala Leu Asn Ser Cys Ser Ile Pro 195 200 205 Val Ser Val Glu Ala Phe Leu Met Gln Ala Ser Gly Val Arg Trp Cys 210 215 220 Val Val His Gly Arg Leu Leu Ser Ala Asp Thr Lys Gly Trp Val Arg 225 230 235 240 Leu Gln Phe His Ala Gly Gln Ala Trp Val Pro Thr Thr His Arg Arg 245 250 255 Met Ile Ser Leu Phe Leu Leu Pro Ala Cys Ile Phe Pro Ser Pro Gly 260 265 270 Ile Glu Asp Asn Met Leu Cys Pro Asp Cys Ala Lys Arg Asn Lys Lys 275 280 285 Met Met Lys Arg Leu Met Thr Val Glu Lys 290 295 <210> 235 <211> 622 <212> PRT <213> homo sapiens <400> 235 Met Ala Met Ala Pro Ser Pro Ser Leu Val Gln Val Tyr Thr Ser Pro 1 5 10 15 Ala Ala Val Ala Val Trp Glu Trp Gln Asp Gly Leu Gly Thr Trp His 20 25 30 Pro Tyr Ser Ala Thr Val Cys Ser Phe Ile Glu Gln Gln Phe Val Gln 35 40 45 Gln Lys Gly Gln Arg Phe Gly Leu Gly Ser Leu Ala His Ser Ile Pro 50 55 60 Leu Gly Gln Ala Asp Pro Ser Leu Ala Pro Tyr Ile Ile Asp Leu Pro 65 70 75 80 Ser Trp Thr Gln Phe Arg Gln Asp Thr Gly Thr Met Arg Ala Val Arg 85 90 95 Arg His Leu Phe Pro Gln His Ser Ala Pro Gly Arg Gly Val Val Trp 100 105 110 Glu Trp Leu Ser Asp Asp Gly Ser Trp Thr Ala Tyr Glu Ala Ser Val 115 120 125 Cys Asp Tyr Leu Glu Gln Gln Val Ala Arg Gly Asn Gln Leu Val Asp 130 135 140 Leu Ala Pro Leu Gly Tyr Asn Tyr Thr Val Asn Tyr Thr Thr His Thr 145 150 155 160 Gln Thr Asn Lys Thr Ser Ser Phe Cys Arg Ser Val Arg Arg Gln Ala 165 170 175 Gly Pro Pro Tyr Pro Val Thr Thr Ile Ile Ala Pro Pro Gly His Thr 180 185 190 Gly Val Ala Cys Ser Cys His Gln Cys Leu Ser Gly Ser Arg Thr Gly 195 200 205 Pro Val Ser Gly Arg Tyr Arg His Ser Met Thr Asn Leu Pro Ala Tyr 210 215 220 Pro Val Pro Gln His Pro Pro His Arg Thr Ala Ser Val Phe Gly Thr 225 230 235 240 His Gln Ala Phe Ala Pro Tyr Asn Lys Pro Ser Leu Ser Gly Ala Arg 245 250 255 Ser Ala Pro Arg Leu Asn Thr Thr Asn Ala Trp Gly Ala Ala Pro Pro 260 265 270 Ser Leu Gly Ser Gln Pro Leu Tyr Arg Ser Ser Leu Ser His Leu Gly 275 280 285 Pro Gln His Leu Pro Pro Gly Ser Ser Thr Ser Gly Ala Val Ser Ala 290 295 300 Ser Leu Pro Ser Gly Pro Ser Ser Ser Pro Gly Ser Val Pro Ala Thr 305 310 315 320 Val Pro Met Gln Met Pro Lys Pro Ser Arg Val Gln Gln Ala Leu Ala 325 330 335 Gly Met Thr Ser Val Leu Met Ser Ala Ile Gly Leu Pro Val Cys Leu 340 345 350 Ser Arg Ala Pro Gln Pro Thr Ser Pro Pro Ala Ser Arg Leu Ala Ser 355 360 365 Lys Ser His Gly Ser Val Lys Arg Leu Arg Lys Met Ser Val Lys Gly 370 375 380 Ala Thr Pro Lys Pro Glu Pro Glu Pro Glu Gln Val Ile Lys Asn Tyr 385 390 395 400 Thr Glu Glu Leu Lys Val Pro Pro Asp Glu Asp Cys Ile Ile Cys Met 405 410 415 Glu Lys Leu Ser Thr Ala Ser Gly Tyr Ser Asp Val Thr Asp Ser Lys 420 425 430 Ala Ile Gly Ser Leu Ala Val Gly His Leu Thr Lys Cys Ser His Ala 435 440 445 Phe His Leu Leu Cys Leu Leu Ala Met Tyr Cys Asn Gly Asn Lys Asp 450 455 460 Gly Ser Leu Gln Cys Pro Ser Cys Lys Thr Ile Tyr Gly Glu Lys Thr 465 470 475 480 Gly Thr Gln Pro Gln Gly Lys Met Glu Val Leu Arg Phe Gln Met Ser 485 490 495 Leu Pro Gly His Glu Asp Cys Gly Thr Ile Leu Ile Val Tyr Ser Ile 500 505 510 Pro His Gly Ile Gln Gly Pro Glu His Pro Asn Pro Gly Lys Pro Phe 515 520 525 Thr Ala Arg Gly Phe Pro Arg Gln Cys Tyr Leu Pro Asp Asn Ala Gln 530 535 540 Gly Arg Lys Val Leu Glu Leu Leu Lys Val Ala Trp Lys Arg Arg Leu 545 550 555 560 Ile Phe Thr Val Gly Thr Ser Ser Thr Thr Gly Glu Thr Asp Thr Val 565 570 575 Val Trp Asn Glu Ile His His Lys Thr Glu Met Asp Arg Asn Ile Thr 580 585 590 Gly His Gly Tyr Pro Asp Pro Asn Tyr Leu Gln Asn Val Leu Ala Glu 595 600 605 Leu Ala Ala Gln Gly Val Thr Glu Asp Cys Leu Glu Gln Gln 610 615 620 <210> 236 <211> 907 <212> PRT <213> homo sapiens <400> 236 Met Glu Ser Ala Ile Ala Glu Gly Gly Ala Ser Arg Phe Ser Ala Ser 1 5 10 15 Ser Gly Gly Gly Gly Ser Arg Gly Ala Pro Gln His Tyr Pro Lys Thr 20 25 30 Ala Gly Asn Ser Glu Phe Leu Gly Lys Thr Pro Gly Gln Asn Ala Gln 35 40 45 Lys Trp Ile Pro Ala Arg Ser Thr Arg Arg Asp Asp Asn Ser Ala Ala 50 55 60 Asn Asn Ser Ala Asn Glu Lys Glu Arg His Asp Ala Ile Phe Arg Lys 65 70 75 80 Val Arg Gly Ile Leu Asn Lys Leu Thr Pro Glu Lys Phe Asp Lys Leu 85 90 95 Cys Leu Glu Leu Leu Asn Val Gly Val Glu Ser Lys Leu Ile Leu Lys 100 105 110 Gly Val Ile Leu Leu Ile Val Asp Lys Ala Leu Glu Glu Pro Lys Tyr 115 120 125 Ser Ser Leu Tyr Ala Gln Leu Cys Leu Arg Leu Ala Glu Asp Ala Pro 130 135 140 Asn Phe Asp Gly Pro Ala Ala Glu Gly Gln Pro Gly Gln Lys Gln Ser 145 150 155 160 Thr Thr Phe Arg Arg Leu Leu Ile Ser Lys Leu Gln Asp Glu Phe Glu 165 170 175 Asn Arg Thr Arg Asn Val Asp Val Tyr Asp Lys Arg Glu Asn Pro Leu 180 185 190 Leu Pro Glu Glu Glu Glu Gln Arg Ala Ile Ala Lys Ile Lys Met Leu 195 200 205 Gly Asn Ile Lys Phe Ile Gly Glu Leu Gly Lys Leu Asp Leu Ile His 210 215 220 Glu Ser Ile Leu His Lys Cys Ile Lys Thr Leu Leu Glu Lys Lys Lys 225 230 235 240 Arg Val Gln Leu Lys Asp Met Gly Glu Asp Leu Glu Cys Leu Cys Gln 245 250 255 Ile Met Arg Thr Val Gly Pro Arg Leu Asp His Glu Arg Ala Lys Ser 260 265 270 Leu Met Asp Gln Tyr Phe Ala Arg Met Cys Ser Leu Met Leu Ser Lys 275 280 285 Glu Leu Pro Ala Arg Ile Arg Phe Leu Leu Gln Asp Thr Val Glu Leu 290 295 300 Arg Glu His His Trp Val Pro Arg Lys Ala Phe Leu Asp Asn Gly Pro 305 310 315 320 Lys Thr Ile Asn Gln Ile Arg Gln Asp Ala Val Lys Asp Leu Gly Val 325 330 335 Phe Ile Pro Ala Pro Met Ala Gln Gly Met Arg Ser Asp Phe Phe Leu 340 345 350 Glu Gly Pro Phe Met Pro Pro Arg Met Lys Met Asp Arg Asp Pro Leu 355 360 365 Gly Gly Leu Ala Asp Met Phe Gly Gln Met Pro Gly Ser Gly Ile Gly 370 375 380 Thr Gly Pro Gly Val Ile Gln Asp Arg Phe Ser Pro Thr Met Gly Arg 385 390 395 400 His Arg Ser Asn Gln Leu Phe Asn Gly His Gly Gly His Ile Met Pro 405 410 415 Pro Thr Gln Ser Gln Phe Gly Glu Met Gly Gly Lys Phe Met Lys Ser 420 425 430 Gln Gly Leu Ser Gln Leu Tyr His Asn Gln Ser Gln Gly Leu Leu Ser 435 440 445 Gln Leu Gln Gly Gln Ser Lys Asp Met Pro Pro Arg Phe Ser Lys Lys 450 455 460 Gly Gln Leu Asn Ala Asp Glu Ile Ser Leu Arg Pro Ala Gln Ser Phe 465 470 475 480 Leu Met Asn Lys Asn Gln Val Pro Lys Leu Gln Pro Gln Ile Thr Met 485 490 495 Ile Pro Pro Ser Ala Gln Pro Pro Arg Thr Gln Thr Pro Pro Leu Gly 500 505 510 Gln Thr Pro Gln Leu Gly Leu Lys Thr Asn Pro Pro Leu Ile Gln Glu 515 520 525 Lys Pro Ala Lys Thr Ser Lys Lys Pro Pro Pro Ser Lys Glu Glu Leu 530 535 540 Leu Lys Leu Thr Glu Thr Val Val Thr Glu Tyr Leu Asn Ser Gly Asn 545 550 555 560 Ala Asn Glu Ala Val Asn Gly Val Arg Glu Met Arg Ala Pro Lys His 565 570 575 Phe Leu Pro Glu Met Leu Ser Lys Val Ile Ile Leu Ser Leu Asp Arg 580 585 590 Ser Asp Glu Asp Lys Glu Lys Ala Ser Ser Leu Ile Ser Leu Leu Lys 595 600 605 Gln Glu Gly Ile Ala Thr Ser Asp Asn Phe Met Gln Ala Phe Leu Asn 610 615 620 Val Leu Asp Gln Cys Pro Lys Leu Glu Val Asp Ile Pro Leu Val Lys 625 630 635 640 Ser Tyr Leu Ala Gln Phe Ala Ala Arg Ala Ile Ile Ser Glu Leu Val 645 650 655 Ser Ile Ser Glu Leu Ala Gln Pro Leu Glu Ser Gly Thr His Phe Pro 660 665 670 Leu Phe Leu Leu Cys Leu Gln Gln Leu Ala Lys Leu Gln Asp Arg Glu 675 680 685 Trp Leu Thr Glu Leu Phe Gln Gln Ser Lys Val Asn Met Gln Lys Met 690 695 700 Leu Pro Glu Ile Asp Gln Asn Lys Asp Arg Met Leu Glu Ile Leu Glu 705 710 715 720 Gly Lys Gly Leu Ser Phe Leu Phe Pro Leu Leu Lys Leu Glu Lys Glu 725 730 735 Leu Leu Lys Gln Ile Lys Leu Asp Pro Ser Pro Gln Thr Ile Tyr Lys 740 745 750 Trp Ile Lys Asp Asn Ile Ser Pro Lys Leu His Val Asp Lys Gly Phe 755 760 765 Val Asn Ile Leu Met Thr Ser Phe Leu Gln Tyr Ile Ser Ser Glu Val 770 775 780 Asn Pro Pro Ser Asp Glu Thr Asp Ser Ser Ser Ala Pro Ser Lys Glu 785 790 795 800 Gln Leu Glu Gln Glu Lys Gln Leu Leu Leu Ser Phe Lys Pro Val Met 805 810 815 Gln Lys Phe Leu His Asp His Val Asp Leu Gln Val Ser Ala Leu Tyr 820 825 830 Ala Leu Gln Val His Cys Tyr Asn Ser Asn Phe Pro Lys Gly Met Leu 835 840 845 Leu Arg Phe Phe Val His Phe Tyr Asp Met Glu Ile Ile Glu Glu Glu 850 855 860 Ala Phe Leu Ala Trp Lys Glu Asp Ile Thr Gln Glu Phe Pro Gly Lys 865 870 875 880 Gly Lys Ala Leu Phe Gln Val Asn Gln Trp Leu Thr Trp Leu Glu Thr 885 890 895 Ala Glu Glu Glu Glu Ser Glu Glu Glu Ala Asp 900 905 <210> 237 <211> 727 <212> PRT <213> homo sapiens <400> 237 Met Pro Pro Pro Ala Asp Ile Val Lys Val Ala Ile Glu Trp Pro Gly 1 5 10 15 Ala Tyr Pro Lys Leu Met Glu Ile Asp Gln Lys Lys Pro Leu Ser Ala 20 25 30 Ile Ile Lys Glu Val Cys Asp Gly Trp Ser Leu Ala Asn His Glu Tyr 35 40 45 Phe Ala Leu Gln His Ala Asp Ser Ser Asn Phe Tyr Ile Thr Glu Lys 50 55 60 Asn Arg Asn Glu Ile Lys Asn Gly Thr Ile Leu Arg Leu Thr Thr Ser 65 70 75 80 Pro Ala Gln Asn Ala Gln Gln Leu His Glu Arg Ile Gln Ser Ser Ser 85 90 95 Met Asp Ala Lys Leu Glu Ala Leu Lys Asp Leu Ala Ser Leu Ser Arg 100 105 110 Asp Val Thr Phe Ala Gln Glu Phe Ile Asn Leu Asp Gly Ile Ser Leu 115 120 125 Leu Thr Gln Met Val Glu Ser Gly Thr Glu Arg Tyr Gln Lys Leu Gln 130 135 140 Lys Ile Met Lys Pro Cys Phe Gly Asp Met Leu Ser Phe Thr Leu Thr 145 150 155 160 Ala Phe Val Glu Leu Met Asp His Gly Ile Val Ser Trp Asp Thr Phe 165 170 175 Ser Val Ala Phe Ile Lys Lys Ile Ala Ser Phe Val Asn Lys Ser Ala 180 185 190 Ile Asp Ile Ser Ile Leu Gln Arg Ser Leu Ala Ile Leu Glu Ser Met 195 200 205 Val Leu Asn Ser His Asp Leu Tyr Gln Lys Val Ala Gln Glu Ile Thr 210 215 220 Ile Gly Gln Leu Ile Pro His Leu Gln Gly Ser Asp Gln Glu Ile Gln 225 230 235 240 Thr Tyr Thr Ile Ala Val Ile Asn Ala Leu Phe Leu Lys Ala Pro Asp 245 250 255 Glu Arg Arg Gln Glu Met Ala Asn Ile Leu Ala Gln Lys Gln Leu Arg 260 265 270 Ser Ile Ile Leu Thr His Val Ile Arg Ala Gln Arg Ala Ile Asn Asn 275 280 285 Glu Met Ala His Gln Leu Tyr Val Leu Gln Val Leu Thr Phe Asn Leu 290 295 300 Leu Glu Asp Arg Met Met Thr Lys Met Asp Pro Gln Asp Gln Ala Gln 305 310 315 320 Arg Asp Ile Ile Phe Glu Leu Arg Arg Ile Ala Phe Asp Ala Glu Ser 325 330 335 Glu Pro Asn Asn Ser Ser Gly Ser Met Glu Lys Arg Lys Ser Met Tyr 340 345 350 Thr Arg Asp Tyr Lys Lys Leu Gly Phe Ile Asn His Val Asn Pro Ala 355 360 365 Met Asp Phe Thr Gln Thr Pro Pro Gly Met Leu Ala Leu Asp Asn Met 370 375 380 Leu Tyr Phe Ala Lys His His Gln Asp Ala Tyr Ile Arg Ile Val Leu 385 390 395 400 Glu Asn Ser Ser Arg Glu Asp Lys His Glu Cys Pro Phe Gly Arg Ser 405 410 415 Ser Ile Glu Leu Thr Lys Met Leu Cys Glu Ile Leu Lys Val Gly Glu 420 425 430 Leu Pro Ser Glu Thr Cys Asn Asp Phe His Pro Met Phe Phe Thr His 435 440 445 Asp Arg Ser Phe Glu Glu Phe Phe Cys Ile Cys Ile Gln Leu Leu Asn 450 455 460 Lys Thr Trp Lys Glu Met Arg Ala Thr Ser Glu Asp Phe Asn Lys Val 465 470 475 480 Met Gln Val Val Lys Glu Gln Val Met Arg Ala Leu Thr Thr Lys Pro 485 490 495 Ser Ser Leu Asp Gln Phe Lys Ser Lys Leu Gln Asn Leu Ser Tyr Thr 500 505 510 Glu Ile Leu Lys Ile Arg Gln Ser Glu Arg Met Asn Gln Glu Asp Phe 515 520 525 Gln Ser Arg Pro Ile Leu Glu Leu Lys Glu Lys Ile Gln Pro Glu Ile 530 535 540 Leu Glu Leu Ile Lys Gln Gln Arg Leu Asn Arg Leu Val Glu Gly Thr 545 550 555 560 Cys Phe Arg Lys Leu Asn Ala Arg Arg Arg Gln Asp Lys Phe Trp Tyr 565 570 575 Cys Arg Leu Ser Pro Asn His Lys Val Leu His Tyr Gly Asp Leu Glu 580 585 590 Glu Ser Pro Gln Gly Glu Val Pro His Asp Ser Leu Gln Asp Lys Leu 595 600 605 Pro Val Ala Asp Ile Lys Ala Val Val Thr Gly Lys Asp Cys Pro His 610 615 620 Met Lys Glu Lys Gly Ala Leu Lys Gln Asn Lys Glu Val Leu Glu Leu 625 630 635 640 Ala Phe Ser Ile Leu Tyr Asp Ser Asn Cys Gln Leu Asn Phe Ile Ala 645 650 655 Pro Asp Lys His Glu Tyr Cys Ile Trp Thr Asp Gly Leu Asn Ala Leu 660 665 670 Leu Gly Lys Asp Met Met Ser Asp Leu Thr Arg Asn Asp Leu Asp Thr 675 680 685 Leu Leu Ser Met Glu Ile Lys Leu Arg Leu Leu Asp Leu Glu Asn Ile 690 695 700 Gln Ile Pro Asp Ala Pro Pro Pro Ile Pro Lys Glu Pro Ser Asn Tyr 705 710 715 720 Asp Phe Val Tyr Asp Cys Asn 725 <210> 238 <211> 270 <212> PRT <213> homo sapiens <400> 238 Met Val Thr Ala Met Asn Val Ser His Glu Val Asn Gln Leu Phe Gln 1 5 10 15 Pro Tyr Asn Phe Glu Leu Ser Lys Asp Met Arg Pro Phe Phe Glu Glu 20 25 30 Tyr Trp Ala Thr Ser Phe Pro Ile Ala Leu Ile Tyr Leu Val Leu Ile 35 40 45 Ala Val Gly Gln Asn Tyr Met Lys Glu Arg Lys Gly Phe Asn Leu Gln 50 55 60 Gly Pro Leu Ile Leu Trp Ser Phe Cys Leu Ala Ile Phe Ser Ile Leu 65 70 75 80 Gly Ala Val Arg Met Trp Gly Ile Met Gly Thr Val Leu Leu Thr Gly 85 90 95 Gly Leu Lys Gln Thr Val Cys Phe Ile Asn Phe Ile Asp Asn Ser Thr 100 105 110 Val Lys Phe Trp Ser Trp Val Phe Leu Leu Ser Lys Val Ile Glu Leu 115 120 125 Gly Asp Thr Ala Phe Ile Ile Leu Arg Lys Arg Pro Leu Ile Phe Ile 130 135 140 His Trp Tyr His His Ser Thr Val Leu Val Tyr Thr Ser Phe Gly Tyr 145 150 155 160 Lys Asn Lys Val Pro Ala Gly Gly Trp Phe Val Thr Met Asn Phe Gly 165 170 175 Val His Ala Ile Met Tyr Thr Tyr Tyr Thr Leu Lys Ala Ala Asn Val 180 185 190 Lys Pro Pro Lys Met Leu Pro Met Leu Ile Thr Ser Leu Gln Ile Leu 195 200 205 Gln Met Phe Val Gly Ala Ile Val Ser Ile Leu Thr Tyr Ile Trp Arg 210 215 220 Gln Asp Gln Gly Cys His Thr Thr Met Glu His Leu Phe Trp Ser Phe 225 230 235 240 Ile Leu Tyr Met Thr Tyr Phe Ile Leu Phe Ala His Phe Phe Cys Gln 245 250 255 Thr Tyr Ile Arg Pro Lys Val Lys Ala Lys Thr Lys Ser Gln 260 265 270 <210> 239 <211> 1142 <212> PRT <213> homo sapiens <400> 239 Met Leu Val Leu Arg Cys Arg Leu Gly Thr Ser Phe Pro Lys Leu Asp 1 5 10 15 Asn Leu Val Pro Lys Gly Lys Met Lys Ile Leu Leu Val Phe Leu Gly 20 25 30 Leu Leu Gly Asn Ser Val Ala Met Pro Met His Met Pro Arg Met Pro 35 40 45 Gly Phe Ser Ser Lys Ser Glu Glu Met Met Arg Tyr Asn Gln Phe Asn 50 55 60 Phe Met Asn Gly Pro His Met Ala His Leu Gly Pro Phe Phe Gly Asn 65 70 75 80 Gly Leu Pro Gln Gln Phe Pro Gln Tyr Gln Met Pro Met Trp Pro Gln 85 90 95 Pro Pro Pro Asn Thr Trp His Pro Arg Lys Ser Ser Ala Pro Lys Arg 100 105 110 His Asn Lys Thr Asp Gln Thr Gln Glu Thr Gln Lys Pro Asn Gln Thr 115 120 125 Gln Ser Lys Lys Pro Pro Gln Lys Arg Pro Leu Lys Gln Pro Ser His 130 135 140 Asn Gln Pro Gln Pro Glu Glu Glu Ala Gln Pro Pro Gln Ala Phe Pro 145 150 155 160 Pro Phe Gly Asn Gly Leu Phe Pro Tyr Gln Gln Pro Pro Trp Gln Ile 165 170 175 Pro Gln Arg Leu Pro Pro Pro Gly Tyr Gly Arg Pro Pro Ile Ser Asn 180 185 190 Glu Glu Gly Gly Asn Pro Tyr Phe Gly Tyr Phe Gly Tyr His Gly Phe 195 200 205 Gly Gly Arg Pro Pro Tyr Tyr Ser Glu Glu Met Phe Glu Gln Asp Phe 210 215 220 Glu Lys Pro Lys Glu Glu Asp Pro Pro Lys Ala Glu Ser Pro Gly Thr 225 230 235 240 Glu Pro Thr Ala Asn Ser Thr Val Thr Glu Thr Asn Ser Thr Gln Pro 245 250 255 Asn Pro Lys Gly Ser Gln Gly Gly Asn Asp Thr Ser Pro Thr Gly Asn 260 265 270 Ser Thr Pro Gly Leu Asn Thr Gly Asn Asn Pro Pro Ala Gln Asn Gly 275 280 285 Ile Gly Pro Leu Pro Ala Val Asn Ala Ser Gly Gln Gly Gly Pro Gly 290 295 300 Ser Gln Ile Pro Trp Arg Pro Ser Gln Pro Asn Ile Arg Glu Asn His 305 310 315 320 Pro Tyr Pro Asn Ile Arg Asn Phe Pro Ser Gly Arg Gln Trp Tyr Phe 325 330 335 Thr Gly Thr Val Met Gly His Arg Gln Asn Arg Pro Phe Tyr Arg Asn 340 345 350 Gln Gln Val Gln Arg Gly Pro Arg Trp Asn Phe Phe Ala Trp Glu Arg 355 360 365 Lys Gln Val Ala Arg Pro Gly Asn Pro Val Tyr His Lys Ala Tyr Pro 370 375 380 Pro Thr Ser Arg Gly Asn Tyr Pro Asn Tyr Ala Gly Asn Pro Ala Asn 385 390 395 400 Leu Arg Arg Lys Pro Gln Gly Pro Asn Lys His Pro Val Gly Thr Thr 405 410 415 Val Ala Pro Leu Gly Pro Lys Pro Gly Pro Val Val Arg Asn Glu Lys 420 425 430 Ile Gln Asn Pro Lys Glu Lys Pro Leu Gly Pro Lys Glu Gln Ile Ile 435 440 445 Val Pro Thr Lys Asn Pro Thr Ser Pro Trp Arg Asn Ser Gln Gln Tyr 450 455 460 Glu Val Asn Lys Ser Asn Tyr Lys Leu Pro His Ser Glu Gly Tyr Met 465 470 475 480 Pro Val Pro Asn Phe Asn Ser Val Asp Gln His Glu Asn Ser Tyr Tyr 485 490 495 Pro Arg Gly Asp Ser Arg Lys Val Pro Asn Ser Asp Gly Gln Thr Gln 500 505 510 Ser Gln Asn Leu Pro Lys Gly Ile Val Leu Gly Ser Arg Arg Met Pro 515 520 525 Tyr Glu Ser Glu Thr Asn Gln Ser Glu Leu Lys His Ser Ser Tyr Gln 530 535 540 Pro Ala Val Tyr Pro Glu Glu Ile Pro Ser Pro Ala Lys Glu His Phe 545 550 555 560 Pro Ala Gly Arg Asn Thr Trp Asp His Gln Glu Ile Ser Pro Pro Phe 565 570 575 Lys Glu Asp Pro Gly Arg Gln Glu Glu His Leu Pro His Pro Ser His 580 585 590 Gly Ser Arg Gly Ser Val Phe Tyr Pro Glu Tyr Asn Pro Tyr Asp Pro 595 600 605 Arg Glu Asn Ser Pro Tyr Leu Arg Gly Asn Thr Trp Asp Glu Arg Asp 610 615 620 Asp Ser Pro Asn Thr Met Gly Gln Lys Glu Ser Pro Leu Tyr Pro Ile 625 630 635 640 Asn Thr Pro Asp Gln Lys Glu Ile Val Pro Tyr Asn Glu Glu Asp Pro 645 650 655 Val Asp Pro Thr Gly Asp Glu Val Phe Pro Gly Gln Asn Arg Trp Gly 660 665 670 Glu Glu Leu Ser Phe Lys Gly Gly Pro Thr Val Arg His Tyr Glu Gly 675 680 685 Glu Gln Tyr Thr Ser Asn Gln Pro Lys Glu Tyr Leu Pro Tyr Ser Leu 690 695 700 Asp Asn Pro Ser Lys Pro Arg Glu Asp Phe Tyr Tyr Ser Glu Phe Tyr 705 710 715 720 Pro Trp Ser Pro Asp Glu Asn Phe Pro Ser Tyr Asn Thr Ala Ser Thr 725 730 735 Met Pro Pro Pro Ile Glu Ser Arg Gly Tyr Tyr Val Asn Asn Ala Ala 740 745 750 Gly Pro Glu Glu Ser Thr Leu Phe Pro Ser Arg Asn Ser Trp Asp His 755 760 765 Arg Ile Gln Ala Gln Gly Gln Arg Glu Arg Arg Pro Tyr Phe Asn Arg 770 775 780 Asn Ile Trp Asp Gln Ala Thr His Leu Gln Lys Ala Pro Ala Arg Pro 785 790 795 800 Pro Asp Gln Lys Gly Asn Gln Pro Tyr Tyr Ser Asn Thr Pro Ala Gly 805 810 815 Leu Gln Lys Asn Pro Ile Trp His Glu Gly Glu Asn Leu Asn Tyr Gly 820 825 830 Met Gln Ile Thr Arg Met Asn Ser Pro Glu Arg Glu His Ser Ser Phe 835 840 845 Pro Asn Phe Ile Pro Pro Ser Tyr Pro Ser Gly Gln Lys Glu Ala His 850 855 860 Leu Phe His Leu Ser Gln Arg Gly Ser Cys Cys Ala Gly Ser Ser Thr 865 870 875 880 Gly Pro Lys Asp Asn Pro Leu Ala Leu Gln Asp Tyr Thr Pro Ser Tyr 885 890 895 Gly Leu Ala Pro Gly Glu Asn Gln Asp Thr Ser Pro Leu Tyr Thr Asp 900 905 910 Gly Ser His Thr Lys Gln Thr Arg Asp Ile Ile Ser Pro Thr Ser Ile 915 920 925 Leu Pro Gly Gln Arg Asn Ser Ser Glu Lys Arg Glu Ser Gln Asn Pro 930 935 940 Phe Arg Asp Asp Val Ser Thr Leu Arg Arg Asn Thr Pro Cys Ser Ile 945 950 955 960 Lys Asn Gln Leu Gly Gln Lys Glu Ile Met Pro Phe Pro Glu Ala Ser 965 970 975 Ser Leu Gln Ser Lys Asn Thr Pro Cys Leu Lys Asn Asp Leu Gly Gly 980 985 990 Asp Gly Asn Asn Ile Leu Glu Gln Val Phe Glu Asp Asn Gln Leu Asn 995 1000 1005 Glu Arg Thr Val Asp Leu Thr Pro Glu Gln Leu Val Ile Gly Thr 1010 1015 1020 Pro Asp Glu Gly Ser Asn Pro Glu Gly Ile Gln Ser Gln Val Gln 1025 1030 1035 Glu Asn Glu Ser Glu Arg Gln Gln Gln Arg Pro Ser Asn Ile Leu 1040 1045 1050 His Leu Pro Cys Phe Gly Ser Lys Leu Ala Lys His His Ser Ser 1055 1060 1065 Thr Thr Gly Thr Pro Ser Ser Asp Gly Arg Gln Ser Pro Phe Asp 1070 1075 1080 Gly Asp Ser Ile Thr Pro Thr Glu Asn Pro Asn Thr Leu Val Glu 1085 1090 1095 Leu Ala Thr Glu Glu Gln Phe Lys Ser Ile Asn Val Asp Pro Leu 1100 1105 1110 Asp Ala Asp Glu His Ser Pro Phe Glu Phe Leu Gln Arg Gly Thr 1115 1120 1125 Asn Val Gln Asp Gln Val Gln Asp Cys Leu Leu Leu Gln Ala 1130 1135 1140 <210> 240 <211> 362 <212> PRT <213> homo sapiens <400> 240 Met Thr Gln Glu Leu Ser Phe Gln Lys Phe Ile Glu Gln Ser Asp Leu 1 5 10 15 Leu Gly Glu Leu Lys Tyr Asp Phe Asn Glu Lys Asp Glu Phe Arg His 20 25 30 Thr Glu Thr Gln Arg Pro Phe Val Phe Asn Tyr Tyr Glu Asn Val Leu 35 40 45 Glu Lys Asn Ser Lys Arg Tyr Gln Ala Leu Gly His Leu Leu Glu Gln 50 55 60 Tyr Ile Tyr Glu Leu Leu Glu Lys Val Cys Lys Leu Glu Lys Val Tyr 65 70 75 80 Ile Pro Pro Glu Ala Asp Lys Glu Glu Pro Arg Ser Phe Phe Phe Met 85 90 95 Ser Glu Lys Ala Leu Thr Asn His His Ser Ala Leu Leu Ile Leu Leu 100 105 110 Gln Asp His Gly Val Phe Arg Ala Gly Gln Trp Ser Gln Gln Ala Ile 115 120 125 Ile His His Gly Leu Gln His Gly Ser Gln Ile Pro Cys Ile Gln Met 130 135 140 Ala Leu Gln Ala His Tyr Asp Val Ile Val Leu Asn Pro Asn Asp Asn 145 150 155 160 Phe Val Glu Pro Lys Val Glu Lys Glu Trp Lys Gly Leu Leu Thr Gln 165 170 175 Asn Ile Glu Ser Ser Ser Leu Lys Met Val Gln Gly Gly Ser Phe Phe 180 185 190 Ser Leu Gln His Pro Pro Lys Cys Ile Pro Lys Arg Cys Ser Asn Thr 195 200 205 Pro Glu Glu His Thr Ala Tyr Ile Trp Asp Tyr Phe Ile Ser Lys Thr 210 215 220 Glu Gly Lys Asp Ile Ala Phe Ile Val His Gly Tyr Gly Gly Leu Val 225 230 235 240 Phe Met Asp Leu Leu Val Arg Arg Arg Trp Glu Val Met Ser Lys Val 245 250 255 Tyr Ala Val Ala Leu Ile Asp Ser Glu His His Val Gly His Gln Leu 260 265 270 Gly Ser Asp Val Gln Leu Leu Ala Trp Ile Lys His His Cys Arg Glu 275 280 285 Trp Val Thr Ser Pro Lys Pro Leu Asp Lys Pro Ala Ala Thr Val Phe 290 295 300 Lys Lys Glu Phe Pro Met Val Ser Ala Gly Thr Glu Lys Tyr Ile Leu 305 310 315 320 Ala Pro Ser Ser Ser Leu Gln Ser Ile Phe Lys Tyr Phe Lys Lys Ala 325 330 335 Leu Lys Ala Arg Thr Thr Ile Asn Phe Ser Arg Met Pro Ile Val Thr 340 345 350 Arg Ser Ser Thr Lys Arg Lys Gln Ser Ala 355 360 <210> 241 <211> 374 <212> PRT <213> homo sapiens <400> 241 Met Trp Phe Leu Thr Thr Leu Leu Leu Trp Val Pro Val Asp Gly Gln 1 5 10 15 Val Asp Thr Thr Lys Ala Val Ile Thr Leu Gln Pro Pro Trp Val Ser 20 25 30 Val Phe Gln Glu Glu Thr Val Thr Leu His Cys Glu Val Leu His Leu 35 40 45 Pro Gly Ser Ser Ser Thr Gln Trp Phe Leu Asn Gly Thr Ala Thr Gln 50 55 60 Thr Ser Thr Pro Ser Tyr Arg Ile Thr Ser Ala Ser Val Asn Asp Ser 65 70 75 80 Gly Glu Tyr Arg Cys Gln Arg Gly Leu Ser Gly Arg Ser Asp Pro Ile 85 90 95 Gln Leu Glu Ile His Arg Gly Trp Leu Leu Leu Gln Val Ser Ser Arg 100 105 110 Val Phe Thr Glu Gly Glu Pro Leu Ala Leu Arg Cys His Ala Trp Lys 115 120 125 Asp Lys Leu Val Tyr Asn Val Leu Tyr Tyr Arg Asn Gly Lys Ala Phe 130 135 140 Lys Phe Phe His Trp Asn Ser Asn Leu Thr Ile Leu Lys Thr Asn Ile 145 150 155 160 Ser His Asn Gly Thr Tyr His Cys Ser Gly Met Gly Lys His Arg Tyr 165 170 175 Thr Ser Ala Gly Ile Ser Val Thr Val Lys Glu Leu Phe Pro Ala Pro 180 185 190 Val Leu Asn Ala Ser Val Thr Ser Pro Leu Leu Glu Gly Asn Leu Val 195 200 205 Thr Leu Ser Cys Glu Thr Lys Leu Leu Leu Gln Arg Pro Gly Leu Gln 210 215 220 Leu Tyr Phe Ser Phe Tyr Met Gly Ser Lys Thr Leu Arg Gly Arg Asn 225 230 235 240 Thr Ser Ser Glu Tyr Gln Ile Leu Thr Ala Arg Arg Glu Asp Ser Gly 245 250 255 Leu Tyr Trp Cys Glu Ala Ala Thr Glu Asp Gly Asn Val Leu Lys Arg 260 265 270 Ser Pro Glu Leu Glu Leu Gln Val Leu Gly Leu Gln Leu Pro Thr Pro 275 280 285 Val Trp Phe His Val Leu Phe Tyr Leu Ala Val Gly Ile Met Phe Leu 290 295 300 Val Asn Thr Val Leu Trp Val Thr Ile Arg Lys Glu Leu Lys Arg Lys 305 310 315 320 Lys Lys Trp Asp Leu Glu Ile Ser Leu Asp Ser Gly His Glu Lys Lys 325 330 335 Val Ile Ser Ser Leu Gln Glu Asp Arg His Leu Glu Glu Glu Leu Lys 340 345 350 Cys Gln Glu Gln Lys Glu Glu Gln Leu Gln Glu Gly Val His Arg Lys 355 360 365 Glu Pro Gln Gly Ala Thr 370 <210> 242 <211> 330 <212> PRT <213> homo sapiens <400> 242 Met Leu Pro Asp Trp Lys Ser Ser Leu Ile Leu Met Ala Tyr Ile Ile 1 5 10 15 Ile Phe Leu Thr Gly Leu Pro Ala Asn Leu Leu Ala Leu Arg Ala Phe 20 25 30 Val Gly Arg Ile Arg Gln Pro Gln Pro Ala Pro Val His Ile Leu Leu 35 40 45 Leu Ser Leu Thr Leu Ala Asp Leu Leu Leu Leu Leu Leu Leu Pro Phe 50 55 60 Lys Ile Ile Glu Ala Ala Ser Asn Phe Arg Trp Tyr Leu Pro Lys Val 65 70 75 80 Val Cys Ala Leu Thr Ser Phe Gly Phe Tyr Ser Ser Ile Tyr Cys Ser 85 90 95 Thr Trp Leu Leu Ala Gly Ile Ser Ile Glu Arg Tyr Leu Gly Val Ala 100 105 110 Phe Pro Val Gln Tyr Lys Leu Ser Arg Arg Pro Leu Tyr Gly Val Ile 115 120 125 Ala Ala Leu Val Ala Trp Val Met Ser Phe Gly His Cys Thr Ile Val 130 135 140 Ile Ile Val Gln Tyr Leu Asn Thr Thr Glu Gln Val Arg Ser Gly Asn 145 150 155 160 Glu Ile Thr Cys Tyr Glu Asn Phe Thr Asp Asn Gln Leu Asp Val Val 165 170 175 Leu Pro Val Arg Leu Glu Leu Cys Leu Val Leu Phe Phe Ile Pro Met 180 185 190 Ala Val Thr Ile Phe Cys Tyr Trp Arg Phe Val Trp Ile Met Leu Ser 195 200 205 Gln Pro Leu Val Gly Ala Gln Arg Arg Arg Arg Ala Val Gly Leu Ala 210 215 220 Val Val Thr Leu Leu Asn Phe Leu Val Cys Phe Gly Pro Tyr Asn Val 225 230 235 240 Ser His Leu Val Gly Tyr His Gln Arg Lys Ser Pro Trp Trp Arg Ser 245 250 255 Ile Ala Val Val Phe Ser Ser Leu Asn Ala Ser Leu Asp Pro Leu Leu 260 265 270 Phe Tyr Phe Ser Ser Ser Val Val Arg Arg Ala Phe Gly Arg Gly Leu 275 280 285 Gln Val Leu Arg Asn Gln Gly Ser Ser Leu Leu Gly Arg Arg Gly Lys 290 295 300 Asp Thr Ala Glu Gly Thr Asn Glu Asp Arg Gly Val Gly Gln Gly Glu 305 310 315 320 Gly Met Pro Ser Ser Asp Phe Thr Thr Glu 325 330 <210> 243 <211> 243 <212> PRT <213> homo sapiens <400> 243 Met Ala Ala Ala Ile Ala Ser Ser Leu Ile Arg Gln Lys Arg Gln Ala 1 5 10 15 Arg Glu Ser Asn Ser Asp Arg Val Ser Ala Ser Lys Arg Arg Ser Ser 20 25 30 Pro Ser Lys Asp Gly Arg Ser Leu Cys Glu Arg His Val Leu Gly Val 35 40 45 Phe Ser Lys Val Arg Phe Cys Ser Gly Arg Lys Arg Pro Val Arg Arg 50 55 60 Arg Pro Glu Pro Gln Leu Lys Gly Ile Val Thr Arg Leu Phe Ser Gln 65 70 75 80 Gln Gly Tyr Phe Leu Gln Met His Pro Asp Gly Thr Ile Asp Gly Thr 85 90 95 Lys Asp Glu Asn Ser Asp Tyr Thr Leu Phe Asn Leu Ile Pro Val Gly 100 105 110 Leu Arg Val Val Ala Ile Gln Gly Val Lys Ala Ser Leu Tyr Val Ala 115 120 125 Met Asn Gly Glu Gly Tyr Leu Tyr Ser Ser Asp Val Phe Thr Pro Glu 130 135 140 Cys Lys Phe Lys Glu Ser Val Phe Glu Asn Tyr Tyr Val Ile Tyr Ser 145 150 155 160 Ser Thr Leu Tyr Arg Gln Gln Glu Ser Gly Arg Ala Trp Phe Leu Gly 165 170 175 Leu Asn Lys Glu Gly Gln Ile Met Lys Gly Asn Arg Val Lys Lys Thr 180 185 190 Lys Pro Ser Ser His Phe Val Pro Lys Pro Ile Glu Val Cys Met Tyr 195 200 205 Arg Glu Pro Ser Leu His Glu Ile Gly Glu Lys Gln Gly Arg Ser Arg 210 215 220 Lys Ser Ser Gly Thr Pro Thr Met Asn Gly Gly Lys Val Val Asn Gln 225 230 235 240 Asp Ser Thr <210> 244 <211> 165 <212> PRT <213> homo sapiens <400> 244 Met Val Thr Lys Trp Trp Gly Gln Asp Pro Pro Val Gln Leu Arg Ser 1 5 10 15 Gln Leu Met Leu Trp Ile Met Glu Leu Ile Leu Trp Lys Phe Gln Ser 20 25 30 Ser Val Val Gly Ser Ser Val Val Thr Trp Lys Ile Ser Asp Val Ala 35 40 45 Gly Pro His Gly Asp His Ser Cys Ser Leu Gln His Leu Glu Gln Ile 50 55 60 Ile Gly Ser Val Ser Asn Tyr Pro Arg Tyr Thr Gly Ser Arg Ser Cys 65 70 75 80 Asp Arg Gly Glu Asn Pro Val Ser Leu Ser Lys Arg Ile Lys Cys Thr 85 90 95 Trp Met Leu Gly Ala Ser Gly Phe Pro Pro Arg Cys Pro Ser Gly Arg 100 105 110 Asp His Ser Arg Asp His Pro Gly Lys Ser Gln Val Pro Ala Leu Glu 115 120 125 Leu Ala Asn Gln Leu Ala Ala Trp Gly Leu Trp Ser Ser Val Val Lys 130 135 140 Ser Trp Gly Phe Arg Ala Gly Glu Thr Glu Ala Pro Ile Ser Ala Leu 145 150 155 160 Ser Ser Ala His Ala 165 <210> 245 <211> 312 <212> PRT <213> homo sapiens <400> 245 Met Ala Gln Pro Tyr Pro Pro Ala Gln Tyr Pro Pro Pro Pro Gln Asn 1 5 10 15 Gly Ile Pro Ala Glu Tyr Ala Pro Pro Pro Pro His Pro Thr Gln Asp 20 25 30 Tyr Ser Gly Gln Thr Pro Val Pro Thr Glu His Gly Met Thr Leu Tyr 35 40 45 Thr Pro Ala Gln Thr His Pro Glu Gln Pro Gly Ser Glu Ala Ser Thr 50 55 60 Gln Pro Ile Ala Gly Thr Gln Thr Val Pro Gln Thr Asp Glu Ala Ala 65 70 75 80 Gln Thr Asp Ser Gln Pro Leu His Pro Ser Asp Pro Thr Glu Lys Gln 85 90 95 Gln Pro Lys Arg Leu His Val Ser Asn Ile Pro Phe Arg Phe Arg Asp 100 105 110 Pro Asp Leu Arg Gln Met Phe Gly Gln Phe Gly Lys Ile Leu Asp Val 115 120 125 Glu Ile Ile Phe Asn Glu Arg Gly Ser Lys Gly Phe Gly Phe Val Thr 130 135 140 Phe Glu Thr Ser Ser Asp Ala Asp Arg Ala Arg Glu Lys Leu Asn Gly 145 150 155 160 Thr Ile Val Glu Gly Arg Lys Ile Glu Val Asn Asn Ala Thr Ala Arg 165 170 175 Val Met Thr Asn Lys Lys Thr Gly Asn Pro Tyr Thr Asn Gly Trp Lys 180 185 190 Leu Asn Pro Val Val Gly Ala Val Tyr Gly Pro Glu Phe Tyr Ala Val 195 200 205 Thr Gly Phe Pro Tyr Pro Thr Thr Gly Thr Ala Val Ala Tyr Arg Gly 210 215 220 Ala His Leu Arg Gly Arg Gly Arg Ala Val Tyr Asn Thr Phe Arg Ala 225 230 235 240 Ala Pro Pro Pro Pro Pro Ile Pro Thr Tyr Gly Ala Val Val Tyr Gln 245 250 255 Asp Gly Phe Tyr Gly Ala Glu Ile Tyr Gly Gly Tyr Ala Ala Tyr Arg 260 265 270 Tyr Ala Gln Pro Ala Ala Ala Ala Ala Ala Tyr Ser Asp Ser Tyr Gly 275 280 285 Arg Val Tyr Ala Ala Ala Asp Pro Tyr His His Thr Ile Gly Pro Ala 290 295 300 Ala Thr Tyr Ser Ile Gly Thr Met 305 310 <210> 246 <211> 163 <212> PRT <213> homo sapiens <400> 246 Met Cys Met Asn Thr Ser Ile His Ala His Thr Tyr Ala Arg Thr His 1 5 10 15 Thr His Ser Val Phe Met Ser Ser Asn Val Thr Val Phe Gln Trp Met 20 25 30 Arg Leu Met Arg Ala Ser Ser Arg Ser Phe Thr Gln Ala Ile Pro Ala 35 40 45 Gly Gln Leu Leu Gln Thr Ala Cys Ser His Leu Phe Thr Thr Gln Asn 50 55 60 Thr Cys Gln Asn Ala Leu Gly Asn Asn Thr Arg Leu Gln His Thr Glu 65 70 75 80 Lys Val Arg Leu Ser Ile Gly Leu Ala Asp Phe Gly Leu Pro Gly Ile 85 90 95 Ala Arg Asn Thr Phe Val Val Pro Asp Ser Ile Ser Arg Tyr Cys Arg 100 105 110 Glu Gly Ser Val Ile Gly Lys Cys Cys Pro Ser Arg Lys Ser Ala Leu 115 120 125 Leu Asn Lys Gln Gly Ser Leu Lys Lys Phe Lys Ile Thr Arg Gly Glu 130 135 140 Thr Gln Pro Gly Val Thr Ile Ser Val Leu Glu Leu Ala Glu Ile Asp 145 150 155 160 Gln Arg Phe <210> 247 <211> 2386 <212> PRT <213> homo sapiens <400> 247 Met Leu Arg Gly Pro Gly Pro Gly Leu Leu Leu Leu Ala Val Gln Cys 1 5 10 15 Leu Gly Thr Ala Val Pro Ser Thr Gly Ala Ser Lys Ser Lys Arg Gln 20 25 30 Ala Gln Gln Met Val Gln Pro Gln Ser Pro Val Ala Val Ser Gln Ser 35 40 45 Lys Pro Gly Cys Tyr Asp Asn Gly Lys His Tyr Gln Ile Asn Gln Gln 50 55 60 Trp Glu Arg Thr Tyr Leu Gly Asn Ala Leu Val Cys Thr Cys Tyr Gly 65 70 75 80 Gly Ser Arg Gly Phe Asn Cys Glu Ser Lys Pro Glu Ala Glu Glu Thr 85 90 95 Cys Phe Asp Lys Tyr Thr Gly Asn Thr Tyr Arg Val Gly Asp Thr Tyr 100 105 110 Glu Arg Pro Lys Asp Ser Met Ile Trp Asp Cys Thr Cys Ile Gly Ala 115 120 125 Gly Arg Gly Arg Ile Ser Cys Thr Ile Ala Asn Arg Cys His Glu Gly 130 135 140 Gly Gln Ser Tyr Lys Ile Gly Asp Thr Trp Arg Arg Pro His Glu Thr 145 150 155 160 Gly Gly Tyr Met Leu Glu Cys Val Cys Leu Gly Asn Gly Lys Gly Glu 165 170 175 Trp Thr Cys Lys Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly 180 185 190 Thr Ser Tyr Val Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp 195 200 205 Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr 210 215 220 Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr 225 230 235 240 Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu 245 250 255 Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg 260 265 270 His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp 275 280 285 Val Arg Ala Ala Val Tyr Gln Pro Gln Pro His Pro Gln Pro Pro Pro 290 295 300 Tyr Gly His Cys Val Thr Asp Ser Gly Val Val Tyr Ser Val Gly Met 305 310 315 320 Gln Trp Leu Lys Thr Gln Gly Asn Lys Gln Met Leu Cys Thr Cys Leu 325 330 335 Gly Asn Gly Val Ser Cys Gln Glu Thr Ala Val Thr Gln Thr Tyr Gly 340 345 350 Gly Asn Ser Asn Gly Glu Pro Cys Val Leu Pro Phe Thr Tyr Asn Gly 355 360 365 Arg Thr Phe Tyr Ser Cys Thr Thr Glu Gly Arg Gln Asp Gly His Leu 370 375 380 Trp Cys Ser Thr Thr Ser Asn Tyr Glu Gln Asp Gln Lys Tyr Ser Phe 385 390 395 400 Cys Thr Asp His Thr Val Leu Val Gln Thr Arg Gly Gly Asn Ser Asn 405 410 415 Gly Ala Leu Cys His Phe Pro Phe Leu Tyr Asn Asn His Asn Tyr Thr 420 425 430 Asp Cys Thr Ser Glu Gly Arg Arg Asp Asn Met Lys Trp Cys Gly Thr 435 440 445 Thr Gln Asn Tyr Asp Ala Asp Gln Lys Phe Gly Phe Cys Pro Met Ala 450 455 460 Ala His Glu Glu Ile Cys Thr Thr Asn Glu Gly Val Met Tyr Arg Ile 465 470 475 480 Gly Asp Gln Trp Asp Lys Gln His Asp Met Gly His Met Met Arg Cys 485 490 495 Thr Cys Val Gly Asn Gly Arg Gly Glu Trp Thr Cys Ile Ala Tyr Ser 500 505 510 Gln Leu Arg Asp Gln Cys Ile Val Asp Asp Ile Thr Tyr Asn Val Asn 515 520 525 Asp Thr Phe His Lys Arg His Glu Glu Gly His Met Leu Asn Cys Thr 530 535 540 Cys Phe Gly Gln Gly Arg Gly Arg Trp Lys Cys Asp Pro Val Asp Gln 545 550 555 560 Cys Gln Asp Ser Glu Thr Gly Thr Phe Tyr Gln Ile Gly Asp Ser Trp 565 570 575 Glu Lys Tyr Val His Gly Val Arg Tyr Gln Cys Tyr Cys Tyr Gly Arg 580 585 590 Gly Ile Gly Glu Trp His Cys Gln Pro Leu Gln Thr Tyr Pro Ser Ser 595 600 605 Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn 610 615 620 Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys 625 630 635 640 Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu 645 650 655 Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys 660 665 670 Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly 675 680 685 His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr Ser Thr Ser Thr 690 695 700 Pro Val Thr Ser Asn Thr Val Thr Gly Glu Thr Thr Pro Phe Ser Pro 705 710 715 720 Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser Ser Phe 725 730 735 Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe Arg Val 740 745 750 Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu Asp Leu 755 760 765 Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro Gly Arg 770 775 780 Lys Tyr Ile Val Asn Val Tyr Gln Ile Ser Glu Asp Gly Glu Gln Ser 785 790 795 800 Leu Ile Leu Ser Thr Ser Gln Thr Thr Ala Pro Asp Ala Pro Pro Asp 805 810 815 Thr Thr Val Asp Gln Val Asp Asp Thr Ser Ile Val Val Arg Trp Ser 820 825 830 Arg Pro Gln Ala Pro Ile Thr Gly Tyr Arg Ile Val Tyr Ser Pro Ser 835 840 845 Val Glu Gly Ser Ser Thr Glu Leu Asn Leu Pro Glu Thr Ala Asn Ser 850 855 860 Val Thr Leu Ser Asp Leu Gln Pro Gly Val Gln Tyr Asn Ile Thr Ile 865 870 875 880 Tyr Ala Val Glu Glu Asn Gln Glu Ser Thr Pro Val Val Ile Gln Gln 885 890 895 Glu Thr Thr Gly Thr Pro Arg Ser Asp Thr Val Pro Ser Pro Arg Asp 900 905 910 Leu Gln Phe Val Glu Val Thr Asp Val Lys Val Thr Ile Met Trp Thr 915 920 925 Pro Pro Glu Ser Ala Val Thr Gly Tyr Arg Val Asp Val Ile Pro Val 930 935 940 Asn Leu Pro Gly Glu His Gly Gln Arg Leu Pro Ile Ser Arg Asn Thr 945 950 955 960 Phe Ala Glu Val Thr Gly Leu Ser Pro Gly Val Thr Tyr Tyr Phe Lys 965 970 975 Val Phe Ala Val Ser His Gly Arg Glu Ser Lys Pro Leu Thr Ala Gln 980 985 990 Gln Thr Thr Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu 995 1000 1005 Thr Asp Ser Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln 1010 1015 1020 Ile Thr Gly Tyr Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln 1025 1030 1035 Pro Arg Gln Tyr Asn Val Gly Pro Ser Val Ser Lys Tyr Pro Leu 1040 1045 1050 Arg Asn Leu Gln Pro Ala Ser Glu Tyr Thr Val Ser Leu Val Ala 1055 1060 1065 Ile Lys Gly Asn Gln Glu Ser Pro Lys Ala Thr Gly Val Phe Thr 1070 1075 1080 Thr Leu Gln Pro Gly Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val 1085 1090 1095 Thr Glu Thr Thr Ile Val Ile Thr Trp Thr Pro Ala Pro Arg Ile 1100 1105 1110 Gly Phe Lys Leu Gly Val Arg Pro Ser Gln Gly Gly Glu Ala Pro 1115 1120 1125 Arg Glu Val Thr Ser Asp Ser Gly Ser Ile Val Val Ser Gly Leu 1130 1135 1140 Thr Pro Gly Val Glu Tyr Val Tyr Thr Ile Gln Val Leu Arg Asp 1145 1150 1155 Gly Gln Glu Arg Asp Ala Pro Ile Val Asn Lys Val Val Thr Pro 1160 1165 1170 Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala Asn Pro Asp Thr 1175 1180 1185 Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr Pro Asp Ile 1190 1195 1200 Thr Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln Gln Gly 1205 1210 1215 Asn Ser Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys Thr 1220 1225 1230 Phe Asp Asn Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr 1235 1240 1245 Thr Val Lys Asp Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile 1250 1255 1260 Ile Pro Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn Ile 1265 1270 1275 Gly Pro Asp Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser Ile 1280 1285 1290 Asp Leu Thr Asn Phe Leu Val Arg Tyr Ser Pro Val Lys Asn Glu 1295 1300 1305 Glu Asp Val Ala Glu Leu Ser Ile Ser Pro Ser Asp Asn Ala Val 1310 1315 1320 Val Leu Thr Asn Leu Leu Pro Gly Thr Glu Tyr Val Val Ser Val 1325 1330 1335 Ser Ser Val Tyr Glu Gln His Glu Ser Thr Pro Leu Arg Gly Arg 1340 1345 1350 Gln Lys Thr Gly Leu Asp Ser Pro Thr Gly Ile Asp Phe Ser Asp 1355 1360 1365 Ile Thr Ala Asn Ser Phe Thr Val His Trp Ile Ala Pro Arg Ala 1370 1375 1380 Thr Ile Thr Gly Tyr Arg Ile Arg His His Pro Glu His Phe Ser 1385 1390 1395 Gly Arg Pro Arg Glu Asp Arg Val Pro His Ser Arg Asn Ser Ile 1400 1405 1410 Thr Leu Thr Asn Leu Thr Pro Gly Thr Glu Tyr Val Val Ser Ile 1415 1420 1425 Val Ala Leu Asn Gly Arg Glu Glu Ser Pro Leu Leu Ile Gly Gln 1430 1435 1440 Gln Ser Thr Val Ser Asp Val Pro Arg Asp Leu Glu Val Val Ala 1445 1450 1455 Ala Thr Pro Thr Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala Val 1460 1465 1470 Thr Val Arg Tyr Tyr Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn 1475 1480 1485 Ser Pro Val Gln Glu Phe Thr Val Pro Gly Ser Lys Ser Thr Ala 1490 1495 1500 Thr Ile Ser Gly Leu Lys Pro Gly Val Asp Tyr Thr Ile Thr Val 1505 1510 1515 Tyr Ala Val Thr Gly Arg Gly Asp Ser Pro Ala Ser Ser Lys Pro 1520 1525 1530 Ile Ser Ile Asn Tyr Arg Thr Glu Ile Asp Lys Pro Ser Gln Met 1535 1540 1545 Gln Val Thr Asp Val Gln Asp Asn Ser Ile Ser Val Lys Trp Leu 1550 1555 1560 Pro Ser Ser Ser Pro Val Thr Gly Tyr Arg Val Thr Thr Thr Pro 1565 1570 1575 Lys Asn Gly Pro Gly Pro Thr Lys Thr Lys Thr Ala Gly Pro Asp 1580 1585 1590 Gln Thr Glu Met Thr Ile Glu Gly Leu Gln Pro Thr Val Glu Tyr 1595 1600 1605 Val Val Ser Val Tyr Ala Gln Asn Pro Ser Gly Glu Ser Gln Pro 1610 1615 1620 Leu Val Gln Thr Ala Val Thr Asn Ile Asp Arg Pro Lys Gly Leu 1625 1630 1635 Ala Phe Thr Asp Val Asp Val Asp Ser Ile Lys Ile Ala Trp Glu 1640 1645 1650 Ser Pro Gln Gly Gln Val Ser Arg Tyr Arg Val Thr Tyr Ser Ser 1655 1660 1665 Pro Glu Asp Gly Ile His Glu Leu Phe Pro Ala Pro Asp Gly Glu 1670 1675 1680 Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro Gly Ser Glu Tyr 1685 1690 1695 Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu Ser Gln Pro 1700 1705 1710 Leu Ile Gly Thr Gln Ser Thr Ala Ile Pro Ala Pro Thr Asp Leu 1715 1720 1725 Lys Phe Thr Gln Val Thr Pro Thr Ser Leu Ser Ala Gln Trp Thr 1730 1735 1740 Pro Pro Asn Val Gln Leu Thr Gly Tyr Arg Val Arg Val Thr Pro 1745 1750 1755 Lys Glu Lys Thr Gly Pro Met Lys Glu Ile Asn Leu Ala Pro Asp 1760 1765 1770 Ser Ser Ser Val Val Val Ser Gly Leu Met Val Ala Thr Lys Tyr 1775 1780 1785 Glu Val Ser Val Tyr Ala Leu Lys Asp Thr Leu Thr Ser Arg Pro 1790 1795 1800 Ala Gln Gly Val Val Thr Thr Leu Glu Asn Val Ser Pro Pro Arg 1805 1810 1815 Arg Ala Arg Val Thr Asp Ala Thr Glu Thr Thr Ile Thr Ile Ser 1820 1825 1830 Trp Arg Thr Lys Thr Glu Thr Ile Thr Gly Phe Gln Val Asp Ala 1835 1840 1845 Val Pro Ala Asn Gly Gln Thr Pro Ile Gln Arg Thr Ile Lys Pro 1850 1855 1860 Asp Val Arg Ser Tyr Thr Ile Thr Gly Leu Gln Pro Gly Thr Asp 1865 1870 1875 Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp Asn Ala Arg Ser Ser 1880 1885 1890 Pro Val Val Ile Asp Ala Ser Thr Ala Ile Asp Ala Pro Ser Asn 1895 1900 1905 Leu Arg Phe Leu Ala Thr Thr Pro Asn Ser Leu Leu Val Ser Trp 1910 1915 1920 Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr Ile Ile Lys Tyr Glu 1925 1930 1935 Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro Arg Pro Arg Pro 1940 1945 1950 Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro Gly Thr Glu 1955 1960 1965 Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys Ser Glu 1970 1975 1980 Pro Leu Ile Gly Arg Lys Lys Thr Asp Glu Leu Pro Gln Leu Val 1985 1990 1995 Thr Leu Pro His Pro Asn Leu His Gly Pro Glu Ile Leu Asp Val 2000 2005 2010 Pro Ser Thr Val Gln Lys Thr Pro Phe Val Thr His Pro Gly Tyr 2015 2020 2025 Asp Thr Gly Asn Gly Ile Gln Leu Pro Gly Thr Ser Gly Gln Gln 2030 2035 2040 Pro Ser Val Gly Gln Gln Met Ile Phe Glu Glu His Gly Phe Arg 2045 2050 2055 Arg Thr Thr Pro Pro Thr Thr Ala Thr Pro Ile Arg His Arg Pro 2060 2065 2070 Arg Pro Tyr Pro Pro Asn Val Gly Glu Glu Ile Gln Ile Gly His 2075 2080 2085 Ile Pro Arg Glu Asp Val Asp Tyr His Leu Tyr Pro His Gly Pro 2090 2095 2100 Gly Leu Asn Pro Asn Ala Ser Thr Gly Gln Glu Ala Leu Ser Gln 2105 2110 2115 Thr Thr Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr Ile 2120 2125 2130 Ile Ser Cys His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln Phe 2135 2140 2145 Arg Val Pro Gly Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu Thr 2150 2155 2160 Arg Gly Ala Thr Tyr Asn Val Ile Val Glu Ala Leu Lys Asp Gln 2165 2170 2175 Gln Arg His Lys Val Arg Glu Glu Val Val Thr Val Gly Asn Ser 2180 2185 2190 Val Asn Glu Gly Leu Asn Gln Pro Thr Asp Asp Ser Cys Phe Asp 2195 2200 2205 Pro Tyr Thr Val Ser His Tyr Ala Val Gly Asp Glu Trp Glu Arg 2210 2215 2220 Met Ser Glu Ser Gly Phe Lys Leu Leu Cys Gln Cys Leu Gly Phe 2225 2230 2235 Gly Ser Gly His Phe Arg Cys Asp Ser Ser Arg Trp Cys His Asp 2240 2245 2250 Asn Gly Val Asn Tyr Lys Ile Gly Glu Lys Trp Asp Arg Gln Gly 2255 2260 2265 Glu Asn Gly Gln Met Met Ser Cys Thr Cys Leu Gly Asn Gly Lys 2270 2275 2280 Gly Glu Phe Lys Cys Asp Pro His Glu Ala Thr Cys Tyr Asp Asp 2285 2290 2295 Gly Lys Thr Tyr His Val Gly Glu Gln Trp Gln Lys Glu Tyr Leu 2300 2305 2310 Gly Ala Ile Cys Ser Cys Thr Cys Phe Gly Gly Gln Arg Gly Trp 2315 2320 2325 Arg Cys Asp Asn Cys Arg Arg Pro Gly Gly Glu Pro Ser Pro Glu 2330 2335 2340 Gly Thr Thr Gly Gln Ser Tyr Asn Gln Tyr Ser Gln Arg Tyr His 2345 2350 2355 Gln Arg Thr Asn Thr Asn Val Asn Cys Pro Ile Glu Cys Phe Met 2360 2365 2370 Pro Leu Asp Val Gln Ala Asp Arg Glu Asp Ser Arg Glu 2375 2380 2385 <210> 248 <211> 715 <212> PRT <213> homo sapiens <400> 248 Met Met Gln Glu Ser Ala Thr Glu Thr Ile Ser Asn Ser Ser Met Asn 1 5 10 15 Gln Asn Gly Met Ser Thr Leu Ser Ser Gln Leu Asp Ala Gly Ser Arg 20 25 30 Asp Gly Arg Ser Ser Gly Asp Thr Ser Ser Glu Val Ser Thr Val Glu 35 40 45 Leu Leu His Leu Gln Gln Gln Gln Ala Leu Gln Ala Ala Arg Gln Leu 50 55 60 Leu Leu Gln Gln Gln Thr Ser Gly Leu Lys Ser Pro Lys Ser Ser Asp 65 70 75 80 Lys Gln Arg Pro Leu Gln Val Pro Val Ser Val Ala Met Met Thr Pro 85 90 95 Gln Val Ile Thr Pro Gln Gln Met Gln Gln Ile Leu Gln Gln Gln Val 100 105 110 Leu Ser Pro Gln Gln Leu Gln Ala Leu Leu Gln Gln Gln Gln Ala Val 115 120 125 Met Leu Gln Gln Gln Gln Leu Gln Glu Phe Tyr Lys Lys Gln Gln Glu 130 135 140 Gln Leu His Leu Gln Leu Leu Gln Gln Gln Gln Gln Gln Gln Gln Gln 145 150 155 160 Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 165 170 175 Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln His 180 185 190 Pro Gly Lys Gln Ala Lys Glu Gln Gln Gln Gln Gln Gln Gln Gln Gln 195 200 205 Gln Leu Ala Ala Gln Gln Leu Val Phe Gln Gln Gln Leu Leu Gln Met 210 215 220 Gln Gln Leu Gln Gln Gln Gln His Leu Leu Ser Leu Gln Arg Gln Gly 225 230 235 240 Leu Ile Ser Ile Pro Pro Gly Gln Ala Ala Leu Pro Val Gln Ser Leu 245 250 255 Pro Gln Ala Gly Leu Ser Pro Ala Glu Ile Gln Gln Leu Trp Lys Glu 260 265 270 Val Thr Gly Val His Ser Met Glu Asp Asn Gly Ile Lys His Gly Gly 275 280 285 Leu Asp Leu Thr Thr Asn Asn Ser Ser Ser Thr Thr Ser Ser Asn Thr 290 295 300 Ser Lys Ala Ser Pro Pro Ile Thr His His Ser Ile Val Asn Gly Gln 305 310 315 320 Ser Ser Val Leu Ser Ala Arg Arg Asp Ser Ser Ser His Glu Glu Thr 325 330 335 Gly Ala Ser His Thr Leu Tyr Gly His Gly Val Cys Lys Trp Pro Gly 340 345 350 Cys Glu Ser Ile Cys Glu Asp Phe Gly Gln Phe Leu Lys His Leu Asn 355 360 365 Asn Glu His Ala Leu Asp Asp Arg Ser Thr Ala Gln Cys Arg Val Gln 370 375 380 Met Gln Val Val Gln Gln Leu Glu Ile Gln Leu Ser Lys Glu Arg Glu 385 390 395 400 Arg Leu Gln Ala Met Met Thr His Leu His Met Arg Pro Ser Glu Pro 405 410 415 Lys Pro Ser Pro Lys Pro Leu Asn Leu Val Ser Ser Val Thr Met Ser 420 425 430 Lys Asn Met Leu Glu Thr Ser Pro Gln Ser Leu Pro Gln Thr Pro Thr 435 440 445 Thr Pro Thr Ala Pro Val Thr Pro Ile Thr Gln Gly Pro Ser Val Ile 450 455 460 Thr Pro Ala Ser Val Pro Asn Val Gly Ala Ile Arg Arg Arg His Ser 465 470 475 480 Asp Lys Tyr Asn Ile Pro Met Ser Ser Glu Ile Ala Pro Asn Tyr Glu 485 490 495 Phe Tyr Lys Asn Ala Asp Val Arg Pro Pro Phe Thr Tyr Ala Thr Leu 500 505 510 Ile Arg Gln Ala Ile Met Glu Ser Ser Asp Arg Gln Leu Thr Leu Asn 515 520 525 Glu Ile Tyr Ser Trp Phe Thr Arg Thr Phe Ala Tyr Phe Arg Arg Asn 530 535 540 Ala Ala Thr Trp Lys Asn Ala Val Arg His Asn Leu Ser Leu His Lys 545 550 555 560 Cys Phe Val Arg Val Glu Asn Val Lys Gly Ala Val Trp Thr Val Asp 565 570 575 Glu Val Glu Tyr Gln Lys Arg Arg Ser Gln Lys Ile Thr Gly Ser Pro 580 585 590 Thr Leu Val Lys Asn Ile Pro Thr Ser Leu Gly Tyr Gly Ala Ala Leu 595 600 605 Asn Ala Ser Leu Gln Ala Ala Leu Ala Glu Ser Ser Leu Pro Leu Leu 610 615 620 Ser Asn Pro Gly Leu Ile Asn Asn Ala Ser Ser Gly Leu Leu Gln Ala 625 630 635 640 Val His Glu Asp Leu Asn Gly Ser Leu Asp His Ile Asp Ser Asn Gly 645 650 655 Asn Ser Ser Pro Gly Cys Ser Pro Gln Pro His Ile His Ser Ile His 660 665 670 Val Lys Glu Glu Pro Val Ile Ala Glu Asp Glu Asp Cys Pro Met Ser 675 680 685 Leu Val Thr Thr Ala Asn His Ser Pro Glu Leu Glu Asp Asp Arg Glu 690 695 700 Ile Glu Glu Glu Pro Leu Ser Glu Asp Leu Glu 705 710 715 <210> 249 <211> 445 <212> PRT <213> homo sapiens <400> 249 Met Asn Glu Glu Tyr Asp Val Ile Val Leu Gly Thr Gly Leu Thr Glu 1 5 10 15 Cys Ile Leu Ser Gly Ile Met Ser Val Asn Gly Lys Lys Val Leu His 20 25 30 Met Asp Arg Asn Pro Tyr Tyr Gly Gly Glu Ser Ala Ser Ile Thr Pro 35 40 45 Leu Glu Asp Leu Tyr Lys Arg Phe Lys Ile Pro Gly Ser Pro Pro Glu 50 55 60 Ser Met Gly Arg Gly Arg Asp Trp Asn Val Asp Leu Ile Pro Lys Phe 65 70 75 80 Leu Met Ala Asn Gly Gln Leu Val Lys Met Leu Leu Tyr Thr Glu Val 85 90 95 Thr Arg Tyr Leu Asp Phe Lys Val Thr Glu Gly Ser Phe Val Tyr Lys 100 105 110 Gly Gly Lys Ile Tyr Lys Val Pro Ser Thr Glu Ala Glu Ala Leu Ala 115 120 125 Ser Ser Leu Met Gly Leu Phe Glu Lys Arg Arg Phe Arg Lys Phe Leu 130 135 140 Val Tyr Val Ala Asn Phe Asp Glu Lys Asp Pro Arg Thr Phe Glu Gly 145 150 155 160 Ile Asp Pro Lys Lys Thr Thr Met Arg Asp Val Tyr Lys Lys Phe Asp 165 170 175 Leu Gly Gln Asp Val Ile Asp Phe Thr Gly His Ala Leu Ala Leu Tyr 180 185 190 Arg Thr Asp Asp Tyr Leu Asp Gln Pro Cys Tyr Glu Thr Ile Asn Arg 195 200 205 Ile Lys Leu Tyr Ser Glu Ser Leu Ala Arg Tyr Gly Lys Ser Pro Tyr 210 215 220 Leu Tyr Pro Leu Tyr Gly Leu Gly Glu Leu Pro Gln Gly Phe Ala Arg 225 230 235 240 Leu Ser Ala Ile Tyr Gly Gly Thr Tyr Met Leu Asn Lys Pro Ile Glu 245 250 255 Glu Ile Ile Val Gln Asn Gly Lys Val Ile Gly Val Lys Ser Glu Gly 260 265 270 Glu Ile Ala Arg Cys Lys Gln Leu Ile Cys Asp Pro Ser Tyr Val Lys 275 280 285 Asp Arg Val Glu Lys Val Gly Gln Val Ile Arg Val Ile Cys Ile Leu 290 295 300 Ser His Pro Ile Lys Asn Thr Asn Asp Ala Asn Ser Cys Gln Ile Ile 305 310 315 320 Ile Pro Gln Asn Gln Val Asn Arg Lys Ser Asp Ile Tyr Val Cys Met 325 330 335 Ile Ser Phe Ala His Asn Val Ala Ala Gln Gly Lys Tyr Ile Ala Ile 340 345 350 Val Ser Thr Thr Val Glu Thr Lys Glu Pro Glu Lys Glu Ile Arg Pro 355 360 365 Ala Leu Glu Leu Leu Glu Pro Ile Glu Gln Lys Phe Val Ser Ile Ser 370 375 380 Asp Leu Leu Val Pro Lys Asp Leu Gly Thr Glu Ser Gln Ile Phe Ile 385 390 395 400 Ser Arg Thr Tyr Asp Ala Thr Thr His Phe Glu Thr Thr Cys Asp Asp 405 410 415 Ile Lys Asn Ile Tyr Lys Arg Met Thr Gly Ser Glu Phe Asp Phe Glu 420 425 430 Glu Met Lys Arg Lys Lys Asn Asp Ile Tyr Gly Glu Asp 435 440 445 <210> 250 <211> 218 <212> PRT <213> homo sapiens <400> 250 Met Thr Ser Glu Phe Phe Ala Ala Gln Leu Arg Ala Gln Ile Ser Asp 1 5 10 15 Asp Thr Thr His Pro Ile Ser Tyr Tyr Lys Pro Glu Phe Tyr Thr Pro 20 25 30 Val Asp Gly Gly Thr Ala His Leu Ser Val Val Ala Glu Asp Gly Ser 35 40 45 Ala Val Ser Ala Thr Ser Thr Ile Asn Leu Tyr Phe Gly Ser Lys Val 50 55 60 Arg Ser Pro Val Ser Glu Ile Leu Phe Asn Asp Glu Met Asp Asp Phe 65 70 75 80 Ser Ser Pro Asn Ile Thr Asn Glu Phe Gly Val Pro Pro Ser Pro Ala 85 90 95 Asn Phe Ile Gln Pro Gly Lys Gln Pro Leu Ser Ser Met Cys Pro Thr 100 105 110 Ile Met Val Gly Gln Asp Gly Gln Pro Pro Ser His Ala Asp His Thr 115 120 125 Pro Met Pro Gln Ala Ile Ile Tyr Asn Leu Trp Phe Gly Tyr Asp Val 130 135 140 Lys Arg Ala Val Glu Glu Pro Arg Leu His Asn Gln Leu Leu Pro Asn 145 150 155 160 Val Thr Thr Val Glu Arg Asn Ile Asp Gln Ala Val Thr Ala Ala Leu 165 170 175 Glu Thr Arg His His His Thr Gln Ile Ala Ser Thr Phe Ile Ala Val 180 185 190 Val Gln Ala Ile Val Arg Thr Ala Gly Gly Trp Ala Ala Ala Ser Asp 195 200 205 Ser Arg Lys Gly Gly Glu Pro Ala Gly Tyr 210 215 <210> 251 <211> 553 <212> PRT <213> homo sapiens <400> 251 Met Ala Ala Pro Lys Thr Ala Ala Val Gly Pro Leu Val Gly Ala Val 1 5 10 15 Val Gln Gly Thr Asn Ser Thr Arg Phe Leu Val Phe Asn Ser Lys Thr 20 25 30 Ala Glu Leu Leu Ser His His Lys Val Glu Leu Thr Gln Glu Phe Pro 35 40 45 Lys Glu Gly Trp Val Glu Gln Asp Pro Lys Glu Ile Leu Gln Ser Val 50 55 60 Tyr Glu Cys Ile Ala Arg Thr Cys Glu Lys Leu Asp Glu Leu Asn Ile 65 70 75 80 Asp Ile Ser Asn Ile Lys Ala Val Gly Val Ser Asn Gln Arg Glu Thr 85 90 95 Thr Val Ile Trp Asp Lys Leu Thr Gly Glu Pro Leu Tyr Asn Ala Val 100 105 110 Val Trp Leu Asp Leu Arg Thr Gln Thr Thr Val Glu Asp Leu Ser Lys 115 120 125 Lys Ile Pro Gly Asn Ser Asn Phe Val Lys Ser Lys Thr Gly Leu Pro 130 135 140 Leu Ser Thr Tyr Phe Ser Ala Val Lys Leu Arg Trp Met Leu Asp Asn 145 150 155 160 Val Arg Asn Val Gln Lys Ala Val Glu Glu Gly Arg Ala Leu Phe Gly 165 170 175 Thr Ile Asp Ser Trp Leu Ile Trp Ser Leu Thr Gly Gly Val Asn Gly 180 185 190 Gly Val His Cys Thr Asp Val Thr Asn Ala Ser Arg Thr Met Leu Phe 195 200 205 Asn Ile His Ser Leu Glu Trp Asp Lys Glu Leu Cys Asp Phe Phe Glu 210 215 220 Ile Pro Met Asp Leu Leu Pro Asn Val Phe Ser Ser Ser Glu Ile Tyr 225 230 235 240 Gly Leu Ile Lys Thr Gly Ala Leu Glu Gly Val Pro Ile Ser Gly Cys 245 250 255 Leu Gly Asp Gln Cys Ala Ala Leu Val Gly Gln Met Cys Phe Gln Glu 260 265 270 Gly Gln Ala Lys Asn Thr Tyr Gly Thr Gly Cys Phe Leu Leu Cys Asn 275 280 285 Thr Gly Arg Lys Cys Val Phe Ser Glu His Gly Leu Leu Thr Thr Val 290 295 300 Ala Tyr Lys Leu Gly Arg Glu Lys Pro Ala Tyr Tyr Ala Leu Glu Gly 305 310 315 320 Ser Val Ala Ile Ala Gly Ala Val Ile Arg Trp Leu Arg Asp Asn Leu 325 330 335 Gly Ile Ile Glu Thr Ser Gly Asp Ile Glu Arg Leu Ala Lys Glu Val 340 345 350 Gly Thr Ser Tyr Gly Cys Tyr Phe Val Pro Ala Phe Ser Gly Leu Tyr 355 360 365 Ala Pro Tyr Trp Glu Pro Ser Ala Arg Gly Ile Leu Cys Gly Leu Thr 370 375 380 Gln Phe Thr Asn Lys Cys His Ile Ala Phe Ala Ala Leu Glu Ala Val 385 390 395 400 Cys Phe Gln Thr Arg Glu Ile Leu Glu Ala Met Asn Arg Asp Cys Gly 405 410 415 Ile Pro Leu Arg His Leu Gln Val Asp Gly Gly Met Thr Asn Asn Lys 420 425 430 Val Leu Met Gln Leu Gln Ala Asp Ile Leu His Ile Pro Val Ile Lys 435 440 445 Pro Phe Met Pro Glu Thr Thr Ala Leu Gly Ala Ala Met Ala Ala Gly 450 455 460 Ala Ala Glu Gly Val Ser Val Trp Ser Leu Glu Pro Gln Ala Leu Ser 465 470 475 480 Val Leu Arg Met Glu Arg Phe Glu Pro Gln Ile Gln Ala Thr Glu Ser 485 490 495 Glu Ile Arg Tyr Ala Thr Trp Lys Lys Ala Val Met Lys Ser Met Gly 500 505 510 Trp Val Thr Ser Gln Ser Pro Glu Gly Gly Asp Pro Ser Ile Phe Ser 515 520 525 Ser Leu Pro Leu Gly Phe Phe Ile Val Ser Ser Met Val Met Leu Ile 530 535 540 Gly Ala Arg Tyr Ile Ser Gly Val Pro 545 550 <210> 252 <211> 363 <212> PRT <213> homo sapiens <400> 252 Met Gly Pro Gly Glu Ala Leu Leu Ala Gly Leu Leu Val Met Val Leu 1 5 10 15 Ala Val Ala Leu Leu Ser Asn Ala Leu Val Leu Leu Cys Cys Ala Tyr 20 25 30 Ser Ala Glu Leu Arg Thr Arg Ala Ser Gly Val Leu Leu Val Asn Leu 35 40 45 Ser Leu Gly His Leu Leu Leu Ala Ala Leu Asp Met Pro Phe Thr Leu 50 55 60 Leu Gly Val Met Arg Gly Arg Thr Pro Ser Ala Pro Gly Ala Cys Gln 65 70 75 80 Val Ile Gly Phe Leu Asp Thr Phe Leu Ala Ser Asn Ala Ala Leu Ser 85 90 95 Val Ala Ala Leu Ser Ala Asp Gln Trp Leu Ala Val Gly Phe Pro Leu 100 105 110 Arg Tyr Ala Gly Arg Leu Arg Pro Arg Tyr Ala Gly Leu Leu Leu Gly 115 120 125 Cys Ala Trp Gly Gln Ser Leu Ala Phe Ser Gly Ala Ala Leu Gly Cys 130 135 140 Ser Trp Leu Gly Tyr Ser Ser Ala Phe Ala Ser Cys Ser Leu Arg Leu 145 150 155 160 Pro Pro Glu Pro Glu Arg Pro Arg Phe Ala Ala Phe Thr Ala Thr Leu 165 170 175 His Ala Val Gly Phe Val Leu Pro Leu Ala Val Leu Cys Leu Thr Ser 180 185 190 Leu Gln Val His Arg Val Ala Arg Arg His Cys Gln Arg Met Asp Thr 195 200 205 Val Thr Met Lys Ala Leu Ala Leu Leu Ala Asp Leu His Pro Ser Val 210 215 220 Arg Gln Arg Cys Leu Ile Gln Gln Lys Arg Arg Arg His Arg Ala Thr 225 230 235 240 Arg Lys Ile Gly Ile Ala Ile Ala Thr Phe Leu Ile Cys Phe Ala Pro 245 250 255 Tyr Val Met Thr Arg Leu Ala Glu Leu Val Pro Phe Val Thr Val Asn 260 265 270 Ala Gln Trp Gly Ile Leu Ser Lys Cys Leu Thr Tyr Ser Lys Ala Val 275 280 285 Ala Asp Pro Phe Thr Tyr Ser Leu Leu Arg Arg Pro Phe Arg Gln Val 290 295 300 Leu Ala Gly Met Val His Arg Leu Leu Lys Arg Thr Pro Arg Pro Ala 305 310 315 320 Ser Thr His Asp Ser Ser Leu Asp Val Ala Gly Met Val His Gln Leu 325 330 335 Leu Lys Arg Thr Pro Arg Pro Ala Ser Thr His Asn Gly Ser Val Asp 340 345 350 Thr Glu Asn Asp Ser Cys Leu Gln Gln Thr His 355 360 <210> 253 <211> 349 <212> PRT <213> homo sapiens <400> 253 Met Ala Ile Pro Ile Thr Val Leu Asp Cys Asp Leu Leu Leu Tyr Gly 1 5 10 15 Arg Gly His Arg Thr Leu Asp Arg Phe Lys Leu Asp Asp Val Thr Asp 20 25 30 Glu Tyr Leu Met Ser Met Tyr Gly Phe Pro Arg Gln Phe Ile Tyr Tyr 35 40 45 Leu Val Glu Leu Leu Gly Ala Asn Leu Ser Arg Pro Thr Gln Arg Ser 50 55 60 Arg Ala Ile Ser Pro Glu Thr Gln Val Leu Ala Ala Leu Gly Phe Tyr 65 70 75 80 Thr Ser Gly Ser Phe Gln Thr Arg Met Gly Asp Ala Ile Gly Ile Ser 85 90 95 Gln Ala Ser Met Ser Arg Cys Val Ala Asn Val Thr Glu Ala Leu Val 100 105 110 Glu Arg Ala Ser Gln Phe Ile Arg Phe Pro Ala Asp Glu Ala Ser Ile 115 120 125 Gln Ala Leu Lys Asp Glu Phe Tyr Gly Leu Ala Gly Met Pro Gly Val 130 135 140 Met Gly Val Val Asp Cys Ile His Val Ala Ile Lys Ala Pro Asn Ala 145 150 155 160 Glu Asp Leu Ser Tyr Val Asn Arg Lys Gly Leu His Ser Leu Asn Cys 165 170 175 Leu Met Val Cys Asp Ile Arg Gly Thr Leu Met Thr Val Glu Thr Asn 180 185 190 Trp Pro Gly Ser Leu Gln Asp Cys Ala Val Leu Gln Gln Ser Ser Leu 195 200 205 Ser Ser Gln Phe Glu Ala Gly Met His Lys Asp Ser Trp Leu Leu Gly 210 215 220 Asp Ser Ser Phe Phe Leu Arg Thr Trp Leu Met Thr Pro Leu His Ile 225 230 235 240 Pro Glu Thr Pro Ala Glu Tyr Arg Tyr Asn Met Ala His Ser Ala Thr 245 250 255 His Ser Val Ile Glu Lys Thr Phe Arg Thr Leu Cys Ser Arg Phe Arg 260 265 270 Cys Leu Asp Gly Ser Lys Gly Ala Leu Gln Tyr Ser Pro Glu Lys Ser 275 280 285 Ser His Ile Ile Leu Ala Cys Cys Val Leu His Asn Ile Ser Leu Glu 290 295 300 His Gly Met Asp Val Trp Ser Ser Pro Met Thr Gly Pro Met Glu Gln 305 310 315 320 Pro Pro Glu Glu Glu Tyr Glu His Met Glu Ser Leu Asp Leu Glu Ala 325 330 335 Asp Arg Ile Arg Gln Glu Leu Met Leu Thr His Phe Ser 340 345 <210> 254 <211> 484 <212> PRT <213> homo sapiens <400> 254 Met Asp Leu Gly Lys Asp Gln Ser His Leu Lys His His Gln Thr Pro 1 5 10 15 Asp Pro His Gln Glu Glu Asn His Ser Pro Glu Val Ile Gly Thr Trp 20 25 30 Ser Leu Arg Asn Arg Glu Leu Leu Arg Lys Arg Lys Ala Glu Val His 35 40 45 Glu Lys Glu Thr Ser Gln Trp Leu Phe Gly Glu Gln Lys Lys Arg Lys 50 55 60 Gln Gln Arg Thr Gly Lys Gly Asn Arg Arg Gly Arg Lys Arg Gln Gln 65 70 75 80 Asn Thr Glu Leu Lys Val Glu Pro Gln Pro Gln Ile Glu Lys Glu Ile 85 90 95 Val Glu Lys Ala Leu Ala Pro Ile Glu Lys Lys Thr Glu Pro Pro Gly 100 105 110 Ser Ile Thr Lys Val Phe Pro Ser Val Ala Ser Pro Gln Lys Val Val 115 120 125 Pro Glu Glu His Phe Ser Glu Ile Cys Gln Glu Ser Asn Ile Tyr Gln 130 135 140 Glu Asn Phe Ser Glu Tyr Gln Glu Ile Ala Val Gln Asn His Ser Ser 145 150 155 160 Glu Thr Cys Gln His Val Ser Glu Pro Glu Asp Leu Ser Pro Lys Met 165 170 175 Tyr Gln Glu Ile Ser Val Leu Gln Asp Asn Ser Ser Lys Ile Cys Gln 180 185 190 Asp Met Lys Glu Pro Glu Asp Asn Ser Pro Asn Thr Cys Gln Val Ile 195 200 205 Ser Val Ile Gln Asp His Pro Phe Lys Met Tyr Gln Asp Met Ala Lys 210 215 220 Arg Glu Asp Leu Ala Pro Lys Met Cys Gln Glu Ala Ala Val Pro Lys 225 230 235 240 Ile Leu Pro Cys Pro Thr Ser Glu Asp Thr Ala Asp Leu Ala Gly Cys 245 250 255 Ser Leu Gln Ala Tyr Pro Lys Pro Asp Val Pro Lys Gly Tyr Ile Leu 260 265 270 Asp Thr Asp Gln Asn Pro Ala Glu Pro Glu Glu Tyr Asn Glu Thr Asp 275 280 285 Gln Gly Ile Ala Glu Thr Glu Gly Leu Phe Pro Lys Ile Gln Glu Ile 290 295 300 Ala Glu Pro Lys Asp Leu Ser Thr Lys Thr His Gln Glu Ser Ala Glu 305 310 315 320 Pro Lys Tyr Leu Pro His Lys Thr Cys Asn Glu Ile Ile Val Pro Lys 325 330 335 Ala Pro Ser His Lys Thr Ile Gln Glu Thr Pro His Ser Glu Asp Tyr 340 345 350 Ser Ile Glu Ile Asn Gln Glu Thr Pro Gly Ser Glu Lys Tyr Ser Pro 355 360 365 Glu Thr Tyr Gln Glu Ile Pro Gly Leu Glu Glu Tyr Ser Pro Glu Ile 370 375 380 Tyr Gln Glu Thr Ser Gln Leu Glu Glu Tyr Ser Pro Glu Ile Tyr Gln 385 390 395 400 Glu Thr Pro Gly Pro Glu Asp Leu Ser Thr Glu Thr Tyr Lys Asn Lys 405 410 415 Asp Val Pro Lys Glu Cys Phe Pro Glu Pro His Gln Glu Thr Gly Gly 420 425 430 Pro Gln Gly Gln Asp Pro Lys Ala His Gln Glu Asp Ala Lys Asp Ala 435 440 445 Tyr Thr Phe Pro Gln Glu Met Lys Glu Lys Pro Lys Glu Glu Pro Gly 450 455 460 Ile Pro Ala Ile Leu Asn Glu Ser His Pro Glu Asn Asp Val Tyr Ser 465 470 475 480 Tyr Val Leu Phe <210> 255 <211> 131 <212> PRT <213> homo sapiens <400> 255 Met Ser Gly Arg Gly Lys Gln Gly Gly Lys Ala Arg Ala Lys Ser Lys 1 5 10 15 Ser Arg Ser Ser Arg Ala Gly Leu Gln Phe Pro Val Gly Arg Ile His 20 25 30 Arg Leu Leu Arg Lys Gly Asn Tyr Ala Glu Arg Ile Gly Ala Gly Ala 35 40 45 Pro Val Tyr Leu Ala Ala Val Leu Glu Tyr Leu Thr Ala Glu Ile Leu 50 55 60 Glu Leu Ala Gly Asn Ala Ser Arg Asp Asn Lys Lys Thr Arg Ile Ile 65 70 75 80 Pro Arg His Leu Gln Leu Ala Ile Arg Asn Asp Glu Glu Leu Asn Lys 85 90 95 Leu Leu Gly Gly Val Thr Ile Ala Gln Gly Gly Val Leu Pro Asn Ile 100 105 110 Gln Ala Val Leu Leu Pro Lys Lys Thr Glu Ser His His His Lys Ala 115 120 125 Gln Ser Lys 130 <210> 256 <211> 90 <212> PRT <213> homo sapiens <400> 256 Met Pro Lys Arg Lys Ala Glu Gly Asp Ala Lys Gly Asp Lys Ala Lys 1 5 10 15 Val Lys Asp Glu Pro Gln Arg Arg Ser Ala Arg Leu Ser Ala Lys Pro 20 25 30 Ala Pro Pro Lys Pro Glu Pro Lys Pro Lys Lys Ala Pro Ala Lys Lys 35 40 45 Gly Glu Lys Val Pro Lys Gly Lys Lys Gly Lys Ala Asp Ala Gly Lys 50 55 60 Glu Gly Asn Asn Pro Ala Glu Asn Gly Asp Ala Lys Thr Asp Gln Ala 65 70 75 80 Gln Lys Ala Glu Gly Ala Gly Asp Ala Lys 85 90 <210> 257 <211> 330 <212> PRT <213> homo sapiens <400> 257 Met Thr Thr Ser Leu Leu Leu His Pro Arg Trp Pro Glu Ser Leu Met 1 5 10 15 Tyr Val Tyr Glu Asp Ser Ala Ala Glu Ser Gly Ile Gly Gly Gly Gly 20 25 30 Gly Gly Gly Gly Gly Gly Thr Gly Gly Ala Gly Gly Gly Cys Ser Gly 35 40 45 Ala Ser Pro Gly Lys Ala Pro Ser Met Asp Gly Leu Gly Ser Ser Cys 50 55 60 Pro Ala Ser His Cys Arg Asp Leu Leu Pro His Pro Val Leu Gly Arg 65 70 75 80 Pro Pro Ala Pro Leu Gly Ala Pro Gln Gly Ala Val Tyr Thr Asp Ile 85 90 95 Pro Ala Pro Glu Ala Ala Arg Gln Cys Ala Pro Pro Pro Ala Pro Pro 100 105 110 Thr Ser Ser Ser Ala Thr Leu Gly Tyr Gly Tyr Pro Phe Gly Gly Ser 115 120 125 Tyr Tyr Gly Cys Arg Leu Ser His Asn Val Asn Leu Gln Gln Lys Pro 130 135 140 Cys Ala Tyr His Pro Gly Asp Lys Tyr Pro Glu Pro Ser Gly Ala Leu 145 150 155 160 Pro Gly Asp Asp Leu Ser Ser Arg Ala Lys Glu Phe Ala Phe Tyr Pro 165 170 175 Ser Phe Ala Ser Ser Tyr Gln Ala Met Pro Gly Tyr Leu Asp Val Ser 180 185 190 Val Val Pro Gly Ile Ser Gly His Pro Glu Pro Arg His Asp Ala Leu 195 200 205 Ile Pro Val Glu Gly Tyr Gln His Trp Ala Leu Ser Asn Gly Trp Asp 210 215 220 Ser Gln Val Tyr Cys Ser Lys Glu Gln Ser Gln Ser Ala His Leu Trp 225 230 235 240 Lys Ser Pro Phe Pro Asp Val Val Pro Leu Gln Pro Glu Val Ser Ser 245 250 255 Tyr Arg Arg Gly Arg Lys Lys Arg Val Pro Tyr Thr Lys Val Gln Leu 260 265 270 Lys Glu Leu Glu Lys Glu Tyr Ala Ala Ser Lys Phe Ile Thr Lys Glu 275 280 285 Lys Arg Arg Arg Ile Ser Ala Thr Thr Asn Leu Ser Glu Arg Gln Val 290 295 300 Thr Ile Trp Phe Gln Asn Arg Arg Val Lys Glu Lys Lys Val Val Ser 305 310 315 320 Lys Ser Lys Ala Pro His Leu His Ser Thr 325 330 <210> 258 <211> 371 <212> PRT <213> homo sapiens <400> 258 Met Ala Ala Pro Ala Leu Arg Leu Cys His Ile Ala Phe His Val Pro 1 5 10 15 Ala Gly Gln Pro Leu Ala Arg Asn Leu Gln Arg Leu Phe Gly Phe Gln 20 25 30 Pro Leu Ala Ser Arg Glu Val Asp Gly Trp Arg Gln Leu Ala Leu Arg 35 40 45 Ser Gly Asp Ala Val Phe Leu Val Asn Glu Gly Ala Gly Ser Gly Glu 50 55 60 Pro Leu Tyr Gly Leu Asp Pro Arg His Ala Val Pro Ser Ala Thr Asn 65 70 75 80 Leu Cys Phe Asp Val Ala Asp Ala Gly Ala Ala Thr Arg Glu Leu Ala 85 90 95 Ala Leu Gly Cys Ser Val Pro Val Pro Pro Val Arg Val Arg Asp Ala 100 105 110 Gln Gly Ala Ala Thr Tyr Ala Val Val Ser Ser Pro Ala Gly Ile Leu 115 120 125 Ser Leu Thr Leu Leu Glu Arg Ala Gly Tyr Arg Gly Pro Phe Leu Pro 130 135 140 Gly Phe Arg Pro Val Ser Ser Ala Pro Gly Pro Gly Trp Val Ser Arg 145 150 155 160 Val Asp His Leu Thr Leu Ala Cys Thr Pro Gly Ser Ser Pro Thr Leu 165 170 175 Leu Arg Trp Phe His Asp Cys Leu Gly Phe Cys His Leu Pro Leu Ser 180 185 190 Pro Gly Glu Asp Pro Glu Leu Gly Leu Glu Met Thr Ala Gly Phe Gly 195 200 205 Leu Gly Gly Leu Arg Leu Thr Ala Leu Gln Ala Gln Pro Gly Ser Ile 210 215 220 Val Pro Thr Leu Val Leu Ala Glu Ser Leu Pro Gly Ala Thr Thr Arg 225 230 235 240 Gln Asp Gln Val Glu Gln Phe Leu Ala Arg His Lys Gly Pro Gly Leu 245 250 255 Gln His Val Gly Leu Tyr Thr Pro Asn Ile Val Glu Ala Thr Glu Gly 260 265 270 Val Ala Thr Ala Gly Gly Gln Phe Leu Ala Pro Pro Gly Ala Tyr Tyr 275 280 285 Gln Gln Pro Gly Lys Glu Arg Gln Ile Arg Ala Ala Gly His Glu Pro 290 295 300 His Leu Leu Ala Arg Gln Gly Ile Leu Leu Asp Gly Asp Lys Gly Lys 305 310 315 320 Phe Leu Leu Gln Val Phe Thr Lys Ser Leu Phe Thr Glu Asp Thr Phe 325 330 335 Phe Leu Glu Leu Ile Gln Arg Gln Gly Ala Thr Gly Phe Gly Gln Gly 340 345 350 Asn Ile Arg Ala Leu Trp Gln Ser Val Gln Glu Gln Ser Ala Arg Ser 355 360 365 Gln Glu Ala 370 <210> 259 <211> 115 <212> PRT <213> homo sapiens <400> 259 Met Leu Gly Leu Leu Gly Ser Thr Ala Leu Val Gly Trp Ile Thr Gly 1 5 10 15 Ala Ala Val Ala Val Leu Leu Leu Leu Leu Leu Leu Ala Thr Cys Leu 20 25 30 Phe His Gly Arg Gln Asp Cys Asp Val Glu Arg Asn Arg Thr Ala Ala 35 40 45 Gly Gly Asn Arg Val Arg Arg Ala Gln Pro Trp Pro Phe Arg Arg Arg 50 55 60 Gly His Leu Gly Ile Phe His His His Arg His Pro Gly His Val Ser 65 70 75 80 His Val Pro Asn Val Gly Leu His His His His His Pro Arg His Thr 85 90 95 Pro His His Leu His His His His His Pro His Arg His His Pro Arg 100 105 110 His Ala Arg 115 <210> 260 <211> 487 <212> PRT <213> homo sapiens <400> 260 Met Ser Leu Pro Asn Ser Ser Cys Leu Leu Glu Asp Lys Met Cys Glu 1 5 10 15 Gly Asn Lys Thr Thr Met Ala Ser Pro Gln Leu Met Pro Leu Val Val 20 25 30 Val Leu Ser Thr Ile Cys Leu Val Thr Val Gly Leu Asn Leu Leu Val 35 40 45 Leu Tyr Ala Val Arg Ser Glu Arg Lys Leu His Thr Val Gly Asn Leu 50 55 60 Tyr Ile Val Ser Leu Ser Val Ala Asp Leu Ile Val Gly Ala Val Val 65 70 75 80 Met Pro Met Asn Ile Leu Tyr Leu Leu Met Ser Lys Trp Ser Leu Gly 85 90 95 Arg Pro Leu Cys Leu Phe Trp Leu Ser Met Asp Tyr Val Ala Ser Thr 100 105 110 Ala Ser Ile Phe Ser Val Phe Ile Leu Cys Ile Asp Arg Tyr Arg Ser 115 120 125 Val Gln Gln Pro Leu Arg Tyr Leu Lys Tyr Arg Thr Lys Thr Arg Ala 130 135 140 Ser Ala Thr Ile Leu Gly Ala Trp Phe Leu Ser Phe Leu Trp Val Ile 145 150 155 160 Pro Ile Leu Gly Trp Asn His Phe Met Gln Gln Thr Ser Val Arg Arg 165 170 175 Glu Asp Lys Cys Glu Thr Asp Phe Tyr Asp Val Thr Trp Phe Lys Val 180 185 190 Met Thr Ala Ile Ile Asn Phe Tyr Leu Pro Thr Leu Leu Met Leu Trp 195 200 205 Phe Tyr Ala Lys Ile Tyr Lys Ala Val Arg Gln His Cys Gln His Arg 210 215 220 Glu Leu Ile Asn Arg Ser Leu Pro Ser Phe Ser Glu Ile Lys Leu Arg 225 230 235 240 Pro Glu Asn Pro Lys Gly Asp Ala Lys Lys Pro Gly Lys Glu Ser Pro 245 250 255 Trp Glu Val Leu Lys Arg Lys Pro Lys Asp Ala Gly Gly Gly Ser Val 260 265 270 Leu Lys Ser Pro Ser Gln Thr Pro Lys Glu Met Lys Ser Pro Val Val 275 280 285 Phe Ser Gln Glu Asp Asp Arg Glu Val Asp Lys Leu Tyr Cys Phe Pro 290 295 300 Leu Asp Ile Val His Met Gln Ala Ala Ala Glu Gly Ser Ser Arg Asp 305 310 315 320 Tyr Val Ala Val Asn Arg Ser His Gly Gln Leu Lys Thr Asp Glu Gln 325 330 335 Gly Leu Asn Thr His Gly Ala Ser Glu Ile Ser Glu Asp Gln Met Leu 340 345 350 Gly Asp Ser Gln Ser Phe Ser Arg Thr Asp Ser Asp Thr Thr Thr Glu 355 360 365 Thr Ala Pro Gly Lys Gly Lys Leu Arg Ser Gly Ser Asn Thr Gly Leu 370 375 380 Asp Tyr Ile Lys Phe Thr Trp Lys Arg Leu Arg Ser His Ser Arg Gln 385 390 395 400 Tyr Val Ser Gly Leu His Met Asn Arg Glu Arg Lys Ala Ala Lys Gln 405 410 415 Leu Gly Phe Ile Met Ala Ala Phe Ile Leu Cys Trp Ile Pro Tyr Phe 420 425 430 Ile Phe Phe Met Val Ile Ala Phe Cys Lys Asn Cys Cys Asn Glu His 435 440 445 Leu His Met Phe Thr Ile Trp Leu Gly Tyr Ile Asn Ser Thr Leu Asn 450 455 460 Pro Leu Ile Tyr Pro Leu Cys Asn Glu Asn Phe Lys Lys Thr Phe Lys 465 470 475 480 Arg Ile Leu His Ile Arg Ser 485 <210> 261 <211> 390 <212> PRT <213> homo sapiens <400> 261 Met Gly Gln Arg Leu Ser Gly Gly Arg Ser Cys Leu Asp Val Pro Gly 1 5 10 15 Arg Leu Leu Pro Gln Pro Pro Pro Pro Pro Pro Pro Val Arg Arg Lys 20 25 30 Leu Ala Leu Leu Phe Ala Met Leu Cys Val Trp Leu Tyr Met Phe Leu 35 40 45 Tyr Ser Cys Ala Gly Ser Cys Ala Ala Ala Pro Gly Leu Leu Leu Leu 50 55 60 Gly Ser Gly Ser Arg Ala Ala His Asp Pro Pro Ala Leu Ala Thr Ala 65 70 75 80 Pro Asp Gly Thr Pro Pro Arg Leu Pro Phe Arg Ala Pro Pro Ala Thr 85 90 95 Pro Leu Ala Ser Gly Lys Glu Met Ala Glu Gly Ala Ala Ser Pro Glu 100 105 110 Glu Gln Ser Pro Glu Val Pro Asp Ser Pro Ser Pro Ile Ser Ser Phe 115 120 125 Phe Ser Gly Ser Gly Ser Lys Gln Leu Pro Gln Ala Ile Ile Ile Gly 130 135 140 Val Lys Lys Gly Gly Thr Arg Ala Leu Leu Glu Phe Leu Arg Val His 145 150 155 160 Pro Asp Val Arg Ala Val Gly Ala Glu Pro His Phe Phe Asp Arg Ser 165 170 175 Tyr Asp Lys Gly Leu Ala Trp Tyr Arg Asp Leu Met Pro Arg Thr Leu 180 185 190 Asp Gly Gln Ile Thr Met Glu Lys Thr Pro Ser Tyr Phe Val Thr Arg 195 200 205 Glu Ala Pro Ala Arg Ile Ser Ala Met Ser Lys Asp Thr Lys Leu Ile 210 215 220 Val Val Val Arg Asp Pro Val Thr Arg Ala Ile Ser Asp Tyr Thr Gln 225 230 235 240 Thr Leu Ser Lys Arg Pro Asp Ile Pro Thr Phe Glu Ser Leu Thr Phe 245 250 255 Lys Asn Arg Thr Ala Gly Leu Ile Asp Thr Ser Trp Ser Ala Ile Gln 260 265 270 Ile Gly Ile Tyr Ala Lys His Leu Glu His Trp Leu Arg His Phe Pro 275 280 285 Ile Arg Gln Met Leu Phe Val Ser Gly Glu Arg Leu Ile Ser Asp Pro 290 295 300 Ala Gly Glu Leu Gly Arg Val Gln Asp Phe Leu Gly Leu Lys Arg Ile 305 310 315 320 Ile Thr Asp Lys His Phe Tyr Phe Asn Lys Thr Lys Gly Phe Pro Cys 325 330 335 Leu Lys Lys Ala Glu Gly Ser Ser Arg Pro His Cys Leu Gly Lys Thr 340 345 350 Lys Gly Arg Thr His Pro Glu Ile Asp Arg Glu Val Val Arg Arg Leu 355 360 365 Arg Glu Phe Tyr Arg Pro Phe Asn Leu Lys Phe Tyr Gln Met Thr Gly 370 375 380 His Asp Phe Gly Trp Asp 385 390 <210> 262 <211> 372 <212> PRT <213> homo sapiens <400> 262 Met Gly Trp Ser Cys Leu Val Thr Gly Ala Gly Gly Leu Leu Gly Gln 1 5 10 15 Arg Ile Val Arg Leu Leu Val Glu Glu Lys Glu Leu Lys Glu Ile Arg 20 25 30 Ala Leu Asp Lys Ala Phe Arg Pro Glu Leu Arg Glu Glu Phe Ser Lys 35 40 45 Leu Gln Asn Arg Thr Lys Leu Thr Val Leu Glu Gly Asp Ile Leu Asp 50 55 60 Glu Pro Phe Leu Lys Arg Ala Cys Gln Asp Val Ser Val Val Ile His 65 70 75 80 Thr Ala Cys Ile Ile Asp Val Phe Gly Val Thr His Arg Glu Ser Ile 85 90 95 Met Asn Val Asn Val Lys Gly Thr Gln Leu Leu Leu Glu Ala Cys Val 100 105 110 Gln Ala Ser Val Pro Val Phe Ile Tyr Thr Ser Ser Ile Glu Val Ala 115 120 125 Gly Pro Asn Ser Tyr Lys Glu Ile Ile Gln Asn Gly His Glu Glu Glu 130 135 140 Pro Leu Glu Asn Thr Trp Pro Thr Pro Tyr Pro Tyr Ser Lys Lys Leu 145 150 155 160 Ala Glu Lys Ala Val Leu Ala Ala Asn Gly Trp Asn Leu Lys Asn Gly 165 170 175 Asp Thr Leu Tyr Thr Cys Ala Leu Arg Pro Thr Tyr Ile Tyr Gly Glu 180 185 190 Gly Gly Pro Phe Leu Ser Ala Ser Ile Asn Glu Ala Leu Asn Asn Asn 195 200 205 Gly Ile Leu Ser Ser Val Gly Lys Phe Ser Thr Val Asn Pro Val Tyr 210 215 220 Val Gly Asn Val Ala Trp Ala His Ile Leu Ala Leu Arg Ala Leu Arg 225 230 235 240 Asp Pro Lys Lys Ala Pro Ser Val Arg Gly Gln Phe Tyr Tyr Ile Ser 245 250 255 Asp Asp Thr Pro His Gln Ser Tyr Asp Asn Leu Asn Tyr Ile Leu Ser 260 265 270 Lys Glu Phe Gly Leu Arg Leu Asp Ser Arg Trp Ser Leu Pro Leu Thr 275 280 285 Leu Met Tyr Trp Ile Gly Phe Leu Leu Glu Val Val Ser Phe Leu Leu 290 295 300 Ser Pro Ile Tyr Ser Tyr Gln Pro Pro Phe Asn Arg His Thr Val Thr 305 310 315 320 Leu Ser Asn Ser Val Phe Thr Phe Ser Tyr Lys Lys Ala Gln Arg Asp 325 330 335 Leu Ala Tyr Lys Pro Leu Tyr Ser Trp Glu Glu Ala Lys Gln Lys Thr 340 345 350 Val Glu Trp Val Gly Ser Leu Val Asp Arg His Lys Glu Thr Leu Lys 355 360 365 Ser Lys Thr Gln 370 <210> 263 <211> 482 <212> PRT <213> homo sapiens <400> 263 Met Asp Ser Phe Gly Gln Pro Arg Pro Glu Asp Asn Gln Ser Val Val 1 5 10 15 Arg Arg Met Gln Lys Lys Tyr Trp Lys Thr Lys Gln Val Phe Ile Lys 20 25 30 Ala Thr Gly Lys Lys Glu Asp Glu His Leu Val Ala Ser Asp Ala Glu 35 40 45 Leu Asp Ala Lys Leu Glu Val Phe His Ser Val Gln Glu Thr Cys Thr 50 55 60 Glu Leu Leu Lys Ile Ile Glu Lys Tyr Gln Leu Arg Leu Asn Val Ile 65 70 75 80 Ser Glu Glu Glu Asn Glu Leu Gly Leu Phe Leu Lys Phe Gln Ala Glu 85 90 95 Arg Asp Ala Thr Gln Ala Gly Lys Met Met Asp Ala Thr Gly Lys Ala 100 105 110 Leu Cys Ser Ser Ala Lys Gln Arg Leu Ala Leu Cys Thr Pro Leu Ser 115 120 125 Arg Leu Lys Gln Glu Val Ala Thr Phe Ser Gln Arg Ala Val Ser Asp 130 135 140 Thr Leu Met Thr Ile Asn Arg Met Glu Gln Ala Arg Thr Glu Tyr Arg 145 150 155 160 Gly Ala Leu Leu Trp Met Lys Asp Val Ser Gln Glu Leu Asp Pro Asp 165 170 175 Thr Leu Lys Gln Met Glu Lys Phe Arg Lys Val Gln Met Gln Val Arg 180 185 190 Asn Ser Lys Ala Ser Phe Asp Lys Leu Lys Met Asp Val Cys Gln Lys 195 200 205 Val Asp Leu Leu Gly Ala Ser Arg Cys Asn Met Leu Ser His Ser Leu 210 215 220 Thr Thr Tyr Gln Arg Thr Leu Leu Gly Phe Trp Lys Lys Thr Ala Arg 225 230 235 240 Met Met Ser Gln Ile His Glu Ala Cys Ile Gly Phe His Pro Tyr Asp 245 250 255 Phe Val Ala Leu Lys Gln Leu Gln Asp Thr Pro Ser Lys Ile Ser Glu 260 265 270 Asp Asn Lys Asp Glu Gln Ile Gly Gly Phe Leu Thr Glu Gln Leu Asn 275 280 285 Lys Leu Val Leu Ser Asp Glu Glu Ala Ser Phe Glu Ser Glu Gln Ala 290 295 300 Asn Lys Asp His Asn Glu Lys His Ser Gln Met Arg Glu Phe Gly Ala 305 310 315 320 Pro Gln Phe Ser Asn Ser Glu Asn Val Ala Lys Asp Leu Pro Val Asp 325 330 335 Ser Leu Glu Gly Glu Asp Phe Glu Lys Glu Phe Ser Phe Leu Asn Asn 340 345 350 Leu Leu Ser Ser Gly Ser Ser Ser Thr Ser Glu Phe Thr Gln Glu Cys 355 360 365 Gln Thr Ala Phe Gly Ser Pro Ser Ala Ser Leu Thr Ser Gln Glu Pro 370 375 380 Ser Met Gly Ser Glu Pro Leu Ala His Ser Ser Arg Phe Leu Pro Ser 385 390 395 400 Gln Leu Phe Asp Leu Gly Phe His Val Ala Gly Ala Phe Asn Asn Trp 405 410 415 Val Ser Gln Glu Glu Ser Glu Leu Cys Leu Ser His Thr Asp Asn Gln 420 425 430 Pro Val Pro Ser Gln Ser Pro Lys Lys Leu Thr Arg Ser Pro Asn Asn 435 440 445 Gly Asn Gln Asp Met Ser Ala Trp Phe Asn Leu Phe Ala Asp Leu Asp 450 455 460 Pro Leu Ser Asn Pro Asp Ala Ile Gly His Ser Asp Asp Glu Leu Leu 465 470 475 480 Asn Ala <210> 264 <211> 420 <212> PRT <213> homo sapiens <400> 264 Met Leu His Phe His Tyr Tyr Asp Thr Ser Asn Lys Ile Met Glu Pro 1 5 10 15 His Arg Pro Asn Val Lys Thr Ala Val Pro Leu Ser Leu Glu Ser Tyr 20 25 30 His Ile Ser Glu Glu Tyr Gly Phe Leu Leu Pro Asp Ser Leu Lys Glu 35 40 45 Leu Pro Asp His Tyr Arg Pro Trp Met Glu Ile Ala Asn Lys Leu Pro 50 55 60 Gln Leu Ile Asp Ala His Gln Leu Gln Ala His Val Asp Lys Met Pro 65 70 75 80 Leu Leu Ser Cys Gln Phe Leu Lys Gly His Arg Glu Gln Arg Leu Ala 85 90 95 His Leu Val Leu Ser Phe Leu Thr Met Gly Tyr Val Trp Gln Glu Gly 100 105 110 Glu Ala Gln Pro Ala Glu Val Leu Pro Arg Asn Leu Ala Leu Pro Phe 115 120 125 Val Glu Val Ser Arg Asn Leu Gly Leu Pro Pro Ile Leu Val His Ser 130 135 140 Asp Leu Val Leu Thr Asn Trp Thr Lys Lys Asp Pro Asp Gly Phe Leu 145 150 155 160 Glu Ile Gly Asn Leu Glu Thr Ile Ile Ser Phe Pro Gly Gly Glu Ser 165 170 175 Leu His Gly Phe Ile Leu Val Thr Ala Leu Val Glu Lys Glu Ala Val 180 185 190 Pro Gly Ile Lys Ala Leu Val Gln Ala Thr Asn Ala Ile Leu Gln Pro 195 200 205 Asn Gln Glu Ala Leu Leu Gln Ala Leu Gln Arg Leu Arg Leu Ser Ile 210 215 220 Gln Asp Ile Thr Lys Thr Leu Gly Gln Met His Asp Tyr Val Asp Pro 225 230 235 240 Asp Ile Phe Tyr Ala Gly Ile Arg Ile Phe Leu Ser Gly Trp Lys Asp 245 250 255 Asn Pro Ala Met Pro Ala Gly Leu Met Tyr Glu Gly Val Ser Gln Glu 260 265 270 Pro Leu Lys Tyr Ser Gly Gly Ser Ala Ala Gln Ser Thr Val Leu His 275 280 285 Ala Phe Asp Glu Phe Leu Gly Ile Arg His Ser Lys Glu Ser Gly Asp 290 295 300 Phe Leu Tyr Arg Met Arg Asp Tyr Met Pro Pro Ser His Lys Ala Phe 305 310 315 320 Ile Glu Asp Ile His Ser Ala Pro Ser Leu Arg Asp Tyr Ile Leu Ser 325 330 335 Ser Gly Gln Asp His Leu Leu Thr Ala Tyr Asn Gln Cys Val Gln Ala 340 345 350 Leu Ala Glu Leu Arg Ser Tyr His Ile Thr Met Val Thr Lys Tyr Leu 355 360 365 Ile Thr Ala Ala Ala Lys Ala Lys His Gly Lys Pro Asn His Leu Pro 370 375 380 Gly Pro Pro Gln Ala Leu Lys Asp Arg Gly Thr Gly Gly Thr Ala Val 385 390 395 400 Met Ser Phe Leu Lys Ser Val Arg Asp Lys Thr Leu Glu Ser Ile Leu 405 410 415 His Pro Arg Gly 420 <210> 265 <211> 178 <212> PRT <213> homo sapiens <400> 265 Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val 1 5 10 15 Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His 20 25 30 Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe 35 40 45 Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu 50 55 60 Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys 65 70 75 80 Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro 85 90 95 Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu 100 105 110 Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg 115 120 125 Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn 130 135 140 Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu 145 150 155 160 Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile 165 170 175 Arg Asn <210> 266 <211> 155 <212> PRT <213> homo sapiens <400> 266 Met Thr Pro Gly Lys Thr Ser Leu Val Ser Leu Leu Leu Leu Leu Ser 1 5 10 15 Leu Glu Ala Ile Val Lys Ala Gly Ile Thr Ile Pro Arg Asn Pro Gly 20 25 30 Cys Pro Asn Ser Glu Asp Lys Asn Phe Pro Arg Thr Val Met Val Asn 35 40 45 Leu Asn Ile His Asn Arg Asn Thr Asn Thr Asn Pro Lys Arg Ser Ser 50 55 60 Asp Tyr Tyr Asn Arg Ser Thr Ser Pro Trp Asn Leu His Arg Asn Glu 65 70 75 80 Asp Pro Glu Arg Tyr Pro Ser Val Ile Trp Glu Ala Lys Cys Arg His 85 90 95 Leu Gly Cys Ile Asn Ala Asp Gly Asn Val Asp Tyr His Met Asn Ser 100 105 110 Val Pro Ile Gln Gln Glu Ile Leu Val Leu Arg Arg Glu Pro Pro His 115 120 125 Cys Pro Asn Ser Phe Arg Leu Glu Lys Ile Leu Val Ser Val Gly Cys 130 135 140 Thr Cys Val Thr Pro Ile Val His His Val Ala 145 150 155 <210> 267 <211> 193 <212> PRT <213> homo sapiens <400> 267 Met Ala Ala Glu Pro Val Glu Asp Asn Cys Ile Asn Phe Val Ala Met 1 5 10 15 Lys Phe Ile Asp Asn Thr Leu Tyr Phe Ile Ala Glu Asp Asp Glu Asn 20 25 30 Leu Glu Ser Asp Tyr Phe Gly Lys Leu Glu Ser Lys Leu Ser Val Ile 35 40 45 Arg Asn Leu Asn Asp Gln Val Leu Phe Ile Asp Gln Gly Asn Arg Pro 50 55 60 Leu Phe Glu Asp Met Thr Asp Ser Asp Cys Arg Asp Asn Ala Pro Arg 65 70 75 80 Thr Ile Phe Ile Ile Ser Met Tyr Lys Asp Ser Gln Pro Arg Gly Met 85 90 95 Ala Val Thr Ile Ser Val Lys Cys Glu Lys Ile Ser Thr Leu Ser Cys 100 105 110 Glu Asn Lys Ile Ile Ser Phe Lys Glu Met Asn Pro Pro Asp Asn Ile 115 120 125 Lys Asp Thr Lys Ser Asp Ile Ile Phe Phe Gln Arg Ser Val Pro Gly 130 135 140 His Asp Asn Lys Met Gln Phe Glu Ser Ser Ser Tyr Glu Gly Tyr Phe 145 150 155 160 Leu Ala Cys Glu Lys Glu Arg Asp Leu Phe Lys Leu Ile Leu Lys Lys 165 170 175 Glu Asp Glu Leu Gly Asp Arg Ser Ile Met Phe Thr Val Gln Asn Glu 180 185 190 Asp <210> 268 <211> 269 <212> PRT <213> homo sapiens <400> 268 Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser 1 5 10 15 Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met 20 25 30 Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile 35 40 45 Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala 50 55 60 Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro 65 70 75 80 Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe 85 90 95 Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala 100 105 110 Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp 115 120 125 Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala 130 135 140 Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met 145 150 155 160 Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu 165 170 175 Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp 180 185 190 Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys 195 200 205 Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn 210 215 220 Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr 225 230 235 240 Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly 245 250 255 Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser 260 265 <210> 269 <211> 597 <212> PRT <213> homo sapiens <400> 269 Met Ala Ala Val Gln Ala Ala Glu Val Lys Val Asp Gly Ser Glu Pro 1 5 10 15 Lys Leu Ser Lys Asn Glu Leu Lys Arg Arg Leu Lys Ala Glu Lys Lys 20 25 30 Val Ala Glu Lys Glu Ala Lys Gln Lys Glu Leu Ser Glu Lys Gln Leu 35 40 45 Ser Gln Ala Thr Ala Ala Ala Thr Asn His Thr Thr Asp Asn Gly Val 50 55 60 Gly Pro Glu Glu Glu Ser Val Asp Pro Asn Gln Tyr Tyr Lys Ile Arg 65 70 75 80 Ser Gln Ala Ile His Gln Leu Lys Val Asn Gly Glu Asp Pro Tyr Pro 85 90 95 His Lys Phe His Val Asp Ile Ser Leu Thr Asp Phe Ile Gln Lys Tyr 100 105 110 Ser His Leu Gln Pro Gly Asp His Leu Thr Asp Ile Thr Leu Lys Val 115 120 125 Ala Gly Arg Ile His Ala Lys Arg Ala Ser Gly Gly Lys Leu Ile Phe 130 135 140 Tyr Asp Leu Arg Gly Glu Gly Val Lys Leu Gln Val Met Ala Asn Ser 145 150 155 160 Arg Asn Tyr Lys Ser Glu Glu Glu Phe Ile His Ile Asn Asn Lys Leu 165 170 175 Arg Arg Gly Asp Ile Ile Gly Val Gln Gly Asn Pro Gly Lys Thr Lys 180 185 190 Lys Gly Glu Leu Ser Ile Ile Pro Tyr Glu Ile Thr Leu Leu Ser Pro 195 200 205 Cys Leu His Met Leu Pro His Leu His Phe Gly Leu Lys Asp Lys Glu 210 215 220 Thr Arg Tyr Arg Gln Arg Tyr Leu Asp Leu Ile Leu Asn Asp Phe Val 225 230 235 240 Arg Gln Lys Phe Ile Ile Arg Ser Lys Ile Ile Thr Tyr Ile Arg Ser 245 250 255 Phe Leu Asp Glu Leu Gly Phe Leu Glu Ile Glu Thr Pro Met Met Asn 260 265 270 Ile Ile Pro Gly Gly Ala Val Ala Lys Pro Phe Ile Thr Tyr His Asn 275 280 285 Glu Leu Asp Met Asn Leu Tyr Met Arg Ile Ala Pro Glu Leu Tyr His 290 295 300 Lys Met Leu Val Val Gly Gly Ile Asp Arg Val Tyr Glu Ile Gly Arg 305 310 315 320 Gln Phe Arg Asn Glu Gly Ile Asp Leu Thr His Asn Pro Glu Phe Thr 325 330 335 Thr Cys Glu Phe Tyr Met Ala Tyr Ala Asp Tyr His Asp Leu Met Glu 340 345 350 Ile Thr Glu Lys Met Val Ser Gly Met Val Lys His Ile Thr Gly Ser 355 360 365 Tyr Lys Val Thr Tyr His Pro Asp Gly Pro Glu Gly Gln Ala Tyr Asp 370 375 380 Val Asp Phe Thr Pro Pro Phe Arg Arg Ile Asn Met Val Glu Glu Leu 385 390 395 400 Glu Lys Ala Leu Gly Met Lys Leu Pro Glu Thr Asn Leu Phe Glu Thr 405 410 415 Glu Glu Thr Arg Lys Ile Leu Asp Asp Ile Cys Val Ala Lys Ala Val 420 425 430 Glu Cys Pro Pro Pro Arg Thr Thr Ala Arg Leu Leu Asp Lys Leu Val 435 440 445 Gly Glu Phe Leu Glu Val Thr Cys Ile Asn Pro Thr Phe Ile Cys Asp 450 455 460 His Pro Gln Ile Met Ser Pro Leu Ala Lys Trp His Arg Ser Lys Glu 465 470 475 480 Gly Leu Thr Glu Arg Phe Glu Leu Phe Val Met Lys Lys Glu Ile Cys 485 490 495 Asn Ala Tyr Thr Glu Leu Asn Asp Pro Met Arg Gln Arg Gln Leu Phe 500 505 510 Glu Glu Gln Ala Lys Ala Lys Ala Ala Gly Asp Asp Glu Ala Met Phe 515 520 525 Ile Asp Glu Asn Phe Cys Thr Ala Leu Glu Tyr Gly Leu Pro Pro Thr 530 535 540 Ala Gly Trp Gly Met Gly Ile Asp Arg Val Ala Met Phe Leu Thr Asp 545 550 555 560 Ser Asn Asn Ile Lys Glu Val Leu Leu Phe Pro Ala Met Lys Pro Glu 565 570 575 Asp Lys Lys Glu Asn Val Ala Thr Thr Asp Thr Leu Glu Ser Thr Thr 580 585 590 Val Gly Thr Ser Val 595 <210> 270 <211> 674 <212> PRT <213> homo sapiens <400> 270 Met Gln Ser Arg Glu Asp Ala Pro Arg Ser Arg Arg Leu Ala Ser Pro 1 5 10 15 Arg Gly Gly Lys Arg Pro Lys Lys Ile His Lys Pro Thr Val Ser Ala 20 25 30 Phe Phe Thr Gly Pro Glu Glu Leu Lys Asp Thr Ala His Ser Ala Ala 35 40 45 Leu Leu Ala Gln Leu Lys Ser Phe Tyr Asp Ala Arg Leu Leu Cys Asp 50 55 60 Val Thr Ile Glu Val Val Thr Pro Gly Ser Gly Pro Gly Thr Gly Arg 65 70 75 80 Leu Phe Pro Cys Asn Arg Asn Val Leu Ala Ala Ala Cys Pro Tyr Phe 85 90 95 Lys Ser Met Phe Thr Gly Gly Met Tyr Glu Ser Gln Gln Ala Ser Val 100 105 110 Thr Met His Asp Val Asp Ala Glu Ser Phe Glu Val Leu Val Asp Tyr 115 120 125 Cys Tyr Thr Gly Arg Val Ser Leu Ser Glu Ala Asn Val Glu Arg Leu 130 135 140 Tyr Ala Ala Ser Asp Met Leu Gln Leu Glu Tyr Val Arg Glu Ala Cys 145 150 155 160 Ala Ser Phe Leu Ala Arg Arg Leu Asp Leu Thr Asn Cys Thr Ala Ile 165 170 175 Leu Lys Phe Ala Asp Ala Phe Gly His Arg Lys Leu Arg Ser Gln Ala 180 185 190 Gln Ser Tyr Ile Ala Gln Asn Phe Lys Gln Leu Ser His Met Gly Ser 195 200 205 Ile Arg Glu Glu Thr Leu Ala Asp Leu Thr Leu Ala Gln Leu Leu Ala 210 215 220 Val Leu Arg Leu Asp Ser Leu Asp Val Glu Ser Glu Gln Thr Val Cys 225 230 235 240 His Val Ala Val Gln Trp Leu Glu Ala Ala Pro Lys Glu Arg Gly Pro 245 250 255 Ser Ala Ala Glu Val Phe Lys Cys Val Arg Trp Met His Phe Thr Glu 260 265 270 Glu Asp Gln Asp Tyr Leu Glu Gly Leu Leu Thr Lys Pro Ile Val Lys 275 280 285 Lys Tyr Cys Leu Asp Val Ile Glu Gly Ala Leu Gln Met Arg Tyr Gly 290 295 300 Asp Leu Leu Tyr Lys Ser Leu Val Pro Val Pro Asn Ser Ser Ser Ser 305 310 315 320 Ser Ser Ser Ser Asn Ser Leu Val Ser Ala Ala Glu Asn Pro Pro Gln 325 330 335 Arg Leu Gly Met Cys Ala Lys Glu Met Val Ile Phe Phe Gly His Pro 340 345 350 Arg Asp Pro Phe Leu Cys Cys Asp Pro Tyr Ser Gly Asp Leu Tyr Lys 355 360 365 Val Pro Ser Pro Leu Thr Cys Leu Ala His Thr Arg Thr Val Thr Thr 370 375 380 Leu Ala Val Cys Ile Ser Pro Asp His Asp Ile Tyr Leu Ala Ala Gln 385 390 395 400 Pro Arg Thr Asp Leu Trp Val Tyr Lys Pro Ala Gln Asn Ser Trp Gln 405 410 415 Gln Leu Ala Asp Arg Leu Leu Cys Arg Glu Gly Met Asp Val Ala Tyr 420 425 430 Leu Asn Gly Tyr Ile Tyr Ile Leu Gly Gly Arg Asp Pro Ile Thr Gly 435 440 445 Val Lys Leu Lys Glu Val Glu Cys Tyr Asn Val Lys Arg Asn Gln Trp 450 455 460 Ala Leu Val Ala Pro Leu Pro His Ser Phe Leu Ser Phe Asp Leu Met 465 470 475 480 Val Ile Arg Asp Tyr Leu Tyr Ala Leu Asn Ser Lys Arg Met Phe Cys 485 490 495 Tyr Asp Pro Ser His Asn Met Trp Leu Lys Cys Val Ser Leu Lys Arg 500 505 510 Asn Asp Phe Gln Glu Ala Cys Val Phe Asn Glu Glu Ile Tyr Cys Ile 515 520 525 Cys Asp Ile Pro Val Met Lys Val Tyr Asn Pro Val Arg Ala Glu Trp 530 535 540 Arg Gln Met Asn Asn Ile Pro Leu Val Ser Glu Thr Asn Asn Tyr Arg 545 550 555 560 Ile Ile Lys His Gly Gln Lys Leu Leu Leu Ile Thr Ser Arg Thr Pro 565 570 575 Gln Trp Lys Lys Asn Arg Val Thr Val Tyr Glu Tyr Asp Ile Arg Gly 580 585 590 Asp Gln Trp Ile Asn Ile Gly Thr Thr Leu Gly Leu Leu Gln Phe Asp 595 600 605 Ser Asn Phe Phe Cys Leu Ser Ala Arg Val Tyr Pro Ser Cys Leu Glu 610 615 620 Pro Gly Gln Ser Phe Leu Thr Glu Glu Glu Glu Ile Pro Ser Glu Ser 625 630 635 640 Ser Thr Glu Trp Asp Leu Gly Gly Phe Ser Glu Pro Asp Ser Glu Ser 645 650 655 Gly Ser Ser Ser Ser Leu Ser Asp Asp Asp Phe Trp Val Arg Val Ala 660 665 670 Pro Gln <210> 271 <211> 499 <212> PRT <213> homo sapiens <400> 271 Met Thr Val Ala Thr Gly Asp Pro Ala Asp Glu Ala Ala Ala Leu Pro 1 5 10 15 Gly His Pro Gln Asp Thr Tyr Asp Pro Glu Ala Asp His Glu Cys Cys 20 25 30 Glu Arg Val Val Ile Asn Ile Ser Gly Leu Arg Phe Glu Thr Gln Leu 35 40 45 Lys Thr Leu Ala Gln Phe Pro Glu Thr Leu Leu Gly Asp Pro Lys Lys 50 55 60 Arg Met Arg Tyr Phe Asp Pro Leu Arg Asn Glu Tyr Phe Phe Asp Arg 65 70 75 80 Asn Arg Pro Ser Phe Asp Ala Ile Leu Tyr Tyr Tyr Gln Ser Gly Gly 85 90 95 Arg Leu Arg Arg Pro Val Asn Val Pro Leu Asp Ile Phe Ser Glu Glu 100 105 110 Ile Arg Phe Tyr Glu Leu Gly Glu Glu Ala Met Glu Met Phe Arg Glu 115 120 125 Asp Glu Gly Tyr Ile Lys Glu Glu Glu Arg Pro Leu Pro Glu Asn Glu 130 135 140 Phe Gln Arg Gln Val Trp Leu Leu Phe Glu Tyr Pro Glu Ser Ser Gly 145 150 155 160 Pro Ala Arg Ile Ile Ala Ile Val Ser Val Met Val Ile Leu Ile Ser 165 170 175 Ile Val Ser Phe Cys Leu Glu Thr Leu Pro Ile Phe Arg Asp Glu Asn 180 185 190 Glu Asp Met His Gly Ser Gly Val Thr Phe His Thr Tyr Ser Asn Ser 195 200 205 Thr Ile Gly Tyr Gln Gln Ser Thr Ser Phe Thr Asp Pro Phe Phe Ile 210 215 220 Val Glu Thr Leu Cys Ile Ile Trp Phe Ser Phe Glu Phe Leu Val Arg 225 230 235 240 Phe Phe Ala Cys Pro Ser Lys Ala Gly Phe Phe Thr Asn Ile Met Asn 245 250 255 Ile Ile Asp Ile Val Ala Ile Ile Pro Tyr Phe Ile Thr Leu Gly Thr 260 265 270 Glu Leu Ala Glu Lys Pro Glu Asp Ala Gln Gln Gly Gln Gln Ala Met 275 280 285 Ser Leu Ala Ile Leu Arg Val Ile Arg Leu Val Arg Val Phe Arg Ile 290 295 300 Phe Lys Leu Ser Arg His Ser Lys Gly Leu Gln Ile Leu Gly Gln Thr 305 310 315 320 Leu Lys Ala Ser Met Arg Glu Leu Gly Leu Leu Ile Phe Phe Leu Phe 325 330 335 Ile Gly Val Ile Leu Phe Ser Ser Ala Val Tyr Phe Ala Glu Ala Asp 340 345 350 Glu Arg Glu Ser Gln Phe Pro Ser Ile Pro Asp Ala Phe Trp Trp Ala 355 360 365 Val Val Ser Met Thr Thr Val Gly Tyr Gly Asp Met Val Pro Thr Thr 370 375 380 Ile Gly Gly Lys Ile Val Gly Ser Leu Cys Ala Ile Ala Gly Val Leu 385 390 395 400 Thr Ile Ala Leu Pro Val Pro Val Ile Val Ser Asn Phe Asn Tyr Phe 405 410 415 Tyr His Arg Glu Thr Glu Gly Glu Glu Gln Ala Gln Tyr Leu Gln Val 420 425 430 Thr Ser Cys Pro Lys Ile Pro Ser Ser Pro Asp Leu Lys Lys Ser Arg 435 440 445 Ser Ala Ser Thr Ile Ser Lys Ser Asp Tyr Met Glu Ile Gln Glu Gly 450 455 460 Val Asn Asn Ser Asn Glu Asp Phe Arg Glu Glu Asn Leu Lys Thr Ala 465 470 475 480 Asn Cys Thr Leu Ala Asn Thr Asn Tyr Val Asn Ile Thr Lys Met Leu 485 490 495 Thr Asp Val <210> 272 <211> 1044 <212> PRT <213> homo sapiens <400> 272 Met Lys Pro Gly Cys Ala Ala Gly Ser Pro Gly Asn Glu Trp Ile Phe 1 5 10 15 Phe Ser Thr Asp Glu Ile Thr Thr Arg Tyr Arg Asn Thr Met Ser Asn 20 25 30 Gly Gly Leu Gln Arg Ser Val Ile Leu Ser Ala Leu Ile Leu Leu Arg 35 40 45 Ala Val Thr Gly Phe Ser Gly Asp Gly Arg Ala Ile Trp Ser Lys Asn 50 55 60 Pro Asn Phe Thr Pro Val Asn Glu Ser Gln Leu Phe Leu Tyr Asp Thr 65 70 75 80 Phe Pro Lys Asn Phe Phe Trp Gly Ile Gly Thr Gly Ala Leu Gln Val 85 90 95 Glu Gly Ser Trp Lys Lys Asp Gly Lys Gly Pro Ser Ile Trp Asp His 100 105 110 Phe Ile His Thr His Leu Lys Asn Val Ser Ser Thr Asn Gly Ser Ser 115 120 125 Asp Ser Tyr Ile Phe Leu Glu Lys Asp Leu Ser Ala Leu Asp Phe Ile 130 135 140 Gly Val Ser Phe Tyr Gln Phe Ser Ile Ser Trp Pro Arg Leu Phe Pro 145 150 155 160 Asp Gly Ile Val Thr Val Ala Asn Ala Lys Gly Leu Gln Tyr Tyr Ser 165 170 175 Thr Leu Leu Asp Ala Leu Val Leu Arg Asn Ile Glu Pro Ile Val Thr 180 185 190 Leu Tyr His Trp Asp Leu Pro Leu Ala Leu Gln Glu Lys Tyr Gly Gly 195 200 205 Trp Lys Asn Asp Thr Ile Ile Asp Ile Phe Asn Asp Tyr Ala Thr Tyr 210 215 220 Cys Phe Gln Met Phe Gly Asp Arg Val Lys Tyr Trp Ile Thr Ile His 225 230 235 240 Asn Pro Tyr Leu Val Ala Trp His Gly Tyr Gly Thr Gly Met His Ala 245 250 255 Pro Gly Glu Lys Gly Asn Leu Ala Ala Val Tyr Thr Val Gly His Asn 260 265 270 Leu Ile Lys Ala His Ser Lys Val Trp His Asn Tyr Asn Thr His Phe 275 280 285 Arg Pro His Gln Lys Gly Trp Leu Ser Ile Thr Leu Gly Ser His Trp 290 295 300 Ile Glu Pro Asn Arg Ser Glu Asn Thr Met Asp Ile Phe Lys Cys Gln 305 310 315 320 Gln Ser Met Val Ser Val Leu Gly Trp Phe Ala Asn Pro Ile His Gly 325 330 335 Asp Gly Asp Tyr Pro Glu Gly Met Arg Lys Lys Leu Phe Ser Val Leu 340 345 350 Pro Ile Phe Ser Glu Ala Glu Lys His Glu Met Arg Gly Thr Ala Asp 355 360 365 Phe Phe Ala Phe Ser Phe Gly Pro Asn Asn Phe Lys Pro Leu Asn Thr 370 375 380 Met Ala Lys Met Gly Gln Asn Val Ser Leu Asn Leu Arg Glu Ala Leu 385 390 395 400 Asn Trp Ile Lys Leu Glu Tyr Asn Asn Pro Arg Ile Leu Ile Ala Glu 405 410 415 Asn Gly Trp Phe Thr Asp Ser Arg Val Lys Thr Glu Asp Thr Thr Ala 420 425 430 Ile Tyr Met Met Lys Asn Phe Leu Ser Gln Val Leu Gln Ala Ile Arg 435 440 445 Leu Asp Glu Ile Arg Val Phe Gly Tyr Thr Ala Trp Ser Leu Leu Asp 450 455 460 Gly Phe Glu Trp Gln Asp Ala Tyr Thr Ile Arg Arg Gly Leu Phe Tyr 465 470 475 480 Val Asp Phe Asn Ser Lys Gln Lys Glu Arg Lys Pro Lys Ser Ser Ala 485 490 495 His Tyr Tyr Lys Gln Ile Ile Arg Glu Asn Gly Phe Ser Leu Lys Glu 500 505 510 Ser Thr Pro Asp Val Gln Gly Gln Phe Pro Cys Asp Phe Ser Trp Gly 515 520 525 Val Thr Glu Ser Val Leu Lys Pro Glu Ser Val Ala Ser Ser Pro Gln 530 535 540 Phe Ser Asp Pro His Leu Tyr Val Trp Asn Ala Thr Gly Asn Arg Leu 545 550 555 560 Leu His Arg Val Glu Gly Val Arg Leu Lys Thr Arg Pro Ala Gln Cys 565 570 575 Thr Asp Phe Val Asn Ile Lys Lys Gln Leu Glu Met Leu Ala Arg Met 580 585 590 Lys Val Thr His Tyr Arg Phe Ala Leu Asp Trp Ala Ser Val Leu Pro 595 600 605 Thr Gly Asn Leu Ser Ala Val Asn Arg Gln Ala Leu Arg Tyr Tyr Arg 610 615 620 Cys Val Val Ser Glu Gly Leu Lys Leu Gly Ile Ser Ala Met Val Thr 625 630 635 640 Leu Tyr Tyr Pro Thr His Ala His Leu Gly Leu Pro Glu Pro Leu Leu 645 650 655 His Ala Asp Gly Trp Leu Asn Pro Ser Thr Ala Glu Ala Phe Gln Ala 660 665 670 Tyr Ala Gly Leu Cys Phe Gln Glu Leu Gly Asp Leu Val Lys Leu Trp 675 680 685 Ile Thr Ile Asn Glu Pro Asn Arg Leu Ser Asp Ile Tyr Asn Arg Ser 690 695 700 Gly Asn Asp Thr Tyr Gly Ala Ala His Asn Leu Leu Val Ala His Ala 705 710 715 720 Leu Ala Trp Arg Leu Tyr Asp Arg Gln Phe Arg Pro Ser Gln Arg Gly 725 730 735 Ala Val Ser Leu Ser Leu His Ala Asp Trp Ala Glu Pro Ala Asn Pro 740 745 750 Tyr Ala Asp Ser His Trp Arg Ala Ala Glu Arg Phe Leu Gln Phe Glu 755 760 765 Ile Ala Trp Phe Ala Glu Pro Leu Phe Lys Thr Gly Asp Tyr Pro Ala 770 775 780 Ala Met Arg Glu Tyr Ile Ala Ser Lys His Arg Arg Gly Leu Ser Ser 785 790 795 800 Ser Ala Leu Pro Arg Leu Thr Glu Ala Glu Arg Arg Leu Leu Lys Gly 805 810 815 Thr Val Asp Phe Cys Ala Leu Asn His Phe Thr Thr Arg Phe Val Met 820 825 830 His Glu Gln Leu Ala Gly Ser Arg Tyr Asp Ser Asp Arg Asp Ile Gln 835 840 845 Phe Leu Gln Asp Ile Thr Arg Leu Ser Ser Pro Thr Arg Leu Ala Val 850 855 860 Ile Pro Trp Gly Val Arg Lys Leu Leu Arg Trp Val Arg Arg Asn Tyr 865 870 875 880 Gly Asp Met Asp Ile Tyr Ile Thr Ala Ser Gly Ile Asp Asp Gln Ala 885 890 895 Leu Glu Asp Asp Arg Leu Arg Lys Tyr Tyr Leu Gly Lys Tyr Leu Gln 900 905 910 Glu Val Leu Lys Ala Tyr Leu Ile Asp Lys Val Arg Ile Lys Gly Tyr 915 920 925 Tyr Ala Phe Lys Leu Ala Glu Glu Lys Ser Lys Pro Arg Phe Gly Phe 930 935 940 Phe Thr Ser Asp Phe Lys Ala Lys Ser Ser Ile Gln Phe Tyr Asn Lys 945 950 955 960 Val Ile Ser Ser Arg Gly Phe Pro Phe Glu Asn Ser Ser Ser Arg Cys 965 970 975 Ser Gln Thr Gln Glu Asn Thr Glu Cys Thr Val Cys Leu Phe Leu Val 980 985 990 Gln Lys Lys Pro Leu Ile Phe Leu Gly Cys Cys Phe Phe Ser Thr Leu 995 1000 1005 Val Leu Leu Leu Ser Ile Ala Ile Phe Gln Arg Gln Lys Arg Arg 1010 1015 1020 Lys Phe Trp Lys Ala Lys Asn Leu Gln His Ile Pro Leu Lys Lys 1025 1030 1035 Gly Lys Arg Val Val Ser 1040 <210> 273 <211> 486 <212> PRT <213> homo sapiens <400> 273 Met Asp Ser Ser Val Ile Gln Arg Lys Lys Val Ala Val Ile Gly Gly 1 5 10 15 Gly Leu Val Gly Ser Leu Gln Ala Cys Phe Leu Ala Lys Arg Asn Phe 20 25 30 Gln Ile Asp Val Tyr Glu Ala Arg Glu Asp Thr Arg Val Ala Thr Phe 35 40 45 Thr Arg Gly Arg Ser Ile Asn Leu Ala Leu Ser His Arg Gly Arg Gln 50 55 60 Ala Leu Lys Ala Val Gly Leu Glu Asp Gln Ile Val Ser Gln Gly Ile 65 70 75 80 Pro Met Arg Ala Arg Met Ile His Ser Leu Ser Gly Lys Lys Ser Ala 85 90 95 Ile Pro Tyr Gly Thr Lys Ser Gln Tyr Ile Leu Ser Val Ser Arg Glu 100 105 110 Asn Leu Asn Lys Asp Leu Leu Thr Ala Ala Glu Lys Tyr Pro Asn Val 115 120 125 Lys Met His Phe Asn His Arg Leu Leu Lys Cys Asn Pro Glu Glu Gly 130 135 140 Met Ile Thr Val Leu Gly Ser Asp Lys Val Pro Lys Asp Val Thr Cys 145 150 155 160 Asp Leu Ile Val Gly Cys Asp Gly Ala Tyr Ser Thr Val Arg Ser His 165 170 175 Leu Met Lys Lys Pro Arg Phe Asp Tyr Ser Gln Gln Tyr Ile Pro His 180 185 190 Gly Tyr Met Glu Leu Thr Ile Pro Pro Lys Asn Gly Asp Tyr Ala Met 195 200 205 Glu Pro Asn Tyr Leu His Ile Trp Pro Arg Asn Thr Phe Met Met Ile 210 215 220 Ala Leu Pro Asn Met Asn Lys Ser Phe Thr Cys Thr Leu Phe Met Pro 225 230 235 240 Phe Glu Glu Phe Glu Lys Leu Leu Thr Ser Asn Asp Val Val Asp Phe 245 250 255 Phe Gln Lys Tyr Phe Pro Asp Ala Ile Pro Leu Ile Gly Glu Lys Leu 260 265 270 Leu Val Gln Asp Phe Phe Leu Leu Pro Ala Gln Pro Met Ile Ser Val 275 280 285 Lys Cys Ser Ser Phe His Phe Lys Ser His Cys Val Leu Leu Gly Asp 290 295 300 Ala Ala His Ala Ile Val Pro Phe Phe Gly Gln Gly Met Asn Ala Gly 305 310 315 320 Phe Glu Asp Cys Leu Val Phe Asp Glu Leu Met Asp Lys Phe Ser Asn 325 330 335 Asp Leu Ser Leu Cys Leu Pro Val Phe Ser Arg Leu Arg Ile Pro Asp 340 345 350 Asp His Ala Ile Ser Asp Leu Ser Met Tyr Asn Tyr Ile Glu Met Arg 355 360 365 Ala His Val Asn Ser Ser Trp Phe Ile Phe Gln Lys Asn Met Glu Arg 370 375 380 Phe Leu His Ala Ile Met Pro Ser Thr Phe Ile Pro Leu Tyr Thr Met 385 390 395 400 Val Thr Phe Ser Arg Ile Arg Tyr His Glu Ala Val Gln Arg Trp His 405 410 415 Trp Gln Lys Lys Val Ile Asn Lys Gly Leu Phe Phe Leu Gly Ser Leu 420 425 430 Ile Ala Ile Ser Ser Thr Tyr Leu Leu Ile His Tyr Met Ser Pro Arg 435 440 445 Ser Phe Leu Arg Leu Arg Arg Pro Trp Asn Trp Ile Ala His Phe Arg 450 455 460 Asn Thr Thr Cys Phe Pro Ala Lys Ala Val Asp Ser Leu Glu Gln Ile 465 470 475 480 Ser Asn Leu Ile Ser Arg 485 <210> 274 <211> 584 <212> PRT <213> homo sapiens <400> 274 Met Ser Val Arg Tyr Ser Ser Ser Lys His Tyr Ser Ser Ser Arg Ser 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Gly Cys Gly Gly Gly Gly Gly Val Ser 20 25 30 Ser Leu Arg Ile Ser Ser Ser Lys Gly Ser Leu Gly Gly Gly Phe Ser 35 40 45 Ser Gly Gly Phe Ser Gly Gly Ser Phe Ser Arg Gly Ser Ser Gly Gly 50 55 60 Gly Cys Phe Gly Gly Ser Ser Gly Gly Tyr Gly Gly Leu Gly Gly Phe 65 70 75 80 Gly Gly Gly Ser Phe Arg Gly Ser Tyr Gly Ser Ser Ser Phe Gly Gly 85 90 95 Ser Tyr Gly Gly Ile Phe Gly Gly Gly Ser Phe Gly Gly Gly Ser Phe 100 105 110 Gly Gly Gly Ser Phe Gly Gly Gly Gly Phe Gly Gly Gly Gly Phe Gly 115 120 125 Gly Gly Phe Gly Gly Gly Phe Gly Gly Asp Gly Gly Leu Leu Ser Gly 130 135 140 Asn Glu Lys Val Thr Met Gln Asn Leu Asn Asp Arg Leu Ala Ser Tyr 145 150 155 160 Leu Asp Lys Val Arg Ala Leu Glu Glu Ser Asn Tyr Glu Leu Glu Gly 165 170 175 Lys Ile Lys Glu Trp Tyr Glu Lys His Gly Asn Ser His Gln Gly Glu 180 185 190 Pro Arg Asp Tyr Ser Lys Tyr Tyr Lys Thr Ile Asp Asp Leu Lys Asn 195 200 205 Gln Ile Leu Asn Leu Thr Thr Asp Asn Ala Asn Ile Leu Leu Gln Ile 210 215 220 Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg Leu Lys Tyr Glu Asn 225 230 235 240 Glu Val Ala Leu Arg Gln Ser Val Glu Ala Asp Ile Asn Gly Leu Arg 245 250 255 Arg Val Leu Asp Glu Leu Thr Leu Thr Lys Ala Asp Leu Glu Met Gln 260 265 270 Ile Glu Ser Leu Thr Glu Glu Leu Ala Tyr Leu Lys Lys Asn His Glu 275 280 285 Glu Glu Met Lys Asp Leu Arg Asn Val Ser Thr Gly Asp Val Asn Val 290 295 300 Glu Met Asn Ala Ala Pro Gly Val Asp Leu Thr Gln Leu Leu Asn Asn 305 310 315 320 Met Arg Ser Gln Tyr Glu Gln Leu Ala Glu Gln Asn Arg Lys Asp Ala 325 330 335 Glu Ala Trp Phe Asn Glu Lys Ser Lys Glu Leu Thr Thr Glu Ile Asp 340 345 350 Asn Asn Ile Glu Gln Ile Ser Ser Tyr Lys Ser Glu Ile Thr Glu Leu 355 360 365 Arg Arg Asn Val Gln Ala Leu Glu Ile Glu Leu Gln Ser Gln Leu Ala 370 375 380 Leu Lys Gln Ser Leu Glu Ala Ser Leu Ala Glu Thr Glu Gly Arg Tyr 385 390 395 400 Cys Val Gln Leu Ser Gln Ile Gln Ala Gln Ile Ser Ala Leu Glu Glu 405 410 415 Gln Leu Gln Gln Ile Arg Ala Glu Thr Glu Cys Gln Asn Thr Glu Tyr 420 425 430 Gln Gln Leu Leu Asp Ile Lys Ile Arg Leu Glu Asn Glu Ile Gln Thr 435 440 445 Tyr Arg Ser Leu Leu Glu Gly Glu Gly Ser Ser Gly Gly Gly Gly Arg 450 455 460 Gly Gly Gly Ser Phe Gly Gly Gly Tyr Gly Gly Gly Ser Ser Gly Gly 465 470 475 480 Gly Ser Ser Gly Gly Gly His Gly Gly Gly His Gly Gly Ser Ser Gly 485 490 495 Gly Gly Tyr Gly Gly Gly Ser Ser Gly Gly Gly Ser Ser Gly Gly Gly 500 505 510 Tyr Gly Gly Gly Ser Ser Ser Gly Gly His Gly Gly Ser Ser Ser Gly 515 520 525 Gly Tyr Gly Gly Gly Ser Ser Gly Gly Gly Gly Gly Gly Tyr Gly Gly 530 535 540 Gly Ser Ser Gly Gly Gly Ser Ser Ser Gly Gly Gly Tyr Gly Gly Gly 545 550 555 560 Ser Ser Ser Gly Gly His Lys Ser Ser Ser Ser Gly Ser Val Gly Glu 565 570 575 Ser Ser Ser Lys Gly Pro Arg Tyr 580 <210> 275 <211> 295 <212> PRT <213> homo sapiens <400> 275 Met Glu Leu Ser Gln Leu Leu Asn Glu Ile Arg Ala Asn Tyr Glu Lys 1 5 10 15 Ile Leu Thr Arg Asn Gln Ile Glu Thr Val Leu Ser Thr Arg Ile Gln 20 25 30 Leu Glu Glu Asp Ile Ser Lys Lys Met Asp Lys Asp Glu Glu Ala Leu 35 40 45 Lys Ala Ala Gln Ala Glu Leu Lys Glu Ala Arg Arg Gln Trp His His 50 55 60 Leu Gln Val Glu Ile Glu Ser Leu His Ala Val Glu Arg Gly Leu Glu 65 70 75 80 Asn Ser Leu His Ala Ser Glu Gln His Tyr Gln Met Gln Leu Gln Asp 85 90 95 Leu Glu Thr Val Ile Glu Gly Leu Glu Lys Glu Leu Gln Glu Val Arg 100 105 110 Arg Gly Ile Glu Lys Gln Leu Gln Glu His Glu Met Leu Leu Asn Thr 115 120 125 Lys Met Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg His Leu Leu Glu 130 135 140 Lys Glu Glu Ile Arg Tyr Tyr Gly Cys Ile Gln Gly Gly Lys Lys Asp 145 150 155 160 Lys Lys Pro Thr Thr Ser Arg Val Gly Phe Val Leu Pro Ser Ala Ile 165 170 175 Ile Asn Glu Ile Ser Phe Thr Thr Lys Val Pro Gln Lys Tyr Glu Asn 180 185 190 Glu Asn Val Glu Thr Val Thr Lys Gln Ala Ile Leu Asn Gly Ser Ile 195 200 205 Val Lys Glu Ser Thr Glu Ala His Gly Thr Ile Gln Thr Glu Lys Val 210 215 220 Asp Glu Val Ile Lys Glu Trp Glu Gly Ser Phe Phe Lys Asp Asn Pro 225 230 235 240 Arg Leu Arg Lys Lys Ser Val Ser Leu Arg Phe Asp Leu His Leu Ala 245 250 255 Ala Thr Asp Glu Gly Cys Leu Glu Thr Lys Gln Asp Asn Leu Pro Asp 260 265 270 Ile Glu Val Arg Leu Ile Met Arg Arg Ser Cys Ser Ile Pro Ser Ile 275 280 285 Lys Pro Pro Ser Thr Ala Asn 290 295 <210> 276 <211> 176 <212> PRT <213> homo sapiens <400> 276 Met Lys Pro Leu Leu Leu Ala Val Ser Leu Gly Leu Ile Ala Ala Leu 1 5 10 15 Gln Ala His His Leu Leu Ala Ser Asp Glu Glu Ile Gln Asp Val Ser 20 25 30 Gly Thr Trp Tyr Leu Lys Ala Met Thr Val Asp Arg Glu Phe Pro Glu 35 40 45 Met Asn Leu Glu Ser Val Thr Pro Met Thr Leu Thr Thr Leu Glu Gly 50 55 60 Gly Asn Leu Glu Ala Lys Val Thr Met Leu Ile Ser Gly Arg Cys Gln 65 70 75 80 Glu Val Lys Ala Val Leu Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr 85 90 95 Ala Asp Gly Gly Lys His Val Ala Tyr Ile Ile Arg Ser His Val Lys 100 105 110 Asp His Tyr Ile Phe Tyr Cys Glu Gly Glu Leu His Gly Lys Pro Val 115 120 125 Arg Gly Val Lys Leu Val Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala 130 135 140 Leu Glu Asp Phe Glu Lys Ala Ala Gly Ala Arg Gly Leu Ser Thr Glu 145 150 155 160 Ser Ile Leu Ile Pro Arg Gln Ser Glu Thr Cys Ser Pro Gly Ser Asp 165 170 175 <210> 277 <211> 911 <212> PRT <213> homo sapiens <400> 277 Met Ala Ala Ser Gln Thr Ser Gln Thr Val Ala Ser His Val Pro Phe 1 5 10 15 Ala Asp Leu Cys Ser Thr Leu Glu Arg Ile Gln Lys Ser Lys Gly Arg 20 25 30 Ala Glu Lys Ile Arg His Phe Arg Glu Phe Leu Asp Ser Trp Arg Lys 35 40 45 Phe His Asp Ala Leu His Lys Asn His Lys Asp Val Thr Asp Ser Phe 50 55 60 Tyr Pro Ala Met Arg Leu Ile Leu Pro Gln Leu Glu Arg Glu Arg Met 65 70 75 80 Ala Tyr Gly Ile Lys Glu Thr Met Leu Ala Lys Leu Tyr Ile Glu Leu 85 90 95 Leu Asn Leu Pro Arg Asp Gly Lys Asp Ala Leu Lys Leu Leu Asn Tyr 100 105 110 Arg Thr Pro Thr Gly Thr His Gly Asp Ala Gly Asp Phe Ala Met Ile 115 120 125 Ala Tyr Phe Val Leu Lys Pro Arg Cys Leu Gln Lys Gly Ser Leu Thr 130 135 140 Ile Gln Gln Val Asn Asp Leu Leu Asp Ser Ile Ala Ser Asn Asn Ser 145 150 155 160 Ala Lys Arg Lys Asp Leu Ile Lys Lys Ser Leu Leu Gln Leu Ile Thr 165 170 175 Gln Ser Ser Ala Leu Glu Gln Lys Trp Leu Ile Arg Met Ile Ile Lys 180 185 190 Asp Leu Lys Leu Gly Val Ser Gln Gln Thr Ile Phe Ser Val Phe His 195 200 205 Asn Asp Ala Ala Glu Leu His Asn Val Thr Thr Asp Leu Glu Lys Val 210 215 220 Cys Arg Gln Leu His Asp Pro Ser Val Gly Leu Ser Asp Ile Ser Ile 225 230 235 240 Thr Leu Phe Ser Ala Phe Lys Pro Met Leu Ala Ala Ile Ala Asp Ile 245 250 255 Glu His Ile Glu Lys Asp Met Lys His Gln Ser Phe Tyr Ile Glu Thr 260 265 270 Lys Leu Asp Gly Glu Arg Met Gln Met His Lys Asp Gly Asp Val Tyr 275 280 285 Lys Tyr Phe Ser Arg Asn Gly Tyr Asn Tyr Thr Asp Gln Phe Gly Ala 290 295 300 Ser Pro Thr Glu Gly Ser Leu Thr Pro Phe Ile His Asn Ala Phe Lys 305 310 315 320 Ala Asp Ile Gln Ile Cys Ile Leu Asp Gly Glu Met Met Ala Tyr Asn 325 330 335 Pro Asn Thr Gln Thr Phe Met Gln Lys Gly Thr Lys Phe Asp Ile Lys 340 345 350 Arg Met Val Glu Asp Ser Asp Leu Gln Thr Cys Tyr Cys Val Phe Asp 355 360 365 Val Leu Met Val Asn Asn Lys Lys Leu Gly His Glu Thr Leu Arg Lys 370 375 380 Arg Tyr Glu Ile Leu Ser Ser Ile Phe Thr Pro Ile Pro Gly Arg Ile 385 390 395 400 Glu Ile Val Gln Lys Thr Gln Ala His Thr Lys Asn Glu Val Ile Asp 405 410 415 Ala Leu Asn Glu Ala Ile Asp Lys Arg Glu Glu Gly Ile Met Val Lys 420 425 430 Gln Pro Leu Ser Ile Tyr Lys Pro Asp Lys Arg Gly Glu Gly Trp Leu 435 440 445 Lys Ile Lys Pro Glu Tyr Val Ser Gly Leu Met Asp Glu Leu Asp Ile 450 455 460 Leu Ile Val Gly Gly Tyr Trp Gly Lys Gly Ser Arg Gly Gly Met Met 465 470 475 480 Ser His Phe Leu Cys Ala Val Ala Glu Lys Pro Pro Pro Gly Glu Lys 485 490 495 Pro Ser Val Phe His Thr Leu Ser Arg Val Gly Ser Gly Cys Thr Met 500 505 510 Lys Glu Leu Tyr Asp Leu Gly Leu Lys Leu Ala Lys Tyr Trp Lys Pro 515 520 525 Phe His Arg Lys Ala Pro Pro Ser Ser Ile Leu Cys Gly Thr Glu Lys 530 535 540 Pro Glu Val Tyr Ile Glu Pro Cys Asn Ser Val Ile Val Gln Ile Lys 545 550 555 560 Ala Ala Glu Ile Val Pro Ser Asp Met Tyr Lys Thr Gly Cys Thr Leu 565 570 575 Arg Phe Pro Arg Ile Glu Lys Ile Arg Asp Asp Lys Glu Trp His Glu 580 585 590 Cys Met Thr Leu Asp Asp Leu Glu Gln Leu Arg Gly Lys Ala Ser Gly 595 600 605 Lys Leu Ala Ser Lys His Leu Tyr Ile Gly Gly Asp Asp Glu Pro Gln 610 615 620 Glu Lys Lys Arg Lys Ala Ala Pro Lys Met Lys Lys Val Ile Gly Ile 625 630 635 640 Ile Glu His Leu Lys Ala Pro Asn Leu Thr Asn Val Asn Lys Ile Ser 645 650 655 Asn Ile Phe Glu Asp Val Glu Phe Cys Val Met Ser Gly Thr Asp Ser 660 665 670 Gln Pro Lys Pro Asp Leu Glu Asn Arg Ile Ala Glu Phe Gly Gly Tyr 675 680 685 Ile Val Gln Asn Pro Gly Pro Asp Thr Tyr Cys Val Ile Ala Gly Ser 690 695 700 Glu Asn Ile Arg Val Lys Asn Ile Ile Leu Ser Asn Lys His Asp Val 705 710 715 720 Val Lys Pro Ala Trp Leu Leu Glu Cys Phe Lys Thr Lys Ser Phe Val 725 730 735 Pro Trp Gln Pro Arg Phe Met Ile His Met Cys Pro Ser Thr Lys Glu 740 745 750 His Phe Ala Arg Glu Tyr Asp Cys Tyr Gly Asp Ser Tyr Phe Ile Asp 755 760 765 Thr Asp Leu Asn Gln Leu Lys Glu Val Phe Ser Gly Ile Lys Asn Ser 770 775 780 Asn Glu Gln Thr Pro Glu Glu Met Ala Ser Leu Ile Ala Asp Leu Glu 785 790 795 800 Tyr Arg Tyr Ser Trp Asp Cys Ser Pro Leu Ser Met Phe Arg Arg His 805 810 815 Thr Val Tyr Leu Asp Ser Tyr Ala Val Ile Asn Asp Leu Ser Thr Lys 820 825 830 Asn Glu Gly Thr Arg Leu Ala Ile Lys Ala Leu Glu Leu Arg Phe His 835 840 845 Gly Ala Lys Val Val Ser Cys Leu Ala Glu Gly Val Ser His Val Ile 850 855 860 Ile Gly Glu Asp His Ser Arg Val Ala Asp Phe Lys Ala Phe Arg Arg 865 870 875 880 Thr Phe Lys Arg Lys Phe Lys Ile Leu Lys Glu Ser Trp Val Thr Asp 885 890 895 Ser Ile Asp Lys Cys Glu Leu Gln Glu Glu Asn Gln Tyr Leu Ile 900 905 910 <210> 278 <211> 94 <212> PRT <213> homo sapiens <400> 278 Met Ala His His Ser Leu Asn Thr Phe Tyr Ile Trp His Asn Asn Val 1 5 10 15 Leu His Thr His Leu Val Phe Phe Leu Pro His Leu Leu Asn Gln Pro 20 25 30 Phe Ser Arg Gly Ser Phe Leu Ile Trp Leu Leu Leu Cys Trp Asn Ser 35 40 45 Trp Tyr His Leu Arg Thr Leu Arg Arg Gln Ala Asn Gln Ala Asn Lys 50 55 60 Leu Ser Met Met Leu Leu Arg Val Lys Gln Ser Pro Gly Thr Lys Leu 65 70 75 80 Cys His Gly Asp Ser Glu Leu Thr Ser Gly Leu Leu Ala Thr 85 90 <210> 279 <211> 117 <212> PRT <213> homo sapiens <400> 279 Met Phe Thr Leu Leu Leu Ser Asn Tyr Tyr Ser Arg Leu Glu Gly Trp 1 5 10 15 Met Met Asp Asn Asn Phe Ser His His Trp Lys Gly Met Phe Pro Thr 20 25 30 Glu Thr Glu Ser Thr Val Phe Cys Leu Phe Val Tyr Leu Phe Ile Phe 35 40 45 Val Phe Glu Thr Ala Ser Gly Phe Val Ala Gln Thr Gly Val His Trp 50 55 60 Cys Asn Leu Gly Ser Leu Gln Pro Leu Pro Pro Gly Phe Lys Arg Phe 65 70 75 80 Ser Cys Leu Ser Leu Pro Ser Ser Leu Asp Tyr Arg His Ala Pro Pro 85 90 95 Cys Leu Ala Asn Phe Tyr Ile Phe Ser Gly Asp Arg Val Ser Pro Cys 100 105 110 Trp Pro Asp Trp Ser 115 <210> 280 <211> 129 <212> PRT <213> homo sapiens <400> 280 Met Ala Lys Ser Leu Arg Ser Lys Trp Lys Arg Lys Met Arg Ala Glu 1 5 10 15 Lys Arg Lys Lys Asn Ala Pro Lys Glu Ala Ser Arg Leu Lys Ser Ile 20 25 30 Leu Lys Leu Asp Gly Asp Val Leu Met Lys Asp Val Gln Glu Ile Ala 35 40 45 Thr Val Val Val Pro Lys Pro Lys His Cys Gln Glu Lys Met Gln Cys 50 55 60 Glu Val Lys Asp Glu Lys Asp Asp Met Lys Met Glu Thr Asp Ile Lys 65 70 75 80 Arg Asn Lys Lys Thr Leu Leu Asp Gln His Gly Gln Tyr Pro Ile Trp 85 90 95 Met Asn Gln Arg Gln Arg Lys Arg Leu Lys Ala Lys Arg Glu Lys Arg 100 105 110 Lys Gly Lys Ser Lys Ala Lys Ala Val Lys Val Ala Lys Gly Leu Ala 115 120 125 Trp <210> 281 <211> 106 <212> PRT <213> homo sapiens <400> 281 Met Asn Arg Asn Ile Leu Glu Glu Met Leu Gln Tyr Leu Leu Ile Asp 1 5 10 15 Trp Ile Val Gly Asp Gln Phe Glu Ile Gln Leu Asn Gln Gln Leu Trp 20 25 30 Ser Leu Ile Pro Asn Asn Asp Val Arg Arg Leu Val Ser His Val Ile 35 40 45 Arg Thr Leu Lys Thr Asp Cys Thr Glu Thr His Leu Gln Leu Ala Cys 50 55 60 Ala Lys Leu Ile Ser Arg Thr Gly Leu Leu Met Lys Leu Leu Ser Glu 65 70 75 80 Gln Gln Glu Leu Arg Thr Val Ser Met Thr Ala Trp Lys Pro Arg Met 85 90 95 Asn Arg Lys Ser Arg Ser Arg Met Arg Ser 100 105 <210> 282 <211> 1247 <212> PRT <213> homo sapiens <400> 282 Met Leu Arg Leu Val Ala Ala Cys Pro Glu Ser Cys Val Val Cys Thr 1 5 10 15 Lys Asp Val Thr Leu Cys His Gln Leu Thr Tyr Ile Val Ala Ala Pro 20 25 30 Met Thr Thr Arg Val Leu Ile Ile Thr Asp Gly Tyr Leu Ser Ser Ile 35 40 45 Glu Ser Thr Asn Leu Ser Leu Leu Phe Asn Leu Ala Leu Leu Ser Leu 50 55 60 Ser Arg Asn Gly Ile Glu Asp Val Gln Glu Asp Ala Leu His Gly Leu 65 70 75 80 Thr Met Leu Arg Thr Leu Leu Leu Glu His Asn Gln Ile Ser Ser Ser 85 90 95 Ser Leu Thr Asp His Thr Phe Ser Lys Leu His Ser Leu Gln Val Leu 100 105 110 Val Leu Ser Asn Asn Ala Leu Arg Thr Leu Arg Gly Ser Trp Phe Arg 115 120 125 Asn Thr Ser Gly Leu Thr Arg Leu Gln Leu Asp Gly Asn Gln Ile Thr 130 135 140 Asn Leu Thr Asp Ser Ser Phe Gly Gly Thr Asn Leu His Ser Leu Arg 145 150 155 160 Tyr Leu Asp Leu Ser Asn Asn Phe Ile Ser Tyr Ile Gly Lys Asp Ala 165 170 175 Phe Arg Pro Leu Pro Gln Leu Gln Glu Val Asp Leu Ser Arg Asn Arg 180 185 190 Leu Ala His Met Pro Asp Val Phe Thr Pro Leu Lys Gln Leu Ile Leu 195 200 205 Leu Ser Leu Asp Lys Asn Gln Trp Ser Cys Thr Cys Asp Leu His Pro 210 215 220 Leu Ala Arg Phe Leu Arg Asn Tyr Ile Lys Ser Ser Ala His Thr Leu 225 230 235 240 Arg Asn Ala Lys Asp Leu Asn Cys Gln Pro Ser Thr Ala Ala Val Ala 245 250 255 Ala Ala Gln Ser Val Leu Arg Leu Ser Glu Thr Asn Cys Asp Ser Lys 260 265 270 Ala Pro Asn Phe Thr Leu Val Leu Lys Asp Arg Ser Pro Leu Leu Pro 275 280 285 Gly Pro Asp Val Ala Leu Leu Thr Val Leu Gly Phe Ala Gly Ala Val 290 295 300 Gly Leu Thr Cys Leu Gly Leu Val Val Phe Asn Trp Lys Leu His Gln 305 310 315 320 Gly Lys Ala Asn Glu His Thr Ser Glu Asn Leu Cys Cys Arg Thr Phe 325 330 335 Asp Glu Pro Leu Cys Ala His Glu Ala Arg Asn Tyr His Thr Lys Gly 340 345 350 Tyr Cys Asn Cys His Leu Thr Gln Glu Asn Glu Ile Lys Val Met Ser 355 360 365 Thr Val Gly Ser Arg Lys Glu Met Pro Leu Leu Gln Glu Asn Ser His 370 375 380 Gln Ala Thr Ser Ala Ser Glu Ser Ala Thr Leu Asp Gly Ser Phe Arg 385 390 395 400 Asn Leu Lys Lys Lys Asp Arg Gly Val Gly Ser Thr Leu Phe Cys Gln 405 410 415 Asp Gly Arg Leu Leu His Ser Glu Cys Ser Glu Pro Pro Gly Asn Met 420 425 430 Arg Ala Phe Asn Glu Ala Gly Leu Leu Thr Thr Tyr Asn Pro Arg Lys 435 440 445 Val Gln Lys Leu Trp Asn Leu Glu Pro Gly Glu Val Gln Pro Gln Thr 450 455 460 Leu Gln His His Ile Ile Arg Thr Glu Asp Ile Ser Ser Asp Ile Phe 465 470 475 480 Arg Arg Arg Tyr Ala Thr Pro Ala Ser Ala Leu Ala Gly Glu Ser Leu 485 490 495 Glu Lys Arg Leu Thr Asn Glu Ser Trp Gln Pro Pro Ile Glu Lys Glu 500 505 510 Asp Asn Gly Leu His Pro His Arg Gln Arg His Phe Ile Thr Ser Ser 515 520 525 Ser Ser Lys Pro Cys Glu Pro Glu Glu His Tyr Val Gln Lys Ile Val 530 535 540 Gln Lys Asn Arg Ser Lys Tyr Asp Asp Pro Cys Gly Leu Leu Lys Gln 545 550 555 560 Ser Lys Pro Arg Tyr Phe Gln Pro Asn Asn Ser Leu Ile Cys Lys Tyr 565 570 575 Val Pro Cys Glu Gln Phe Glu Asp Tyr Met Lys Glu Lys Lys Pro Asn 580 585 590 Arg Arg Gln His Ser Lys Pro Glu Lys Glu Gln Ile Gln Ile Asn Ser 595 600 605 Ala Ile Glu Lys Phe Leu Met Ser Glu Asp Asn Ile Asp Leu Ser Gly 610 615 620 Leu Ser Thr Lys Thr Lys Lys Ala Tyr Ser Pro Lys Arg Val Ile Phe 625 630 635 640 His Asp Pro Asp Leu Val Glu Ile Asn Arg Ser Met Met Ser Pro Lys 645 650 655 Ile Ser Thr Pro Trp Lys Arg Gln Lys Asn Gln Ser Asn Gln Leu Thr 660 665 670 Lys Leu Asp Val Lys Lys Phe Ser Asn Thr Gly Glu Arg Asn Lys Gly 675 680 685 Glu Lys Trp Phe Thr Asn Ser Trp Val Leu Lys Arg Lys Arg Thr Pro 690 695 700 Gln Ser Asp Leu Lys Gly Lys Ile Lys Gly Gln Asn Leu Lys Leu Asn 705 710 715 720 Leu His Pro Phe Arg Lys Val Arg Val His Pro Glu Lys Ser Leu Ser 725 730 735 Ser Leu Pro Lys Gln Cys Lys Gln Val Leu Leu Pro Pro Lys Lys Leu 740 745 750 Ser Lys Thr Ser Glu Thr Glu Ala Lys Ile Asn Thr Val Cys Ser Ala 755 760 765 Asp Phe Leu Gln Gln Ser Glu Ser Ser Asn Tyr Val Arg Leu Thr Ser 770 775 780 Lys Arg Leu Pro Leu Lys His Asp Ser Lys Gln Thr Pro Tyr Tyr Gln 785 790 795 800 Arg Asn Thr Lys Arg Ala Pro Leu Leu Ser Ala Asn Asn Leu Arg Val 805 810 815 Val Asn Gln Ser Ser Ile Glu Ser Ser Cys Tyr Ser Ala Gly His Ile 820 825 830 Pro Asp Gly Asn Thr Ser Lys Leu Pro Gln Pro Thr Pro Thr Asp Ala 835 840 845 Glu His Arg His Ser His Ser Gln Phe Ser Thr Glu Gln Met Glu Asp 850 855 860 Ala Thr Gln Leu Glu Ser Lys Val Leu Ser Tyr Leu Ala Thr Thr Trp 865 870 875 880 Glu Asn Thr Gly Ser Asp Val Leu Pro Phe Gln His Ser Arg Arg Ala 885 890 895 Thr Asp Gln Gly Thr Thr Glu Ser Thr Glu His Met Gly Gln Asn Val 900 905 910 Ser Lys Thr Ser Glu Leu Asn Gln Phe Ser Leu Ser Pro Arg Asn Gln 915 920 925 Thr Gln Leu Leu Asp Ala His Lys Thr Asp Ser Tyr Asn Lys Glu Tyr 930 935 940 Thr Leu Asp Gln Asn Glu Ala Leu Gln His Arg Glu Gln Asn Ser Ser 945 950 955 960 His Ala Gln Leu Glu Asn Lys Glu Lys Thr Leu Met Thr Lys Pro Gln 965 970 975 Ile Ser His Gln Ile Val Glu Asn Cys Ile Met Asp Lys Glu Glu Asn 980 985 990 Asp Val Glu Lys Lys Leu Ser Lys Thr Glu Thr Tyr Asp Ser Ser Leu 995 1000 1005 Ile Pro Gln Thr Gln Ser Lys Asn Asn Leu Ser Phe Met Lys Thr 1010 1015 1020 Asn Ser Ile Pro Tyr Gln Asn Arg Ile Glu Leu Pro Lys Asp Ile 1025 1030 1035 Ser Thr Ser Pro Val Ser Ser Gln Ala Val Trp His Leu Thr Asn 1040 1045 1050 Ser Ser Glu Lys Gly Ile Asp Ser Thr Asn Ala Leu Pro Arg Asn 1055 1060 1065 Asp Gly Thr Glu Ala Leu Glu Ile Lys Ile Val Gly Lys Glu Glu 1070 1075 1080 Lys Asn Met Leu Asp Glu Ser Lys Thr Asp Ser Ser Met Leu Thr 1085 1090 1095 Gln Ile Ser Gln Met Thr Leu Lys Gly Ile Thr Lys Glu Arg Gln 1100 1105 1110 Gln Thr Trp Glu Asn Gly Thr Ser Glu Lys Tyr Ile Leu His Asp 1115 1120 1125 Ala Ser Ser Ala Glu Glu Thr Ile Thr Ala Lys Asp Leu Ser Ile 1130 1135 1140 Thr Ser Ser His Glu Thr Gln Asn Arg Ile Leu Cys Ser Glu Val 1145 1150 1155 Asp Pro Glu Val Asn Ser Asn Val His Asn Phe Arg Glu Val Gln 1160 1165 1170 Asn Ile Gln Pro Asp Lys Asp Ser Ala His Lys Glu Gly Ala Met 1175 1180 1185 Thr Val Glu Thr His Glu Ala Leu Ser Phe Leu Pro Gly Leu Lys 1190 1195 1200 Asp Ser Phe Glu Ala Glu Asn Glu Val Phe Leu Val Pro Ser Arg 1205 1210 1215 Ile Asn Glu Ala Glu Asn Ser Ala Pro Lys Pro Val Leu Tyr Pro 1220 1225 1230 Pro Ser Ala Glu Tyr Ala Thr Thr Ser Pro Leu Glu Thr Glu 1235 1240 1245 <210> 283 <211> 205 <212> PRT <213> homo sapiens <400> 283 Met Thr Pro Pro Glu Arg Leu Phe Leu Pro Arg Val Cys Gly Thr Thr 1 5 10 15 Leu His Leu Leu Leu Leu Gly Leu Leu Leu Val Leu Leu Pro Gly Ala 20 25 30 Gln Gly Leu Pro Gly Val Gly Leu Thr Pro Ser Ala Ala Gln Thr Ala 35 40 45 Arg Gln His Pro Lys Met His Leu Ala His Ser Thr Leu Lys Pro Ala 50 55 60 Ala His Leu Ile Gly Asp Pro Ser Lys Gln Asn Ser Leu Leu Trp Arg 65 70 75 80 Ala Asn Thr Asp Arg Ala Phe Leu Gln Asp Gly Phe Ser Leu Ser Asn 85 90 95 Asn Ser Leu Leu Val Pro Thr Ser Gly Ile Tyr Phe Val Tyr Ser Gln 100 105 110 Val Val Phe Ser Gly Lys Ala Tyr Ser Pro Lys Ala Thr Ser Ser Pro 115 120 125 Leu Tyr Leu Ala His Glu Val Gln Leu Phe Ser Ser Gln Tyr Pro Phe 130 135 140 His Val Pro Leu Leu Ser Ser Gln Lys Met Val Tyr Pro Gly Leu Gln 145 150 155 160 Glu Pro Trp Leu His Ser Met Tyr His Gly Ala Ala Phe Gln Leu Thr 165 170 175 Gln Gly Asp Gln Leu Ser Thr His Thr Asp Gly Ile Pro His Leu Val 180 185 190 Leu Ser Pro Ser Thr Val Phe Phe Gly Ala Phe Ala Leu 195 200 205 <210> 284 <211> 88 <212> PRT <213> homo sapiens <400> 284 Met Ala Ser Ser Asp Val Lys Pro Lys Ser Val Ser His Ala Lys Lys 1 5 10 15 Trp Ser Glu Glu Ile Glu Asn Leu Tyr Arg Phe Gln Gln Ala Gly Tyr 20 25 30 Arg Asp Glu Thr Glu Tyr Arg Gln Val Lys Gln Val Ser Met Val Asp 35 40 45 Arg Trp Pro Glu Thr Gly Tyr Val Lys Lys Leu Gln Arg Arg Asp Asn 50 55 60 Thr Phe Tyr Tyr Tyr Asn Lys Gln Arg Glu Cys Asp Asp Lys Glu Val 65 70 75 80 His Lys Val Lys Ile Tyr Ala Tyr 85 <210> 285 <211> 378 <212> PRT <213> homo sapiens <400> 285 Met Ala Gly Ser Tyr Pro Glu Gly Ala Pro Ala Val Leu Ala Asp Lys 1 5 10 15 Arg Gln Gln Phe Gly Ser Arg Phe Leu Arg Asp Pro Ala Arg Val Phe 20 25 30 His His Asn Ala Trp Asp Asn Val Glu Trp Ser Glu Glu Gln Ala Ala 35 40 45 Ala Ala Glu Arg Lys Val Gln Glu Asn Ser Ile Gln Arg Val Cys Gln 50 55 60 Glu Lys Gln Val Asp Tyr Glu Ile Asn Ala His Lys Tyr Trp Asn Asp 65 70 75 80 Phe Tyr Lys Ile His Glu Asn Gly Phe Phe Lys Asp Arg His Trp Leu 85 90 95 Phe Thr Glu Phe Pro Glu Leu Ala Pro Ser Gln Asn Gln Asn His Leu 100 105 110 Lys Asp Trp Phe Leu Glu Asn Lys Ser Glu Val Pro Glu Cys Arg Asn 115 120 125 Asn Glu Asp Gly Pro Gly Leu Ile Met Glu Glu Gln His Lys Cys Ser 130 135 140 Ser Lys Ser Leu Glu His Lys Thr Gln Thr Leu Pro Val Glu Glu Asn 145 150 155 160 Val Thr Gln Lys Ile Ser Asp Leu Glu Ile Cys Ala Asp Glu Phe Pro 165 170 175 Gly Ser Ser Ala Thr Tyr Arg Ile Leu Glu Val Gly Cys Gly Val Gly 180 185 190 Asn Thr Val Phe Pro Ile Leu Gln Thr Asn Asn Asp Pro Gly Leu Phe 195 200 205 Val Tyr Cys Cys Asp Phe Ser Ser Thr Ala Ile Glu Leu Val Gln Thr 210 215 220 Asn Ser Glu Tyr Asp Pro Ser Arg Cys Phe Ala Phe Val His Asp Leu 225 230 235 240 Cys Asp Glu Glu Lys Ser Tyr Pro Val Pro Lys Gly Ser Leu Asp Ile 245 250 255 Ile Ile Leu Ile Phe Val Leu Ser Ala Ile Val Pro Asp Lys Met Gln 260 265 270 Lys Ala Ile Asn Arg Leu Ser Arg Leu Leu Lys Pro Gly Gly Met Met 275 280 285 Leu Leu Arg Asp Tyr Gly Arg Tyr Asp Met Ala Gln Leu Arg Phe Lys 290 295 300 Lys Gly Gln Cys Leu Ser Gly Asn Phe Tyr Val Arg Gly Asp Gly Thr 305 310 315 320 Arg Val Tyr Phe Phe Thr Gln Glu Glu Leu Asp Thr Leu Phe Thr Thr 325 330 335 Ala Gly Leu Glu Lys Val Gln Asn Leu Val Asp Arg Arg Leu Gln Val 340 345 350 Asn Arg Gly Lys Gln Leu Thr Met Tyr Arg Val Trp Ile Gln Cys Lys 355 360 365 Tyr Cys Lys Pro Leu Leu Ser Ser Thr Ser 370 375 <210> 286 <211> 447 <212> PRT <213> homo sapiens <400> 286 Met Arg Phe Arg Ile Tyr Lys Arg Lys Val Leu Ile Leu Thr Leu Val 1 5 10 15 Val Ala Ala Cys Gly Phe Val Leu Trp Ser Ser Asn Gly Arg Gln Arg 20 25 30 Lys Asn Glu Ala Leu Ala Pro Pro Leu Leu Asp Ala Glu Pro Ala Arg 35 40 45 Gly Ala Gly Gly Arg Gly Gly Asp His Pro Ser Val Ala Val Gly Ile 50 55 60 Arg Arg Val Ser Asn Val Ser Ala Ala Ser Leu Val Pro Ala Val Pro 65 70 75 80 Gln Pro Glu Ala Asp Asn Leu Thr Leu Arg Tyr Arg Ser Leu Val Tyr 85 90 95 Gln Leu Asn Phe Asp Gln Thr Leu Arg Asn Val Asp Lys Ala Gly Thr 100 105 110 Trp Ala Pro Arg Glu Leu Val Leu Val Val Gln Val His Asn Arg Pro 115 120 125 Glu Tyr Leu Arg Leu Leu Leu Asp Ser Leu Arg Lys Ala Gln Gly Ile 130 135 140 Asp Asn Val Leu Val Ile Phe Ser His Asp Phe Trp Ser Thr Glu Ile 145 150 155 160 Asn Gln Leu Ile Ala Gly Val Asn Phe Cys Pro Val Leu Gln Val Phe 165 170 175 Phe Pro Phe Ser Ile Gln Leu Tyr Pro Asn Glu Phe Pro Gly Ser Asp 180 185 190 Pro Arg Asp Cys Pro Arg Asp Leu Pro Lys Asn Ala Ala Leu Lys Leu 195 200 205 Gly Cys Ile Asn Ala Glu Tyr Pro Asp Ser Phe Gly His Tyr Arg Glu 210 215 220 Ala Lys Phe Ser Gln Thr Lys His His Trp Trp Trp Lys Leu His Phe 225 230 235 240 Val Trp Glu Arg Val Lys Ile Leu Arg Asp Tyr Ala Gly Leu Ile Leu 245 250 255 Phe Leu Glu Glu Asp His Tyr Leu Ala Pro Asp Phe Tyr His Val Phe 260 265 270 Lys Lys Met Trp Lys Leu Lys Gln Gln Glu Cys Pro Glu Cys Asp Val 275 280 285 Leu Ser Leu Gly Thr Tyr Ser Ala Ser Arg Ser Phe Tyr Gly Met Ala 290 295 300 Asp Lys Val Asp Val Lys Thr Trp Lys Ser Thr Glu His Asn Met Gly 305 310 315 320 Leu Ala Leu Thr Arg Asn Ala Tyr Gln Lys Leu Ile Glu Cys Thr Asp 325 330 335 Thr Phe Cys Thr Tyr Asp Asp Tyr Asn Trp Asp Trp Thr Leu Gln Tyr 340 345 350 Leu Thr Val Ser Cys Leu Pro Lys Phe Trp Lys Val Leu Val Pro Gln 355 360 365 Ile Pro Arg Ile Phe His Ala Gly Asp Cys Gly Met His His Lys Lys 370 375 380 Thr Cys Arg Pro Ser Thr Gln Ser Ala Gln Ile Glu Ser Leu Leu Asn 385 390 395 400 Asn Asn Lys Gln Tyr Met Phe Pro Glu Thr Leu Thr Ile Ser Glu Lys 405 410 415 Phe Thr Val Val Ala Ile Ser Pro Pro Arg Lys Asn Gly Gly Trp Gly 420 425 430 Asp Ile Arg Asp His Glu Leu Cys Lys Ser Tyr Arg Arg Leu Gln 435 440 445 <210> 287 <211> 343 <212> PRT <213> homo sapiens <400> 287 Met Trp Ser His Leu Asn Arg Leu Leu Phe Trp Ser Ile Phe Ser Ser 1 5 10 15 Val Thr Cys Arg Lys Ala Val Leu Asp Cys Glu Ala Met Lys Thr Asn 20 25 30 Glu Phe Pro Ser Pro Cys Leu Asp Ser Lys Thr Lys Val Val Met Lys 35 40 45 Gly Gln Asn Val Ser Met Phe Cys Ser His Lys Asn Lys Ser Leu Gln 50 55 60 Ile Thr Tyr Ser Leu Phe Arg Arg Lys Thr His Leu Gly Thr Gln Asp 65 70 75 80 Gly Lys Gly Glu Pro Ala Ile Phe Asn Leu Ser Ile Thr Glu Ala His 85 90 95 Glu Ser Gly Pro Tyr Lys Cys Lys Ala Gln Val Thr Ser Cys Ser Lys 100 105 110 Tyr Ser Arg Asp Phe Ser Phe Thr Ile Val Asp Pro Val Thr Ser Pro 115 120 125 Val Leu Asn Ile Met Val Ile Gln Thr Glu Thr Asp Arg His Ile Thr 130 135 140 Leu His Cys Leu Ser Val Asn Gly Ser Leu Pro Ile Asn Tyr Thr Phe 145 150 155 160 Phe Glu Asn His Val Ala Ile Ser Pro Ala Ile Ser Lys Tyr Asp Arg 165 170 175 Glu Pro Ala Glu Phe Asn Leu Thr Lys Lys Asn Pro Gly Glu Glu Glu 180 185 190 Glu Tyr Arg Cys Glu Ala Lys Asn Arg Leu Pro Asn Tyr Ala Thr Tyr 195 200 205 Ser His Pro Val Thr Met Pro Ser Thr Gly Gly Asp Ser Cys Pro Phe 210 215 220 Cys Leu Lys Leu Leu Leu Pro Gly Leu Leu Leu Leu Leu Val Val Ile 225 230 235 240 Ile Leu Ile Leu Ala Phe Trp Val Leu Pro Lys Tyr Lys Thr Arg Lys 245 250 255 Ala Met Arg Asn Asn Val Pro Arg Asp Arg Gly Asp Thr Ala Met Glu 260 265 270 Val Gly Ile Tyr Ala Asn Ile Leu Glu Lys Gln Ala Lys Glu Glu Ser 275 280 285 Val Pro Glu Val Gly Ser Arg Pro Cys Val Ser Thr Ala Gln Asp Glu 290 295 300 Ala Lys His Ser Gln Glu Leu Gln Tyr Ala Thr Pro Val Phe Gln Glu 305 310 315 320 Val Ala Pro Arg Glu Gln Glu Ala Cys Asp Ser Tyr Lys Ser Gly Tyr 325 330 335 Val Tyr Ser Glu Leu Asn Phe 340 <210> 288 <211> 513 <212> PRT <213> homo sapiens <400> 288 Met Lys Arg Leu Leu Leu Leu Phe Leu Phe Phe Ile Thr Phe Ser Ser 1 5 10 15 Ala Phe Pro Leu Val Arg Met Thr Glu Asn Glu Glu Asn Met Gln Leu 20 25 30 Ala Gln Ala Tyr Leu Asn Gln Phe Tyr Ser Leu Glu Ile Glu Gly Asn 35 40 45 His Leu Val Gln Ser Lys Asn Arg Ser Leu Ile Asp Asp Lys Ile Arg 50 55 60 Glu Met Gln Ala Phe Phe Gly Leu Thr Val Thr Gly Lys Leu Asp Ser 65 70 75 80 Asn Thr Leu Glu Ile Met Lys Thr Pro Arg Cys Gly Val Pro Asp Val 85 90 95 Gly Gln Tyr Gly Tyr Thr Leu Pro Gly Trp Arg Lys Tyr Asn Leu Thr 100 105 110 Tyr Arg Ile Ile Asn Tyr Thr Pro Asp Met Ala Arg Ala Ala Val Asp 115 120 125 Glu Ala Ile Gln Glu Gly Leu Glu Val Trp Ser Lys Val Thr Pro Leu 130 135 140 Lys Phe Thr Lys Ile Ser Lys Gly Ile Ala Asp Ile Met Ile Ala Phe 145 150 155 160 Arg Thr Arg Val His Gly Arg Cys Pro Arg Tyr Phe Asp Gly Pro Leu 165 170 175 Gly Val Leu Gly His Ala Phe Pro Pro Gly Pro Gly Leu Gly Gly Asp 180 185 190 Thr His Phe Asp Glu Asp Glu Asn Trp Thr Lys Asp Gly Ala Gly Phe 195 200 205 Asn Leu Phe Leu Val Ala Ala His Glu Phe Gly His Ala Leu Gly Leu 210 215 220 Ser His Ser Asn Asp Gln Thr Ala Leu Met Phe Pro Asn Tyr Val Ser 225 230 235 240 Leu Asp Pro Arg Lys Tyr Pro Leu Ser Gln Asp Asp Ile Asn Gly Ile 245 250 255 Gln Ser Ile Tyr Gly Gly Leu Pro Lys Glu Pro Ala Lys Pro Lys Glu 260 265 270 Pro Thr Ile Pro His Ala Cys Asp Pro Asp Leu Thr Phe Asp Ala Ile 275 280 285 Thr Thr Phe Arg Arg Glu Val Met Phe Phe Lys Gly Arg His Leu Trp 290 295 300 Arg Ile Tyr Tyr Asp Ile Thr Asp Val Glu Phe Glu Leu Ile Ala Ser 305 310 315 320 Phe Trp Pro Ser Leu Pro Ala Asp Leu Gln Ala Ala Tyr Glu Asn Pro 325 330 335 Arg Asp Lys Ile Leu Val Phe Lys Asp Glu Asn Phe Trp Met Ile Arg 340 345 350 Gly Tyr Ala Val Leu Pro Asp Tyr Pro Lys Ser Ile His Thr Leu Gly 355 360 365 Phe Pro Gly Arg Val Lys Lys Ile Asp Ala Ala Val Cys Asp Lys Thr 370 375 380 Thr Arg Lys Thr Tyr Phe Phe Val Gly Ile Trp Cys Trp Arg Phe Asp 385 390 395 400 Glu Met Thr Gln Thr Met Asp Lys Gly Phe Pro Gln Arg Val Val Lys 405 410 415 His Phe Pro Gly Ile Ser Ile Arg Val Asp Ala Ala Phe Gln Tyr Lys 420 425 430 Gly Phe Phe Phe Phe Ser Arg Gly Ser Lys Gln Phe Glu Tyr Asp Ile 435 440 445 Lys Thr Lys Asn Ile Thr Arg Ile Met Arg Thr Asn Thr Trp Phe Gln 450 455 460 Cys Lys Glu Pro Lys Asn Ser Ser Phe Gly Phe Asp Ile Asn Lys Glu 465 470 475 480 Lys Ala His Ser Gly Gly Ile Lys Ile Leu Tyr His Lys Ser Leu Ser 485 490 495 Leu Phe Ile Phe Gly Ile Val His Leu Leu Lys Asn Thr Ser Ile Tyr 500 505 510 Gln <210> 289 <211> 466 <212> PRT <213> homo sapiens <400> 289 Met Thr Leu Lys Ala Ser Glu Gly Glu Ser Gly Gly Ser Met His Thr 1 5 10 15 Ala Leu Ser Asp Leu Tyr Leu Glu His Leu Leu Gln Lys Arg Ser Arg 20 25 30 Pro Glu Ala Val Ser His Pro Leu Asn Thr Val Thr Glu Asp Met Tyr 35 40 45 Thr Asn Gly Ser Pro Ala Pro Gly Ser Pro Ala Gln Val Lys Gly Gln 50 55 60 Glu Val Arg Lys Val Arg Leu Ile Gln Phe Glu Lys Val Thr Glu Glu 65 70 75 80 Pro Met Gly Ile Thr Leu Lys Leu Asn Glu Lys Gln Ser Cys Thr Val 85 90 95 Ala Arg Ile Leu His Gly Gly Met Ile His Arg Gln Gly Ser Leu His 100 105 110 Val Gly Asp Glu Ile Leu Glu Ile Asn Gly Thr Asn Val Thr Asn His 115 120 125 Ser Val Asp Gln Leu Gln Lys Ala Met Lys Glu Thr Lys Gly Met Ile 130 135 140 Ser Leu Lys Val Ile Pro Asn Gln Gln Ser Arg Leu Pro Ala Leu Gln 145 150 155 160 Met Phe Met Arg Ala Gln Phe Asp Tyr Asp Pro Lys Lys Asp Asn Leu 165 170 175 Ile Pro Cys Lys Glu Ala Gly Leu Lys Phe Ala Thr Gly Asp Ile Ile 180 185 190 Gln Ile Ile Asn Lys Asp Asp Ser Asn Trp Trp Gln Gly Arg Val Glu 195 200 205 Gly Ser Ser Lys Glu Ser Ala Gly Leu Ile Pro Ser Pro Glu Leu Gln 210 215 220 Glu Trp Arg Val Ala Ser Met Ala Gln Ser Ala Pro Ser Glu Ala Pro 225 230 235 240 Ser Cys Ser Pro Phe Gly Lys Lys Lys Lys Tyr Lys Asp Lys Tyr Leu 245 250 255 Ala Lys His Ser Ser Ile Phe Asp Gln Leu Asp Val Val Ser Tyr Glu 260 265 270 Glu Val Val Arg Leu Pro Ala Phe Lys Arg Lys Thr Leu Val Leu Ile 275 280 285 Gly Ala Ser Gly Val Gly Arg Ser His Ile Lys Asn Ala Leu Leu Ser 290 295 300 Gln Asn Pro Glu Lys Phe Val Tyr Pro Val Pro Tyr Thr Thr Arg Pro 305 310 315 320 Pro Arg Lys Ser Glu Glu Asp Gly Lys Glu Tyr His Phe Ile Ser Thr 325 330 335 Glu Glu Met Thr Arg Asn Ile Ser Ala Asn Glu Phe Leu Glu Phe Gly 340 345 350 Ser Tyr Gln Gly Asn Met Phe Gly Thr Lys Phe Glu Thr Val His Gln 355 360 365 Ile His Lys Gln Asn Lys Ile Ala Ile Leu Asp Ile Glu Pro Gln Thr 370 375 380 Leu Lys Ile Val Arg Thr Ala Glu Leu Ser Pro Phe Ile Val Phe Ile 385 390 395 400 Ala Pro Thr Asp Gln Gly Thr Gln Thr Glu Ala Leu Gln Gln Leu Gln 405 410 415 Lys Asp Ser Glu Ala Ile Arg Ser Gln Tyr Ala His Tyr Phe Asp Leu 420 425 430 Ser Leu Val Asn Asn Gly Val Asp Glu Thr Leu Lys Lys Leu Gln Glu 435 440 445 Ala Phe Asp Gln Ala Cys Ser Ser Pro Gln Trp Val Pro Val Ser Trp 450 455 460 Val Tyr 465 <210> 290 <211> 161 <212> PRT <213> homo sapiens <400> 290 Met Ala Gly Ile Leu Arg Leu Val Val Gln Trp Pro Pro Gly Arg Leu 1 5 10 15 Gln Thr Val Thr Lys Gly Val Glu Ser Leu Ile Cys Thr Asp Trp Ile 20 25 30 Arg His Lys Phe Thr Arg Ser Arg Ile Pro Glu Lys Val Phe Gln Ala 35 40 45 Ser Pro Glu Asp His Glu Lys Tyr Gly Gly Asp Pro Gln Asn Pro His 50 55 60 Lys Leu His Ile Val Thr Arg Ile Lys Ser Thr Arg Arg Arg Pro Tyr 65 70 75 80 Trp Glu Lys Asp Ile Ile Lys Met Leu Gly Leu Glu Lys Ala His Thr 85 90 95 Pro Gln Val His Lys Asn Ile Pro Ser Val Asn Ala Lys Leu Lys Val 100 105 110 Val Lys His Leu Ile Arg Ile Lys Pro Leu Lys Leu Pro Gln Gly Leu 115 120 125 Pro Ala Glu Glu Asn Met Ser Asn Thr Cys Leu Lys Ser Thr Gly Glu 130 135 140 Leu Val Val Gln Trp His Leu Lys Pro Val Glu Gln Lys Ala His Glu 145 150 155 160 Ser <210> 291 <211> 546 <212> PRT <213> homo sapiens <400> 291 Met Thr Pro Leu Val Ser Arg Leu Ser Arg Leu Trp Ala Ile Met Arg 1 5 10 15 Lys Pro Arg Ala Ala Val Gly Ser Gly His Arg Lys Gln Ala Ala Ser 20 25 30 Gln Glu Gly Arg Gln Lys His Ala Lys Asn Asn Ser Gln Ala Lys Pro 35 40 45 Ser Ala Cys Asp Gly Met Ile Ala Glu Cys Pro Gly Ala Pro Ala Gly 50 55 60 Leu Ala Arg Gln Pro Glu Glu Val Val Leu Gln Ala Ser Val Ser Ser 65 70 75 80 Tyr His Leu Phe Arg Asp Val Ala Glu Val Thr Ala Phe Arg Gly Ser 85 90 95 Leu Leu Ser Trp Tyr Asp Gln Glu Lys Arg Asp Leu Pro Trp Arg Arg 100 105 110 Arg Ala Glu Asp Glu Met Asp Leu Asp Arg Arg Ala Tyr Ala Val Trp 115 120 125 Val Ser Glu Val Met Leu Gln Gln Thr Gln Val Ala Thr Val Ile Asn 130 135 140 Tyr Tyr Thr Gly Trp Met Gln Lys Trp Pro Thr Leu Gln Asp Leu Ala 145 150 155 160 Ser Ala Ser Leu Glu Glu Val Asn Gln Leu Trp Ala Gly Leu Gly Tyr 165 170 175 Tyr Ser Arg Gly Arg Arg Leu Gln Glu Gly Ala Arg Lys Val Val Glu 180 185 190 Glu Leu Gly Gly His Met Pro Arg Thr Ala Glu Thr Leu Gln Gln Leu 195 200 205 Leu Pro Gly Val Gly Arg Tyr Thr Ala Gly Ala Ile Ala Ser Ile Ala 210 215 220 Phe Gly Gln Ala Thr Gly Val Val Asp Gly Asn Val Ala Arg Val Leu 225 230 235 240 Cys Arg Val Arg Ala Ile Gly Ala Asp Pro Ser Ser Thr Leu Val Ser 245 250 255 Gln Gln Leu Trp Gly Leu Ala Gln Gln Leu Val Asp Pro Ala Arg Pro 260 265 270 Gly Asp Phe Asn Gln Ala Ala Met Glu Leu Gly Ala Thr Val Cys Thr 275 280 285 Pro Gln Arg Pro Leu Cys Ser Gln Cys Pro Val Glu Ser Leu Cys Arg 290 295 300 Ala Arg Gln Arg Val Glu Gln Glu Gln Leu Leu Ala Ser Gly Ser Leu 305 310 315 320 Ser Gly Ser Pro Asp Val Glu Glu Cys Ala Pro Asn Thr Gly Gln Cys 325 330 335 His Leu Cys Leu Pro Pro Ser Glu Pro Trp Asp Gln Thr Leu Gly Val 340 345 350 Val Asn Phe Pro Arg Lys Ala Ser Arg Lys Pro Pro Arg Glu Glu Ser 355 360 365 Ser Ala Thr Cys Val Leu Glu Gln Pro Gly Ala Leu Gly Ala Gln Ile 370 375 380 Leu Leu Val Gln Arg Pro Asn Ser Gly Leu Leu Ala Gly Leu Trp Glu 385 390 395 400 Phe Pro Ser Val Thr Trp Glu Pro Ser Glu Gln Leu Gln Arg Lys Ala 405 410 415 Leu Leu Gln Glu Leu Gln Arg Trp Ala Gly Pro Leu Pro Ala Thr His 420 425 430 Leu Arg His Leu Gly Glu Val Val His Thr Phe Ser His Ile Lys Leu 435 440 445 Thr Tyr Gln Val Tyr Gly Leu Ala Leu Glu Gly Gln Thr Pro Val Thr 450 455 460 Thr Val Pro Pro Gly Ala Arg Trp Leu Thr Gln Glu Glu Phe His Thr 465 470 475 480 Ala Ala Val Ser Thr Ala Met Lys Lys Val Phe Arg Val Tyr Gln Gly 485 490 495 Gln Gln Pro Gly Thr Cys Met Gly Ser Lys Arg Ser Gln Val Ser Ser 500 505 510 Pro Cys Ser Arg Lys Lys Pro Arg Met Gly Gln Gln Val Leu Asp Asn 515 520 525 Phe Phe Arg Ser His Ile Ser Thr Asp Ala His Ser Leu Asn Ser Ala 530 535 540 Ala Gln 545 <210> 292 <211> 1937 <212> PRT <213> homo sapiens <400> 292 Met Ser Ala Ser Ser Asp Ala Glu Met Ala Val Phe Gly Glu Ala Ala 1 5 10 15 Pro Tyr Leu Arg Lys Ser Glu Lys Glu Arg Ile Glu Ala Gln Asn Lys 20 25 30 Pro Phe Asp Ala Lys Thr Ser Val Phe Val Ala Glu Pro Lys Glu Ser 35 40 45 Tyr Val Lys Ser Thr Ile Gln Ser Lys Glu Gly Gly Lys Val Thr Val 50 55 60 Lys Thr Glu Gly Gly Ala Thr Leu Thr Val Arg Glu Asp Gln Val Phe 65 70 75 80 Pro Met Asn Pro Pro Lys Tyr Asp Lys Ile Glu Asp Met Ala Met Met 85 90 95 Thr His Leu His Glu Pro Gly Val Leu Tyr Asn Leu Lys Glu Arg Tyr 100 105 110 Ala Ala Trp Met Ile Tyr Thr Tyr Ser Gly Leu Phe Cys Val Thr Val 115 120 125 Asn Pro Tyr Lys Trp Leu Pro Val Tyr Lys Pro Glu Val Val Ala Ala 130 135 140 Tyr Arg Gly Lys Lys Arg Gln Glu Ala Pro Pro His Ile Phe Ser Ile 145 150 155 160 Ser Asp Asn Ala Tyr Gln Phe Met Leu Thr Asp Arg Glu Asn Gln Ser 165 170 175 Ile Leu Ile Thr Gly Glu Ser Gly Ala Gly Lys Thr Val Asn Thr Lys 180 185 190 Arg Val Ile Gln Tyr Phe Ala Thr Ile Ala Val Thr Gly Glu Lys Lys 195 200 205 Lys Asp Glu Ser Gly Lys Met Gln Gly Thr Leu Glu Asp Gln Ile Ile 210 215 220 Ser Ala Asn Pro Leu Leu Glu Ala Phe Gly Asn Ala Lys Thr Val Arg 225 230 235 240 Asn Asp Asn Ser Ser Arg Phe Gly Lys Phe Ile Arg Ile His Phe Gly 245 250 255 Thr Thr Gly Lys Leu Ala Ser Ala Asp Ile Glu Thr Tyr Leu Leu Glu 260 265 270 Lys Ser Arg Val Thr Phe Gln Leu Lys Ala Glu Arg Ser Tyr His Ile 275 280 285 Phe Tyr Gln Ile Thr Ser Asn Lys Lys Pro Asp Leu Ile Glu Met Leu 290 295 300 Leu Ile Thr Thr Asn Pro Tyr Asp Tyr Ala Phe Val Ser Gln Gly Glu 305 310 315 320 Ile Thr Val Pro Ser Ile Asp Asp Gln Glu Glu Leu Met Ala Thr Asp 325 330 335 Ser Ala Ile Asp Ile Leu Gly Phe Thr Pro Glu Glu Lys Val Ser Ile 340 345 350 Tyr Lys Leu Thr Gly Ala Val Met His Tyr Gly Asn Met Lys Phe Lys 355 360 365 Gln Lys Gln Arg Glu Glu Gln Ala Glu Pro Asp Gly Thr Glu Val Ala 370 375 380 Asp Lys Ala Ala Tyr Leu Gln Ser Leu Asn Ser Ala Asp Leu Leu Lys 385 390 395 400 Ala Leu Cys Tyr Pro Arg Val Lys Val Gly Asn Glu Tyr Val Thr Lys 405 410 415 Gly Gln Thr Val Gln Gln Val Tyr Asn Ala Val Gly Ala Leu Ala Lys 420 425 430 Ala Val Tyr Glu Lys Met Phe Leu Trp Met Val Thr Arg Ile Asn Gln 435 440 445 Gln Leu Asp Thr Lys Gln Pro Arg Gln Tyr Phe Ile Gly Val Leu Asp 450 455 460 Ile Ala Gly Phe Glu Ile Phe Asp Phe Asn Ser Leu Glu Gln Leu Cys 465 470 475 480 Ile Asn Phe Thr Asn Glu Lys Leu Gln Gln Phe Phe Asn His His Met 485 490 495 Phe Val Leu Glu Gln Glu Glu Tyr Lys Lys Glu Gly Ile Glu Trp Thr 500 505 510 Phe Ile Asp Phe Gly Met Asp Leu Ala Ala Cys Ile Glu Leu Ile Glu 515 520 525 Lys Pro Leu Gly Ile Phe Ser Ile Leu Glu Glu Glu Cys Met Phe Pro 530 535 540 Lys Ala Thr Asp Thr Ser Phe Lys Asn Lys Leu Tyr Asp Gln His Leu 545 550 555 560 Gly Lys Ser Ala Asn Phe Gln Lys Pro Lys Val Val Lys Gly Lys Ala 565 570 575 Glu Ala His Phe Ser Leu Ile His Tyr Ala Gly Thr Val Asp Tyr Asn 580 585 590 Ile Thr Gly Trp Leu Asp Lys Asn Lys Asp Pro Leu Asn Asp Thr Val 595 600 605 Val Gly Leu Tyr Gln Lys Ser Ala Met Lys Thr Leu Ala Ser Leu Phe 610 615 620 Ser Thr Tyr Ala Ser Ala Glu Ala Asp Ser Ser Ala Lys Lys Gly Ala 625 630 635 640 Lys Lys Lys Gly Ser Ser Phe Gln Thr Val Ser Ala Leu Phe Arg Glu 645 650 655 Asn Leu Asn Lys Leu Met Thr Asn Leu Arg Ser Thr His Pro His Phe 660 665 670 Val Arg Cys Ile Ile Pro Asn Glu Thr Lys Thr Pro Gly Ala Met Glu 675 680 685 His Glu Leu Val Leu His Gln Leu Arg Cys Asn Gly Val Leu Glu Gly 690 695 700 Ile Arg Ile Cys Arg Lys Gly Phe Pro Ser Arg Ile Leu Tyr Gly Asp 705 710 715 720 Phe Lys Gln Arg Tyr Lys Val Leu Asn Ala Ser Ala Ile Pro Glu Gly 725 730 735 Gln Phe Ile Asp Ser Lys Lys Ala Ser Glu Lys Leu Leu Ala Ser Ile 740 745 750 Asp Ile Asp His Thr Gln Tyr Lys Phe Gly His Thr Lys Val Phe Phe 755 760 765 Lys Ala Gly Leu Leu Gly Leu Leu Glu Glu Met Arg Asp Glu Lys Leu 770 775 780 Ala Gln Ile Ile Thr Arg Thr Gln Ala Val Cys Arg Gly Phe Leu Met 785 790 795 800 Arg Val Glu Tyr Gln Lys Met Leu Gln Arg Arg Glu Ala Leu Phe Cys 805 810 815 Ile Gln Tyr Asn Val Arg Ala Phe Met Asn Val Lys His Trp Pro Trp 820 825 830 Met Lys Leu Phe Phe Lys Ile Lys Pro Leu Leu Lys Ser Ala Glu Thr 835 840 845 Glu Lys Glu Met Ala Thr Met Lys Glu Glu Phe Gln Lys Thr Lys Asp 850 855 860 Glu Leu Ala Lys Ser Glu Ala Lys Arg Lys Glu Leu Glu Glu Lys Met 865 870 875 880 Val Thr Leu Leu Lys Glu Lys Asn Asp Leu Gln Leu Gln Val Gln Ser 885 890 895 Glu Ala Asp Ser Leu Ala Asp Ala Glu Glu Arg Cys Glu Gln Leu Ile 900 905 910 Lys Asn Lys Ile Gln Leu Glu Ala Lys Ile Lys Glu Val Thr Glu Arg 915 920 925 Ala Glu Glu Glu Glu Glu Ile Asn Ala Glu Leu Thr Ala Lys Lys Arg 930 935 940 Lys Leu Glu Asp Glu Cys Ser Glu Leu Lys Lys Asp Ile Asp Asp Leu 945 950 955 960 Glu Leu Thr Leu Ala Lys Val Glu Lys Glu Lys His Ala Thr Glu Asn 965 970 975 Lys Val Lys Asn Leu Thr Glu Glu Met Ala Gly Leu Asp Glu Thr Ile 980 985 990 Ala Lys Leu Ser Lys Glu Lys Lys Ala Leu Gln Glu Thr His Gln Gln 995 1000 1005 Thr Leu Asp Asp Leu Gln Ala Glu Glu Asp Lys Val Asn Ile Leu 1010 1015 1020 Thr Lys Ala Lys Thr Lys Leu Glu Gln Gln Val Asp Asp Leu Glu 1025 1030 1035 Gly Ser Leu Glu Gln Glu Lys Lys Leu Arg Met Asp Leu Glu Arg 1040 1045 1050 Ala Lys Arg Lys Leu Glu Gly Asp Leu Lys Leu Ala Gln Glu Ser 1055 1060 1065 Thr Met Asp Met Glu Asn Asp Lys Gln Gln Leu Asp Glu Lys Leu 1070 1075 1080 Glu Lys Lys Glu Phe Glu Ile Ser Asn Leu Ile Ser Lys Ile Glu 1085 1090 1095 Asp Glu Gln Ala Val Glu Ile Gln Leu Gln Lys Lys Ile Lys Glu 1100 1105 1110 Leu Gln Ala Arg Ile Glu Glu Leu Gly Glu Glu Ile Glu Ala Glu 1115 1120 1125 Arg Ala Ser Arg Ala Lys Ala Glu Lys Gln Arg Ser Asp Leu Ser 1130 1135 1140 Arg Glu Leu Glu Glu Ile Ser Glu Arg Leu Glu Glu Ala Gly Gly 1145 1150 1155 Ala Thr Ser Ala Gln Val Glu Leu Asn Lys Lys Arg Glu Ala Glu 1160 1165 1170 Phe Gln Lys Leu Arg Arg Asp Leu Glu Glu Ala Thr Leu Gln His 1175 1180 1185 Glu Ala Met Val Ala Ala Leu Arg Lys Lys His Ala Asp Ser Met 1190 1195 1200 Ala Glu Leu Gly Glu Gln Ile Asp Asn Leu Gln Arg Val Lys Gln 1205 1210 1215 Lys Leu Glu Lys Glu Lys Ser Glu Leu Lys Met Glu Thr Asp Asp 1220 1225 1230 Leu Ser Ser Asn Ala Glu Ala Ile Ser Lys Ala Lys Gly Asn Leu 1235 1240 1245 Glu Lys Met Cys Arg Ser Leu Glu Asp Gln Val Ser Glu Leu Lys 1250 1255 1260 Thr Lys Glu Glu Glu Gln Gln Arg Leu Ile Asn Asp Leu Thr Ala 1265 1270 1275 Gln Arg Ala Arg Leu Gln Thr Glu Ala Gly Glu Tyr Ser Arg Gln 1280 1285 1290 Leu Asp Glu Lys Asp Ala Leu Val Ser Gln Leu Ser Arg Ser Lys 1295 1300 1305 Gln Ala Ser Thr Gln Gln Ile Glu Glu Leu Lys His Gln Leu Glu 1310 1315 1320 Glu Glu Thr Lys Ala Lys Asn Ala Leu Ala His Ala Leu Gln Ser 1325 1330 1335 Ser Arg His Asp Cys Asp Leu Leu Arg Glu Gln Tyr Glu Glu Glu 1340 1345 1350 Gln Glu Gly Lys Ala Glu Leu Gln Arg Ala Leu Ser Lys Ala Asn 1355 1360 1365 Ser Glu Val Ala Gln Trp Arg Thr Lys Tyr Glu Thr Asp Ala Ile 1370 1375 1380 Gln Arg Thr Glu Glu Leu Glu Glu Ala Lys Lys Lys Leu Ala Gln 1385 1390 1395 Arg Leu Gln Glu Ala Glu Glu His Val Glu Ala Val Asn Ala Lys 1400 1405 1410 Cys Ala Ser Leu Glu Lys Thr Lys Gln Arg Leu Gln Asn Glu Val 1415 1420 1425 Glu Asp Leu Met Leu Asp Val Glu Arg Ser Asn Ala Ala Cys Ala 1430 1435 1440 Ala Leu Asp Lys Lys Gln Arg Asn Phe Asp Lys Val Leu Ser Glu 1445 1450 1455 Trp Lys Gln Lys Tyr Glu Glu Thr Gln Ala Glu Leu Glu Ala Ser 1460 1465 1470 Gln Lys Glu Ser Arg Ser Leu Ser Thr Glu Leu Phe Lys Val Lys 1475 1480 1485 Asn Val Tyr Glu Glu Ser Leu Asp Gln Leu Glu Thr Leu Arg Arg 1490 1495 1500 Glu Asn Lys Asn Leu Gln Gln Glu Ile Ser Asp Leu Thr Glu Gln 1505 1510 1515 Ile Ala Glu Gly Gly Lys Gln Ile His Glu Leu Glu Lys Ile Lys 1520 1525 1530 Lys Gln Val Glu Gln Glu Lys Cys Glu Ile Gln Ala Ala Leu Glu 1535 1540 1545 Glu Ala Glu Ala Ser Leu Glu His Glu Glu Gly Lys Ile Leu Arg 1550 1555 1560 Ile Gln Leu Glu Leu Asn Gln Val Lys Ser Glu Val Asp Arg Lys 1565 1570 1575 Ile Ala Glu Lys Asp Glu Glu Ile Asp Gln Leu Lys Arg Asn His 1580 1585 1590 Thr Arg Val Val Glu Thr Met Gln Ser Thr Leu Asp Ala Glu Ile 1595 1600 1605 Arg Ser Arg Asn Asp Ala Leu Arg Val Lys Lys Lys Met Glu Gly 1610 1615 1620 Asp Leu Asn Glu Met Glu Ile Gln Leu Asn His Ala Asn Arg Leu 1625 1630 1635 Ala Ala Glu Ser Leu Arg Asn Tyr Arg Asn Thr Gln Gly Ile Leu 1640 1645 1650 Lys Glu Thr Gln Leu His Leu Asp Asp Ala Leu Arg Gly Gln Glu 1655 1660 1665 Asp Leu Lys Glu Gln Leu Ala Ile Val Glu Arg Arg Ala Asn Leu 1670 1675 1680 Leu Gln Ala Glu Ile Glu Glu Leu Trp Ala Thr Leu Glu Gln Thr 1685 1690 1695 Glu Arg Ser Arg Lys Ile Ala Glu Gln Glu Leu Leu Asp Ala Ser 1700 1705 1710 Glu Arg Val Gln Leu Leu His Thr Gln Asn Thr Ser Leu Ile Asn 1715 1720 1725 Thr Lys Lys Lys Leu Glu Asn Asp Val Ser Gln Leu Gln Ser Glu 1730 1735 1740 Val Glu Glu Val Ile Gln Glu Ser Arg Asn Ala Glu Glu Lys Ala 1745 1750 1755 Lys Lys Ala Ile Thr Asp Ala Ala Met Met Ala Glu Glu Leu Lys 1760 1765 1770 Lys Glu Gln Asp Thr Ser Ala His Leu Glu Arg Met Lys Lys Asn 1775 1780 1785 Leu Glu Gln Thr Val Lys Asp Leu Gln His Arg Leu Asp Glu Ala 1790 1795 1800 Glu Gln Leu Ala Leu Lys Gly Gly Lys Lys Gln Ile Gln Lys Leu 1805 1810 1815 Glu Ala Arg Val Arg Glu Leu Glu Gly Glu Val Glu Asn Glu Gln 1820 1825 1830 Lys Arg Asn Ala Glu Ala Val Lys Gly Leu Arg Lys His Glu Arg 1835 1840 1845 Arg Val Lys Glu Leu Thr Tyr Gln Thr Glu Glu Asp Arg Lys Asn 1850 1855 1860 Val Leu Arg Leu Gln Asp Leu Val Asp Lys Leu Gln Ala Lys Val 1865 1870 1875 Lys Ser Tyr Lys Arg Gln Ala Glu Glu Ala Glu Glu Gln Ser Asn 1880 1885 1890 Ala Asn Leu Ser Lys Phe Arg Lys Leu Gln His Glu Leu Glu Glu 1895 1900 1905 Ala Glu Glu Arg Ala Asp Ile Ala Glu Ser Gln Val Asn Lys Leu 1910 1915 1920 Arg Val Lys Ser Arg Glu Val His Thr Lys Ile Ser Ala Glu 1925 1930 1935 <210> 293 <211> 174 <212> PRT <213> homo sapiens <400> 293 Met Met Tyr Ala Leu Phe Leu Leu Ser Val Gly Leu Val Met Gly Phe 1 5 10 15 Val Gly Phe Ser Ser Lys Pro Ser Pro Ile Tyr Gly Gly Leu Val Leu 20 25 30 Ile Val Ser Gly Val Val Gly Cys Val Ile Ile Leu Asn Phe Gly Gly 35 40 45 Gly Tyr Met Gly Leu Met Val Phe Leu Ile Tyr Leu Gly Gly Met Val 50 55 60 Val Val Phe Gly Tyr Thr Thr Ala Met Ala Ile Glu Glu Tyr Pro Glu 65 70 75 80 Ala Trp Gly Ser Gly Val Glu Val Leu Val Ser Val Leu Val Gly Leu 85 90 95 Ala Met Glu Val Gly Leu Val Leu Trp Val Lys Glu Tyr Asp Gly Val 100 105 110 Val Val Val Val Asn Phe Asn Ser Val Gly Ser Trp Met Ile Tyr Glu 115 120 125 Gly Glu Gly Ser Gly Leu Ile Arg Glu Asp Pro Ile Gly Ala Gly Ala 130 135 140 Leu Tyr Asp Tyr Gly Arg Trp Leu Val Val Val Thr Gly Trp Thr Leu 145 150 155 160 Phe Val Gly Val Tyr Ile Val Ile Glu Ile Ala Arg Gly Asn 165 170 <210> 294 <211> 916 <212> PRT <213> homo sapiens <400> 294 Met Ser Tyr Thr Leu Asp Ser Leu Gly Asn Pro Ser Ala Tyr Arg Arg 1 5 10 15 Val Thr Glu Thr Arg Ser Ser Phe Ser Arg Val Ser Gly Ser Pro Ser 20 25 30 Ser Gly Phe Arg Ser Gln Ser Trp Ser Arg Gly Ser Pro Ser Thr Val 35 40 45 Ser Ser Ser Tyr Lys Arg Ser Met Leu Ala Pro Arg Leu Ala Tyr Ser 50 55 60 Ser Ala Met Leu Ser Ser Ala Glu Ser Ser Leu Asp Phe Ser Gln Ser 65 70 75 80 Ser Ser Leu Leu Asn Gly Gly Ser Gly Pro Gly Gly Asp Tyr Lys Leu 85 90 95 Ser Arg Ser Asn Glu Lys Glu Gln Leu Gln Gly Leu Asn Asp Arg Phe 100 105 110 Ala Gly Tyr Ile Glu Lys Val His Tyr Leu Glu Gln Gln Asn Lys Glu 115 120 125 Ile Glu Ala Glu Ile Gln Ala Leu Arg Gln Lys Gln Ala Ser His Ala 130 135 140 Gln Leu Gly Asp Ala Tyr Asp Gln Glu Ile Arg Glu Leu Arg Ala Thr 145 150 155 160 Leu Glu Met Val Asn His Glu Lys Ala Gln Val Gln Leu Asp Ser Asp 165 170 175 His Leu Glu Glu Asp Ile His Arg Leu Lys Glu Arg Phe Glu Glu Glu 180 185 190 Ala Arg Leu Arg Asp Asp Thr Glu Ala Ala Ile Arg Ala Leu Arg Lys 195 200 205 Asp Ile Glu Glu Ala Ser Leu Val Lys Val Glu Leu Asp Lys Lys Val 210 215 220 Gln Ser Leu Gln Asp Glu Val Ala Phe Leu Arg Ser Asn His Glu Glu 225 230 235 240 Glu Val Ala Asp Leu Leu Ala Gln Ile Gln Ala Ser His Ile Thr Val 245 250 255 Glu Arg Lys Asp Tyr Leu Lys Thr Asp Ile Ser Thr Ala Leu Lys Glu 260 265 270 Ile Arg Ser Gln Leu Glu Ser His Ser Asp Gln Asn Met His Gln Ala 275 280 285 Glu Glu Trp Phe Lys Cys Arg Tyr Ala Lys Leu Thr Glu Ala Ala Glu 290 295 300 Gln Asn Lys Glu Ala Ile Arg Ser Ala Lys Glu Glu Ile Ala Glu Tyr 305 310 315 320 Arg Arg Gln Leu Gln Ser Lys Ser Ile Glu Leu Glu Ser Val Arg Gly 325 330 335 Thr Lys Glu Ser Leu Glu Arg Gln Leu Ser Asp Ile Glu Glu Arg His 340 345 350 Asn His Asp Leu Ser Ser Tyr Gln Asp Thr Ile Gln Gln Leu Glu Asn 355 360 365 Glu Leu Arg Gly Thr Lys Trp Glu Met Ala Arg His Leu Arg Glu Tyr 370 375 380 Gln Asp Leu Leu Asn Val Lys Met Ala Leu Asp Ile Glu Ile Ala Ala 385 390 395 400 Tyr Arg Lys Leu Leu Glu Gly Glu Glu Thr Arg Phe Ser Thr Phe Ala 405 410 415 Gly Ser Ile Thr Gly Pro Leu Tyr Thr His Arg Pro Pro Ile Thr Ile 420 425 430 Ser Ser Lys Ile Gln Lys Pro Lys Val Glu Ala Pro Lys Leu Lys Val 435 440 445 Gln His Lys Phe Val Glu Glu Ile Ile Glu Glu Thr Lys Val Glu Asp 450 455 460 Glu Lys Ser Glu Met Glu Glu Ala Leu Thr Ala Ile Thr Glu Glu Leu 465 470 475 480 Ala Val Ser Met Lys Glu Glu Lys Lys Glu Ala Ala Glu Glu Lys Glu 485 490 495 Glu Glu Pro Glu Ala Glu Glu Glu Glu Val Ala Ala Lys Lys Ser Pro 500 505 510 Val Lys Ala Thr Ala Pro Glu Val Lys Glu Glu Glu Gly Glu Lys Glu 515 520 525 Glu Glu Glu Gly Gln Glu Glu Glu Glu Glu Glu Asp Glu Gly Ala Lys 530 535 540 Ser Asp Gln Ala Glu Glu Gly Gly Ser Glu Lys Glu Gly Ser Ser Glu 545 550 555 560 Lys Glu Glu Gly Glu Gln Glu Glu Gly Glu Thr Glu Ala Glu Ala Glu 565 570 575 Gly Glu Glu Ala Glu Ala Lys Glu Glu Lys Lys Val Glu Glu Lys Ser 580 585 590 Glu Glu Val Ala Thr Lys Glu Glu Leu Val Ala Asp Ala Lys Val Glu 595 600 605 Lys Pro Glu Lys Ala Lys Ser Pro Val Pro Lys Ser Pro Val Glu Glu 610 615 620 Lys Gly Lys Ser Pro Val Pro Lys Ser Pro Val Glu Glu Lys Gly Lys 625 630 635 640 Ser Pro Val Pro Lys Ser Pro Val Glu Glu Lys Gly Lys Ser Pro Val 645 650 655 Pro Lys Ser Pro Val Glu Glu Lys Gly Lys Ser Pro Val Ser Lys Ser 660 665 670 Pro Val Glu Glu Lys Ala Lys Ser Pro Val Pro Lys Ser Pro Val Glu 675 680 685 Glu Ala Lys Ser Lys Ala Glu Val Gly Lys Gly Glu Gln Lys Glu Glu 690 695 700 Glu Glu Lys Glu Val Lys Glu Ala Pro Lys Glu Glu Lys Val Glu Lys 705 710 715 720 Lys Glu Glu Lys Pro Lys Asp Val Pro Glu Lys Lys Lys Ala Glu Ser 725 730 735 Pro Val Lys Glu Glu Ala Val Ala Glu Val Val Thr Ile Thr Lys Ser 740 745 750 Val Lys Val His Leu Glu Lys Glu Thr Lys Glu Glu Gly Lys Pro Leu 755 760 765 Gln Gln Glu Lys Glu Lys Glu Lys Ala Gly Gly Glu Gly Gly Ser Glu 770 775 780 Glu Glu Gly Ser Asp Lys Gly Ala Lys Gly Ser Arg Lys Glu Asp Ile 785 790 795 800 Ala Val Asn Gly Glu Val Glu Gly Lys Glu Glu Val Glu Gln Glu Thr 805 810 815 Lys Glu Lys Gly Ser Gly Arg Glu Glu Glu Lys Gly Val Val Thr Asn 820 825 830 Gly Leu Asp Leu Ser Pro Ala Asp Glu Lys Lys Gly Gly Asp Lys Ser 835 840 845 Glu Glu Lys Val Val Val Thr Lys Thr Val Glu Lys Ile Thr Ser Glu 850 855 860 Gly Gly Asp Gly Ala Thr Lys Tyr Ile Thr Lys Ser Val Thr Val Thr 865 870 875 880 Gln Lys Val Glu Glu His Glu Glu Thr Phe Glu Glu Lys Leu Val Ser 885 890 895 Thr Lys Lys Val Glu Lys Val Thr Ser His Ala Ile Val Lys Glu Val 900 905 910 Thr Gln Ser Asp 915 <210> 295 <211> 356 <212> PRT <213> homo sapiens <400> 295 Met Thr Lys Ser Tyr Ser Glu Ser Gly Leu Met Gly Glu Pro Gln Pro 1 5 10 15 Gln Gly Pro Pro Ser Trp Thr Asp Glu Cys Leu Ser Ser Gln Asp Glu 20 25 30 Glu His Glu Ala Asp Lys Lys Glu Asp Asp Leu Glu Thr Met Asn Ala 35 40 45 Glu Glu Asp Ser Leu Arg Asn Gly Gly Glu Glu Glu Asp Glu Asp Glu 50 55 60 Asp Leu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Asp Asp Gln Lys 65 70 75 80 Pro Lys Arg Arg Gly Pro Lys Lys Lys Lys Met Thr Lys Ala Arg Leu 85 90 95 Glu Arg Phe Lys Leu Arg Arg Met Lys Ala Asn Ala Arg Glu Arg Asn 100 105 110 Arg Met His Gly Leu Asn Ala Ala Leu Asp Asn Leu Arg Lys Val Val 115 120 125 Pro Cys Tyr Ser Lys Thr Gln Lys Leu Ser Lys Ile Glu Thr Leu Arg 130 135 140 Leu Ala Lys Asn Tyr Ile Trp Ala Leu Ser Glu Ile Leu Arg Ser Gly 145 150 155 160 Lys Ser Pro Asp Leu Val Ser Phe Val Gln Thr Leu Cys Lys Gly Leu 165 170 175 Ser Gln Pro Thr Thr Asn Leu Val Ala Gly Cys Leu Gln Leu Asn Pro 180 185 190 Arg Thr Phe Leu Pro Glu Gln Asn Gln Asp Met Pro Pro His Leu Pro 195 200 205 Thr Ala Ser Ala Ser Phe Pro Val His Pro Tyr Ser Tyr Gln Ser Pro 210 215 220 Gly Leu Pro Ser Pro Pro Tyr Gly Thr Met Asp Ser Ser His Val Phe 225 230 235 240 His Val Lys Pro Pro Pro His Ala Tyr Ser Ala Ala Leu Glu Pro Phe 245 250 255 Phe Glu Ser Pro Leu Thr Asp Cys Thr Ser Pro Ser Phe Asp Gly Pro 260 265 270 Leu Ser Pro Pro Leu Ser Ile Asn Gly Asn Phe Ser Phe Lys His Glu 275 280 285 Pro Ser Ala Glu Phe Glu Lys Asn Tyr Ala Phe Thr Met His Tyr Pro 290 295 300 Ala Ala Thr Leu Ala Gly Ala Gln Ser His Gly Ser Ile Phe Ser Gly 305 310 315 320 Thr Ala Ala Pro Arg Cys Glu Ile Pro Ile Asp Asn Ile Met Ser Phe 325 330 335 Asp Ser His Ser His His Glu Arg Val Met Ser Ala Gln Leu Asn Ala 340 345 350 Ile Phe His Asp 355 <210> 296 <211> 471 <212> PRT <213> homo sapiens <400> 296 Met Gln Ser Asn Lys Thr Phe Asn Leu Glu Lys Gln Asn His Thr Pro 1 5 10 15 Arg Lys His His Gln His His His Gln Gln Gln His His Gln Gln Gln 20 25 30 Gln Gln Gln Pro Pro Pro Pro Pro Ile Pro Ala Asn Gly Gln Gln Ala 35 40 45 Ser Ser Gln Asn Glu Gly Leu Thr Ile Asp Leu Lys Asn Phe Arg Lys 50 55 60 Pro Gly Glu Lys Thr Phe Thr Gln Arg Ser Arg Leu Phe Val Gly Asn 65 70 75 80 Leu Pro Pro Asp Ile Thr Glu Glu Glu Met Arg Lys Leu Phe Glu Lys 85 90 95 Tyr Gly Lys Ala Gly Glu Val Phe Ile His Lys Asp Lys Gly Phe Gly 100 105 110 Phe Ile Arg Leu Glu Thr Arg Thr Leu Ala Glu Ile Ala Lys Val Glu 115 120 125 Leu Asp Asn Met Pro Leu Arg Gly Lys Gln Leu Arg Val Arg Phe Ala 130 135 140 Cys His Ser Ala Ser Leu Thr Val Arg Asn Leu Pro Gln Tyr Val Ser 145 150 155 160 Asn Glu Leu Leu Glu Glu Ala Phe Ser Val Phe Gly Gln Val Glu Arg 165 170 175 Ala Val Val Ile Val Asp Asp Arg Gly Arg Pro Ser Gly Lys Gly Ile 180 185 190 Val Glu Phe Ser Gly Lys Pro Ala Ala Arg Lys Ala Leu Asp Arg Cys 195 200 205 Ser Glu Gly Ser Phe Leu Leu Thr Thr Phe Pro Arg Pro Val Thr Val 210 215 220 Glu Pro Met Asp Gln Leu Asp Asp Glu Glu Gly Leu Pro Glu Lys Leu 225 230 235 240 Val Ile Lys Asn Gln Gln Phe His Lys Glu Arg Glu Gln Pro Pro Arg 245 250 255 Phe Ala Gln Pro Gly Ser Phe Glu Tyr Glu Tyr Ala Met Arg Trp Lys 260 265 270 Ala Leu Ile Glu Met Glu Lys Gln Gln Gln Asp Gln Val Asp Arg Asn 275 280 285 Ile Lys Glu Ala Arg Glu Lys Leu Glu Met Glu Met Glu Ala Ala Arg 290 295 300 His Glu His Gln Val Met Leu Met Arg Gln Asp Leu Met Arg Arg Gln 305 310 315 320 Glu Glu Leu Arg Arg Met Glu Glu Leu His Asn Gln Glu Val Gln Lys 325 330 335 Arg Lys Gln Leu Glu Leu Arg Gln Glu Glu Glu Arg Arg Arg Arg Glu 340 345 350 Glu Glu Met Arg Arg Gln Gln Glu Glu Met Met Arg Arg Gln Gln Glu 355 360 365 Gly Phe Lys Gly Thr Phe Pro Asp Ala Arg Glu Gln Glu Ile Arg Met 370 375 380 Gly Gln Met Ala Met Gly Gly Ala Met Gly Ile Asn Asn Arg Gly Ala 385 390 395 400 Met Pro Pro Ala Pro Val Pro Ala Gly Thr Pro Ala Pro Pro Gly Pro 405 410 415 Ala Thr Met Met Pro Asp Gly Thr Leu Gly Leu Thr Pro Pro Thr Thr 420 425 430 Glu Arg Phe Gly Gln Ala Ala Thr Met Glu Gly Ile Gly Ala Ile Gly 435 440 445 Gly Thr Pro Pro Ala Phe Asn Arg Ala Ala Pro Gly Ala Glu Phe Ala 450 455 460 Pro Asn Lys Arg Arg Arg Tyr 465 470 <210> 297 <211> 106 <212> PRT <213> homo sapiens <400> 297 Met Pro Thr Val Lys Thr Arg Lys Leu Asn Ser Leu Glu Leu Thr Tyr 1 5 10 15 Leu Ala Gln Gly His Thr Met Ser Glu Trp Gly Asn Leu Asp Met Asp 20 25 30 Phe Ser Leu Pro Glu Leu Arg Ala Asp Gln Arg Leu Cys Leu Asn Phe 35 40 45 Gln Asp Pro Phe Leu Pro Leu Val Asp Ala His Gly Ile Glu Lys Cys 50 55 60 Arg Ala Phe Ser Phe Ser Val Glu Lys Phe Cys Leu Pro Leu Val Met 65 70 75 80 Lys Gly Ile Leu Gln Lys Gly Val Ser Pro Leu Asn Ser Ser Ile Asp 85 90 95 Tyr Gly Arg Leu Ala Lys Lys Glu Ser Leu 100 105 <210> 298 <211> 445 <212> PRT <213> homo sapiens <400> 298 Met Asp Leu Glu Leu Asp Glu Tyr Tyr Asn Lys Thr Leu Ala Thr Glu 1 5 10 15 Asn Asn Thr Ala Ala Thr Arg Asn Ser Asp Phe Pro Val Trp Asp Asp 20 25 30 Tyr Lys Ser Ser Val Asp Asp Leu Gln Tyr Phe Leu Ile Gly Leu Tyr 35 40 45 Thr Phe Val Ser Leu Leu Gly Phe Met Gly Asn Leu Leu Ile Leu Met 50 55 60 Ala Leu Met Lys Lys Arg Asn Gln Lys Thr Thr Val Asn Phe Leu Ile 65 70 75 80 Gly Asn Leu Ala Phe Ser Asp Ile Leu Val Val Leu Phe Cys Ser Pro 85 90 95 Phe Thr Leu Thr Ser Val Leu Leu Asp Gln Trp Met Phe Gly Lys Val 100 105 110 Met Cys His Ile Met Pro Phe Leu Gln Cys Val Ser Val Leu Val Ser 115 120 125 Thr Leu Ile Leu Ile Ser Ile Ala Ile Val Arg Tyr His Met Ile Lys 130 135 140 His Pro Ile Ser Asn Asn Leu Thr Ala Asn His Gly Tyr Phe Leu Ile 145 150 155 160 Ala Thr Val Trp Thr Leu Gly Phe Ala Ile Cys Ser Pro Leu Pro Val 165 170 175 Phe His Ser Leu Val Glu Leu Gln Glu Thr Phe Gly Ser Ala Leu Leu 180 185 190 Ser Ser Arg Tyr Leu Cys Val Glu Ser Trp Pro Ser Asp Ser Tyr Arg 195 200 205 Ile Ala Phe Thr Ile Ser Leu Leu Leu Val Gln Tyr Ile Leu Pro Leu 210 215 220 Val Cys Leu Thr Val Ser His Thr Ser Val Cys Arg Ser Ile Ser Cys 225 230 235 240 Gly Leu Ser Asn Lys Glu Asn Arg Leu Glu Glu Asn Glu Met Ile Asn 245 250 255 Leu Thr Leu His Pro Ser Lys Lys Ser Gly Pro Gln Val Lys Leu Ser 260 265 270 Gly Ser His Lys Trp Ser Tyr Ser Phe Ile Lys Lys His Arg Arg Arg 275 280 285 Tyr Ser Lys Lys Thr Ala Cys Val Leu Pro Ala Pro Glu Arg Pro Ser 290 295 300 Gln Glu Asn His Ser Arg Ile Leu Pro Glu Asn Phe Gly Ser Val Arg 305 310 315 320 Ser Gln Leu Ser Ser Ser Ser Lys Phe Ile Pro Gly Val Pro Thr Cys 325 330 335 Phe Glu Ile Lys Pro Glu Glu Asn Ser Asp Val His Glu Leu Arg Val 340 345 350 Lys Arg Ser Val Thr Arg Ile Lys Lys Arg Ser Arg Ser Val Phe Tyr 355 360 365 Arg Leu Thr Ile Leu Ile Leu Val Phe Ala Val Ser Trp Met Pro Leu 370 375 380 His Leu Phe His Val Val Thr Asp Phe Asn Asp Asn Leu Ile Ser Asn 385 390 395 400 Arg His Phe Lys Leu Val Tyr Cys Ile Cys His Leu Leu Gly Met Met 405 410 415 Ser Cys Cys Leu Asn Pro Ile Leu Tyr Gly Phe Leu Asn Asn Gly Ile 420 425 430 Lys Ala Asp Leu Val Ser Leu Ile His Cys Leu His Met 435 440 445 <210> 299 <211> 109 <212> PRT <213> homo sapiens <400> 299 Met Ser Ile Thr Asp Val Leu Ser Ala Asp Asp Ile Ala Ala Ala Leu 1 5 10 15 Gln Glu Cys Arg Asp Pro Asp Thr Phe Glu Pro Gln Lys Phe Phe Gln 20 25 30 Thr Ser Gly Leu Ser Lys Met Ser Ala Asn Gln Val Lys Asp Val Phe 35 40 45 Arg Phe Ile Asp Asn Asp Gln Ser Gly Tyr Leu Asp Glu Glu Glu Leu 50 55 60 Lys Phe Phe Leu Gln Lys Phe Glu Ser Gly Ala Arg Glu Leu Thr Glu 65 70 75 80 Ser Glu Thr Lys Ser Leu Met Ala Ala Ala Asp Asn Asp Gly Asp Gly 85 90 95 Lys Ile Gly Ala Glu Glu Phe Gln Glu Met Val His Ser 100 105 <210> 300 <211> 109 <212> PRT <213> homo sapiens <400> 300 Met Ser Ile Thr Asp Val Leu Ser Ala Asp Asp Ile Ala Ala Ala Leu 1 5 10 15 Gln Glu Cys Gln Asp Pro Asp Thr Phe Glu Pro Gln Lys Phe Phe Gln 20 25 30 Thr Ser Gly Leu Ser Lys Met Ser Ala Ser Gln Val Lys Asp Val Phe 35 40 45 Arg Phe Ile Asp Asn Asp Gln Ser Gly Tyr Leu Asp Glu Glu Glu Leu 50 55 60 Lys Phe Phe Leu Gln Lys Phe Glu Ser Gly Ala Arg Glu Leu Thr Glu 65 70 75 80 Ser Glu Thr Lys Ser Leu Met Ala Ala Ala Asp Asn Asp Gly Asp Gly 85 90 95 Lys Ile Gly Ala Glu Glu Phe Gln Glu Met Val His Ser 100 105 <210> 301 <211> 303 <212> PRT <213> homo sapiens <400> 301 Met Ser Phe Ser Ser Leu Pro Thr Glu Ile Gln Ser Leu Leu Phe Leu 1 5 10 15 Thr Phe Leu Thr Ile Tyr Leu Val Thr Leu Met Gly Asn Cys Leu Ile 20 25 30 Ile Leu Val Thr Leu Ala Asp Pro Met Leu His Ser Pro Met Tyr Phe 35 40 45 Phe Leu Arg Asn Leu Ser Phe Leu Glu Ile Gly Phe Asn Leu Val Ile 50 55 60 Val Pro Lys Met Leu Gly Thr Leu Leu Ala Gln Asp Thr Thr Ile Ser 65 70 75 80 Phe Leu Gly Cys Ala Thr Gln Met Tyr Phe Phe Phe Phe Phe Gly Val 85 90 95 Ala Glu Cys Phe Leu Leu Ala Thr Met Ala Tyr Asp Arg Tyr Val Ala 100 105 110 Ile Cys Ser Pro Leu His Tyr Pro Val Ile Met Asn Gln Arg Thr Arg 115 120 125 Ala Lys Leu Ala Ala Ala Ser Trp Phe Pro Gly Phe Pro Val Ala Thr 130 135 140 Val Gln Thr Thr Trp Leu Phe Ser Phe Pro Phe Cys Gly Thr Asn Lys 145 150 155 160 Val Asn His Phe Phe Cys Asp Ser Pro Pro Val Leu Arg Leu Val Cys 165 170 175 Ala Asp Thr Ala Leu Phe Glu Ile Tyr Ala Ile Val Gly Thr Ile Leu 180 185 190 Val Val Met Ile Pro Cys Leu Leu Ile Leu Cys Ser Tyr Thr His Ile 195 200 205 Ala Ala Ala Ile Leu Lys Ile Pro Ser Ala Lys Gly Lys Asn Lys Ala 210 215 220 Phe Ser Thr Cys Ser Ser His Leu Leu Val Val Ser Leu Phe Tyr Ile 225 230 235 240 Ser Leu Ser Leu Thr Tyr Phe Arg Pro Lys Ser Asn Asn Ser Pro Glu 245 250 255 Gly Lys Lys Leu Leu Ser Leu Ser Tyr Thr Val Met Thr Pro Met Leu 260 265 270 Asn Pro Ile Ile Tyr Ser Leu Arg Asn Asn Glu Val Lys Asn Ala Leu 275 280 285 Ser Arg Thr Val Ser Lys Ala Leu Ala Leu Arg Asn Cys Ile Pro 290 295 300 <210> 302 <211> 310 <212> PRT <213> homo sapiens <400> 302 Met Glu Ser Asn Gln Thr Trp Ile Thr Glu Val Ile Leu Leu Gly Phe 1 5 10 15 Gln Val Asp Pro Ala Leu Glu Leu Phe Leu Phe Gly Phe Phe Leu Leu 20 25 30 Phe Tyr Ser Leu Thr Leu Met Gly Asn Gly Ile Ile Leu Gly Leu Ile 35 40 45 Tyr Leu Asp Ser Arg Leu His Thr Pro Met Tyr Val Phe Leu Ser His 50 55 60 Leu Ala Ile Val Asp Met Ser Tyr Ala Ser Ser Thr Val Pro Lys Met 65 70 75 80 Leu Ala Asn Leu Val Met His Lys Lys Val Ile Ser Phe Ala Pro Cys 85 90 95 Ile Leu Gln Thr Phe Leu Tyr Leu Ala Phe Ala Ile Thr Glu Cys Leu 100 105 110 Ile Leu Val Met Met Cys Tyr Asp Arg Tyr Val Ala Ile Cys His Pro 115 120 125 Leu Gln Tyr Thr Leu Ile Met Asn Trp Arg Val Cys Thr Val Leu Ala 130 135 140 Ser Thr Cys Trp Ile Phe Ser Phe Leu Leu Ala Leu Val His Ile Thr 145 150 155 160 Leu Ile Leu Arg Leu Pro Phe Cys Gly Pro Gln Lys Ile Asn His Phe 165 170 175 Phe Cys Gln Ile Met Ser Val Phe Lys Leu Ala Cys Ala Asp Thr Arg 180 185 190 Leu Asn Gln Val Val Leu Phe Ala Gly Ser Ala Phe Ile Leu Val Gly 195 200 205 Pro Leu Cys Leu Val Leu Val Ser Tyr Leu His Ile Leu Val Ala Ile 210 215 220 Leu Arg Ile Gln Ser Gly Glu Gly Arg Arg Lys Ala Phe Ser Thr Cys 225 230 235 240 Ser Ser His Leu Cys Val Val Gly Leu Phe Phe Gly Ser Ala Ile Val 245 250 255 Met Tyr Met Ala Pro Lys Ser Ser His Ser Gln Glu Arg Arg Lys Ile 260 265 270 Leu Ser Leu Phe Tyr Ser Leu Phe Asn Pro Ile Leu Asn Pro Leu Ile 275 280 285 Tyr Ser Leu Arg Asn Ala Glu Val Lys Gly Ala Leu Lys Arg Val Leu 290 295 300 Trp Lys Gln Arg Ser Met 305 310 <210> 303 <211> 330 <212> PRT <213> homo sapiens <400> 303 Met Cys Ser Phe Phe Leu Cys Gln Thr Gly Lys Gln Ala Lys Ile Ser 1 5 10 15 Met Gly Glu Glu Asn Gln Thr Phe Val Ser Lys Phe Ile Phe Leu Gly 20 25 30 Leu Ser Gln Asp Leu Gln Thr Gln Ile Leu Leu Phe Ile Leu Phe Leu 35 40 45 Ile Ile Tyr Leu Leu Thr Val Leu Gly Asn Gln Leu Ile Ile Ile Leu 50 55 60 Ile Phe Leu Asp Ser Arg Leu His Thr Pro Met Tyr Phe Phe Leu Arg 65 70 75 80 Asn Leu Ser Phe Ala Asp Leu Cys Phe Ser Thr Ser Ile Val Pro Gln 85 90 95 Val Leu Val His Phe Leu Val Lys Arg Lys Thr Ile Ser Phe Tyr Gly 100 105 110 Cys Met Thr Gln Ile Ile Val Phe Leu Leu Val Gly Cys Thr Glu Cys 115 120 125 Ala Leu Leu Ala Val Met Ser Tyr Asp Arg Tyr Val Ala Val Cys Lys 130 135 140 Pro Leu Tyr Tyr Ser Thr Ile Met Thr Gln Arg Val Cys Leu Trp Leu 145 150 155 160 Ser Phe Arg Ser Trp Ala Ser Gly Ala Leu Val Ser Leu Val Asp Thr 165 170 175 Ser Phe Thr Phe His Leu Pro Tyr Trp Gly Gln Asn Ile Ile Asn His 180 185 190 Tyr Phe Cys Glu Pro Pro Ala Leu Leu Lys Leu Ala Ser Ile Asp Thr 195 200 205 Tyr Ser Thr Glu Met Ala Ile Phe Ser Met Gly Val Val Ile Leu Leu 210 215 220 Ala Pro Val Ser Leu Ile Leu Gly Ser Tyr Trp Asn Ile Ile Ser Thr 225 230 235 240 Val Ile Gln Met Gln Ser Gly Glu Gly Arg Leu Lys Ala Phe Ser Thr 245 250 255 Cys Gly Ser His Leu Ile Val Val Val Leu Phe Tyr Gly Ser Gly Ile 260 265 270 Phe Thr Tyr Met Arg Pro Asn Ser Lys Thr Thr Lys Glu Leu Asp Lys 275 280 285 Met Ile Ser Val Phe Tyr Thr Ala Val Thr Pro Met Leu Asn Pro Ile 290 295 300 Ile Tyr Ser Leu Arg Asn Lys Asp Val Lys Gly Ala Leu Arg Lys Leu 305 310 315 320 Val Gly Arg Lys Cys Phe Ser His Arg Gln 325 330 <210> 304 <211> 312 <212> PRT <213> homo sapiens <400> 304 Met Ala Arg Glu Asn Ser Thr Phe Asn Ser Asp Phe Ile Leu Leu Gly 1 5 10 15 Ile Phe Asn His Ser Pro Thr His Thr Phe Leu Phe Phe Leu Val Leu 20 25 30 Ala Ile Phe Ser Val Ala Phe Met Gly Asn Ser Val Met Val Leu Leu 35 40 45 Ile Tyr Leu Asp Thr Gln Leu His Thr Pro Met Tyr Leu Leu Leu Ser 50 55 60 Gln Leu Ser Leu Met Asp Leu Met Leu Ile Cys Thr Thr Val Pro Lys 65 70 75 80 Met Ala Phe Asn Tyr Leu Ser Gly Ser Lys Ser Ile Ser Met Ala Gly 85 90 95 Cys Ala Thr Gln Ile Phe Phe Tyr Thr Ser Leu Leu Gly Ser Glu Cys 100 105 110 Phe Leu Leu Ala Val Met Ala Tyr Asp Arg Tyr Thr Ala Ile Cys His 115 120 125 Pro Leu Arg Tyr Thr Asn Leu Met Ser Pro Lys Ile Cys Gly Leu Met 130 135 140 Thr Ala Phe Ser Trp Ile Leu Gly Ser Thr Asp Gly Ile Ile Asp Val 145 150 155 160 Val Ala Thr Phe Ser Phe Ser Tyr Cys Gly Ser Arg Glu Ile Ala His 165 170 175 Phe Phe Cys Asp Phe Pro Ser Leu Leu Ile Leu Ser Cys Ser Asp Thr 180 185 190 Ser Ile Phe Glu Lys Ile Leu Phe Ile Cys Cys Ile Val Met Ile Val 195 200 205 Phe Pro Val Ala Ile Ile Ile Ala Ser Tyr Ala Arg Val Ile Leu Ala 210 215 220 Val Ile His Met Gly Ser Gly Glu Gly Arg Arg Lys Ala Phe Thr Thr 225 230 235 240 Cys Ser Ser His Leu Leu Val Val Gly Met Tyr Tyr Gly Ala Ala Leu 245 250 255 Phe Met Tyr Ile Arg Pro Thr Ser Asp Arg Ser Pro Thr Gln Asp Lys 260 265 270 Met Val Ser Val Phe Tyr Thr Ile Leu Thr Pro Met Leu Asn Pro Leu 275 280 285 Ile Tyr Ser Leu Arg Asn Lys Glu Val Thr Arg Ala Phe Met Lys Ile 290 295 300 Leu Gly Lys Gly Lys Ser Gly Glu 305 310 <210> 305 <211> 324 <212> PRT <213> homo sapiens <400> 305 Met Gly Met Glu Gly Leu Leu Gln Asn Ser Thr Asn Phe Val Leu Thr 1 5 10 15 Gly Leu Ile Thr His Pro Ala Phe Pro Gly Leu Leu Phe Ala Ile Val 20 25 30 Phe Ser Ile Phe Val Val Ala Ile Thr Ala Asn Leu Val Met Ile Leu 35 40 45 Leu Ile His Met Asp Ser Arg Leu His Thr Pro Met Tyr Phe Leu Leu 50 55 60 Ser Gln Leu Ser Ile Met Asp Thr Ile Tyr Ile Cys Ile Thr Val Pro 65 70 75 80 Lys Met Leu Gln Asp Leu Leu Ser Lys Asp Lys Thr Ile Ser Phe Leu 85 90 95 Gly Cys Ala Val Gln Ile Phe Leu Tyr Leu Thr Leu Ile Gly Gly Glu 100 105 110 Phe Phe Leu Leu Gly Leu Met Ala Tyr Asp Arg Tyr Val Ala Val Cys 115 120 125 Asn Pro Leu Arg Tyr Pro Leu Leu Met Asn Arg Arg Val Cys Leu Phe 130 135 140 Met Val Val Gly Ser Trp Val Gly Gly Ser Leu Asp Gly Phe Met Leu 145 150 155 160 Thr Pro Val Thr Met Ser Phe Pro Phe Cys Arg Ser Arg Glu Ile Asn 165 170 175 His Phe Phe Cys Glu Ile Pro Ala Val Leu Lys Leu Ser Cys Thr Asp 180 185 190 Thr Ser Leu Tyr Glu Thr Leu Met Tyr Ala Cys Cys Val Leu Met Leu 195 200 205 Leu Ile Pro Leu Ser Val Ile Ser Val Ser Tyr Thr His Ile Leu Leu 210 215 220 Thr Val His Arg Met Asn Ser Ala Glu Gly Arg Arg Lys Ala Phe Ala 225 230 235 240 Thr Cys Ser Ser His Ile Met Val Val Ser Val Phe Tyr Gly Ala Ala 245 250 255 Phe Tyr Thr Asn Val Leu Pro His Ser Tyr His Thr Pro Glu Lys Asp 260 265 270 Lys Val Val Ser Ala Phe Tyr Thr Ile Leu Thr Pro Met Leu Asn Pro 275 280 285 Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val Ala Ala Ala Leu Arg Lys 290 295 300 Val Leu Gly Arg Cys Gly Ser Ser Gln Ser Ile Arg Val Ala Thr Val 305 310 315 320 Ile Arg Lys Gly <210> 306 <211> 323 <212> PRT <213> homo sapiens <400> 306 Met Gly Met Glu Gly Leu Leu Gln Asn Ser Thr Asn Phe Val Leu Thr 1 5 10 15 Gly Leu Ile Thr His Pro Ala Phe Pro Gly Leu Leu Phe Ala Val Val 20 25 30 Phe Ser Ile Phe Val Val Ala Ile Thr Ala Asn Leu Val Met Ile Leu 35 40 45 Leu Ile His Met Asp Ser Arg Leu His Thr Pro Met Tyr Phe Leu Leu 50 55 60 Ser Gln Leu Ser Ile Met Asp Thr Ile Tyr Ile Cys Ile Thr Val Pro 65 70 75 80 Lys Met Leu Gln Asp Leu Leu Ser Lys Asp Lys Thr Ile Ser Phe Leu 85 90 95 Gly Cys Ala Val Gln Ile Phe Tyr Leu Thr Leu Ile Gly Gly Glu Phe 100 105 110 Phe Leu Leu Gly Leu Met Ala Tyr Asp Arg Tyr Val Ala Val Cys Asn 115 120 125 Pro Leu Arg Tyr Pro Leu Leu Met Asn Arg Arg Val Cys Leu Phe Met 130 135 140 Val Val Gly Ser Trp Val Gly Gly Ser Leu Asp Gly Phe Met Leu Thr 145 150 155 160 Pro Val Thr Met Ser Phe Pro Phe Cys Arg Ser Arg Glu Ile Asn His 165 170 175 Phe Phe Cys Glu Ile Pro Ala Val Leu Lys Leu Ser Cys Thr Asp Thr 180 185 190 Ser Leu Tyr Glu Thr Leu Met Tyr Ala Cys Cys Val Leu Met Leu Leu 195 200 205 Ile Pro Leu Ser Val Ile Ser Val Ser Tyr Thr His Ile Leu Leu Thr 210 215 220 Val His Arg Met Asn Ser Ala Glu Gly Arg Arg Lys Ala Phe Ala Thr 225 230 235 240 Cys Ser Ser His Ile Met Val Val Ser Val Phe Tyr Gly Ala Ala Phe 245 250 255 Tyr Thr Asn Val Leu Pro His Ser Tyr His Thr Pro Glu Lys Asp Lys 260 265 270 Val Val Ser Ala Phe Tyr Thr Ile Leu Thr Pro Met Leu Asn Pro Leu 275 280 285 Ile Tyr Ser Leu Arg Asn Lys Asp Val Ala Ala Ala Leu Arg Lys Val 290 295 300 Leu Gly Arg Cys Gly Ser Ser Gln Ser Ile Arg Val Ala Thr Val Ile 305 310 315 320 Arg Lys Gly <210> 307 <211> 311 <212> PRT <213> homo sapiens <400> 307 Met Glu Met Glu Asn Cys Thr Arg Val Lys Glu Phe Ile Phe Leu Gly 1 5 10 15 Leu Thr Gln Asn Arg Glu Val Ser Leu Val Leu Phe Leu Phe Leu Leu 20 25 30 Leu Val Tyr Val Thr Thr Leu Leu Gly Asn Leu Leu Ile Met Val Thr 35 40 45 Val Thr Cys Glu Ser Arg Leu His Thr Pro Met Tyr Phe Leu Leu His 50 55 60 Asn Leu Ser Ile Ala Asp Ile Cys Phe Ser Ser Ile Thr Val Pro Lys 65 70 75 80 Val Leu Val Asp Leu Leu Ser Glu Arg Lys Thr Ile Ser Phe Asn His 85 90 95 Cys Phe Thr Gln Met Phe Leu Phe His Leu Ile Gly Gly Val Asp Val 100 105 110 Phe Ser Leu Ser Val Met Ala Leu Asp Arg Tyr Val Ala Ile Ser Lys 115 120 125 Pro Leu His Tyr Ala Thr Ile Met Ser Arg Asp His Cys Ile Gly Leu 130 135 140 Thr Val Ala Ala Trp Leu Gly Gly Phe Val His Ser Ile Val Gln Ile 145 150 155 160 Ser Leu Leu Leu Pro Leu Pro Phe Cys Gly Pro Asn Val Leu Asp Thr 165 170 175 Phe Tyr Cys Asp Val His Arg Val Leu Lys Leu Ala His Thr Asp Ile 180 185 190 Phe Ile Leu Glu Leu Leu Met Ile Ser Asn Asn Gly Leu Leu Thr Thr 195 200 205 Leu Trp Phe Phe Leu Leu Leu Val Ser Tyr Ile Val Ile Leu Ser Leu 210 215 220 Pro Lys Ser Gln Ala Gly Glu Gly Arg Arg Lys Ala Ile Ser Thr Cys 225 230 235 240 Thr Ser His Ile Thr Val Val Thr Leu His Phe Val Pro Cys Ile Tyr 245 250 255 Val Tyr Ala Arg Pro Phe Thr Ala Leu Pro Met Asp Lys Ala Ile Ser 260 265 270 Val Thr Phe Thr Val Ile Ser Pro Leu Leu Asn Pro Leu Ile Tyr Thr 275 280 285 Leu Arg Asn His Glu Met Lys Ser Ala Met Arg Arg Leu Lys Arg Arg 290 295 300 Leu Val Pro Ser Asp Arg Lys 305 310 <210> 308 <211> 307 <212> PRT <213> homo sapiens <400> 308 Met Glu Thr Gly Asn Leu Thr Trp Val Ser Asp Phe Val Phe Leu Gly 1 5 10 15 Leu Ser Gln Thr Arg Glu Leu Gln Arg Phe Leu Phe Leu Met Phe Leu 20 25 30 Phe Val Tyr Ile Thr Thr Val Met Gly Asn Ile Leu Ile Ile Ile Thr 35 40 45 Val Thr Ser Asp Ser Gln Leu His Thr Pro Met Tyr Phe Leu Leu Arg 50 55 60 Asn Leu Ala Val Leu Asp Leu Cys Phe Ser Ser Val Thr Ala Pro Lys 65 70 75 80 Met Leu Val Asp Leu Leu Ser Glu Lys Lys Thr Ile Ser Tyr Gln Gly 85 90 95 Cys Met Gly Gln Ile Phe Phe Phe His Phe Leu Gly Gly Ala Met Val 100 105 110 Phe Phe Leu Ser Val Met Ala Phe Asp Arg Leu Ile Ala Ile Ser Arg 115 120 125 Pro Leu Arg Tyr Val Thr Val Met Asn Thr Gln Leu Trp Val Gly Leu 130 135 140 Val Val Ala Thr Trp Val Gly Gly Phe Val His Ser Ile Val Gln Leu 145 150 155 160 Ala Leu Met Leu Pro Leu Pro Phe Cys Gly Pro Asn Ile Leu Asp Asn 165 170 175 Phe Tyr Cys Asp Val Pro Gln Val Leu Arg Leu Ala Cys Thr Asp Thr 180 185 190 Ser Leu Leu Glu Phe Leu Lys Ile Ser Asn Ser Gly Leu Leu Asp Val 195 200 205 Val Trp Phe Phe Leu Leu Leu Met Ser Tyr Leu Phe Ile Leu Val Met 210 215 220 Leu Arg Ser His Pro Gly Glu Ala Arg Arg Lys Ala Ala Ser Thr Cys 225 230 235 240 Thr Thr His Ile Ile Val Val Ser Met Ile Phe Val Pro Ser Ile Tyr 245 250 255 Leu Tyr Ala Arg Pro Phe Thr Pro Phe Pro Met Asp Lys Leu Val Ser 260 265 270 Ile Gly His Thr Val Met Thr Pro Met Leu Asn Pro Met Ile Tyr Thr 275 280 285 Leu Arg Asn Gln Asp Met Gln Ala Ala Val Arg Arg Leu Gly Arg His 290 295 300 Arg Leu Val 305 <210> 309 <211> 312 <212> PRT <213> homo sapiens <400> 309 Met Ala Asp Asp Asn Phe Thr Val Val Thr Glu Phe Ile Leu Leu Gly 1 5 10 15 Leu Thr Asp His Ala Glu Leu Lys Ala Val Leu Phe Val Val Phe Leu 20 25 30 Val Ile Tyr Ala Ile Thr Leu Leu Arg Asn Leu Gly Met Ile Leu Leu 35 40 45 Ile Gln Ile Thr Ser Lys Leu His Thr Pro Met Tyr Phe Leu Leu Ser 50 55 60 Cys Leu Ser Phe Val Asp Ala Cys Tyr Ser Ser Ala Ile Ala Pro Lys 65 70 75 80 Met Leu Val Asn Leu Leu Val Val Lys Ala Thr Ile Ser Phe Ser Ala 85 90 95 Cys Met Val Gln His Leu Cys Phe Gly Val Phe Ile Thr Thr Glu Gly 100 105 110 Phe Leu Leu Ser Val Met Ala Tyr Asp Arg Tyr Val Ala Ile Val Ser 115 120 125 Pro Leu Leu Tyr Thr Val Ala Met Ser Asp Arg Lys Cys Val Glu Leu 130 135 140 Val Thr Gly Ser Trp Ile Gly Gly Ile Val Asn Thr Leu Ile His Thr 145 150 155 160 Ile Ser Leu Arg Arg Leu Ser Phe Cys Arg Leu Asn Ala Val Ser His 165 170 175 Phe Phe Cys Asp Ile Pro Ser Leu Leu Lys Leu Ser Cys Ser Asp Thr 180 185 190 Ser Met Asn Glu Leu Leu Leu Leu Thr Phe Ser Gly Val Ile Ala Met 195 200 205 Ala Thr Phe Leu Thr Val Ile Ile Ser Tyr Ile Phe Ile Ala Phe Ala 210 215 220 Ser Leu Arg Ile His Ser Ala Ser Gly Arg Gln Gln Ala Phe Ser Thr 225 230 235 240 Cys Ala Ser His Leu Thr Ala Val Thr Ile Phe Tyr Gly Thr Leu Ile 245 250 255 Phe Ser Tyr Ile Gln Pro Ser Ser Gln Tyr Phe Val Glu Gln Glu Lys 260 265 270 Val Val Ser Met Phe Tyr Thr Leu Gly Ile Pro Met Leu Asn Leu Leu 275 280 285 Ile His Ser Leu Arg Asn Lys Asp Val Lys Glu Ala Val Lys Arg Ala 290 295 300 Ile Glu Met Lys His Phe Leu Cys 305 310 <210> 310 <211> 315 <212> PRT <213> homo sapiens <400> 310 Met Leu Ser Pro Asn His Thr Ile Val Thr Glu Phe Ile Leu Leu Gly 1 5 10 15 Leu Thr Asp Asp Pro Val Leu Glu Lys Ile Leu Phe Gly Val Phe Leu 20 25 30 Ala Ile Tyr Leu Ile Thr Leu Ala Gly Asn Leu Cys Met Ile Leu Leu 35 40 45 Ile Arg Thr Asn Ser Gln Leu Gln Thr Pro Met Tyr Phe Phe Leu Gly 50 55 60 His Leu Ser Phe Val Asp Ile Cys Tyr Ser Ser Asn Val Thr Pro Asn 65 70 75 80 Met Leu His Asn Phe Leu Ser Glu Gln Lys Thr Ile Ser Tyr Ala Gly 85 90 95 Cys Phe Thr Gln Cys Leu Leu Phe Ile Ala Leu Val Ile Thr Glu Phe 100 105 110 Tyr Phe Leu Ala Ser Met Ala Leu Asp Arg Tyr Val Ala Ile Cys Ser 115 120 125 Pro Leu His Tyr Ser Ser Arg Met Ser Lys Asn Ile Cys Ile Ser Leu 130 135 140 Val Thr Val Pro Tyr Met Tyr Gly Phe Leu Asn Gly Leu Ser Gln Thr 145 150 155 160 Leu Leu Thr Phe His Leu Ser Phe Cys Gly Ser Leu Glu Ile Asn His 165 170 175 Phe Tyr Cys Ala Asp Pro Pro Leu Ile Met Leu Ala Cys Ser Asp Thr 180 185 190 Arg Val Lys Lys Met Ala Met Phe Val Val Ala Gly Phe Thr Leu Ser 195 200 205 Ser Ser Leu Phe Ile Ile Leu Leu Ser Tyr Leu Phe Ile Phe Ala Ala 210 215 220 Ile Phe Arg Ile Arg Ser Ala Glu Gly Arg His Lys Ala Phe Ser Thr 225 230 235 240 Cys Ala Ser His Leu Thr Ile Val Thr Leu Phe Tyr Gly Thr Leu Phe 245 250 255 Cys Met Tyr Val Arg Pro Pro Ser Glu Lys Ser Val Glu Glu Ser Lys 260 265 270 Ile Ile Ala Val Phe Tyr Thr Phe Leu Ser Pro Met Leu Asn Pro Leu 275 280 285 Ile Tyr Ser Leu Arg Asn Arg Asp Val Ile Leu Ala Ile Gln Gln Met 290 295 300 Ile Arg Gly Lys Ser Phe Cys Lys Ile Ala Val 305 310 315 <210> 311 <211> 312 <212> PRT <213> homo sapiens <400> 311 Met Met Gly Arg Arg Asn Asp Thr Asn Val Ala Asp Phe Ile Leu Thr 1 5 10 15 Gly Leu Ser Asp Ser Glu Glu Val Gln Met Ala Leu Phe Met Leu Phe 20 25 30 Leu Leu Ile Tyr Leu Ile Thr Met Leu Gly Asn Val Gly Met Leu Leu 35 40 45 Ile Ile Arg Leu Asp Leu Gln Leu His Thr Pro Met Tyr Phe Phe Leu 50 55 60 Thr His Leu Ser Phe Ile Asp Leu Ser Tyr Ser Thr Val Val Thr Pro 65 70 75 80 Lys Thr Leu Ala Asn Leu Leu Thr Ser Asn Tyr Ile Ser Phe Thr Gly 85 90 95 Cys Phe Ala Gln Met Phe Cys Phe Val Phe Leu Gly Thr Ala Glu Cys 100 105 110 Tyr Leu Leu Ser Ser Met Ala Tyr Asp Arg Tyr Ala Ala Ile Cys Ser 115 120 125 Pro Leu His Tyr Thr Val Ile Met Pro Lys Arg Leu Cys Leu Ala Leu 130 135 140 Ile Thr Gly Pro Tyr Val Ile Gly Phe Met Asp Ser Phe Val Asn Val 145 150 155 160 Val Ser Met Ser Arg Leu His Phe Cys Asp Ser Asn Ile Ile His His 165 170 175 Phe Phe Cys Asp Thr Ser Pro Ile Leu Ala Leu Ser Cys Thr Asp Thr 180 185 190 Asp Asn Thr Glu Met Leu Ile Phe Ile Ile Ala Gly Ser Thr Leu Met 195 200 205 Val Ser Leu Ile Thr Ile Ser Ala Ser Tyr Val Ser Ile Leu Ser Thr 210 215 220 Ile Leu Lys Ile Asn Ser Thr Ser Gly Lys Gln Lys Ala Phe Ser Thr 225 230 235 240 Cys Val Ser His Leu Leu Gly Val Thr Ile Phe Tyr Gly Thr Met Ile 245 250 255 Phe Thr Tyr Leu Lys Pro Arg Lys Ser Tyr Ser Leu Gly Arg Asp Gln 260 265 270 Val Ala Pro Val Phe Tyr Thr Ile Val Ile Pro Met Leu Asn Pro Leu 275 280 285 Ile Tyr Ser Leu Arg Asn Arg Glu Val Lys Asn Ala Leu Ile Arg Val 290 295 300 Met Gln Arg Arg Gln Asp Ser Arg 305 310 <210> 312 <211> 305 <212> PRT <213> homo sapiens <400> 312 Met Gln Arg Ser Asn His Thr Val Thr Glu Phe Ile Leu Leu Gly Phe 1 5 10 15 Thr Thr Asp Pro Gly Met Gln Leu Gly Leu Phe Val Val Phe Leu Gly 20 25 30 Val Tyr Ser Leu Thr Val Val Gly Asn Ser Thr Leu Ile Val Leu Ile 35 40 45 Cys Asn Asp Ser Cys Leu His Thr Pro Met Tyr Phe Phe Thr Gly Asn 50 55 60 Leu Ser Phe Leu Asp Leu Trp Tyr Ser Ser Val Tyr Thr Pro Lys Ile 65 70 75 80 Leu Val Thr Cys Ile Ser Glu Asp Lys Ser Ile Ser Phe Ala Gly Cys 85 90 95 Leu Cys Gln Phe Phe Phe Ser Ala Gly Leu Ala Tyr Ser Glu Cys Tyr 100 105 110 Leu Leu Ala Ala Val Ala Tyr Asp Arg Tyr Val Ala Ile Ser Lys Pro 115 120 125 Leu Leu Tyr Ala Gln Ala Met Ser Ile Lys Leu Cys Ala Leu Leu Val 130 135 140 Ala Val Ser Tyr Cys Gly Gly Phe Ile Asn Ser Ser Ile Ile Thr Lys 145 150 155 160 Lys Thr Phe Ser Phe Asn Phe Cys Arg Glu Asn Ile Ile Asp Asp Phe 165 170 175 Phe Cys Asp Leu Leu Pro Leu Val Glu Leu Ala Cys Gly Glu Lys Gly 180 185 190 Gly Tyr Lys Ile Met Met Tyr Phe Leu Leu Ala Ser Asn Val Ile Cys 195 200 205 Pro Ala Val Leu Ile Leu Ala Ser Tyr Leu Phe Ile Ile Thr Ser Val 210 215 220 Leu Arg Ile Ser Ser Ser Lys Gly Tyr Leu Lys Ala Phe Ser Thr Cys 225 230 235 240 Ser Ser His Leu Thr Ser Val Thr Leu Tyr Tyr Gly Ser Ile Leu Tyr 245 250 255 Ile Tyr Ala Leu Pro Arg Ser Ser Tyr Ser Phe Asp Met Asp Lys Ile 260 265 270 Val Ser Thr Phe Tyr Thr Val Val Phe Pro Met Leu Asn Leu Met Ile 275 280 285 Tyr Ser Leu Arg Asn Lys Asp Val Lys Glu Ala Leu Lys Lys Leu Leu 290 295 300 Pro 305 <210> 313 <211> 201 <212> PRT <213> homo sapiens <400> 313 Met Ala Leu Ser Trp Val Leu Thr Val Leu Ser Leu Leu Pro Leu Leu 1 5 10 15 Glu Ala Gln Ile Pro Leu Cys Ala Asn Leu Val Pro Val Pro Ile Thr 20 25 30 Asn Ala Thr Leu Asp Arg Ile Thr Gly Lys Trp Phe Tyr Ile Ala Ser 35 40 45 Ala Phe Arg Asn Glu Glu Tyr Asn Lys Ser Val Gln Glu Ile Gln Ala 50 55 60 Thr Phe Phe Tyr Phe Thr Pro Asn Lys Thr Glu Asp Thr Ile Phe Leu 65 70 75 80 Arg Glu Tyr Gln Thr Arg Gln Asn Gln Cys Phe Tyr Asn Ser Ser Tyr 85 90 95 Leu Asn Val Gln Arg Glu Asn Gly Thr Val Ser Arg Tyr Glu Gly Gly 100 105 110 Arg Glu His Val Ala His Leu Leu Phe Leu Arg Asp Thr Lys Thr Leu 115 120 125 Met Phe Gly Ser Tyr Leu Asp Asp Glu Lys Asn Trp Gly Leu Ser Phe 130 135 140 Tyr Ala Asp Lys Pro Glu Thr Thr Lys Glu Gln Leu Gly Glu Phe Tyr 145 150 155 160 Glu Ala Leu Asp Cys Leu Cys Ile Pro Arg Ser Asp Val Met Tyr Thr 165 170 175 Asp Trp Lys Lys Asp Lys Cys Glu Pro Leu Glu Lys Gln His Glu Lys 180 185 190 Glu Arg Lys Gln Glu Glu Gly Glu Ser 195 200 <210> 314 <211> 2925 <212> PRT <213> homo sapiens <400> 314 Met Gly Val Leu Ala Ser Ala Leu Cys Trp Leu Leu Cys Val Trp Leu 1 5 10 15 Pro Trp Gly Glu Gln Ala Ala Glu Ser Leu Arg Val Gln Arg Leu Gly 20 25 30 Glu Arg Val Val Asp Ser Gly Arg Ser Gly Ala Arg Gly Met Arg Asn 35 40 45 Val Lys Gly Met Arg Asn Gly Pro Ala Gln Thr Arg Val Ser Ser Ser 50 55 60 Ser Ser His Gln Glu Ala Thr Leu Ala Met Gly Asp Lys Ala Thr Val 65 70 75 80 Val Gly Gly Gln Gln Ala Glu Ala Pro Asp Ser Val Ala Met Ser Ser 85 90 95 Trp Glu Arg Arg Leu His Arg Ala Lys Cys Ala Pro Ser Tyr Leu Phe 100 105 110 Ser Cys Phe Asn Gly Gly Glu Cys Val His Pro Ala Phe Cys Asp Cys 115 120 125 Arg Arg Phe Asn Ala Thr Gly Pro Arg Cys Gln Met Val Tyr Asn Ala 130 135 140 Gly Pro Glu Arg Asp Ser Ile Cys Arg Ala Trp Gly Gln His His Val 145 150 155 160 Glu Thr Phe Asp Gly Leu Tyr Tyr Tyr Leu Ser Gly Lys Gly Ser Tyr 165 170 175 Thr Leu Val Gly Arg His Glu Pro Glu Gly Gln Ser Phe Ser Ile Gln 180 185 190 Val His Asn Asp Pro Gln Cys Gly Ser Ser Pro Tyr Thr Cys Ser Arg 195 200 205 Ala Val Ser Leu Phe Phe Val Gly Glu Gln Glu Ile His Leu Ala Lys 210 215 220 Glu Val Thr His Gly Gly Met Arg Val Gln Leu Pro His Val Met Gly 225 230 235 240 Ser Ala Arg Leu Gln Gln Leu Ala Gly Tyr Val Ile Val Arg His Gln 245 250 255 Ser Ala Phe Thr Leu Ala Trp Asp Gly Ala Ser Ala Val Tyr Ile Lys 260 265 270 Met Ser Pro Glu Leu Leu Gly Trp Thr His Gly Leu Cys Gly Asn Asn 275 280 285 Asn Ala Asp Pro Lys Asp Asp Leu Val Thr Ser Ser Gly Lys Leu Thr 290 295 300 Asp Asp Val Val Glu Phe Val His Ser Trp Gln Glu Gln Ala Pro Asn 305 310 315 320 Gln Pro Pro Gly Pro Thr Thr Ser Ser Leu Pro Arg Pro Pro Cys Leu 325 330 335 Gln Gln Asn Pro Gly Thr Met Gln Gly Val Tyr Glu Gln Cys Glu Ala 340 345 350 Leu Leu Arg Pro Pro Phe Asp Ala Cys His Ala Tyr Val Ser Pro Leu 355 360 365 Pro Phe Thr Ala Ser Cys Thr Ser Asp Leu Cys Gln Ser Met Gly Asp 370 375 380 Val Ala Thr Trp Cys Arg Ala Leu Ala Glu Tyr Ala Arg Ala Cys Ala 385 390 395 400 Gln Ala Gly Arg Pro Leu Gln Gly Trp Arg Thr Gln Leu Arg Gln Cys 405 410 415 Thr Val His Cys Lys Glu Lys Ala Phe Thr Tyr Asn Glu Cys Ile Ala 420 425 430 Cys Cys Pro Ala Ser Cys His Pro Arg Ala Ser Cys Val Asp Ser Glu 435 440 445 Ile Ala Cys Val Asp Gly Cys Tyr Cys Pro Asn Gly Leu Ile Phe Glu 450 455 460 Asp Gly Gly Cys Val Ala Pro Ala Glu Cys Pro Cys Glu Phe His Gly 465 470 475 480 Thr Leu Tyr Pro Pro Gly Ser Val Val Lys Glu Asp Cys Asn Thr Cys 485 490 495 Thr Cys Thr Ser Gly Lys Trp Glu Cys Ser Thr Ala Val Cys Pro Ala 500 505 510 Glu Cys Ser Val Thr Gly Asp Ile His Phe Thr Thr Phe Asp Gly Arg 515 520 525 Arg Tyr Thr Phe Pro Ala Thr Cys Gln Tyr Ile Leu Ala Lys Ser Arg 530 535 540 Ser Ser Gly Thr Phe Thr Val Thr Leu Gln Asn Ala Pro Cys Gly Leu 545 550 555 560 Asn Gln Asp Gly Ala Cys Val Gln Ser Val Ser Val Ile Leu His Gln 565 570 575 Asp Pro Arg Arg Gln Val Thr Leu Thr Gln Ala Gly Asp Val Leu Leu 580 585 590 Phe Asp Gln Tyr Lys Ile Ile Pro Pro Tyr Thr Asp Asp Ala Phe Glu 595 600 605 Ile Arg Arg Leu Ser Ser Val Phe Leu Arg Val Arg Thr Asn Val Gly 610 615 620 Val Arg Val Leu Tyr Asp Arg Glu Gly Leu Arg Leu Tyr Leu Gln Val 625 630 635 640 Asp Gln Arg Trp Val Glu Asp Thr Val Gly Leu Cys Gly Thr Phe Asn 645 650 655 Gly Asn Thr Gln Asp Asp Phe Leu Ser Pro Val Gly Val Pro Glu Ser 660 665 670 Thr Pro Gln Leu Phe Gly Asn Ser Trp Lys Thr Leu Ser Ala Cys Ser 675 680 685 Pro Leu Val Ser Gly Ser Pro Leu Asp Pro Cys Asp Val His Leu Gln 690 695 700 Ala Ala Ser Tyr Ser Val Gln Ala Cys Ser Val Leu Thr Gly Glu Met 705 710 715 720 Phe Ala Pro Cys Ser Ala Phe Leu Ser Pro Val Pro Tyr Phe Glu Gln 725 730 735 Cys Arg Arg Asp Ala Cys Arg Cys Gly Gln Pro Cys Leu Cys Ala Thr 740 745 750 Leu Ala His Tyr Ala His Leu Cys Arg Arg His Gly Leu Pro Val Asp 755 760 765 Phe Arg Ala Arg Leu Pro Ala Cys Ala Leu Ser Cys Glu Ala Ser Lys 770 775 780 Glu Tyr Ser Pro Cys Val Ala Pro Cys Gly Arg Thr Cys Gln Asp Leu 785 790 795 800 Ala Ser Pro Glu Ala Cys Gly Val Asp Gly Gly Asp Asp Leu Ser Arg 805 810 815 Asp Glu Cys Val Glu Gly Cys Ala Cys Pro Pro Asp Thr Tyr Leu Asp 820 825 830 Thr Gln Ala Asp Leu Cys Val Pro Arg Asn Gln Cys Ser Cys His Phe 835 840 845 Gln Gly Val Asp Tyr Pro Pro Gly Asp Ser Asp Ile Pro Ser Leu Gly 850 855 860 His Cys His Cys Lys Asp Gly Val Met Ser Cys Asp Ser Arg Ala Pro 865 870 875 880 Ala Ala Ala Cys Pro Ala Gly Gln Val Phe Val Asn Cys Ser Asp Leu 885 890 895 His Thr Asp Leu Glu Leu Ser Arg Glu Arg Thr Cys Glu Gln Gln Leu 900 905 910 Leu Asn Leu Ser Val Ser Ala Arg Gly Pro Cys Leu Ser Gly Cys Ala 915 920 925 Cys Pro Gln Gly Leu Leu Arg His Gly Asp Ala Cys Phe Leu Pro Glu 930 935 940 Glu Cys Pro Cys Thr Trp Lys Gly Lys Glu Tyr Phe Pro Gly Asp Gln 945 950 955 960 Val Met Ser Pro Cys His Thr Cys Val Cys Gln Arg Gly Ser Phe Gln 965 970 975 Cys Thr Leu His Pro Cys Ala Ser Thr Cys Thr Ala Tyr Gly Asp Arg 980 985 990 His Tyr Arg Thr Phe Asp Gly Leu Pro Phe Asp Phe Val Gly Ala Cys 995 1000 1005 Lys Val His Leu Val Lys Ser Thr Ser Asp Val Ser Phe Ser Val 1010 1015 1020 Ile Val Glu Asn Val Asn Cys Tyr Ser Ser Gly Met Ile Cys Arg 1025 1030 1035 Lys Phe Ile Ser Ile Asn Val Gly Asn Ser Leu Ile Val Phe Asp 1040 1045 1050 Asp Asp Ser Gly Asn Pro Ser Pro Glu Ser Phe Leu Asp Asp Lys 1055 1060 1065 Gln Glu Val His Thr Trp Arg Val Gly Phe Phe Thr Leu Val His 1070 1075 1080 Phe Pro Gln Glu His Ile Thr Leu Leu Trp Asp Gln Arg Thr Thr 1085 1090 1095 Val His Val Gln Ala Gly Pro Gln Trp Gln Gly Gln Leu Ala Gly 1100 1105 1110 Leu Cys Gly Asn Phe Asp Leu Lys Thr Ile Asn Glu Met Arg Thr 1115 1120 1125 Pro Glu Asn Leu Glu Leu Thr Asn Pro Gln Glu Phe Gly Ser Ser 1130 1135 1140 Trp Ala Ala Val Glu Cys Pro Asp Thr Leu Asp Pro Arg Asp Met 1145 1150 1155 Cys Val Leu Asn Pro Leu Arg Glu Pro Phe Ala Lys Lys Glu Cys 1160 1165 1170 Ser Ile Leu Leu Ser Glu Val Phe Glu Ile Cys His Pro Val Val 1175 1180 1185 Asp Val Thr Trp Phe Tyr Ser Asn Cys Leu Thr Asp Thr Cys Gly 1190 1195 1200 Cys Ser Gln Gly Gly Asp Cys Glu Cys Phe Cys Ala Ser Val Ser 1205 1210 1215 Ala Tyr Ala His Gln Cys Cys Gln His Gly Val Ala Val Asp Trp 1220 1225 1230 Arg Thr Pro Arg Leu Cys Pro Tyr Asp Cys Asp Phe Phe Asn Lys 1235 1240 1245 Val Leu Gly Lys Gly Pro Tyr Gln Leu Ser Ser Leu Ala Ala Gly 1250 1255 1260 Gly Ala Leu Val Gly Met Lys Ala Val Gly Asp Asp Ile Val Leu 1265 1270 1275 Val Arg Thr Glu Asp Val Ala Pro Ala Asp Ile Val Ser Phe Leu 1280 1285 1290 Leu Thr Ala Ala Leu Tyr Lys Ala Lys Ala His Asp Pro Asp Val 1295 1300 1305 Val Ser Leu Glu Ala Ala Asp Arg Pro Asn Phe Phe Leu His Val 1310 1315 1320 Thr Ala Asn Gly Ser Leu Glu Leu Ala Lys Trp Gln Gly Arg Asp 1325 1330 1335 Thr Phe Gln Gln His Ala Ser Phe Leu Leu His Arg Gly Thr Arg 1340 1345 1350 Gln Ala Gly Leu Val Ala Leu Glu Ser Leu Ala Lys Pro Ser Ser 1355 1360 1365 Phe Leu Tyr Val Ser Gly Ala Val Leu Ala Leu Arg Leu Tyr Glu 1370 1375 1380 His Thr Glu Val Phe Arg Arg Gly Thr Leu Phe Arg Leu Leu Asp 1385 1390 1395 Ala Lys Pro Ser Gly Ala Ala Tyr Pro Ile Cys Glu Trp Arg Tyr 1400 1405 1410 Asp Ala Cys Ala Ser Pro Cys Phe Gln Thr Cys Arg Asp Pro Arg 1415 1420 1425 Ala Ala Ser Cys Arg Asp Val Pro Arg Val Glu Gly Cys Val Pro 1430 1435 1440 Val Cys Pro Thr Pro Gln Val Leu Asp Glu Val Thr Gln Arg Cys 1445 1450 1455 Val Tyr Leu Glu Asp Cys Val Glu Pro Ala Val Trp Val Pro Thr 1460 1465 1470 Glu Ala Leu Gly Asn Glu Thr Leu Pro Pro Ser Gln Gly Leu Pro 1475 1480 1485 Thr Pro Ser Asp Glu Glu Pro Gln Leu Ser Gln Glu Ser Pro Arg 1490 1495 1500 Thr Pro Thr His Arg Pro Ala Leu Thr Pro Ala Ala Pro Leu Thr 1505 1510 1515 Thr Ala Leu Asn Pro Pro Val Thr Ala Thr Glu Glu Pro Val Val 1520 1525 1530 Ser Pro Gly Pro Thr Gln Thr Thr Leu Gln Gln Pro Leu Glu Leu 1535 1540 1545 Thr Ala Ser Gln Leu Pro Ala Gly Pro Thr Glu Ser Pro Ala Ser 1550 1555 1560 Lys Gly Val Thr Ala Ser Leu Leu Ala Ile Pro His Thr Pro Glu 1565 1570 1575 Ser Ser Ser Leu Pro Val Ala Leu Gln Thr Pro Thr Pro Gly Met 1580 1585 1590 Val Ser Gly Ala Met Glu Thr Thr Arg Val Thr Val Ile Phe Ala 1595 1600 1605 Gly Ser Pro Asn Ile Thr Val Ser Ser Arg Ser Pro Pro Ala Pro 1610 1615 1620 Arg Phe Pro Leu Met Thr Lys Ala Val Thr Val Arg Gly His Gly 1625 1630 1635 Ser Leu Pro Val Arg Thr Thr Pro Pro Gln Pro Ser Leu Thr Ala 1640 1645 1650 Ser Pro Ser Ser Arg Pro Val Ala Ser Pro Gly Ala Ile Ser Arg 1655 1660 1665 Ser Pro Thr Ser Ser Gly Ser His Lys Ala Val Leu Thr Pro Ala 1670 1675 1680 Val Thr Lys Val Ile Ser Arg Thr Gly Val Pro Gln Pro Thr Gln 1685 1690 1695 Ala Gln Ser Ala Ser Ser Pro Ser Thr Pro Leu Thr Val Ala Gly 1700 1705 1710 Thr Ala Ala Glu Gln Val Pro Val Ser Pro Leu Ala Thr Arg Ser 1715 1720 1725 Leu Glu Ile Val Leu Ser Thr Glu Lys Gly Glu Ala Gly His Ser 1730 1735 1740 Gln Pro Met Gly Ser Pro Ala Ser Pro Gln Pro His Pro Leu Pro 1745 1750 1755 Ser Ala Pro Pro Arg Pro Ala Gln His Thr Thr Met Ala Thr Arg 1760 1765 1770 Ser Pro Ala Leu Pro Pro Glu Thr Pro Ala Ala Ala Ser Leu Ser 1775 1780 1785 Thr Ala Thr Asp Gly Leu Ala Ala Thr Pro Phe Met Ser Leu Glu 1790 1795 1800 Ser Thr Arg Pro Ser Gln Leu Leu Ser Gly Leu Pro Pro Asp Thr 1805 1810 1815 Ser Leu Pro Leu Ala Lys Val Gly Thr Ser Ala Pro Val Ala Thr 1820 1825 1830 Pro Gly Pro Lys Ala Ser Val Ile Thr Thr Pro Leu Gln Pro Gln 1835 1840 1845 Ala Thr Thr Leu Pro Ala Gln Thr Leu Ser Pro Val Leu Pro Phe 1850 1855 1860 Thr Pro Ala Ala Met Thr Gln Ala His Pro Pro Thr His Ile Ala 1865 1870 1875 Pro Pro Ala Ala Gly Thr Ala Pro Gly Leu Leu Leu Gly Ala Thr 1880 1885 1890 Leu Pro Thr Ser Gly Val Leu Pro Val Ala Glu Gly Thr Ala Ser 1895 1900 1905 Met Val Ser Val Val Pro Arg Lys Ser Thr Thr Gly Lys Val Ala 1910 1915 1920 Ile Leu Ser Lys Gln Val Ser Leu Pro Thr Ser Met Tyr Gly Ser 1925 1930 1935 Ala Glu Gly Gly Pro Thr Glu Leu Thr Pro Ala Thr Ser His Pro 1940 1945 1950 Leu Thr Pro Leu Val Ala Glu Pro Glu Gly Ala Gln Ala Gly Thr 1955 1960 1965 Ala Leu Pro Val Pro Thr Ser Tyr Ala Leu Ser Arg Val Ser Ala 1970 1975 1980 Arg Thr Ala Pro Gln Asp Ser Met Leu Val Leu Leu Pro Gln Leu 1985 1990 1995 Ala Glu Ala His Gly Thr Ser Ala Gly Pro His Leu Ala Ala Glu 2000 2005 2010 Pro Val Asp Glu Ala Thr Thr Glu Pro Ser Gly Arg Ser Ala Pro 2015 2020 2025 Ala Leu Ser Ile Val Glu Gly Leu Ala Glu Ala Leu Ala Thr Thr 2030 2035 2040 Thr Glu Ala Asn Thr Ser Thr Thr Cys Val Pro Ile Ala Glu Gln 2045 2050 2055 Asp Cys Val Arg His Ile Cys Leu Glu Gly Gln Leu Ile Arg Val 2060 2065 2070 Asn Gln Ser Gln His Cys Pro Gln Gly Ala Ala Pro Pro Arg Cys 2075 2080 2085 Gly Ile Leu Gly Leu Ala Val Arg Val Gly Gly Asp Arg Cys Cys 2090 2095 2100 Pro Leu Trp Glu Cys Ala Cys Arg Cys Ser Ile Phe Pro Asp Leu 2105 2110 2115 Ser Phe Val Thr Phe Asp Gly Ser His Val Ala Leu Phe Lys Glu 2120 2125 2130 Ala Ile Tyr Ile Leu Ser Gln Ser Pro Asp Glu Met Leu Thr Val 2135 2140 2145 His Val Leu Asp Cys Lys Ser Ala Asn Leu Gly His Leu Asn Trp 2150 2155 2160 Pro Pro Phe Cys Leu Val Met Leu Asn Met Thr His Leu Ala His 2165 2170 2175 Gln Val Thr Ile Asp Arg Phe Asn Arg Lys Val Thr Val Asp Leu 2180 2185 2190 Gln Pro Val Trp Pro Pro Val Ser Arg Tyr Gly Phe Arg Ile Glu 2195 2200 2205 Asp Thr Gly His Met Tyr Met Ile Leu Thr Pro Ser Asp Ile Gln 2210 2215 2220 Ile Gln Trp Leu His Ser Ser Gly Leu Met Ile Val Glu Ala Ser 2225 2230 2235 Lys Thr Ser Lys Ala Gln Gly His Gly Leu Cys Gly Ile Cys Asp 2240 2245 2250 Gly Asp Ala Ala Asn Asp Leu Thr Leu Lys Asp Gly Ser Val Val 2255 2260 2265 Gly Gly Ala Glu Asp Pro Ala Pro Phe Leu Asp Ser Trp Gln Val 2270 2275 2280 Pro Ser Ser Leu Thr Ser Val Gly Gln Thr Arg Phe Arg Pro Asp 2285 2290 2295 Ser Cys Ala Thr Thr Asp Cys Ser Pro Cys Leu Arg Met Val Ser 2300 2305 2310 Asn Arg Thr Phe Ser Ala Cys His Arg Phe Val Pro Pro Glu Ser 2315 2320 2325 Phe Cys Glu Leu Trp Ile Arg Asp Thr Lys Tyr Val Gln Gln Pro 2330 2335 2340 Cys Val Ala Leu Thr Val Tyr Val Ala Met Cys His Lys Phe His 2345 2350 2355 Val Cys Ile Glu Trp Arg Arg Ser Asp Tyr Cys Pro Phe Leu Cys 2360 2365 2370 Ser Ser Asp Ser Thr Tyr Gln Ala Cys Val Thr Ala Cys Glu Pro 2375 2380 2385 Pro Lys Thr Cys Gln Asp Gly Ile Leu Gly Pro Leu Asp Pro Glu 2390 2395 2400 His Cys Gln Val Leu Gly Glu Gly Cys Val Cys Ser Glu Gly Thr 2405 2410 2415 Ile Leu His Arg Arg His Ser Ala Leu Cys Ile Pro Glu Ala Lys 2420 2425 2430 Cys Ala Cys Thr Asp Ser Met Gly Val Pro Arg Ala Leu Gly Glu 2435 2440 2445 Thr Trp Asn Ser Ser Leu Ser Gly Cys Cys Gln His Gln Cys Gln 2450 2455 2460 Ala Pro Asp Thr Ile Val Pro Val Asp Leu Gly Cys Pro Ser Pro 2465 2470 2475 Arg Pro Glu Ser Cys Leu Arg Phe Gly Glu Val Ala Leu Leu Leu 2480 2485 2490 Pro Thr Lys Asp Pro Cys Cys Leu Gly Thr Val Cys Val Cys Asn 2495 2500 2505 Gln Thr Leu Cys Glu Gly Leu Ala Pro Thr Cys Arg Pro Gly His 2510 2515 2520 Arg Leu Leu Thr His Phe Gln Glu Asp Ser Cys Cys Pro Ser Tyr 2525 2530 2535 Ser Cys Glu Cys Asp Pro Asp Leu Cys Glu Ala Glu Leu Val Pro 2540 2545 2550 Ser Cys Arg Gln Asp Gln Ile Leu Ile Thr Gly Arg Leu Gly Asp 2555 2560 2565 Ser Cys Cys Thr Ser Tyr Phe Cys Ala Cys Gly Asp Cys Pro Asp 2570 2575 2580 Ser Ile Pro Glu Cys Gln Glu Gly Glu Ala Leu Thr Val His Arg 2585 2590 2595 Asn Thr Thr Glu Leu Cys Cys Pro Leu Tyr Gln Cys Val Cys Glu 2600 2605 2610 Asn Phe Arg Cys Pro Gln Val Gln Cys Gly Leu Gly Thr Ala Leu 2615 2620 2625 Val Glu Val Trp Ser Pro Asp Arg Cys Cys Pro Tyr Lys Ser Cys 2630 2635 2640 Glu Cys Asp Cys Asp Thr Ile Pro Val Pro Arg Cys His Leu Trp 2645 2650 2655 Glu Lys Ser Gln Leu Asp Glu Glu Phe Met His Ser Val Glu Asn 2660 2665 2670 Val Cys Gly Cys Ala Lys Tyr Glu Cys Val Lys Ala Pro Val Cys 2675 2680 2685 Leu Ser Arg Glu Leu Gly Val Met Gln Pro Gly Gln Thr Val Val 2690 2695 2700 Glu Leu Ser Ala Asp Gly Val Cys His Thr Ser Arg Cys Thr Thr 2705 2710 2715 Val Leu Asp Pro Leu Thr Asn Phe Tyr Gln Ile Asn Thr Thr Ser 2720 2725 2730 Val Leu Cys Asp Ile His Cys Glu Ala Asn Gln Glu Tyr Glu His 2735 2740 2745 Pro Arg Asp Leu Ala Ala Cys Cys Gly Ser Cys Arg Asn Val Ser 2750 2755 2760 Cys Leu Phe Thr Phe Pro Asn Gly Thr Thr Ser Leu Phe Leu Pro 2765 2770 2775 Gly Ala Ser Trp Ile Ala Asp Cys Ala Arg His His Cys Ser Ser 2780 2785 2790 Thr Pro Leu Gly Ala Val Leu Val Arg Ser Pro Ile Ser Cys Pro 2795 2800 2805 Pro Leu Asn Glu Thr Glu Cys Ala Lys Val Gly Gly Ser Val Val 2810 2815 2820 Pro Ser Leu Glu Gly Cys Cys Arg Thr Cys Lys Glu Asp Gly Arg 2825 2830 2835 Ser Cys Lys Lys Val Thr Ile Arg Met Thr Ile Arg Lys Asn Glu 2840 2845 2850 Cys Arg Ser Ser Thr Pro Val Asn Leu Val Ser Cys Asp Gly Arg 2855 2860 2865 Cys Pro Ser Ala Ser Ile Tyr Asn Tyr Asn Ile Asn Thr Tyr Ala 2870 2875 2880 Arg Phe Cys Lys Cys Cys Arg Glu Val Gly Leu Gln Arg Arg Ser 2885 2890 2895 Val Gln Leu Phe Cys Ala Thr Asn Ala Thr Trp Val Pro Tyr Thr 2900 2905 2910 Val Gln Glu Pro Thr Asp Cys Ala Cys Gln Trp Ser 2915 2920 2925 <210> 315 <211> 111 <212> PRT <213> homo sapiens <400> 315 Met Ser Glu His Val Arg Thr Arg Ser Gln Ser Ser Glu Arg Gly Asn 1 5 10 15 Asp Gln Glu Ser Ser Gln Pro Val Gly Ser Val Ile Val Gln Glu Pro 20 25 30 Thr Glu Glu Lys Arg Gln Glu Glu Glu Pro Pro Thr Asp Asn Gln Gly 35 40 45 Ile Ala Pro Ser Gly Glu Ile Glu Asn Glu Gly Ala Pro Ala Val Gln 50 55 60 Gly Pro Asp Met Glu Ala Phe Gln Gln Glu Leu Ala Leu Leu Lys Ile 65 70 75 80 Glu Asp Glu Pro Gly Asp Gly Pro Asp Val Arg Glu Gly Ile Met Pro 85 90 95 Thr Phe Asp Leu Thr Lys Val Leu Glu Ala Gly Asp Ala Gln Pro 100 105 110 <210> 316 <211> 500 <212> PRT <213> homo sapiens <400> 316 Met Ala Thr Val Ile Pro Gly Asp Leu Ser Glu Val Arg Asp Thr Gln 1 5 10 15 Lys Val Pro Ser Gly Lys Arg Lys Arg Gly Glu Thr Lys Pro Arg Lys 20 25 30 Asn Phe Pro Cys Gln Leu Cys Asp Lys Ala Phe Asn Ser Val Glu Lys 35 40 45 Leu Lys Val His Ser Tyr Ser His Thr Gly Glu Arg Pro Tyr Lys Cys 50 55 60 Ile Gln Gln Asp Cys Thr Lys Ala Phe Val Ser Lys Tyr Lys Leu Gln 65 70 75 80 Arg His Met Ala Thr His Ser Pro Glu Lys Thr His Lys Cys Asn Tyr 85 90 95 Cys Glu Lys Met Phe His Arg Lys Asp His Leu Lys Asn His Leu His 100 105 110 Thr His Asp Pro Asn Lys Glu Thr Phe Lys Cys Glu Glu Cys Gly Lys 115 120 125 Asn Tyr Asn Thr Lys Leu Gly Phe Lys Arg His Leu Ala Leu His Ala 130 135 140 Ala Thr Ser Gly Asp Leu Thr Cys Lys Val Cys Leu Gln Thr Phe Glu 145 150 155 160 Ser Thr Gly Val Leu Leu Glu His Leu Lys Ser His Ala Gly Lys Ser 165 170 175 Ser Gly Gly Val Lys Glu Lys Lys His Gln Cys Glu His Cys Asp Arg 180 185 190 Arg Phe Tyr Thr Arg Lys Asp Val Arg Arg His Met Val Val His Thr 195 200 205 Gly Arg Lys Asp Phe Leu Cys Gln Tyr Cys Ala Gln Arg Phe Gly Arg 210 215 220 Lys Asp His Leu Thr Arg His Met Lys Lys Ser His Asn Gln Glu Leu 225 230 235 240 Leu Lys Val Lys Thr Glu Pro Val Asp Phe Leu Asp Pro Phe Thr Cys 245 250 255 Asn Val Ser Val Pro Ile Lys Asp Glu Leu Leu Pro Val Met Ser Leu 260 265 270 Pro Ser Ser Glu Leu Leu Ser Lys Pro Phe Thr Asn Thr Leu Gln Leu 275 280 285 Asn Leu Tyr Asn Thr Pro Phe Gln Ser Met Gln Ser Ser Gly Ser Ala 290 295 300 His Gln Met Ile Thr Thr Leu Pro Leu Gly Met Thr Cys Pro Ile Asp 305 310 315 320 Met Asp Thr Val His Pro Ser His His Leu Ser Phe Lys Tyr Pro Phe 325 330 335 Ser Ser Thr Ser Tyr Ala Ile Ser Ile Pro Glu Lys Glu Gln Pro Leu 340 345 350 Lys Gly Glu Ile Glu Ser Tyr Leu Met Glu Leu Gln Gly Gly Val Pro 355 360 365 Ser Ser Ser Gln Asp Ser Gln Ala Ser Ser Ser Ser Lys Leu Gly Leu 370 375 380 Asp Pro Gln Ile Gly Ser Leu Asp Asp Gly Ala Gly Asp Leu Ser Leu 385 390 395 400 Ser Lys Ser Ser Ile Ser Ile Ser Asp Pro Leu Asn Thr Pro Ala Leu 405 410 415 Asp Phe Ser Gln Leu Phe Asn Phe Ile Pro Leu Asn Gly Pro Pro Tyr 420 425 430 Asn Pro Leu Ser Val Gly Ser Leu Gly Met Ser Tyr Ser Gln Glu Glu 435 440 445 Ala His Ser Ser Val Ser Gln Leu Pro Pro Gln Thr Gln Asp Leu Gln 450 455 460 Asp Pro Ala Asn Thr Ile Gly Leu Gly Ser Leu His Ser Leu Ser Ala 465 470 475 480 Ala Phe Thr Ser Ser Leu Ser Thr Ser Thr Thr Leu Pro Arg Phe His 485 490 495 Gln Ala Phe Gln 500 <210> 317 <211> 167 <212> PRT <213> homo sapiens <400> 317 Ser Ser Glu Met Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg 1 5 10 15 Gly Phe Ile Thr Lys Ala Ile Asn Ser Cys His Thr Ser Ser Leu Ala 20 25 30 Thr Pro Glu Asp Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe 35 40 45 Leu Ser Leu Ile Val Ser Ile Leu Arg Ser Trp Asn Glu Pro Leu Tyr 50 55 60 His Leu Val Thr Glu Val Arg Gly Met Gln Glu Ala Pro Glu Ala Ile 65 70 75 80 Leu Ser Lys Ala Val Glu Ile Glu Glu Gln Thr Lys Arg Leu Leu Glu 85 90 95 Gly Met Glu Leu Ile Val Ser Gln Val His Pro Glu Thr Lys Glu Asn 100 105 110 Glu Ile Tyr Pro Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp 115 120 125 Glu Glu Ser Arg Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg 130 135 140 Arg Asp Ser His Lys Ile Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg 145 150 155 160 Ile Ile His Asn Asn Asn Cys 165 <210> 318 <211> 2335 <212> PRT <213> homo sapiens <400> 318 Met Ala Gly Val Phe Pro Tyr Arg Gly Pro Gly Asn Pro Val Pro Gly 1 5 10 15 Pro Leu Ala Pro Leu Pro Asp Tyr Met Ser Glu Glu Lys Leu Gln Glu 20 25 30 Lys Ala Arg Lys Trp Gln Gln Leu Gln Ala Lys Arg Tyr Ala Glu Lys 35 40 45 Arg Lys Phe Gly Phe Val Asp Ala Gln Lys Glu Asp Met Pro Pro Glu 50 55 60 His Val Arg Lys Ile Ile Arg Asp His Gly Asp Met Thr Asn Arg Lys 65 70 75 80 Phe Arg His Asp Lys Arg Val Tyr Leu Gly Ala Leu Lys Tyr Met Pro 85 90 95 His Ala Val Leu Lys Leu Leu Glu Asn Met Pro Met Pro Trp Glu Gln 100 105 110 Ile Arg Asp Val Pro Val Leu Tyr His Ile Thr Gly Ala Ile Ser Phe 115 120 125 Val Asn Glu Ile Pro Trp Val Ile Glu Pro Val Tyr Ile Ser Gln Trp 130 135 140 Gly Ser Met Trp Ile Met Met Arg Arg Glu Lys Arg Asp Arg Arg His 145 150 155 160 Phe Lys Arg Met Arg Phe Pro Pro Phe Asp Asp Glu Glu Pro Pro Leu 165 170 175 Asp Tyr Ala Asp Asn Ile Leu Asp Val Glu Pro Leu Glu Ala Ile Gln 180 185 190 Leu Glu Leu Asp Pro Glu Glu Asp Ala Pro Val Leu Asp Trp Phe Tyr 195 200 205 Asp His Gln Pro Leu Arg Asp Ser Arg Lys Tyr Val Asn Gly Ser Thr 210 215 220 Tyr Gln Arg Trp Gln Phe Thr Leu Pro Met Met Ser Thr Leu Tyr Arg 225 230 235 240 Leu Ala Asn Gln Leu Leu Thr Asp Leu Val Asp Asp Asn Tyr Phe Tyr 245 250 255 Leu Phe Asp Leu Lys Ala Phe Phe Thr Ser Lys Ala Leu Asn Met Ala 260 265 270 Ile Pro Gly Gly Pro Lys Phe Glu Pro Leu Val Arg Asp Ile Asn Leu 275 280 285 Gln Asp Glu Asp Trp Asn Glu Phe Asn Asp Ile Asn Lys Ile Ile Ile 290 295 300 Arg Gln Pro Ile Arg Thr Glu Tyr Lys Ile Ala Phe Pro Tyr Leu Tyr 305 310 315 320 Asn Asn Leu Pro His His Val His Leu Thr Trp Tyr His Thr Pro Asn 325 330 335 Val Val Phe Ile Lys Thr Glu Asp Pro Asp Leu Pro Ala Phe Tyr Phe 340 345 350 Asp Pro Leu Ile Asn Pro Ile Ser His Arg His Ser Val Lys Ser Gln 355 360 365 Glu Pro Leu Pro Asp Asp Asp Glu Glu Phe Glu Leu Pro Glu Phe Val 370 375 380 Glu Pro Phe Leu Lys Asp Thr Pro Leu Tyr Thr Asp Asn Thr Ala Asn 385 390 395 400 Gly Ile Ala Leu Leu Trp Ala Pro Arg Pro Phe Asn Leu Arg Ser Gly 405 410 415 Arg Thr Arg Arg Ala Leu Asp Ile Pro Leu Val Lys Asn Trp Tyr Arg 420 425 430 Glu His Cys Pro Ala Gly Gln Pro Val Lys Val Arg Val Ser Tyr Gln 435 440 445 Lys Leu Leu Lys Tyr Tyr Val Leu Asn Ala Leu Lys His Arg Pro Pro 450 455 460 Lys Ala Gln Lys Lys Arg Tyr Leu Phe Arg Ser Phe Lys Ala Thr Lys 465 470 475 480 Phe Phe Gln Ser Thr Lys Leu Asp Trp Val Glu Val Gly Leu Gln Val 485 490 495 Cys Arg Gln Gly Tyr Asn Met Leu Asn Leu Leu Ile His Arg Lys Asn 500 505 510 Leu Asn Tyr Leu His Leu Asp Tyr Asn Phe Asn Leu Lys Pro Val Lys 515 520 525 Thr Leu Thr Thr Lys Glu Arg Lys Lys Ser Arg Phe Gly Asn Ala Phe 530 535 540 His Leu Cys Arg Glu Val Leu Arg Leu Thr Lys Leu Val Val Asp Ser 545 550 555 560 His Val Gln Tyr Arg Leu Gly Asn Val Asp Ala Phe Gln Leu Ala Asp 565 570 575 Gly Leu Gln Tyr Ile Phe Ala His Val Gly Gln Leu Thr Gly Met Tyr 580 585 590 Arg Tyr Lys Tyr Lys Leu Met Arg Gln Ile Arg Met Cys Lys Asp Leu 595 600 605 Lys His Leu Ile Tyr Tyr Arg Phe Asn Thr Gly Pro Val Gly Lys Gly 610 615 620 Pro Gly Cys Gly Phe Trp Ala Ala Gly Trp Arg Val Trp Leu Phe Phe 625 630 635 640 Met Arg Gly Ile Thr Pro Leu Leu Glu Arg Trp Leu Gly Asn Leu Leu 645 650 655 Ala Arg Gln Phe Glu Gly Arg His Ser Lys Gly Val Ala Lys Thr Val 660 665 670 Thr Lys Gln Arg Val Glu Ser His Phe Asp Leu Glu Leu Arg Ala Ala 675 680 685 Val Met His Asp Ile Leu Asp Met Met Pro Glu Gly Ile Lys Gln Asn 690 695 700 Lys Ala Arg Thr Ile Leu Gln His Leu Ser Glu Ala Trp Arg Cys Trp 705 710 715 720 Lys Ala Asn Ile Pro Trp Lys Val Pro Gly Leu Pro Thr Pro Ile Glu 725 730 735 Asn Met Ile Leu Arg Tyr Val Lys Ala Lys Ala Asp Trp Trp Thr Asn 740 745 750 Thr Ala His Tyr Asn Arg Glu Arg Ile Arg Arg Gly Ala Thr Val Asp 755 760 765 Lys Thr Val Cys Lys Lys Asn Leu Gly Arg Leu Thr Arg Leu Tyr Leu 770 775 780 Lys Ala Glu Gln Glu Arg Gln His Asn Tyr Leu Lys Asp Gly Pro Tyr 785 790 795 800 Ile Thr Ala Glu Glu Ala Val Ala Val Tyr Thr Thr Thr Val His Trp 805 810 815 Leu Glu Ser Arg Arg Phe Ser Pro Ile Pro Phe Pro Pro Leu Ser Tyr 820 825 830 Lys His Asp Thr Lys Leu Leu Ile Leu Ala Leu Glu Arg Leu Lys Glu 835 840 845 Ala Tyr Ser Val Lys Ser Arg Leu Asn Gln Ser Gln Arg Glu Glu Leu 850 855 860 Gly Leu Ile Glu Gln Ala Tyr Asp Asn Pro His Glu Ala Leu Ser Arg 865 870 875 880 Ile Lys Arg His Leu Leu Thr Gln Arg Ala Phe Lys Glu Val Gly Ile 885 890 895 Glu Phe Met Asp Leu Tyr Ser His Leu Val Pro Val Tyr Asp Val Glu 900 905 910 Pro Leu Glu Lys Ile Thr Asp Ala Tyr Leu Asp Gln Tyr Leu Trp Tyr 915 920 925 Glu Ala Asp Lys Arg Arg Leu Phe Pro Pro Trp Ile Lys Pro Ala Asp 930 935 940 Thr Glu Pro Pro Pro Leu Leu Val Tyr Lys Trp Cys Gln Gly Ile Asn 945 950 955 960 Asn Leu Gln Asp Val Trp Glu Thr Ser Glu Gly Glu Cys Asn Val Met 965 970 975 Leu Glu Ser Arg Phe Glu Lys Met Tyr Glu Lys Ile Asp Leu Thr Leu 980 985 990 Leu Asn Arg Leu Leu Arg Leu Ile Val Asp His Asn Ile Ala Asp Tyr 995 1000 1005 Met Thr Ala Lys Asn Asn Val Val Ile Asn Tyr Lys Asp Met Asn 1010 1015 1020 His Thr Asn Ser Tyr Gly Ile Ile Arg Gly Leu Gln Phe Ala Ser 1025 1030 1035 Phe Ile Val Gln Tyr Tyr Gly Leu Val Met Asp Leu Leu Val Leu 1040 1045 1050 Gly Leu His Arg Ala Ser Glu Met Ala Gly Pro Pro Gln Met Pro 1055 1060 1065 Asn Asp Phe Leu Ser Phe Gln Asp Ile Ala Thr Glu Ala Ala His 1070 1075 1080 Pro Ile Arg Leu Phe Cys Arg Tyr Ile Asp Arg Ile His Ile Phe 1085 1090 1095 Phe Arg Phe Thr Ala Asp Glu Ala Arg Asp Leu Ile Gln Arg Tyr 1100 1105 1110 Leu Thr Glu His Pro Asp Pro Asn Asn Glu Asn Ile Val Gly Tyr 1115 1120 1125 Asn Asn Lys Lys Cys Trp Pro Arg Asp Ala Arg Met Arg Leu Met 1130 1135 1140 Lys His Asp Val Asn Leu Gly Arg Ala Val Phe Trp Asp Ile Lys 1145 1150 1155 Asn Arg Leu Pro Arg Ser Val Thr Thr Val Gln Trp Glu Asn Ser 1160 1165 1170 Phe Val Ser Val Tyr Ser Lys Asp Asn Pro Asn Leu Leu Phe Asn 1175 1180 1185 Met Cys Gly Phe Glu Cys Arg Ile Leu Pro Lys Cys Arg Thr Ser 1190 1195 1200 Tyr Glu Glu Phe Thr His Lys Asp Gly Val Trp Asn Leu Gln Asn 1205 1210 1215 Glu Val Thr Lys Glu Arg Thr Ala Gln Cys Phe Leu Arg Val Asp 1220 1225 1230 Asp Glu Ser Met Gln Arg Phe His Asn Arg Val Arg Gln Ile Leu 1235 1240 1245 Met Ala Ser Gly Ser Thr Thr Phe Thr Lys Ile Val Asn Lys Trp 1250 1255 1260 Asn Thr Ala Leu Ile Gly Leu Met Thr Tyr Phe Arg Glu Ala Val 1265 1270 1275 Val Asn Thr Gln Glu Leu Leu Asp Leu Leu Val Lys Cys Glu Asn 1280 1285 1290 Lys Ile Gln Thr Arg Ile Lys Ile Gly Leu Asn Ser Lys Met Pro 1295 1300 1305 Ser Arg Phe Pro Pro Val Val Phe Tyr Thr Pro Lys Glu Leu Gly 1310 1315 1320 Gly Leu Gly Met Leu Ser Met Gly His Val Leu Ile Pro Gln Ser 1325 1330 1335 Asp Leu Arg Trp Ser Lys Gln Thr Asp Val Gly Ile Thr His Phe 1340 1345 1350 Arg Ser Gly Met Ser His Glu Glu Asp Gln Leu Ile Pro Asn Leu 1355 1360 1365 Tyr Arg Tyr Ile Gln Pro Trp Glu Ser Glu Phe Ile Asp Ser Gln 1370 1375 1380 Arg Val Trp Ala Glu Tyr Ala Leu Lys Arg Gln Glu Ala Ile Ala 1385 1390 1395 Gln Asn Arg Arg Leu Thr Leu Glu Asp Leu Glu Asp Ser Trp Asp 1400 1405 1410 Arg Gly Ile Pro Arg Ile Asn Thr Leu Phe Gln Lys Asp Arg His 1415 1420 1425 Thr Leu Ala Tyr Asp Lys Gly Trp Arg Val Arg Thr Asp Phe Lys 1430 1435 1440 Gln Tyr Gln Val Leu Lys Gln Asn Pro Phe Trp Trp Thr His Gln 1445 1450 1455 Arg His Asp Gly Lys Leu Trp Asn Leu Asn Asn Tyr Arg Thr Asp 1460 1465 1470 Met Ile Gln Ala Leu Gly Gly Val Glu Gly Ile Leu Glu His Thr 1475 1480 1485 Leu Phe Lys Gly Thr Tyr Phe Pro Thr Trp Glu Gly Leu Phe Trp 1490 1495 1500 Glu Lys Ala Ser Gly Phe Glu Glu Ser Met Lys Trp Lys Lys Leu 1505 1510 1515 Thr Asn Ala Gln Arg Ser Gly Leu Asn Gln Ile Pro Asn Arg Arg 1520 1525 1530 Phe Thr Leu Trp Trp Ser Pro Thr Ile Asn Arg Ala Asn Val Tyr 1535 1540 1545 Val Gly Phe Gln Val Gln Leu Asp Leu Thr Gly Ile Phe Met His 1550 1555 1560 Gly Lys Ile Pro Thr Leu Lys Ile Ser Leu Ile Gln Ile Phe Arg 1565 1570 1575 Ala His Leu Trp Gln Lys Ile His Glu Ser Ile Val Met Asp Leu 1580 1585 1590 Cys Gln Val Phe Asp Gln Glu Leu Asp Ala Leu Glu Ile Glu Thr 1595 1600 1605 Val Gln Lys Glu Thr Ile His Pro Arg Lys Ser Tyr Lys Met Asn 1610 1615 1620 Ser Ser Cys Ala Asp Ile Leu Leu Phe Ala Ser Tyr Lys Trp Asn 1625 1630 1635 Val Ser Arg Pro Ser Leu Leu Ala Asp Ser Lys Asp Val Met Asp 1640 1645 1650 Ser Thr Thr Thr Gln Lys Tyr Trp Ile Asp Ile Gln Leu Arg Trp 1655 1660 1665 Gly Asp Tyr Asp Ser His Asp Ile Glu Arg Tyr Ala Arg Ala Lys 1670 1675 1680 Phe Leu Asp Tyr Thr Thr Asp Asn Met Ser Ile Tyr Pro Ser Pro 1685 1690 1695 Thr Gly Val Leu Ile Ala Ile Asp Leu Ala Tyr Asn Leu His Ser 1700 1705 1710 Ala Tyr Gly Asn Trp Phe Pro Gly Ser Lys Pro Leu Ile Gln Gln 1715 1720 1725 Ala Met Ala Lys Ile Met Lys Ala Asn Pro Ala Leu Tyr Val Leu 1730 1735 1740 Arg Glu Arg Ile Arg Lys Gly Leu Gln Leu Tyr Ser Ser Glu Pro 1745 1750 1755 Thr Glu Pro Tyr Leu Ser Ser Gln Asn Tyr Gly Glu Leu Phe Ser 1760 1765 1770 Asn Gln Ile Ile Trp Phe Val Asp Asp Thr Asn Val Tyr Arg Val 1775 1780 1785 Thr Ile His Lys Thr Phe Glu Gly Asn Leu Thr Thr Lys Pro Ile 1790 1795 1800 Asn Gly Ala Ile Phe Ile Phe Asn Pro Arg Thr Gly Gln Leu Phe 1805 1810 1815 Leu Lys Ile Ile His Thr Ser Val Trp Ala Gly Gln Lys Arg Leu 1820 1825 1830 Gly Gln Leu Ala Lys Trp Lys Thr Ala Glu Glu Val Ala Ala Leu 1835 1840 1845 Ile Arg Ser Leu Pro Val Glu Glu Gln Pro Lys Gln Ile Ile Val 1850 1855 1860 Thr Arg Lys Gly Met Leu Asp Pro Leu Glu Val His Leu Leu Asp 1865 1870 1875 Phe Pro Asn Ile Val Ile Lys Gly Ser Glu Leu Gln Leu Pro Phe 1880 1885 1890 Gln Ala Cys Leu Lys Val Glu Lys Phe Gly Asp Leu Ile Leu Lys 1895 1900 1905 Ala Thr Glu Pro Gln Met Val Leu Phe Asn Leu Tyr Asp Asp Trp 1910 1915 1920 Leu Lys Thr Ile Ser Ser Tyr Thr Ala Phe Ser Arg Leu Ile Leu 1925 1930 1935 Ile Leu Arg Ala Leu His Val Asn Asn Asp Arg Ala Lys Val Ile 1940 1945 1950 Leu Lys Pro Asp Lys Thr Thr Ile Thr Glu Pro His His Ile Trp 1955 1960 1965 Pro Thr Leu Thr Asp Glu Glu Trp Ile Lys Val Glu Val Gln Leu 1970 1975 1980 Lys Asp Leu Ile Leu Ala Asp Tyr Gly Lys Lys Asn Asn Val Asn 1985 1990 1995 Val Ala Ser Leu Thr Gln Ser Glu Ile Arg Asp Ile Ile Leu Gly 2000 2005 2010 Met Glu Ile Ser Ala Pro Ser Gln Gln Arg Gln Gln Ile Ala Glu 2015 2020 2025 Ile Glu Lys Gln Thr Lys Glu Gln Ser Gln Leu Thr Ala Thr Gln 2030 2035 2040 Thr Arg Thr Val Asn Lys His Gly Asp Glu Ile Ile Thr Ser Thr 2045 2050 2055 Thr Ser Asn Tyr Glu Thr Gln Thr Phe Ser Ser Lys Thr Glu Trp 2060 2065 2070 Arg Val Arg Ala Ile Ser Ala Ala Asn Leu His Leu Arg Thr Asn 2075 2080 2085 His Ile Tyr Val Ser Ser Asp Asp Ile Lys Glu Thr Gly Tyr Thr 2090 2095 2100 Tyr Ile Leu Pro Lys Asn Val Leu Lys Lys Phe Ile Cys Ile Ser 2105 2110 2115 Asp Leu Arg Ala Gln Ile Ala Gly Tyr Leu Tyr Gly Val Ser Pro 2120 2125 2130 Pro Asp Asn Pro Gln Val Lys Glu Ile Arg Cys Ile Val Met Val 2135 2140 2145 Pro Gln Trp Gly Thr His Gln Thr Val His Leu Pro Gly Gln Leu 2150 2155 2160 Pro Gln His Glu Tyr Leu Lys Glu Met Glu Pro Leu Gly Trp Ile 2165 2170 2175 His Thr Gln Pro Asn Glu Ser Pro Gln Leu Ser Pro Gln Asp Val 2180 2185 2190 Thr Thr His Ala Lys Ile Met Ala Asp Asn Pro Ser Trp Asp Gly 2195 2200 2205 Glu Lys Thr Ile Ile Ile Thr Cys Ser Phe Thr Pro Gly Ser Cys 2210 2215 2220 Thr Leu Thr Ala Tyr Lys Leu Thr Pro Ser Gly Tyr Glu Trp Gly 2225 2230 2235 Arg Gln Asn Thr Asp Lys Gly Asn Asn Pro Lys Gly Tyr Leu Pro 2240 2245 2250 Ser His Tyr Glu Arg Val Gln Met Leu Leu Ser Asp Arg Phe Leu 2255 2260 2265 Gly Phe Phe Met Val Pro Ala Gln Ser Ser Trp Asn Tyr Asn Phe 2270 2275 2280 Met Gly Val Arg His Asp Pro Asn Met Lys Tyr Glu Leu Gln Leu 2285 2290 2295 Ala Asn Pro Lys Glu Phe Tyr His Glu Val His Arg Pro Ser His 2300 2305 2310 Phe Leu Asn Phe Ala Leu Leu Gln Glu Gly Glu Val Tyr Ser Ala 2315 2320 2325 Asp Arg Glu Asp Leu Tyr Ala 2330 2335 <210> 319 <211> 114 <212> PRT <213> homo sapiens <400> 319 Met Ala Gly Leu Ala Leu Gln Pro Gly Thr Ala Leu Leu Cys Tyr Ser 1 5 10 15 Cys Lys Ala Gln Val Ser Asn Glu Asp Cys Leu Gln Val Glu Asn Cys 20 25 30 Thr Gln Leu Gly Glu Gln Cys Trp Thr Ala Arg Ile Arg Ala Val Gly 35 40 45 Leu Leu Thr Val Ile Ser Lys Gly Cys Ser Leu Asn Cys Val Asp Asp 50 55 60 Ser Gln Asp Tyr Tyr Val Gly Lys Lys Asn Ile Thr Cys Cys Asp Thr 65 70 75 80 Asp Leu Cys Asn Ala Ser Gly Ala His Ala Leu Gln Pro Ala Ala Ala 85 90 95 Ile Leu Ala Leu Leu Pro Ala Leu Gly Leu Leu Leu Trp Gly Pro Gly 100 105 110 Gln Leu <210> 320 <211> 420 <212> PRT <213> homo sapiens <400> 320 Met Ser Ser Pro Arg Asp Phe Arg Ala Glu Pro Val Asn Asp Tyr Glu 1 5 10 15 Gly Asn Asp Ser Glu Ala Glu Asp Leu Asn Phe Arg Glu Thr Leu Pro 20 25 30 Ser Ser Ser Gln Glu Asn Thr Pro Arg Ser Lys Val Phe Glu Asn Lys 35 40 45 Val Asn Ser Glu Lys Val Lys Leu Ser Leu Arg Asn Phe Pro His Asn 50 55 60 Asp Tyr Glu Asp Val Phe Glu Glu Pro Ser Glu Ser Gly Ser Asp Pro 65 70 75 80 Ser Met Trp Thr Ala Arg Gly Pro Phe Arg Arg Asp Arg Trp Ser Ser 85 90 95 Glu Asp Glu Glu Ala Ala Gly Pro Ser Gln Ala Leu Ser Pro Leu Leu 100 105 110 Ser Asp Thr Arg Lys Ile Val Ser Glu Gly Glu Leu Asp Gln Leu Ala 115 120 125 Gln Ile Arg Pro Leu Ile Phe Asn Phe His Glu Gln Thr Ala Ile Lys 130 135 140 Asp Cys Leu Lys Ile Leu Glu Glu Lys Thr Ala Ala Tyr Asp Ile Met 145 150 155 160 Gln Glu Phe Met Ala Leu Glu Leu Lys Asn Leu Pro Gly Glu Phe Asn 165 170 175 Ser Gly Asn Gln Pro Ser Asn Arg Glu Lys Asn Arg Tyr Arg Asp Ile 180 185 190 Leu Pro Tyr Asp Ser Thr Arg Val Pro Leu Gly Lys Ser Lys Asp Tyr 195 200 205 Ile Asn Ala Ser Tyr Ile Arg Ile Val Asn Cys Gly Glu Glu Tyr Phe 210 215 220 Tyr Ile Ala Thr Gln Gly Pro Leu Leu Ser Thr Ile Asp Asp Phe Trp 225 230 235 240 Gln Met Val Leu Glu Asn Asn Ser Asn Val Ile Ala Met Ile Thr Arg 245 250 255 Glu Ile Glu Gly Gly Ile Ile Lys Cys Tyr His Tyr Trp Pro Ile Ser 260 265 270 Leu Lys Lys Pro Leu Glu Leu Lys His Phe Arg Val Phe Leu Glu Asn 275 280 285 Tyr Gln Ile Leu Gln Tyr Phe Ile Ile Arg Met Phe Gln Val Val Glu 290 295 300 Lys Ser Thr Gly Thr Ser His Ser Val Lys Gln Leu Gln Phe Thr Lys 305 310 315 320 Trp Pro Asp His Gly Thr Pro Ala Ser Ala Asp Ser Phe Ile Lys Tyr 325 330 335 Ile Arg Tyr Ala Arg Lys Ser His Leu Thr Gly Pro Met Val Val His 340 345 350 Cys Ser Ala Gly Ile Gly Arg Thr Gly Val Phe Leu Cys Val Asp Val 355 360 365 Val Phe Cys Ala Ile Val Lys Asn Cys Ser Phe Asn Ile Met Asp Ile 370 375 380 Val Ala Gln Met Arg Glu Gln Arg Ser Gly Met Val Gln Thr Lys Glu 385 390 395 400 Gln Tyr His Phe Cys Tyr Asp Ile Val Leu Glu Val Leu Arg Lys Leu 405 410 415 Leu Thr Leu Asp 420 <210> 321 <211> 1051 <212> PRT <213> homo sapiens <400> 321 Met Gln Ala Thr Ala Val Val Glu Thr Ala Ser Gly Lys Gly Tyr His 1 5 10 15 Ser Asn Gly Gly Asn Leu Gln Lys Asp Lys Pro Ser Asn Pro Lys Lys 20 25 30 Glu Asn Leu Leu Leu Ser Ser Asn Gly Cys Asp Glu Val Lys Leu Thr 35 40 45 Phe Pro Asp Asp Asp Trp Asn Ser Ser Thr Leu Glu Gln Arg Ala Asn 50 55 60 Asn Lys Glu Ile Ser Asn Ile Asp Lys Met Asp Leu Leu Glu Pro Phe 65 70 75 80 Phe Ser Val Ser Gln Asp Thr Asn Thr Glu Ser Thr Gln Phe Gln Ser 85 90 95 Ser Glu Leu Glu Asp Ser Thr Asp Tyr Ala Phe Leu Asn Lys Thr Tyr 100 105 110 Ser Ile Pro Tyr Ser Glu Ser Lys Leu Lys Lys Glu Ser Leu Thr Pro 115 120 125 Leu Ser Ser Glu Leu Asp Pro Glu Val Gln Lys Lys Glu Glu Val Phe 130 135 140 Phe Asn Ile Leu Glu His Gln Asp Lys Thr Val Gly Leu Glu Arg Ile 145 150 155 160 Tyr Asn Ile Ser Asp Ala Asn Tyr Arg Glu Ser Ala Glu Asp Thr Gln 165 170 175 Lys His Asp Thr Asp Glu Asp Ser Gln Gln Glu Tyr His Ser Ala Glu 180 185 190 Glu Gln Glu Tyr Ile Ser Asn His Leu Ser Phe Asp Gln Thr Lys Ala 195 200 205 Leu Asp Ile Ser Asn Pro Glu Val Val Glu Leu Gly Asn Ser Gly Tyr 210 215 220 Glu Val Lys Cys Ala Ser Asn Val Glu Asp Asn Arg Val Asn Ser Gly 225 230 235 240 Ser Gly Ser Ile Ile Ser Phe Asp Ser Leu Asp Val Tyr Gly Gln Glu 245 250 255 Glu Ser Leu His Val Ser Lys Phe Gln Asn Ser Val Met Leu Arg Glu 260 265 270 Tyr His Asp Leu Lys His Glu Lys Tyr Lys Glu Gln Glu Thr Asn Ser 275 280 285 Met Tyr His Thr Val Phe Asp Gly Ser Val Leu Arg Ser Asn Ser Pro 290 295 300 Gly Asn Gln Glu Ser Gln Ser Lys Ser Gly Ser Leu Ser Pro Gln Lys 305 310 315 320 Val Leu Lys Met Lys Ile Tyr Thr Glu Asn Met Lys Ser Gln Ile Asn 325 330 335 Glu Gly Lys Asp Phe Cys Gly Asn Lys Ile Val Glu Asn Lys Ile Leu 340 345 350 Leu His Leu Glu Asn Pro Ser Thr Leu Pro Gln Asp Lys Ala Leu Glu 355 360 365 Thr Leu Leu Gln Pro Cys Lys Asp Cys Gln Thr Ser Trp Thr Ser Val 370 375 380 Phe Asp Asp Ser Ile Ile Ser Ala Cys Gly Tyr Tyr Glu Ser Leu Gln 385 390 395 400 Asn Thr Ala Asp Ser Ala Leu Asp Phe Ser Ala Met Leu Pro Lys Ile 405 410 415 Ala Val Arg Asp Asn Gln Ala Ile Glu Asp Asn Thr Ser Leu Lys Val 420 425 430 Ala His Ser Ser Thr Thr Lys Lys Thr Cys Phe His Asn Ile Gly Glu 435 440 445 Met Cys Thr Lys Ser Leu Thr Asp Ala Ala Ser Cys Thr Val Thr Ile 450 455 460 Asn Gln Thr Val Asp Val Ser Thr Asp Phe Arg Ala Cys Phe Thr Thr 465 470 475 480 Ser Arg Ala Thr Ser Ala Arg Pro Ser Val Val Ser Thr Ser Ser Asn 485 490 495 Thr Glu Ile Thr Met Met Asn Lys Lys Arg Pro Asp Glu Trp Gln Asn 500 505 510 Glu Lys Gln Lys Ser Val Ala Cys Ser Thr Asp Trp Ser Tyr Ser Glu 515 520 525 Asp Cys Ile Asp Thr Gln Met Ala Ile Thr Lys Gly Ser Gly Lys Ser 530 535 540 Leu Ser Val Asp Ser Leu Lys Pro Asn Gly Asn Phe Leu Asn Lys Asp 545 550 555 560 Phe Leu Glu Leu Arg Lys Ala Cys Gly Ile Thr Asp Leu Lys Lys His 565 570 575 Pro Glu Arg Glu Phe Gln Leu Phe Lys Asp Thr Glu Lys Asp Leu Pro 580 585 590 Ser Met Cys Cys Gln Lys Ile Met Gln Arg Ala Ile Lys Ala Glu Leu 595 600 605 His Leu Leu Asn Val His Tyr Gln Met Cys Arg Arg His Cys Cys Asp 610 615 620 Ile Tyr Lys Leu Val Met Glu Asn Arg Glu Gly Leu Asn Met Asn Leu 625 630 635 640 Ser Ser Asn Ser Ala Lys Lys Glu Leu Gly Ser Ala Leu Leu Ser Leu 645 650 655 Leu Gly Asp Leu Lys Val Arg Tyr Val Thr Leu Lys Glu Lys Ile His 660 665 670 Lys Gly Ile Pro Leu Glu Glu Leu Pro Pro Leu Ser Leu Glu Ser Lys 675 680 685 Leu Leu Ser Thr Phe Ser Thr Phe Ala Ser Arg Leu Met Lys Lys Glu 690 695 700 Thr His Val Phe Ser Glu Ala Asp Ala Glu Gln Asp Asn Gln Arg Ala 705 710 715 720 His Asp Val Asp Val Ser Ser Asn Leu Lys Lys Thr Leu Ser Gln Met 725 730 735 Ser Leu Ser Ser Asp Asn Ser His Ala Thr Gln Asn Ile Ser Pro Lys 740 745 750 Lys Asp Asp Phe Lys Asn Gly Asp Ile Asn Ala Asp Phe Ser Gln Leu 755 760 765 Lys Leu Gly Asp Lys Asp Cys Arg His Tyr Gln Glu Thr Ser Glu Asp 770 775 780 Trp Ser Asp Ala Lys Glu Ser Leu Thr Gly Val Asp Val Ser Gly Thr 785 790 795 800 Gln Gly Asn Gln Val Glu Gln Asp Thr Trp Asn Leu Asp Leu Thr Gly 805 810 815 Glu Met Lys Asn Val Glu Pro Ser Gln Arg Asp Lys Gly Tyr Leu Ile 820 825 830 His Val Gly Gly Leu Cys Pro Ser Val Ser Glu Ala Asp Leu Arg Ser 835 840 845 His Phe Gln Lys Tyr Gln Val Ser Glu Ile Ser Ile Tyr Asp Ser Thr 850 855 860 Asn Tyr Arg Tyr Ala Ser Leu Ala Phe Thr Lys Asn Ser Asp Ala Lys 865 870 875 880 Ile Ala Val Lys Glu Met Asn Gly Ile Glu Ile Asn Gly Lys Ser Val 885 890 895 Asn Val Trp Pro Val Lys Ile Leu Gly Glu Tyr Thr Ser Pro Leu Ser 900 905 910 Ser Lys Asn Gly Asn Arg Ile Ser Ser Asn Asn Leu Glu Lys Ser Thr 915 920 925 Asn Lys Gln Ile His Ser Glu Phe Ser Ile Ser Arg Leu Pro Arg Thr 930 935 940 Arg Pro Arg Gln Leu Gly Ser Glu Gln Asp Ser Glu Val Phe Pro Ser 945 950 955 960 Asp Gln Gly Val Lys Lys Asn Cys Lys Gln Ile Glu Ser Ala Lys Leu 965 970 975 Leu Pro Asp Thr Pro Val Gln Phe Ile Pro Pro Asn Thr Leu Asn Leu 980 985 990 Arg Ser Phe Thr Lys Ile Ile Lys Arg Leu Ala Glu Leu His Pro Glu 995 1000 1005 Val Ser Arg Asp His Ile Ile Asn Ala Leu Gln Glu Val Arg Ile 1010 1015 1020 Arg His Lys Gly Phe Leu Asn Gly Leu Ser Ile Thr Thr Ile Val 1025 1030 1035 Glu Met Thr Ser Ser Leu Leu Lys Asn Ser Ala Ser Ser 1040 1045 1050 <210> 322 <211> 496 <212> PRT <213> homo sapiens <400> 322 Met Val Glu Ala Asp His Pro Gly Lys Leu Phe Ile Gly Gly Leu Asn 1 5 10 15 Arg Glu Thr Asn Glu Lys Met Leu Lys Ala Val Phe Gly Lys His Gly 20 25 30 Pro Ile Ser Glu Val Leu Leu Ile Lys Asp Arg Thr Ser Lys Ser Arg 35 40 45 Gly Phe Ala Phe Ile Thr Phe Glu Asn Pro Ala Asp Ala Lys Asn Ala 50 55 60 Ala Lys Asp Met Asn Gly Lys Ser Leu His Gly Lys Ala Ile Lys Val 65 70 75 80 Glu Gln Ala Gln Lys Pro Ser Phe Gln Ser Gly Gly Arg Arg Arg Pro 85 90 95 Pro Ala Ser Ser Arg Asn Arg Ser Pro Ser Gly Ser Leu Arg Ser Ala 100 105 110 Arg Gly Ser Arg Gly Gly Thr Arg Gly Trp Leu Pro Ser His Glu Gly 115 120 125 His Leu Asp Asp Gly Gly Tyr Thr Pro Asp Leu Lys Met Ser Tyr Ser 130 135 140 Arg Gly Leu Ile Pro Val Lys Arg Gly Pro Ser Ser Arg Ser Gly Gly 145 150 155 160 Pro Pro Pro Lys Lys Ser Ala Pro Ser Ala Val Ala Arg Ser Asn Ser 165 170 175 Trp Met Gly Ser Gln Gly Pro Met Ser Gln Arg Arg Glu Asn Tyr Gly 180 185 190 Val Pro Pro Arg Arg Ala Thr Ile Ser Ser Trp Arg Asn Asp Arg Met 195 200 205 Ser Thr Arg His Asp Gly Tyr Ala Thr Asn Asp Gly Asn His Pro Ser 210 215 220 Cys Gln Glu Thr Arg Asp Tyr Ala Pro Pro Ser Arg Gly Tyr Ala Tyr 225 230 235 240 Arg Asp Asn Gly His Ser Asn Arg Asp Glu His Ser Ser Arg Gly Tyr 245 250 255 Arg Asn His Arg Ser Ser Arg Glu Thr Arg Asp Tyr Ala Pro Pro Ser 260 265 270 Arg Gly His Ala Tyr Arg Asp Tyr Gly His Ser Arg Arg Asp Glu Ser 275 280 285 Tyr Ser Arg Gly Tyr Arg Asn Arg Arg Ser Ser Arg Glu Thr Arg Glu 290 295 300 Tyr Ala Pro Pro Ser Arg Gly His Gly Tyr Arg Asp Tyr Gly His Ser 305 310 315 320 Arg Arg His Glu Ser Tyr Ser Arg Gly Tyr Arg Asn His Pro Ser Ser 325 330 335 Arg Glu Thr Arg Asp Tyr Ala Pro Pro His Arg Asp Tyr Ala Tyr Arg 340 345 350 Asp Tyr Gly His Ser Ser Trp Asp Glu His Ser Ser Arg Gly Tyr Ser 355 360 365 Tyr His Asp Gly Tyr Gly Glu Ala Leu Gly Arg Asp His Ser Glu His 370 375 380 Leu Ser Gly Ser Ser Tyr Arg Asp Ala Leu Gln Arg Tyr Gly Thr Ser 385 390 395 400 His Gly Ala Pro Pro Ala Arg Gly Pro Arg Met Ser Tyr Gly Gly Ser 405 410 415 Thr Cys His Ala Tyr Ser Asn Thr Arg Asp Arg Tyr Gly Arg Ser Trp 420 425 430 Glu Ser Tyr Ser Ser Cys Gly Asp Phe His Tyr Cys Asp Arg Glu His 435 440 445 Val Cys Arg Lys Asp Gln Arg Asn Pro Pro Ser Leu Gly Arg Val Leu 450 455 460 Pro Asp Pro Arg Glu Ala Cys Gly Ser Ser Ser Tyr Val Ala Ser Ile 465 470 475 480 Val Asp Gly Gly Glu Ser Arg Ser Glu Lys Gly Asp Ser Ser Arg Tyr 485 490 495 <210> 323 <211> 496 <212> PRT <213> homo sapiens <400> 323 Met Val Glu Ala Asp His Pro Gly Lys Leu Phe Ile Gly Gly Leu Asn 1 5 10 15 Arg Glu Thr Asn Glu Lys Met Leu Lys Ala Val Phe Gly Lys His Gly 20 25 30 Pro Ile Ser Glu Val Leu Leu Ile Lys Asp Arg Thr Ser Lys Ser Arg 35 40 45 Gly Phe Ala Phe Ile Thr Phe Glu Asn Pro Ala Asp Ala Lys Asn Ala 50 55 60 Ala Lys Asp Met Asn Gly Thr Ser Leu His Gly Lys Ala Ile Lys Val 65 70 75 80 Glu Gln Ala Lys Lys Pro Ser Phe Gln Ser Gly Gly Arg Arg Arg Pro 85 90 95 Pro Ala Ser Ser Arg Asn Arg Ser Pro Ser Gly Ser Leu Arg Ser Ala 100 105 110 Arg Gly Ser Ser Gly Gly Thr Arg Gly Trp Leu Pro Ser His Glu Gly 115 120 125 His Leu Asp Asp Gly Gly Tyr Thr Pro Asp Leu Lys Met Ser Tyr Ser 130 135 140 Arg Gly Leu Ile Pro Val Lys Arg Gly Pro Ser Ser Arg Ser Gly Gly 145 150 155 160 Pro Pro Pro Lys Lys Ser Ala Pro Ser Ala Val Ala Arg Ser Asn Ser 165 170 175 Trp Met Gly Ser Gln Gly Pro Met Ser Gln Arg Arg Glu Asn Tyr Gly 180 185 190 Val Pro Pro Arg Arg Ala Thr Ile Ser Ser Trp Arg Asn Asp Arg Met 195 200 205 Ser Thr Arg His Asp Gly Tyr Ala Thr Asn Asp Gly Asn His Pro Ser 210 215 220 Cys Gln Glu Thr Arg Asp Tyr Ala Pro Pro Ser Arg Gly Tyr Ala Tyr 225 230 235 240 Arg Asp Asn Gly His Ser Asn Arg Asp Glu His Ser Ser Arg Gly Tyr 245 250 255 Arg Asn His Arg Ser Ser Arg Glu Thr Arg Asp Tyr Ala Pro Pro Ser 260 265 270 Arg Gly His Ala Tyr Arg Asp Tyr Gly His Ser Arg Arg Asp Glu Ser 275 280 285 Tyr Ser Arg Gly Tyr Arg Asn His Arg Ser Ser Arg Glu Thr Arg Glu 290 295 300 Tyr Ala Pro Pro Ser Arg Gly His Gly Tyr Arg Asp Tyr Gly His Ser 305 310 315 320 Arg Arg His Glu Ser Tyr Ser Arg Gly Tyr Arg Asn His Pro Ser Ser 325 330 335 Arg Glu Thr Arg Asp Tyr Ala Pro Pro His Arg Asp Tyr Ala Tyr Arg 340 345 350 Asp Tyr Gly His Ser Ser Trp Asp Glu His Ser Ser Arg Gly Tyr Ser 355 360 365 Tyr His Asp Gly Tyr Gly Glu Ala Leu Gly Arg Asp His Ser Glu His 370 375 380 Leu Ser Gly Ser Ser Tyr Arg Asp Ala Leu Gln Arg Tyr Gly Thr Ser 385 390 395 400 His Gly Ala Pro Pro Ala Arg Gly Pro Arg Met Ser Tyr Gly Gly Ser 405 410 415 Thr Cys His Ala Tyr Ser Asn Thr Arg Asp Arg Tyr Gly Arg Ser Trp 420 425 430 Glu Ser Tyr Ser Ser Cys Gly Asp Phe His Tyr Cys Asp Arg Glu His 435 440 445 Val Cys Arg Lys Asp Gln Arg Asn Pro Pro Ser Leu Gly Arg Val Leu 450 455 460 Pro Asp Pro Arg Glu Ala Tyr Gly Ser Ser Ser Tyr Val Ala Ser Ile 465 470 475 480 Val Asp Gly Gly Glu Ser Arg Ser Glu Lys Gly Asp Ser Ser Arg Tyr 485 490 495 <210> 324 <211> 155 <212> PRT <213> homo sapiens <400> 324 Met Arg His Leu Pro Tyr Phe Cys Arg Gly Gln Val Val Arg Gly Phe 1 5 10 15 Gly Arg Gly Ser Lys Gln Leu Gly Ile Pro Thr Ala Asn Phe Pro Glu 20 25 30 Gln Val Val Asp Asn Leu Pro Ala Asp Ile Ser Thr Gly Ile Tyr Tyr 35 40 45 Gly Trp Ala Ser Val Gly Ser Gly Asp Val His Lys Met Val Val Ser 50 55 60 Ile Gly Trp Asn Pro Tyr Tyr Lys Asn Thr Lys Lys Ser Met Glu Thr 65 70 75 80 His Ile Met His Thr Phe Lys Glu Asp Phe Tyr Gly Glu Ile Leu Asn 85 90 95 Val Ala Ile Val Gly Tyr Leu Arg Pro Glu Lys Asn Phe Asp Ser Leu 100 105 110 Glu Ser Leu Ile Ser Ala Ile Gln Gly Asp Ile Glu Glu Ala Lys Lys 115 120 125 Arg Leu Glu Leu Pro Glu His Leu Lys Ile Lys Glu Asp Asn Phe Phe 130 135 140 Gln Val Ser Lys Ser Lys Ile Met Asn Gly His 145 150 155 <210> 325 <211> 1639 <212> PRT <213> homo sapiens <400> 325 Met Ala Lys Asp Ser Pro Ser Pro Leu Gly Ala Ser Pro Lys Lys Pro 1 5 10 15 Gly Cys Ser Ser Pro Ala Ala Ala Val Leu Glu Asn Gln Arg Arg Glu 20 25 30 Leu Glu Lys Leu Arg Ala Glu Leu Glu Ala Glu Arg Ala Gly Trp Arg 35 40 45 Ala Glu Arg Arg Arg Phe Ala Ala Arg Glu Arg Gln Leu Arg Glu Glu 50 55 60 Ala Glu Arg Glu Arg Arg Gln Leu Ala Asp Arg Leu Arg Ser Lys Trp 65 70 75 80 Glu Ala Gln Arg Ser Arg Glu Leu Arg Gln Leu Gln Glu Glu Met Gln 85 90 95 Arg Glu Arg Glu Ala Glu Ile Arg Gln Leu Leu Arg Trp Lys Glu Ala 100 105 110 Glu Gln Arg Gln Leu Gln Gln Leu Leu His Arg Glu Arg Asp Gly Val 115 120 125 Val Arg Gln Ala Arg Glu Leu Gln Arg Gln Leu Ala Glu Glu Leu Val 130 135 140 Asn Arg Gly His Cys Ser Arg Pro Gly Ala Ser Glu Val Ser Ala Ala 145 150 155 160 Gln Cys Arg Cys Arg Leu Gln Glu Val Leu Ala Gln Leu Arg Trp Gln 165 170 175 Thr Asp Gly Glu Gln Ala Ala Arg Ile Arg Tyr Leu Gln Ala Ala Leu 180 185 190 Glu Val Glu Arg Gln Leu Phe Leu Lys Tyr Ile Leu Ala His Phe Arg 195 200 205 Gly His Pro Ala Leu Ser Gly Ser Pro Asp Pro Gln Ala Val His Ser 210 215 220 Leu Glu Glu Pro Leu Pro Gln Thr Ser Ser Gly Ser Cys His Ala Pro 225 230 235 240 Lys Pro Ala Cys Gln Leu Gly Ser Leu Asp Ser Leu Ser Ala Glu Val 245 250 255 Gly Val Arg Ser Arg Ser Leu Gly Leu Val Ser Ser Ala Cys Ser Ser 260 265 270 Ser Pro Asp Gly Leu Leu Ser Thr His Ala Ser Ser Leu Asp Cys Phe 275 280 285 Ala Pro Ala Cys Ser Arg Ser Leu Asp Ser Thr Arg Ser Leu Pro Lys 290 295 300 Ala Ser Lys Ser Glu Glu Arg Pro Ser Ser Pro Asp Thr Ser Thr Pro 305 310 315 320 Gly Ser Arg Arg Leu Ser Pro Pro Pro Ser Pro Leu Pro Pro Pro Pro 325 330 335 Pro Pro Ser Ala His Arg Lys Leu Ser Asn Pro Arg Gly Gly Glu Gly 340 345 350 Ser Glu Ser Gln Pro Cys Glu Val Leu Thr Pro Ser Pro Pro Gly Leu 355 360 365 Gly His His Glu Leu Ile Lys Leu Asn Trp Leu Leu Ala Lys Ala Leu 370 375 380 Trp Val Leu Ala Arg Arg Cys Tyr Thr Leu Gln Ala Glu Asn Lys Gln 385 390 395 400 Leu Arg Arg Ala Gly Cys Pro Tyr Gln Ala Asp Glu Lys Val Lys Arg 405 410 415 Leu Lys Val Lys Arg Ala Glu Leu Thr Gly Leu Ala Arg Arg Leu Ala 420 425 430 Asp Arg Ala Arg Lys Leu Gln Glu Thr Asn Leu Arg Ala Val Ser Ala 435 440 445 Pro Ile Pro Gly Glu Ser Cys Ala Gly Leu Glu Leu Cys Gln Val Phe 450 455 460 Ala Arg Gln Arg Ala Arg Asp Leu Ser Glu Gln Ala Ser Ala Pro Leu 465 470 475 480 Ala Lys Asp Lys Gln Ile Glu Glu Leu Arg Gln Glu Cys His Leu Leu 485 490 495 Gln Ala Arg Val Ala Ser Gly Pro Cys Ser Asp Leu His Thr Gly Arg 500 505 510 Gly Gly Pro Cys Thr Gln Trp Leu Asn Val Arg Asp Leu Asp Arg Leu 515 520 525 Gln Arg Glu Ser Gln Arg Glu Val Leu Arg Leu Gln Arg Gln Leu Met 530 535 540 Leu Gln Gln Gly Asn Gly Gly Ala Trp Pro Glu Ala Gly Gly Gln Ser 545 550 555 560 Ala Thr Cys Glu Glu Val Arg Arg Gln Met Leu Ala Leu Glu Arg Glu 565 570 575 Leu Asp Gln Arg Arg Arg Glu Cys Gln Glu Leu Gly Ala Gln Ala Ala 580 585 590 Pro Ala Arg Arg Arg Gly Glu Glu Ala Glu Thr Gln Leu Gln Ala Ala 595 600 605 Leu Leu Lys Asn Ala Trp Leu Ala Glu Glu Asn Gly Arg Leu Gln Ala 610 615 620 Lys Thr Asp Trp Val Arg Lys Val Glu Ala Glu Asn Ser Glu Val Arg 625 630 635 640 Gly His Leu Gly Arg Ala Cys Gln Glu Arg Asp Ala Ser Gly Leu Ile 645 650 655 Ala Glu Gln Leu Leu Gln Gln Ala Ala Arg Gly Gln Asp Arg Gln Gln 660 665 670 Gln Leu Gln Arg Asp Pro Gln Lys Ala Leu Cys Asp Leu His Pro Ser 675 680 685 Trp Lys Glu Ile Gln Ala Leu Gln Cys Arg Pro Gly His Pro Pro Glu 690 695 700 Gln Pro Trp Glu Thr Ser Gln Met Pro Glu Ser Gln Val Lys Gly Ser 705 710 715 720 Arg Arg Pro Lys Phe His Ala Arg Pro Glu Asp Tyr Ala Val Ser Gln 725 730 735 Pro Asn Arg Asp Ile Gln Glu Lys Arg Glu Ala Ser Leu Glu Glu Ser 740 745 750 Pro Val Ala Leu Gly Glu Ser Ala Ser Val Pro Gln Val Ser Glu Thr 755 760 765 Val Pro Ala Ser Gln Pro Leu Ser Lys Lys Thr Ser Ser Gln Ser Asn 770 775 780 Ser Ser Ser Glu Gly Ser Met Trp Ala Thr Val Pro Ser Ser Pro Thr 785 790 795 800 Leu Asp Arg Asp Thr Ala Ser Glu Val Asp Asp Leu Glu Pro Asp Ser 805 810 815 Val Ser Leu Ala Leu Glu Met Gly Gly Ser Ala Ala Pro Ala Ala Pro 820 825 830 Lys Leu Lys Ile Phe Met Ala Gln Tyr Asn Tyr Asn Pro Phe Glu Gly 835 840 845 Pro Asn Asp His Pro Glu Gly Glu Leu Pro Leu Thr Ala Gly Asp Tyr 850 855 860 Ile Tyr Ile Phe Gly Asp Met Asp Glu Asp Gly Phe Tyr Glu Gly Glu 865 870 875 880 Leu Glu Asp Gly Arg Arg Gly Leu Val Pro Ser Asn Phe Val Glu Gln 885 890 895 Ile Pro Asp Ser Tyr Ile Pro Gly Cys Leu Pro Ala Lys Ser Pro Asp 900 905 910 Leu Gly Pro Ser Gln Leu Pro Ala Gly Gln Asp Glu Ala Leu Glu Glu 915 920 925 Asp Ser Leu Leu Ser Gly Lys Ala Gln Gly Val Val Asp Arg Gly Leu 930 935 940 Cys Gln Met Val Arg Val Gly Ser Lys Thr Glu Val Ala Thr Glu Ile 945 950 955 960 Leu Asp Thr Lys Thr Glu Ala Cys Gln Leu Gly Leu Leu Gln Ser Met 965 970 975 Gly Lys Gln Gly Leu Ser Arg Pro Leu Leu Gly Thr Lys Gly Val Leu 980 985 990 Arg Met Ala Pro Met Gln Leu His Leu Gln Asn Val Thr Ala Thr Ser 995 1000 1005 Ala Asn Ile Thr Trp Val Tyr Ser Ser His Arg His Pro His Val 1010 1015 1020 Val Tyr Leu Asp Asp Arg Glu His Ala Leu Thr Pro Ala Gly Val 1025 1030 1035 Ser Cys Tyr Thr Phe Gln Gly Leu Cys Pro Gly Thr His Tyr Arg 1040 1045 1050 Ala Arg Val Glu Val Arg Leu Pro Arg Asp Leu Leu Gln Val Tyr 1055 1060 1065 Trp Gly Thr Met Ser Ser Thr Val Thr Phe Asp Thr Leu Leu Ala 1070 1075 1080 Gly Pro Pro Tyr Pro Pro Leu Asp Val Leu Val Glu Arg His Ala 1085 1090 1095 Ser Pro Gly Val Leu Val Val Ser Trp Leu Pro Val Thr Ile Asp 1100 1105 1110 Ser Ala Gly Ser Ser Asn Gly Val Gln Val Thr Gly Tyr Ala Val 1115 1120 1125 Tyr Ala Asp Gly Leu Lys Val Cys Glu Val Ala Asp Ala Thr Ala 1130 1135 1140 Gly Ser Thr Leu Leu Glu Phe Ser Gln Leu Gln Val Pro Leu Thr 1145 1150 1155 Trp Gln Lys Val Ser Val Arg Thr Met Ser Leu Cys Gly Glu Ser 1160 1165 1170 Leu Asp Ser Val Pro Ala Gln Ile Pro Glu Asp Phe Phe Met Cys 1175 1180 1185 His Arg Trp Pro Glu Thr Pro Pro Phe Ser Tyr Thr Cys Gly Asp 1190 1195 1200 Pro Ser Thr Tyr Arg Val Thr Phe Pro Val Cys Pro Gln Lys Leu 1205 1210 1215 Ser Leu Ala Pro Pro Ser Ala Lys Ala Ser Pro His Asn Pro Gly 1220 1225 1230 Ser Cys Gly Glu Pro Gln Ala Lys Phe Leu Glu Ala Phe Phe Glu 1235 1240 1245 Glu Pro Pro Arg Arg Gln Ser Pro Val Ser Asn Leu Gly Ser Glu 1250 1255 1260 Gly Glu Cys Pro Ser Ser Gly Ala Gly Ser Gln Ala Gln Glu Leu 1265 1270 1275 Ala Glu Ala Trp Glu Gly Cys Arg Lys Asp Leu Leu Phe Gln Lys 1280 1285 1290 Ser Pro Gln Asn His Arg Pro Pro Ser Val Ser Asp Gln Pro Gly 1295 1300 1305 Glu Lys Glu Asn Cys Ser Gln His Met Gly Thr Ser Lys Ser Pro 1310 1315 1320 Ala Pro Gly Phe Ile His Leu Arg Thr Glu Cys Gly Pro Arg Lys 1325 1330 1335 Glu Pro Cys Gln Glu Lys Ala Ala Leu Glu Arg Val Leu Arg Gln 1340 1345 1350 Lys Gln Asp Ala Gln Gly Phe Thr Pro Pro Gln Leu Gly Ala Ser 1355 1360 1365 Gln Gln Tyr Ala Ser Asp Phe His Asn Val Leu Lys Glu Glu Gln 1370 1375 1380 Glu Ala Leu Cys Leu Asp Leu Trp Gly Thr Glu Arg Arg Glu Glu 1385 1390 1395 Arg Arg Glu Pro Glu Pro His Ser Arg Gln Gly Gln Ala Leu Gly 1400 1405 1410 Val Lys Arg Gly Cys Gln Leu His Glu Pro Ser Ser Ala Leu Cys 1415 1420 1425 Pro Ala Pro Ser Ala Lys Val Ile Lys Met Pro Arg Gly Gly Pro 1430 1435 1440 Gln Gln Leu Gly Thr Gly Ala Asn Thr Pro Ala Arg Val Phe Val 1445 1450 1455 Ala Leu Ser Asp Tyr Asn Pro Leu Val Met Ser Ala Asn Leu Lys 1460 1465 1470 Ala Ala Glu Glu Glu Leu Val Phe Gln Lys Arg Gln Leu Leu Arg 1475 1480 1485 Val Trp Gly Ser Gln Asp Thr His Asp Phe Tyr Leu Ser Glu Cys 1490 1495 1500 Asn Arg Gln Val Gly Asn Ile Pro Gly Arg Leu Val Ala Glu Met 1505 1510 1515 Glu Val Gly Thr Glu Gln Thr Asp Arg Arg Trp Arg Ser Pro Ala 1520 1525 1530 Gln Gly Asn Leu Pro Ser Val Ala His Leu Glu Asp Phe Gln Gly 1535 1540 1545 Leu Thr Ile Pro Gln Gly Ser Ser Leu Val Leu Gln Gly Asn Ser 1550 1555 1560 Lys Arg Leu Pro Leu Trp Thr Pro Lys Ile Met Ile Ala Ala Leu 1565 1570 1575 Asp Tyr Asp Pro Gly Asp Gly Gln Met Gly Gly Gln Gly Lys Gly 1580 1585 1590 Arg Leu Ala Leu Arg Ala Gly Asp Val Val Met Val Tyr Gly Pro 1595 1600 1605 Met Asp Asp Gln Gly Phe Tyr Tyr Gly Glu Leu Gly Gly His Arg 1610 1615 1620 Gly Leu Val Pro Ala His Leu Leu Asp His Met Ser Leu His Gly 1625 1630 1635 His <210> 326 <211> 203 <212> PRT <213> homo sapiens <400> 326 Met Glu Thr Leu Ser Gln Asp Ser Leu Leu Glu Cys Gln Ile Cys Phe 1 5 10 15 Asn Tyr Tyr Ser Pro Arg Arg Arg Pro Lys Leu Leu Asp Cys Lys His 20 25 30 Thr Cys Cys Ser Val Cys Leu Gln Gln Met Arg Thr Ser Gln Lys Asp 35 40 45 Val Arg Cys Pro Trp Cys Arg Gly Val Thr Lys Leu Pro Pro Gly Phe 50 55 60 Ser Val Ser Gln Leu Pro Asp Asp Pro Glu Val Leu Ala Val Ile Ala 65 70 75 80 Ile Pro His Thr Ser Glu His Thr Pro Val Phe Ile Lys Leu Pro Ser 85 90 95 Asn Gly Cys Tyr Met Leu Pro Leu Pro Ile Ser Lys Glu Arg Ala Leu 100 105 110 Leu Pro Gly Asp Met Gly Cys Arg Leu Leu Pro Gly Ser Gln Gln Lys 115 120 125 Ser Val Thr Val Val Thr Ile Pro Ala Glu Gln Gln Pro Leu Gln Gly 130 135 140 Gly Ala Pro Gln Glu Ala Val Glu Glu Glu Gln Asp Arg Arg Gly Val 145 150 155 160 Val Lys Ser Ser Thr Trp Ser Gly Val Cys Thr Val Ile Leu Val Ala 165 170 175 Cys Val Leu Val Phe Leu Leu Gly Ile Val Leu His Asn Met Ser Cys 180 185 190 Ile Ser Lys Arg Phe Thr Val Ile Ser Cys Gly 195 200 <210> 327 <211> 192 <212> PRT <213> homo sapiens <400> 327 Met Ala Ser Lys Gly Pro Ser Ala Ser Ala Ser Pro Glu Asn Ser Ser 1 5 10 15 Ala Gly Gly Pro Ser Gly Ser Ser Asn Gly Ala Gly Glu Ser Gly Gly 20 25 30 Gln Asp Ser Thr Phe Glu Cys Asn Ile Cys Leu Asp Thr Ala Lys Asp 35 40 45 Ala Val Ile Ser Leu Cys Gly His Leu Phe Cys Trp Pro Cys Leu His 50 55 60 Gln Trp Leu Glu Thr Arg Pro Asn Arg Gln Val Cys Pro Val Cys Lys 65 70 75 80 Ala Gly Ile Ser Arg Asp Lys Val Ile Pro Leu Tyr Gly Arg Gly Ser 85 90 95 Thr Gly Gln Gln Asp Pro Arg Glu Lys Thr Pro Pro Arg Pro Gln Gly 100 105 110 Gln Arg Pro Glu Pro Glu Asn Arg Gly Gly Phe Gln Gly Phe Gly Phe 115 120 125 Gly Asp Gly Gly Phe Gln Met Ser Phe Gly Ile Gly Ala Phe Pro Phe 130 135 140 Gly Ile Phe Ala Thr Ala Phe Asn Ile Asn Asp Gly Arg Pro Pro Pro 145 150 155 160 Ala Val Pro Gly Thr Pro Gln Tyr Val Asp Glu Gln Phe Leu Ser Arg 165 170 175 Leu Phe Leu Phe Val Ala Leu Val Ile Met Phe Trp Leu Leu Ile Ala 180 185 190 <210> 328 <211> 305 <212> PRT <213> homo sapiens <400> 328 Met Asp Leu Ser Gly Val Lys Lys Lys Ser Leu Leu Gly Val Lys Glu 1 5 10 15 Asn Asn Lys Lys Ser Ser Thr Arg Ala Pro Ser Pro Thr Lys Arg Lys 20 25 30 Asp Arg Ser Asp Glu Lys Ser Lys Asp Arg Ser Lys Asp Lys Gly Ala 35 40 45 Thr Lys Glu Ser Ser Glu Lys Asp Arg Gly Arg Asp Lys Thr Arg Lys 50 55 60 Arg Arg Ser Ala Ser Ser Gly Ser Ser Ser Thr Arg Ser Arg Ser Ser 65 70 75 80 Ser Thr Ser Ser Ser Gly Ser Ser Thr Ser Thr Gly Ser Ser Ser Gly 85 90 95 Ser Ser Ser Ser Ser Ala Ser Ser Arg Ser Gly Ser Ser Ser Thr Ser 100 105 110 Arg Ser Ser Ser Ser Ser Ser Ser Ser Gly Ser Pro Ser Pro Ser Arg 115 120 125 Arg Arg His Asp Asn Arg Arg Arg Ser Arg Ser Lys Ser Lys Pro Pro 130 135 140 Lys Arg Asp Glu Lys Glu Arg Lys Arg Arg Ser Pro Ser Pro Lys Pro 145 150 155 160 Thr Lys Val His Ile Gly Arg Leu Thr Arg Asn Val Thr Lys Asp His 165 170 175 Ile Met Glu Ile Phe Ser Thr Tyr Gly Lys Ile Lys Met Ile Asp Met 180 185 190 Pro Val Glu Arg Met His Pro His Leu Ser Lys Gly Tyr Ala Tyr Val 195 200 205 Glu Phe Glu Asn Pro Asp Glu Ala Glu Lys Ala Leu Lys His Met Asp 210 215 220 Gly Gly Gln Ile Asp Gly Gln Glu Ile Thr Ala Thr Ala Val Leu Ala 225 230 235 240 Pro Trp Pro Arg Pro Pro Pro Arg Arg Phe Ser Pro Pro Arg Arg Met 245 250 255 Leu Pro Pro Pro Pro Met Trp Arg Arg Ser Pro Pro Arg Met Arg Arg 260 265 270 Arg Ser Arg Ser Pro Arg Arg Arg Ser Pro Val Arg Arg Arg Ser Arg 275 280 285 Ser Pro Gly Arg Arg Arg His Arg Ser Arg Ser Ser Ser Asn Ser Ser 290 295 300 Arg 305 <210> 329 <211> 499 <212> PRT <213> homo sapiens <400> 329 Met Ser Leu Ala Asp Glu Leu Leu Ala Asp Leu Glu Glu Ala Ala Glu 1 5 10 15 Glu Glu Glu Gly Gly Ser Tyr Gly Glu Glu Glu Glu Glu Pro Ala Ile 20 25 30 Glu Asp Val Gln Glu Glu Thr Gln Leu Asp Leu Ser Gly Asp Ser Val 35 40 45 Lys Thr Ile Ala Lys Leu Trp Asp Ser Lys Met Phe Ala Glu Ile Met 50 55 60 Met Lys Ile Glu Glu Tyr Ile Ser Lys Gln Ala Lys Ala Ser Glu Val 65 70 75 80 Met Gly Pro Val Glu Ala Ala Pro Glu Tyr Arg Val Ile Val Asp Ala 85 90 95 Asn Asn Leu Thr Val Glu Ile Glu Asn Glu Leu Asn Ile Ile His Lys 100 105 110 Phe Ile Arg Asp Lys Tyr Ser Lys Arg Phe Pro Glu Leu Glu Ser Leu 115 120 125 Val Pro Asn Ala Leu Asp Tyr Ile Arg Thr Val Lys Glu Leu Gly Asn 130 135 140 Ser Leu Asp Lys Cys Lys Asn Asn Glu Asn Leu Gln Gln Ile Leu Thr 145 150 155 160 Asn Ala Thr Ile Met Val Val Ser Val Thr Ala Ser Thr Thr Gln Gly 165 170 175 Gln Gln Leu Ser Glu Glu Glu Leu Glu Arg Leu Glu Glu Ala Cys Asp 180 185 190 Met Ala Leu Glu Leu Asn Ala Ser Lys His Arg Ile Tyr Glu Tyr Val 195 200 205 Glu Ser Arg Met Ser Phe Ile Ala Pro Asn Leu Ser Ile Ile Ile Gly 210 215 220 Ala Ser Thr Ala Ala Lys Ile Met Gly Val Ala Gly Gly Leu Thr Asn 225 230 235 240 Leu Ser Lys Met Pro Ala Cys Asn Ile Met Leu Leu Gly Ala Gln Arg 245 250 255 Lys Thr Leu Ser Gly Phe Ser Ser Thr Ser Val Leu Pro His Thr Gly 260 265 270 Tyr Ile Tyr His Ser Asp Ile Val Gln Ser Leu Pro Pro Asp Leu Arg 275 280 285 Arg Lys Ala Ala Arg Leu Val Ala Ala Lys Cys Thr Leu Ala Ala Arg 290 295 300 Val Asp Ser Phe His Glu Ser Thr Glu Gly Lys Val Gly Tyr Glu Leu 305 310 315 320 Lys Asp Glu Ile Glu Arg Lys Phe Asp Lys Trp Gln Glu Pro Pro Pro 325 330 335 Val Lys Gln Val Lys Pro Leu Pro Ala Pro Leu Asp Gly Gln Arg Lys 340 345 350 Lys Arg Gly Gly Arg Arg Tyr Arg Lys Met Lys Glu Arg Leu Gly Leu 355 360 365 Thr Glu Ile Arg Lys Gln Ala Asn Arg Met Ser Phe Gly Glu Ile Glu 370 375 380 Glu Asp Ala Tyr Gln Glu Asp Leu Gly Phe Ser Leu Gly His Leu Gly 385 390 395 400 Lys Ser Gly Ser Gly Arg Val Arg Gln Thr Gln Val Asn Glu Ala Thr 405 410 415 Lys Ala Arg Ile Ser Lys Thr Leu Gln Arg Thr Leu Gln Lys Gln Ser 420 425 430 Val Val Tyr Gly Gly Lys Ser Thr Ile Arg Asp Arg Ser Ser Gly Thr 435 440 445 Ala Ser Ser Val Ala Phe Thr Pro Leu Gln Gly Leu Glu Ile Val Asn 450 455 460 Pro Gln Ala Ala Glu Lys Lys Val Ala Glu Ala Asn Gln Lys Tyr Phe 465 470 475 480 Ser Ser Met Ala Glu Phe Leu Lys Val Lys Gly Glu Lys Ser Gly Leu 485 490 495 Met Ser Thr <210> 330 <211> 378 <212> PRT <213> homo sapiens <400> 330 Met Ala Thr Ala Leu Pro Pro Arg Leu Gln Pro Val Arg Gly Asn Glu 1 5 10 15 Thr Leu Arg Glu His Tyr Gln Tyr Val Gly Lys Leu Ala Gly Arg Leu 20 25 30 Lys Glu Ala Ser Glu Gly Ser Thr Leu Thr Thr Val Leu Phe Leu Val 35 40 45 Ile Cys Ser Phe Ile Val Leu Glu Asn Leu Met Val Leu Ile Ala Ile 50 55 60 Trp Lys Asn Asn Lys Phe His Asn Arg Met Tyr Phe Phe Ile Gly Asn 65 70 75 80 Leu Ala Leu Cys Asp Leu Leu Ala Gly Ile Ala Tyr Lys Val Asn Ile 85 90 95 Leu Met Ser Gly Lys Lys Thr Phe Ser Leu Ser Pro Thr Val Trp Phe 100 105 110 Leu Arg Glu Gly Ser Met Phe Val Ala Leu Gly Ala Ser Thr Cys Ser 115 120 125 Leu Leu Ala Ile Ala Ile Glu Arg His Leu Thr Met Ile Lys Met Arg 130 135 140 Pro Tyr Asp Ala Asn Lys Arg His Arg Val Phe Leu Leu Ile Gly Met 145 150 155 160 Cys Trp Leu Ile Ala Phe Thr Leu Gly Ala Leu Pro Ile Leu Gly Trp 165 170 175 Asn Cys Leu His Asn Leu Pro Asp Cys Ser Thr Ile Leu Pro Leu Tyr 180 185 190 Ser Lys Lys Tyr Ile Ala Phe Cys Ile Ser Ile Phe Thr Ala Ile Leu 195 200 205 Val Thr Ile Val Ile Leu Tyr Ala Arg Ile Tyr Phe Leu Val Lys Ser 210 215 220 Ser Ser Arg Lys Val Ala Asn His Asn Asn Ser Glu Arg Ser Met Ala 225 230 235 240 Leu Leu Arg Thr Val Val Ile Val Val Ser Val Phe Ile Ala Cys Trp 245 250 255 Ser Pro Leu Phe Ile Leu Phe Leu Ile Asp Val Ala Cys Arg Val Gln 260 265 270 Ala Cys Pro Ile Leu Phe Lys Ala Gln Trp Phe Ile Val Leu Ala Val 275 280 285 Leu Asn Ser Ala Met Asn Pro Val Ile Tyr Thr Leu Ala Ser Lys Glu 290 295 300 Met Arg Arg Ala Phe Phe Arg Leu Val Cys Asn Cys Leu Val Arg Gly 305 310 315 320 Arg Gly Ala Arg Ala Ser Pro Ile Gln Pro Ala Leu Asp Pro Ser Arg 325 330 335 Ser Lys Ser Ser Ser Ser Asn Asn Ser Ser His Ser Pro Lys Val Lys 340 345 350 Glu Asp Leu Pro His Thr Ala Pro Ser Ser Cys Ile Met Asp Lys Asn 355 360 365 Ala Ala Leu Gln Asn Gly Ile Phe Cys Asn 370 375 <210> 331 <211> 800 <212> PRT <213> homo sapiens <400> 331 Met Gly Ser Ser Lys Lys His Arg Gly Glu Lys Glu Ala Ala Gly Thr 1 5 10 15 Thr Ala Ala Ala Gly Thr Gly Gly Ala Thr Glu Gln Pro Pro Arg His 20 25 30 Arg Glu His Lys Lys His Lys His Arg Ser Gly Gly Ser Gly Gly Ser 35 40 45 Gly Gly Glu Arg Arg Lys Arg Ser Arg Glu Arg Gly Gly Glu Arg Gly 50 55 60 Ser Gly Arg Arg Gly Ala Glu Ala Glu Ala Arg Ser Ser Thr His Gly 65 70 75 80 Arg Glu Arg Ser Gln Ala Glu Pro Ser Glu Arg Arg Val Lys Arg Glu 85 90 95 Lys Arg Asp Asp Gly Tyr Glu Ala Ala Ala Ser Ser Lys Thr Ser Ser 100 105 110 Gly Asp Ala Ser Ser Leu Ser Ile Glu Glu Thr Asn Lys Leu Arg Ala 115 120 125 Lys Leu Gly Leu Lys Pro Leu Glu Val Asn Ala Ile Lys Lys Glu Ala 130 135 140 Gly Thr Lys Glu Glu Pro Val Thr Ala Asp Val Ile Asn Pro Met Ala 145 150 155 160 Leu Arg Gln Arg Glu Glu Leu Arg Glu Lys Leu Ala Ala Ala Lys Glu 165 170 175 Lys Arg Leu Leu Asn Gln Lys Leu Gly Lys Ile Lys Thr Leu Gly Glu 180 185 190 Asp Asp Pro Trp Leu Asp Asp Thr Ala Ala Trp Ile Glu Arg Ser Arg 195 200 205 Gln Leu Gln Lys Glu Lys Asp Leu Ala Glu Lys Arg Ala Lys Leu Leu 210 215 220 Glu Glu Met Asp Gln Glu Phe Gly Val Ser Thr Leu Val Glu Glu Glu 225 230 235 240 Phe Gly Gln Arg Arg Gln Asp Leu Tyr Ser Ala Arg Asp Leu Gln Gly 245 250 255 Leu Thr Val Glu His Ala Ile Asp Ser Phe Arg Glu Gly Glu Thr Met 260 265 270 Ile Leu Thr Leu Lys Asp Lys Gly Val Leu Gln Glu Glu Glu Asp Val 275 280 285 Leu Val Asn Val Asn Leu Val Asp Lys Glu Arg Ala Glu Lys Asn Val 290 295 300 Glu Leu Arg Lys Lys Lys Pro Asp Tyr Leu Pro Tyr Ala Glu Asp Glu 305 310 315 320 Ser Val Asp Asp Leu Ala Gln Gln Lys Pro Arg Ser Ile Leu Ser Lys 325 330 335 Tyr Asp Glu Glu Leu Glu Gly Glu Arg Pro His Ser Phe Arg Leu Glu 340 345 350 Gln Gly Gly Thr Ala Asp Gly Leu Arg Glu Arg Glu Leu Glu Glu Ile 355 360 365 Arg Ala Lys Leu Arg Leu Gln Ala Gln Ser Leu Ser Thr Val Gly Pro 370 375 380 Arg Leu Ala Ser Glu Tyr Leu Thr Pro Glu Glu Met Val Thr Phe Lys 385 390 395 400 Lys Thr Lys Arg Arg Val Lys Lys Ile Arg Lys Lys Glu Lys Glu Val 405 410 415 Val Val Arg Ala Asp Asp Leu Leu Pro Leu Gly Asp Gln Thr Gln Asp 420 425 430 Gly Asp Phe Gly Ser Arg Leu Arg Gly Arg Gly Arg Arg Arg Val Ser 435 440 445 Glu Val Glu Glu Glu Lys Glu Pro Val Pro Gln Pro Leu Pro Ser Asp 450 455 460 Asp Thr Arg Val Glu Asn Met Asp Ile Ser Asp Glu Glu Glu Gly Gly 465 470 475 480 Ala Pro Pro Pro Gly Ser Pro Gln Val Leu Glu Glu Asp Glu Ala Glu 485 490 495 Leu Glu Leu Gln Lys Gln Leu Glu Lys Gly Arg Arg Leu Arg Gln Leu 500 505 510 Gln Gln Leu Gln Gln Leu Arg Asp Ser Gly Glu Lys Val Val Glu Ile 515 520 525 Val Lys Lys Leu Glu Ser Arg Gln Arg Gly Trp Glu Glu Asp Glu Asp 530 535 540 Pro Glu Arg Lys Gly Ala Ile Val Phe Asn Ala Thr Ser Glu Phe Cys 545 550 555 560 Arg Thr Leu Gly Glu Ile Pro Thr Tyr Gly Leu Ala Gly Asn Arg Glu 565 570 575 Glu Gln Glu Glu Leu Met Asp Phe Glu Arg Asp Glu Glu Arg Ser Ala 580 585 590 Asn Gly Gly Ser Glu Ser Asp Gly Glu Glu Asn Ile Gly Trp Ser Thr 595 600 605 Val Asn Leu Asp Glu Glu Lys Gln Gln Gln Asp Phe Ser Ala Ser Ser 610 615 620 Thr Thr Ile Leu Asp Glu Glu Pro Ile Val Asn Arg Gly Leu Ala Ala 625 630 635 640 Ala Leu Leu Leu Cys Gln Asn Lys Gly Leu Leu Glu Thr Thr Val Gln 645 650 655 Lys Val Ala Arg Val Lys Ala Pro Asn Lys Ser Leu Pro Ser Ala Val 660 665 670 Tyr Cys Ile Glu Asp Lys Met Ala Ile Asp Asp Lys Tyr Ser Arg Arg 675 680 685 Glu Glu Tyr Arg Gly Phe Thr Gln Asp Phe Lys Glu Lys Asp Gly Tyr 690 695 700 Lys Pro Asp Val Lys Ile Glu Tyr Val Asp Glu Thr Gly Arg Lys Leu 705 710 715 720 Thr Pro Lys Glu Ala Phe Arg Gln Leu Ser His Arg Phe His Gly Lys 725 730 735 Gly Ser Gly Lys Met Lys Thr Glu Arg Arg Met Lys Lys Leu Asp Glu 740 745 750 Glu Ala Leu Leu Lys Lys Met Ser Ser Ser Asp Thr Pro Leu Gly Thr 755 760 765 Val Ala Leu Leu Gln Glu Lys Gln Lys Ala Gln Lys Thr Pro Tyr Ile 770 775 780 Val Leu Ser Gly Ser Gly Lys Ser Met Asn Ala Asn Thr Ile Thr Lys 785 790 795 800 <210> 332 <211> 687 <212> PRT <213> homo sapiens <400> 332 Met Ser Asn Arg Asn Asn Asn Lys Leu Pro Ser Asn Leu Pro Gln Leu 1 5 10 15 Gln Asn Leu Ile Lys Arg Asp Pro Pro Ala Tyr Ile Glu Glu Phe Leu 20 25 30 Gln Gln Tyr Asn His Tyr Lys Ser Asn Val Glu Ile Phe Lys Leu Gln 35 40 45 Pro Asn Lys Pro Ser Lys Glu Leu Ala Glu Leu Val Met Phe Met Ala 50 55 60 Gln Ile Ser His Cys Tyr Pro Glu Tyr Leu Ser Asn Phe Pro Gln Glu 65 70 75 80 Val Lys Asp Leu Leu Ser Cys Asn His Thr Val Leu Asp Pro Asp Leu 85 90 95 Arg Met Thr Phe Cys Lys Ala Leu Ile Leu Leu Arg Asn Lys Asn Leu 100 105 110 Ile Asn Pro Ser Ser Leu Leu Glu Leu Phe Phe Glu Leu Phe Arg Cys 115 120 125 His Asp Lys Leu Leu Arg Lys Thr Leu Tyr Thr His Ile Val Thr Asp 130 135 140 Ile Lys Asn Ile Asn Ala Lys His Lys Asn Asn Lys Val Asn Val Val 145 150 155 160 Leu Gln Asn Phe Met Tyr Thr Met Leu Arg Asp Ser Asn Ala Thr Ala 165 170 175 Ala Lys Met Ser Leu Asp Val Met Ile Glu Leu Tyr Arg Arg Asn Ile 180 185 190 Trp Asn Asp Ala Lys Thr Val Asn Val Ile Thr Thr Ala Cys Phe Ser 195 200 205 Lys Val Thr Lys Ile Leu Val Ala Ala Leu Thr Phe Phe Leu Gly Lys 210 215 220 Asp Glu Asp Glu Lys Gln Asp Ser Asp Ser Glu Ser Glu Asp Asp Gly 225 230 235 240 Pro Thr Ala Arg Asp Leu Leu Val Gln Tyr Ala Thr Gly Lys Lys Ser 245 250 255 Ser Lys Asn Lys Lys Lys Leu Glu Lys Ala Met Lys Val Leu Lys Lys 260 265 270 Gln Lys Lys Lys Lys Lys Pro Glu Val Phe Asn Phe Ser Ala Ile His 275 280 285 Leu Ile His Asp Pro Gln Asp Phe Ala Glu Lys Leu Leu Lys Gln Leu 290 295 300 Glu Cys Cys Lys Glu Arg Phe Glu Val Lys Met Met Leu Met Asn Leu 305 310 315 320 Ile Ser Arg Leu Val Gly Ile His Glu Leu Phe Leu Phe Asn Phe Tyr 325 330 335 Pro Phe Leu Gln Arg Phe Leu Gln Pro His Gln Arg Glu Val Thr Lys 340 345 350 Ile Leu Leu Phe Ala Ala Gln Ala Ser His His Leu Val Pro Pro Glu 355 360 365 Ile Ile Gln Ser Leu Leu Met Thr Val Ala Asn Asn Phe Val Thr Asp 370 375 380 Lys Asn Ser Gly Glu Val Met Thr Val Gly Ile Asn Ala Ile Lys Glu 385 390 395 400 Ile Thr Ala Arg Cys Pro Leu Ala Met Thr Glu Glu Leu Leu Gln Asp 405 410 415 Leu Ala Gln Tyr Lys Thr His Lys Asp Lys Asn Val Met Met Ser Ala 420 425 430 Arg Thr Leu Ile His Leu Phe Arg Thr Leu Asn Pro Gln Met Leu Gln 435 440 445 Lys Lys Phe Arg Gly Lys Pro Thr Glu Ala Ser Ile Glu Ala Arg Val 450 455 460 Gln Glu Tyr Gly Glu Leu Asp Ala Lys Asp Tyr Ile Pro Gly Ala Glu 465 470 475 480 Val Leu Glu Val Glu Lys Glu Glu Asn Ala Glu Asn Asp Glu Asp Gly 485 490 495 Trp Glu Ser Thr Ser Leu Ser Glu Glu Glu Asp Ala Asp Gly Glu Trp 500 505 510 Ile Asp Val Gln His Ser Ser Asp Glu Glu Gln Gln Glu Ile Ser Lys 515 520 525 Lys Leu Asn Ser Met Pro Met Glu Glu Arg Lys Ala Lys Ala Ala Ala 530 535 540 Ile Ser Thr Ser Arg Val Leu Thr Gln Glu Asp Phe Gln Lys Ile Arg 545 550 555 560 Met Ala Gln Met Arg Lys Glu Leu Asp Ala Ala Pro Gly Lys Ser Gln 565 570 575 Lys Arg Lys Tyr Ile Glu Ile Asp Ser Asp Glu Glu Pro Arg Gly Glu 580 585 590 Leu Leu Ser Leu Arg Asp Ile Glu Arg Leu His Lys Lys Pro Lys Ser 595 600 605 Asp Lys Glu Thr Arg Leu Ala Thr Ala Met Ala Gly Lys Thr Asp Arg 610 615 620 Lys Glu Phe Val Arg Lys Lys Thr Lys Thr Asn Pro Phe Ser Ser Ser 625 630 635 640 Thr Asn Lys Glu Lys Lys Lys Gln Lys Asn Phe Met Met Met Arg Tyr 645 650 655 Ser Gln Asn Val Arg Ser Lys Asn Lys Arg Ser Phe Arg Glu Lys Gln 660 665 670 Leu Ala Leu Arg Asp Ala Leu Leu Lys Lys Arg Lys Arg Met Lys 675 680 685 <210> 333 <211> 371 <212> PRT <213> homo sapiens <400> 333 Met Trp Arg Ser Leu Gly Leu Ala Leu Ala Leu Cys Leu Leu Pro Ser 1 5 10 15 Gly Gly Thr Glu Ser Gln Asp Gln Ser Ser Leu Cys Lys Gln Pro Pro 20 25 30 Ala Trp Ser Ile Arg Asp Gln Asp Pro Met Leu Asn Ser Asn Gly Ser 35 40 45 Val Thr Val Val Ala Leu Leu Gln Ala Ser Tyr Leu Cys Ile Leu Gln 50 55 60 Ala Ser Lys Leu Glu Asp Leu Arg Val Lys Leu Lys Lys Glu Gly Tyr 65 70 75 80 Ser Asn Ile Ser Tyr Ile Val Val Asn His Gln Gly Ile Ser Ser Arg 85 90 95 Leu Lys Tyr Thr His Leu Lys Asn Lys Val Ser Glu His Ile Pro Val 100 105 110 Tyr Gln Gln Glu Glu Asn Gln Thr Asp Val Trp Thr Leu Leu Asn Gly 115 120 125 Ser Lys Asp Asp Phe Leu Ile Tyr Asp Arg Cys Gly Arg Leu Val Tyr 130 135 140 His Leu Gly Leu Pro Phe Ser Phe Leu Thr Phe Pro Tyr Val Glu Glu 145 150 155 160 Ala Ile Lys Ile Ala Tyr Cys Glu Lys Lys Cys Gly Asn Cys Ser Leu 165 170 175 Thr Thr Leu Lys Asp Glu Asp Phe Cys Lys Arg Val Ser Leu Ala Thr 180 185 190 Val Asp Lys Thr Val Glu Thr Pro Ser Pro His Tyr His His Glu His 195 200 205 His His Asn His Gly His Gln His Leu Gly Ser Ser Glu Leu Ser Glu 210 215 220 Asn Gln Gln Pro Gly Ala Pro Asn Ala Pro Thr His Pro Ala Pro Pro 225 230 235 240 Gly Leu His His His His Lys His Lys Gly Gln His Arg Gln Gly His 245 250 255 Pro Glu Asn Arg Asp Met Pro Ala Ser Glu Asp Leu Gln Asp Leu Gln 260 265 270 Lys Lys Leu Cys Arg Lys Arg Cys Ile Asn Gln Leu Leu Cys Lys Leu 275 280 285 Pro Thr Asp Ser Glu Leu Ala Pro Arg Ser Cys Cys His Cys Arg His 290 295 300 Leu Ile Phe Glu Lys Thr Gly Ser Ala Ile Thr Gln Cys Lys Glu Asn 305 310 315 320 Leu Pro Ser Leu Cys Ser Gln Gly Leu Arg Ala Glu Glu Asn Ile Thr 325 330 335 Glu Ser Cys Gln Arg Leu Pro Pro Ala Ala Gln Ile Ser Gln Gln Leu 340 345 350 Ile Pro Thr Glu Ala Ser Ala Ser Arg Lys Asn Gln Ala Lys Lys Glu 355 360 365 Pro Ser Asn 370 <210> 334 <211> 299 <212> PRT <213> homo sapiens <400> 334 Met Pro Gly Arg Leu Leu Arg Gly Leu Trp Gln Arg Trp Arg Arg Tyr 1 5 10 15 Lys Tyr Arg Phe Val Pro Trp Ile Ala Leu Asn Leu Ser His Asn Pro 20 25 30 Arg Thr Leu Arg Tyr Val Pro Glu Glu Ser Lys Asp Lys Val Ile Ser 35 40 45 Asp Glu Asp Val Leu Gly Thr Leu Leu Lys Val Phe Gln Ala Leu Phe 50 55 60 Leu Asn Asp Phe Asn Lys Gln Ser Glu Ile Leu Ser Met Leu Pro Glu 65 70 75 80 Ser Val Lys Ser Lys Tyr Gln Asp Leu Leu Ala Val Glu His Gln Gly 85 90 95 Val Lys Leu Leu Glu Asn Arg His Gln Gln Gln Ser Thr Phe Lys Pro 100 105 110 Glu Glu Ile Leu Tyr Lys Thr Leu Gly Phe Ser Val Ala Gln Ala Thr 115 120 125 Ser Ser Leu Ile Ser Ala Gly Lys Gly Val Phe Val Thr Lys Gly Leu 130 135 140 Val Pro Lys Gly Ala Val Val Ser Met Tyr Pro Gly Thr Val Tyr Gln 145 150 155 160 Lys Tyr Glu Pro Ile Phe Phe Gln Ser Ile Gly Asn Pro Phe Ile Phe 165 170 175 Arg Cys Leu Asp Gly Val Leu Ile Asp Gly Asn Asp Lys Gly Ile Ser 180 185 190 Lys Val Val Tyr Arg Ser Cys Asn Gly Arg Asp Arg Leu Gly Pro Leu 195 200 205 Lys Met Ser Asp Ser Thr Trp Leu Thr Ser Glu Ile His Asn Pro Leu 210 215 220 Ala Val Gly Gln Tyr Val Asn Asn Cys Ser Asn Asp Arg Ala Ala Asn 225 230 235 240 Val Cys Tyr Gln Glu Phe Asp Val Pro Ala Val Phe Pro Ile Glu Leu 245 250 255 Lys Gln Tyr Leu Pro Asn Ile Ala Tyr Ser Tyr Asp Lys Gln Ser Pro 260 265 270 Leu Arg Cys Val Val Leu Val Ala Leu Arg Asp Ile Asn Gln Gly Glu 275 280 285 Glu Leu Phe Ser Asn Tyr Tyr Thr Ile Val Ser 290 295 <210> 335 <211> 396 <212> PRT <213> homo sapiens <400> 335 Met Leu Pro Leu Leu Leu Leu Pro Leu Leu Trp Gly Gly Ser Leu Gln 1 5 10 15 Glu Lys Pro Val Tyr Glu Leu Gln Val Gln Lys Ser Val Thr Val Gln 20 25 30 Glu Gly Leu Cys Val Leu Val Pro Cys Ser Phe Ser Tyr Pro Trp Arg 35 40 45 Ser Trp Tyr Ser Ser Pro Pro Leu Tyr Val Tyr Trp Phe Arg Asp Gly 50 55 60 Glu Ile Pro Tyr Tyr Ala Glu Val Val Ala Thr Asn Asn Pro Asp Arg 65 70 75 80 Arg Val Lys Pro Glu Thr Gln Gly Arg Phe Arg Leu Leu Gly Asp Val 85 90 95 Gln Lys Lys Asn Cys Ser Leu Ser Ile Gly Asp Ala Arg Met Glu Asp 100 105 110 Thr Gly Ser Tyr Phe Phe Arg Val Glu Arg Gly Arg Asp Val Lys Tyr 115 120 125 Ser Tyr Gln Gln Asn Lys Leu Asn Leu Glu Val Thr Ala Leu Ile Glu 130 135 140 Lys Pro Asp Ile His Phe Leu Glu Pro Leu Glu Ser Gly Arg Pro Thr 145 150 155 160 Arg Leu Ser Cys Ser Leu Pro Gly Ser Cys Glu Ala Gly Pro Pro Leu 165 170 175 Thr Phe Ser Trp Thr Gly Asn Ala Leu Ser Pro Leu Asp Pro Glu Thr 180 185 190 Thr Arg Ser Ser Glu Leu Thr Leu Thr Pro Arg Pro Glu Asp His Gly 195 200 205 Thr Asn Leu Thr Cys Gln Val Lys Arg Gln Gly Ala Gln Val Thr Thr 210 215 220 Glu Arg Thr Val Gln Leu Asn Val Ser Tyr Ala Pro Gln Asn Leu Ala 225 230 235 240 Ile Ser Ile Phe Phe Arg Asn Gly Thr Gly Thr Ala Leu Arg Ile Leu 245 250 255 Ser Asn Gly Met Ser Val Pro Ile Gln Glu Gly Gln Ser Leu Phe Leu 260 265 270 Ala Cys Thr Val Asp Ser Asn Pro Pro Ala Ser Leu Ser Trp Phe Arg 275 280 285 Glu Gly Lys Ala Leu Asn Pro Ser Gln Thr Ser Met Ser Gly Thr Leu 290 295 300 Glu Leu Pro Asn Ile Gly Ala Arg Glu Gly Gly Glu Phe Thr Cys Arg 305 310 315 320 Val Gln His Pro Leu Gly Ser Gln His Leu Ser Phe Ile Leu Ser Val 325 330 335 Gln Arg Ser Ser Ser Ser Cys Ile Cys Val Thr Glu Lys Gln Gln Gly 340 345 350 Ser Trp Pro Leu Val Leu Thr Leu Ile Arg Gly Ala Leu Met Gly Ala 355 360 365 Gly Phe Leu Leu Thr Tyr Gly Leu Thr Trp Ile Tyr Tyr Thr Arg Cys 370 375 380 Gly Gly Pro Gln Gln Ser Arg Ala Glu Arg Pro Gly 385 390 395 <210> 336 <211> 359 <212> PRT <213> homo sapiens <400> 336 Met Gln Ala Ala Ala Leu Pro Glu Glu Ile Arg Trp Leu Leu Glu Asp 1 5 10 15 Ala Glu Glu Phe Leu Ala Glu Gly Leu Arg Asn Glu Asn Leu Ser Ala 20 25 30 Val Ala Arg Asp His Arg Asp His Ile Leu Arg Gly Phe Gln Gln Ile 35 40 45 Lys Ala Arg Tyr Tyr Trp Asp Phe Gln Pro Gln Gly Gly Asp Ile Gly 50 55 60 Gln Asp Ser Ser Asp Asp Asn His Ser Gly Thr Leu Gly Leu Ser Leu 65 70 75 80 Thr Ser Asp Ala Pro Phe Leu Ser Asp Tyr Gln Asp Glu Gly Met Glu 85 90 95 Asp Ile Val Lys Gly Ala Gln Glu Leu Asp Asn Val Ile Lys Gln Gly 100 105 110 Tyr Leu Glu Lys Lys Ser Lys Asp His Ser Phe Phe Gly Ser Glu Trp 115 120 125 Gln Lys Arg Trp Cys Val Val Ser Arg Gly Leu Phe Tyr Tyr Tyr Ala 130 135 140 Asn Glu Lys Ser Lys Gln Pro Lys Gly Thr Phe Leu Ile Lys Gly Tyr 145 150 155 160 Gly Val Arg Met Ala Pro His Leu Arg Arg Asp Ser Lys Lys Glu Ser 165 170 175 Cys Phe Glu Leu Thr Ser Gln Asp Arg Arg Ser Tyr Glu Phe Thr Ala 180 185 190 Thr Ser Pro Ala Glu Ala Arg Asp Trp Val Asp Gln Ile Ser Phe Leu 195 200 205 Leu Lys Asp Leu Ser Ser Leu Thr Ile Pro Tyr Glu Glu Asp Glu Glu 210 215 220 Glu Glu Glu Lys Glu Glu Thr Tyr Asp Asp Ile Asp Gly Phe Asp Ser 225 230 235 240 Pro Ser Cys Gly Ser Gln Cys Arg Pro Thr Ile Leu Pro Gly Ser Val 245 250 255 Gly Ile Lys Glu Pro Thr Glu Glu Lys Glu Glu Glu Asp Ile Tyr Glu 260 265 270 Val Leu Pro Asp Glu Glu His Asp Leu Glu Glu Asp Glu Ser Gly Thr 275 280 285 Arg Arg Lys Gly Val Asp Tyr Ala Ser Tyr Tyr Gln Gly Leu Trp Asp 290 295 300 Cys His Gly Asp Gln Pro Asp Glu Leu Ser Phe Gln Arg Gly Asp Leu 305 310 315 320 Ile Arg Ile Leu Ser Lys Glu Tyr Asn Met Tyr Gly Trp Trp Val Gly 325 330 335 Glu Leu Asn Ser Leu Val Gly Ile Val Pro Lys Glu Tyr Leu Thr Thr 340 345 350 Ala Phe Glu Val Glu Glu Arg 355 <210> 337 <211> 470 <212> PRT <213> homo sapiens <400> 337 Met Ser Leu Leu Gly Arg Asp Tyr Asn Ser Glu Leu Asn Ser Leu Asp 1 5 10 15 Asn Gly Pro Gln Ser Pro Ser Glu Ser Ser Ser Ser Ile Thr Ser Glu 20 25 30 Asn Val His Pro Ala Gly Glu Ala Gly Leu Ser Met Met Gln Thr Leu 35 40 45 Ile His Leu Leu Lys Cys Asn Ile Gly Thr Gly Leu Leu Gly Leu Pro 50 55 60 Leu Ala Ile Lys Asn Ala Gly Leu Leu Val Gly Pro Val Ser Leu Leu 65 70 75 80 Ala Ile Gly Val Leu Thr Val His Cys Met Val Ile Leu Leu Asn Cys 85 90 95 Ala Gln His Leu Ser Gln Arg Leu Gln Lys Thr Phe Val Asn Tyr Gly 100 105 110 Glu Ala Thr Met Tyr Gly Leu Glu Thr Cys Pro Asn Thr Trp Leu Arg 115 120 125 Ala His Ala Val Trp Gly Arg Tyr Thr Val Ser Phe Leu Leu Val Ile 130 135 140 Thr Gln Leu Gly Phe Cys Ser Val Tyr Phe Met Phe Met Ala Asp Asn 145 150 155 160 Leu Gln Gln Met Val Glu Lys Ala His Val Thr Ser Asn Ile Cys Gln 165 170 175 Pro Arg Glu Ile Leu Thr Leu Thr Pro Ile Leu Asp Ile Arg Phe Tyr 180 185 190 Met Leu Ile Ile Leu Pro Phe Leu Ile Leu Leu Val Phe Ile Gln Asn 195 200 205 Leu Lys Val Leu Ser Val Phe Ser Thr Leu Ala Asn Ile Thr Thr Leu 210 215 220 Gly Ser Met Ala Leu Ile Phe Glu Tyr Ile Met Glu Gly Ile Pro Tyr 225 230 235 240 Pro Ser Asn Leu Pro Leu Met Ala Asn Trp Lys Thr Phe Leu Leu Phe 245 250 255 Phe Gly Thr Ala Ile Phe Thr Phe Glu Gly Val Gly Met Val Leu Pro 260 265 270 Leu Lys Asn Gln Met Lys His Pro Gln Gln Phe Ser Phe Val Leu Tyr 275 280 285 Leu Gly Met Ser Ile Val Ile Ile Leu Tyr Ile Leu Leu Gly Thr Leu 290 295 300 Gly Tyr Met Lys Phe Gly Ser Asp Thr Gln Ala Ser Ile Thr Leu Asn 305 310 315 320 Leu Pro Asn Cys Trp Leu Tyr Gln Ser Val Lys Leu Met Tyr Ser Ile 325 330 335 Gly Ile Phe Phe Thr Tyr Ala Leu Gln Phe His Val Pro Ala Glu Ile 340 345 350 Ile Ile Pro Phe Ala Ile Ser Gln Val Ser Glu Ser Trp Ala Leu Phe 355 360 365 Val Asp Leu Ser Val Arg Ser Ala Leu Val Cys Leu Thr Cys Val Ser 370 375 380 Ala Ile Leu Ile Pro Arg Leu Asp Leu Val Ile Ser Leu Val Gly Ser 385 390 395 400 Val Ser Ser Ser Ala Leu Ala Leu Ile Ile Pro Ala Leu Leu Glu Ile 405 410 415 Val Ile Phe Tyr Ser Glu Asp Met Ser Cys Val Thr Ile Ala Lys Asp 420 425 430 Ile Met Ile Ser Ile Val Gly Leu Leu Gly Cys Ile Phe Gly Thr Tyr 435 440 445 Gln Ala Leu Tyr Glu Leu Pro Gln Pro Ile Ser His Ser Met Ala Asn 450 455 460 Ser Thr Gly Val His Ala 465 470 <210> 338 <211> 973 <212> PRT <213> homo sapiens <400> 338 Met Tyr Asn Met Arg Arg Leu Ser Leu Ser Pro Thr Phe Ser Met Gly 1 5 10 15 Phe His Leu Leu Val Thr Val Ser Leu Leu Phe Ser His Val Asp His 20 25 30 Val Ile Ala Glu Thr Glu Met Glu Gly Glu Gly Asn Glu Thr Gly Glu 35 40 45 Cys Thr Gly Ser Tyr Tyr Cys Lys Lys Gly Val Ile Leu Pro Ile Trp 50 55 60 Glu Pro Gln Asp Pro Ser Phe Gly Asp Lys Ile Ala Arg Ala Thr Val 65 70 75 80 Tyr Phe Val Ala Met Val Tyr Met Phe Leu Gly Val Ser Ile Ile Ala 85 90 95 Asp Arg Phe Met Ser Ser Ile Glu Val Ile Thr Ser Gln Glu Lys Glu 100 105 110 Ile Thr Ile Lys Lys Pro Asn Gly Glu Thr Thr Lys Thr Thr Val Arg 115 120 125 Ile Trp Asn Glu Thr Val Ser Asn Leu Thr Leu Met Ala Leu Gly Ser 130 135 140 Ser Ala Pro Glu Ile Leu Leu Ser Val Ile Glu Val Cys Gly His Asn 145 150 155 160 Phe Thr Ala Gly Asp Leu Gly Pro Ser Thr Ile Val Gly Ser Ala Ala 165 170 175 Phe Asn Met Phe Ile Ile Ile Ala Leu Cys Val Tyr Val Val Pro Asp 180 185 190 Gly Glu Thr Arg Lys Ile Lys His Leu Arg Val Phe Phe Val Thr Ala 195 200 205 Ala Trp Ser Ile Phe Ala Tyr Thr Trp Leu Tyr Ile Ile Leu Ser Val 210 215 220 Ile Ser Pro Gly Val Val Glu Val Trp Glu Gly Leu Leu Thr Phe Phe 225 230 235 240 Phe Phe Pro Ile Cys Val Val Phe Ala Trp Val Ala Asp Arg Arg Leu 245 250 255 Leu Phe Tyr Lys Tyr Val Tyr Lys Arg Tyr Arg Ala Gly Lys Gln Arg 260 265 270 Gly Met Ile Ile Glu His Glu Gly Asp Arg Pro Ser Ser Lys Thr Glu 275 280 285 Ile Glu Met Asp Gly Lys Val Val Asn Ser His Val Glu Asn Phe Leu 290 295 300 Asp Gly Ala Leu Val Leu Glu Val Asp Glu Arg Asp Gln Asp Asp Glu 305 310 315 320 Glu Ala Arg Arg Glu Met Ala Arg Ile Leu Lys Glu Leu Lys Gln Lys 325 330 335 His Pro Asp Lys Glu Ile Glu Gln Leu Ile Glu Leu Ala Asn Tyr Gln 340 345 350 Val Leu Ser Gln Gln Gln Lys Ser Arg Ala Phe Tyr Arg Ile Gln Ala 355 360 365 Thr Arg Leu Met Thr Gly Ala Gly Asn Ile Leu Lys Arg His Ala Ala 370 375 380 Asp Gln Ala Arg Lys Ala Val Ser Met His Glu Val Asn Thr Glu Val 385 390 395 400 Thr Glu Asn Asp Pro Val Ser Lys Ile Phe Phe Glu Gln Gly Thr Tyr 405 410 415 Gln Cys Leu Glu Asn Cys Gly Thr Val Ala Leu Thr Ile Ile Arg Arg 420 425 430 Gly Gly Asp Leu Thr Asn Thr Val Phe Val Asp Phe Arg Thr Glu Asp 435 440 445 Gly Thr Ala Asn Ala Gly Ser Asp Tyr Glu Phe Thr Glu Gly Thr Val 450 455 460 Val Phe Lys Pro Gly Asp Thr Gln Lys Glu Ile Arg Val Gly Ile Ile 465 470 475 480 Asp Asp Asp Ile Phe Glu Glu Asp Glu Asn Phe Leu Val His Leu Ser 485 490 495 Asn Val Lys Val Ser Ser Glu Ala Ser Glu Asp Gly Ile Leu Glu Ala 500 505 510 Asn His Val Ser Thr Leu Ala Cys Leu Gly Ser Pro Ser Thr Ala Thr 515 520 525 Val Thr Ile Phe Asp Asp Asp His Ala Gly Ile Phe Thr Phe Glu Glu 530 535 540 Pro Val Thr His Val Ser Glu Ser Ile Gly Ile Met Glu Val Lys Val 545 550 555 560 Leu Arg Thr Ser Gly Ala Arg Gly Asn Val Ile Val Pro Tyr Lys Thr 565 570 575 Ile Glu Gly Thr Ala Arg Gly Gly Gly Glu Asp Phe Glu Asp Thr Cys 580 585 590 Gly Glu Leu Glu Phe Gln Asn Asp Glu Ile Val Lys Thr Ile Ser Val 595 600 605 Lys Val Ile Asp Asp Glu Glu Tyr Glu Lys Asn Lys Thr Phe Phe Leu 610 615 620 Glu Ile Gly Glu Pro Arg Leu Val Glu Met Ser Glu Lys Lys Ala Leu 625 630 635 640 Leu Leu Asn Glu Leu Gly Gly Phe Thr Ile Thr Gly Lys Tyr Leu Phe 645 650 655 Gly Gln Pro Val Phe Arg Lys Val His Ala Arg Glu His Pro Ile Leu 660 665 670 Ser Thr Val Ile Thr Ile Ala Asp Glu Tyr Asp Asp Lys Gln Pro Leu 675 680 685 Thr Ser Lys Glu Glu Glu Glu Arg Arg Ile Ala Glu Met Gly Arg Pro 690 695 700 Ile Leu Gly Glu His Thr Lys Leu Glu Val Ile Ile Glu Glu Ser Tyr 705 710 715 720 Glu Phe Lys Ser Thr Val Asp Lys Leu Ile Lys Lys Thr Asn Leu Ala 725 730 735 Leu Val Val Gly Thr Asn Ser Trp Arg Glu Gln Phe Ile Glu Ala Ile 740 745 750 Thr Val Ser Ala Gly Glu Asp Asp Asp Asp Asp Glu Cys Gly Glu Glu 755 760 765 Lys Leu Pro Ser Cys Phe Asp Tyr Val Met His Phe Leu Thr Val Phe 770 775 780 Trp Lys Val Leu Phe Ala Phe Val Pro Pro Thr Glu Tyr Trp Asn Gly 785 790 795 800 Trp Ala Cys Phe Ile Val Ser Ile Leu Met Ile Gly Leu Leu Thr Ala 805 810 815 Phe Ile Gly Asp Leu Ala Ser His Phe Gly Cys Thr Ile Gly Leu Lys 820 825 830 Asp Ser Val Thr Ala Val Val Phe Val Ala Leu Gly Thr Ser Val Pro 835 840 845 Asp Thr Phe Ala Ser Lys Val Ala Ala Thr Gln Asp Gln Tyr Ala Asp 850 855 860 Ala Ser Ile Gly Asn Val Thr Gly Ser Asn Ala Val Asn Val Phe Leu 865 870 875 880 Gly Ile Gly Val Ala Trp Ser Ile Ala Ala Ile Tyr His Ala Ala Asn 885 890 895 Gly Glu Gln Phe Lys Val Ser Pro Gly Thr Leu Ala Phe Ser Val Thr 900 905 910 Leu Phe Thr Ile Phe Ala Phe Ile Asn Val Gly Val Leu Leu Tyr Arg 915 920 925 Arg Arg Pro Glu Ile Gly Gly Glu Leu Gly Gly Pro Arg Thr Ala Lys 930 935 940 Leu Leu Thr Ser Cys Leu Phe Val Leu Leu Trp Leu Leu Tyr Ile Phe 945 950 955 960 Phe Ser Ser Leu Glu Ala Tyr Cys His Ile Lys Gly Phe 965 970 <210> 339 <211> 724 <212> PRT <213> homo sapiens <400> 339 Met Lys Ser Ala Lys Gly Ile Glu Asn Leu Ala Phe Val Pro Ser Ser 1 5 10 15 Pro Asp Ile Leu Arg Arg Leu Ser Ala Ser Pro Ser Gln Ile Glu Val 20 25 30 Ser Ala Leu Ser Ser Asp Pro Gln Arg Glu Asn Ser Gln Pro Gln Glu 35 40 45 Leu Gln Lys Pro Gln Glu Pro Gln Lys Ser Pro Glu Pro Ser Leu Pro 50 55 60 Ser Ala Pro Pro Asn Val Ser Glu Glu Lys Leu Arg Ser Leu Ser Leu 65 70 75 80 Ser Glu Phe Glu Glu Gly Ser Tyr Gly Trp Arg Asn Phe His Pro Gln 85 90 95 Cys Leu Gln Arg Cys Asn Thr Pro Gly Gly Phe Leu Leu His Tyr Cys 100 105 110 Leu Leu Ala Val Thr Gln Gly Ile Val Val Asn Gly Leu Val Asn Ile 115 120 125 Ser Ile Ser Thr Val Glu Lys Arg Tyr Glu Met Lys Ser Ser Leu Thr 130 135 140 Gly Leu Ile Ser Ser Ser Tyr Asp Ile Ser Phe Cys Leu Leu Ser Leu 145 150 155 160 Phe Val Ser Phe Phe Gly Glu Arg Gly His Lys Pro Arg Trp Leu Ala 165 170 175 Phe Ala Ala Phe Met Ile Gly Leu Gly Ala Leu Val Phe Ser Leu Pro 180 185 190 Gln Phe Phe Ser Gly Glu Tyr Lys Leu Gly Ser Leu Phe Glu Asp Thr 195 200 205 Cys Val Thr Thr Arg Asn Ser Thr Ser Cys Thr Ser Ser Thr Ser Ser 210 215 220 Leu Ser Asn Tyr Leu Tyr Val Phe Ile Leu Gly Gln Leu Leu Leu Gly 225 230 235 240 Ala Gly Gly Thr Pro Leu Tyr Thr Leu Gly Thr Ala Phe Leu Asp Asp 245 250 255 Ser Val Pro Thr His Lys Ser Ser Leu Tyr Ile Gly Thr Gly Tyr Ala 260 265 270 Met Ser Ile Leu Gly Pro Ala Ile Gly Tyr Val Leu Gly Gly Gln Leu 275 280 285 Leu Thr Ile Tyr Ile Asp Val Ala Met Gly Glu Ser Thr Asp Val Thr 290 295 300 Glu Asp Asp Pro Arg Trp Leu Gly Ala Trp Trp Ile Gly Phe Leu Leu 305 310 315 320 Ser Trp Ile Phe Ala Trp Ser Leu Ile Ile Pro Phe Ser Cys Phe Pro 325 330 335 Lys His Leu Pro Gly Thr Ala Glu Ile Gln Ala Gly Lys Thr Ser Gln 340 345 350 Ala His Gln Ser Asn Ser Asn Ala Asp Val Lys Phe Gly Lys Ser Ile 355 360 365 Lys Asp Phe Pro Ala Ala Leu Lys Asn Leu Met Lys Asn Ala Val Phe 370 375 380 Met Cys Leu Val Leu Ser Thr Ser Ser Glu Ala Leu Ile Thr Thr Gly 385 390 395 400 Phe Ala Thr Phe Leu Pro Lys Phe Ile Glu Asn Gln Phe Gly Leu Thr 405 410 415 Ser Ser Phe Ala Ala Thr Leu Gly Gly Ala Val Leu Ile Pro Gly Ala 420 425 430 Ala Leu Gly Gln Ile Leu Gly Gly Phe Leu Val Ser Lys Phe Arg Met 435 440 445 Thr Cys Lys Asn Thr Met Lys Phe Ala Leu Phe Thr Ser Gly Val Ala 450 455 460 Leu Thr Leu Ser Phe Val Phe Met Tyr Ala Lys Cys Glu Asn Glu Pro 465 470 475 480 Phe Ala Gly Val Ser Glu Ser Tyr Asn Gly Thr Gly Glu Leu Gly Asn 485 490 495 Leu Ile Ala Pro Cys Asn Ala Asn Cys Asn Cys Ser Arg Ser Tyr Tyr 500 505 510 Tyr Pro Val Cys Gly Asp Gly Val Gln Tyr Phe Ser Pro Cys Phe Ala 515 520 525 Gly Cys Ser Asn Pro Val Ala His Arg Lys Pro Lys Val Tyr Tyr Asn 530 535 540 Cys Ser Cys Ile Glu Arg Lys Thr Glu Ile Thr Ser Thr Ala Glu Thr 545 550 555 560 Phe Gly Phe Glu Ala Lys Ala Gly Lys Cys Glu Thr His Cys Ala Lys 565 570 575 Leu Pro Ile Phe Leu Cys Ile Phe Phe Ile Val Ile Ile Phe Thr Phe 580 585 590 Met Ala Gly Thr Pro Ile Thr Val Ser Ile Leu Arg Cys Val Asn His 595 600 605 Arg Gln Arg Ser Leu Ala Leu Gly Ile Gln Phe Met Val Leu Arg Leu 610 615 620 Leu Gly Thr Ile Pro Gly Pro Ile Ile Phe Gly Phe Thr Ile Asp Ser 625 630 635 640 Thr Cys Ile Leu Trp Asp Ile Asn Asp Cys Gly Ile Lys Gly Ala Cys 645 650 655 Trp Ile Tyr Asp Asn Ile Lys Met Ala His Met Leu Val Ala Ile Ser 660 665 670 Val Thr Cys Lys Val Ile Thr Met Phe Phe Asn Gly Phe Ala Ile Phe 675 680 685 Leu Tyr Lys Pro Pro Pro Ser Ala Thr Asp Val Ser Phe His Lys Glu 690 695 700 Asn Ala Val Val Thr Asn Val Leu Ala Glu Gln Asp Leu Asn Lys Ile 705 710 715 720 Val Lys Glu Gly <210> 340 <211> 238 <212> PRT <213> homo sapiens <400> 340 Met Ser Glu Asp Leu Ala Lys Gln Leu Ala Ser Tyr Lys Ala Gln Leu 1 5 10 15 Gln Gln Val Glu Ala Ala Leu Ser Gly Asn Gly Glu Asn Glu Asp Leu 20 25 30 Leu Lys Leu Lys Lys Asp Leu Gln Glu Val Ile Glu Leu Thr Lys Asp 35 40 45 Leu Leu Ser Thr Gln Pro Ser Glu Thr Leu Ala Ser Ser Asp Ser Phe 50 55 60 Ala Ser Thr Gln Pro Thr His Ser Trp Lys Val Gly Asp Lys Cys Met 65 70 75 80 Ala Val Trp Ser Glu Asp Gly Gln Cys Tyr Glu Ala Glu Ile Glu Glu 85 90 95 Ile Asp Glu Glu Asn Gly Thr Ala Ala Ile Thr Phe Ala Gly Tyr Gly 100 105 110 Asn Ala Glu Val Thr Pro Leu Leu Asn Leu Lys Pro Val Glu Glu Gly 115 120 125 Arg Lys Ala Lys Glu Asp Ser Gly Asn Lys Pro Met Ser Lys Lys Glu 130 135 140 Met Ile Ala Gln Gln Arg Glu Tyr Lys Lys Lys Lys Ala Leu Lys Lys 145 150 155 160 Ala Gln Arg Ile Lys Glu Leu Glu Gln Glu Arg Glu Asp Gln Lys Val 165 170 175 Lys Trp Gln Gln Phe Asn Asn Arg Ala Tyr Ser Lys Asn Lys Lys Gly 180 185 190 Gln Val Lys Arg Ser Ile Phe Ala Ser Pro Glu Ser Val Thr Gly Lys 195 200 205 Val Gly Val Gly Thr Cys Gly Ile Ala Asp Lys Pro Met Thr Gln Tyr 210 215 220 Gln Asp Thr Ser Lys Tyr Asn Val Arg His Leu Met Pro Gln 225 230 235 <210> 341 <211> 436 <212> PRT <213> homo sapiens <400> 341 Met Leu Lys Val Ser Ala Val Leu Cys Val Cys Ala Ala Ala Trp Cys 1 5 10 15 Ser Gln Ser Leu Ala Ala Ala Ala Ala Val Ala Ala Ala Gly Gly Arg 20 25 30 Ser Asp Gly Gly Asn Phe Leu Asp Asp Lys Gln Trp Leu Thr Thr Ile 35 40 45 Ser Gln Tyr Asp Lys Glu Val Gly Gln Trp Asn Lys Phe Arg Asp Glu 50 55 60 Val Glu Asp Asp Tyr Phe Arg Thr Trp Ser Pro Gly Lys Pro Phe Asp 65 70 75 80 Gln Ala Leu Asp Pro Ala Lys Asp Pro Cys Leu Lys Met Lys Cys Ser 85 90 95 Arg His Lys Val Cys Ile Ala Gln Asp Ser Gln Thr Ala Val Cys Ile 100 105 110 Ser His Arg Arg Leu Thr His Arg Met Lys Glu Ala Gly Val Asp His 115 120 125 Arg Gln Trp Arg Gly Pro Ile Leu Ser Thr Cys Lys Gln Cys Pro Val 130 135 140 Val Tyr Pro Ser Pro Val Cys Gly Ser Asp Gly His Thr Tyr Ser Phe 145 150 155 160 Gln Cys Lys Leu Glu Tyr Gln Ala Cys Val Leu Gly Lys Gln Ile Ser 165 170 175 Val Lys Cys Glu Gly His Cys Pro Cys Pro Ser Asp Lys Pro Thr Ser 180 185 190 Thr Ser Arg Asn Val Lys Arg Ala Cys Ser Asp Leu Glu Phe Arg Glu 195 200 205 Val Ala Asn Arg Leu Arg Asp Trp Phe Lys Ala Leu His Glu Ser Gly 210 215 220 Ser Gln Asn Lys Lys Thr Lys Thr Leu Leu Arg Pro Glu Arg Ser Arg 225 230 235 240 Phe Asp Thr Ser Ile Leu Pro Ile Cys Lys Asp Ser Leu Gly Trp Met 245 250 255 Phe Asn Arg Leu Asp Thr Asn Tyr Asp Leu Leu Leu Asp Gln Ser Glu 260 265 270 Leu Arg Ser Ile Tyr Leu Asp Lys Asn Glu Gln Cys Thr Lys Ala Phe 275 280 285 Phe Asn Ser Cys Asp Thr Tyr Lys Asp Ser Leu Ile Ser Asn Asn Glu 290 295 300 Trp Cys Tyr Cys Phe Gln Arg Gln Gln Asp Pro Pro Cys Gln Thr Glu 305 310 315 320 Leu Ser Asn Ile Gln Lys Arg Gln Gly Val Lys Lys Leu Leu Gly Gln 325 330 335 Tyr Ile Pro Leu Cys Asp Glu Asp Gly Tyr Tyr Lys Pro Thr Gln Cys 340 345 350 His Gly Ser Val Gly Gln Cys Trp Cys Val Asp Arg Tyr Gly Asn Glu 355 360 365 Val Met Gly Ser Arg Ile Asn Gly Val Ala Asp Cys Ala Ile Asp Phe 370 375 380 Glu Ile Ser Gly Asp Phe Ala Ser Gly Asp Phe His Glu Trp Thr Asp 385 390 395 400 Asp Glu Asp Asp Glu Asp Asp Ile Met Asn Asp Glu Asp Glu Ile Glu 405 410 415 Asp Asp Asp Glu Asp Glu Gly Asp Asp Asp Asp Gly Gly Asp Asp His 420 425 430 Asp Val Tyr Ile 435 <210> 342 <211> 406 <212> PRT <213> homo sapiens <400> 342 Met Ile His Thr Asn Leu Lys Lys Lys Phe Ser Cys Cys Val Leu Val 1 5 10 15 Phe Leu Leu Phe Ala Val Ile Cys Val Trp Lys Glu Lys Lys Lys Gly 20 25 30 Ser Tyr Tyr Asp Ser Phe Lys Leu Gln Thr Lys Glu Phe Gln Val Leu 35 40 45 Lys Ser Leu Gly Lys Leu Ala Met Gly Ser Asp Ser Gln Ser Val Ser 50 55 60 Ser Ser Ser Thr Gln Asp Pro His Arg Gly Arg Gln Thr Leu Gly Ser 65 70 75 80 Leu Arg Gly Leu Ala Lys Ala Lys Pro Glu Ala Ser Phe Gln Val Trp 85 90 95 Asn Lys Asp Ser Ser Ser Lys Asn Leu Ile Pro Arg Leu Gln Lys Ile 100 105 110 Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys Val Ser Tyr Lys Gly 115 120 125 Pro Gly Pro Gly Ile Lys Phe Ser Ala Glu Ala Leu Arg Cys His Leu 130 135 140 Arg Asp His Val Asn Val Ser Met Val Glu Val Thr Asp Phe Pro Phe 145 150 155 160 Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys Glu Ser Ile Arg Thr 165 170 175 Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val Ser Ser Ala Gly Ser 180 185 190 Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile Asp Asp His Asp Ala Val 195 200 205 Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe Gln Gln Asp Val Gly 210 215 220 Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln Leu Val Thr Thr Glu 225 230 235 240 Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn Glu Gly Ile Leu Ile Val 245 250 255 Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro Lys Trp Tyr Gln Asn 260 265 270 Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr Tyr Arg Lys Leu His 275 280 285 Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln Met Pro Trp Glu Leu 290 295 300 Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu Ile Gln Pro Asn Pro 305 310 315 320 Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met Met Thr Leu Cys Asp 325 330 335 Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys Arg Lys Thr Asp Val 340 345 350 Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala Cys Thr Met Gly Ala 355 360 365 Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val Lys His Leu Asn Gln 370 375 380 Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys Ala Thr Leu Pro Gly 385 390 395 400 Phe Arg Thr Ile His Cys 405 <210> 343 <211> 436 <212> PRT <213> homo sapiens <400> 343 Met Asp Gln Pro Phe Thr Val Asn Ser Leu Lys Lys Leu Ala Ala Met 1 5 10 15 Pro Asp His Thr Asp Val Ser Leu Ser Pro Glu Glu Arg Val Arg Ala 20 25 30 Leu Ser Lys Leu Gly Cys Asn Ile Thr Ile Ser Glu Asp Ile Thr Pro 35 40 45 Arg Arg Tyr Phe Arg Ser Gly Val Glu Met Glu Arg Met Ala Ser Val 50 55 60 Tyr Leu Glu Glu Gly Asn Leu Glu Asn Ala Phe Val Leu Tyr Asn Lys 65 70 75 80 Phe Ile Thr Leu Phe Val Glu Lys Leu Pro Asn His Arg Asp Tyr Gln 85 90 95 Gln Cys Ala Val Pro Glu Lys Gln Asp Ile Met Lys Lys Leu Lys Glu 100 105 110 Ile Ala Phe Pro Arg Thr Asp Glu Leu Lys Asn Asp Leu Leu Lys Lys 115 120 125 Tyr Asn Val Glu Tyr Gln Glu Tyr Leu Gln Ser Lys Asn Lys Tyr Lys 130 135 140 Ala Glu Ile Leu Lys Lys Leu Glu His Gln Arg Leu Ile Glu Ala Glu 145 150 155 160 Arg Lys Arg Ile Ala Gln Met Arg Gln Gln Gln Leu Glu Ser Glu Gln 165 170 175 Phe Leu Phe Phe Glu Asp Gln Leu Lys Lys Gln Glu Leu Ala Arg Gly 180 185 190 Gln Met Arg Ser Gln Gln Thr Ser Gly Leu Ser Glu Gln Ile Asp Gly 195 200 205 Ser Ala Leu Ser Cys Phe Ser Thr His Gln Asn Asn Ser Leu Leu Asn 210 215 220 Val Phe Ala Asp Gln Pro Asn Lys Ser Asp Ala Thr Asn Tyr Ala Ser 225 230 235 240 His Ser Pro Pro Val Asn Arg Ala Leu Thr Pro Ala Ala Thr Leu Ser 245 250 255 Ala Val Gln Asn Leu Val Val Glu Gly Leu Arg Cys Val Val Leu Pro 260 265 270 Glu Asp Leu Cys His Lys Phe Leu Gln Leu Ala Glu Ser Asn Thr Val 275 280 285 Arg Gly Ile Glu Thr Cys Gly Ile Leu Cys Gly Lys Leu Thr His Asn 290 295 300 Glu Phe Thr Ile Thr His Val Ile Val Pro Lys Gln Ser Ala Gly Pro 305 310 315 320 Asp Tyr Cys Asp Met Glu Asn Val Glu Glu Leu Phe Asn Val Gln Asp 325 330 335 Gln His Asp Leu Leu Thr Leu Gly Trp Ile His Thr His Pro Thr Gln 340 345 350 Thr Ala Phe Leu Ser Ser Val Asp Leu His Thr His Cys Ser Tyr Gln 355 360 365 Leu Met Leu Pro Glu Ala Ile Ala Ile Val Cys Ser Pro Lys His Lys 370 375 380 Asp Thr Gly Ile Phe Arg Leu Thr Asn Ala Gly Met Leu Glu Val Ser 385 390 395 400 Ala Cys Lys Lys Lys Gly Phe His Pro His Thr Lys Glu Pro Arg Leu 405 410 415 Phe Ser Ile Cys Lys His Val Leu Val Lys Asp Ile Lys Ile Ile Val 420 425 430 Leu Asp Leu Arg 435 <210> 344 <211> 278 <212> PRT <213> homo sapiens <400> 344 Met Asp Lys Ser Gly Ile Asp Ser Leu Asp His Val Thr Ser Asp Ala 1 5 10 15 Val Glu Leu Ala Asn Arg Ser Asp Asn Ser Ser Asp Ser Ser Leu Phe 20 25 30 Lys Thr Gln Cys Ile Pro Tyr Ser Pro Lys Gly Glu Lys Arg Asn Pro 35 40 45 Ile Arg Lys Phe Val Arg Thr Pro Glu Ser Val His Ala Ser Asp Ser 50 55 60 Ser Ser Asp Ser Ser Phe Glu Pro Ile Pro Leu Thr Ile Lys Ala Ile 65 70 75 80 Phe Glu Arg Phe Lys Asn Arg Lys Lys Arg Tyr Lys Lys Lys Lys Lys 85 90 95 Arg Arg Tyr Gln Pro Thr Gly Arg Pro Arg Gly Arg Pro Glu Gly Arg 100 105 110 Arg Asn Pro Ile Tyr Ser Leu Ile Asp Lys Lys Lys Gln Phe Arg Ser 115 120 125 Arg Gly Ser Gly Phe Pro Phe Leu Glu Ser Glu Asn Glu Lys Asn Ala 130 135 140 Pro Trp Arg Lys Ile Leu Thr Phe Glu Gln Ala Val Ala Arg Gly Phe 145 150 155 160 Phe Asn Tyr Ile Glu Lys Leu Lys Tyr Glu His His Leu Lys Glu Ser 165 170 175 Leu Lys Gln Met Asn Val Gly Glu Asp Leu Glu Asn Glu Asp Phe Asp 180 185 190 Ser Arg Arg Tyr Lys Phe Leu Asp Asp Asp Gly Ser Ile Ser Pro Ile 195 200 205 Glu Glu Ser Thr Ala Glu Asp Glu Asp Ala Thr His Leu Glu Asp Asn 210 215 220 Glu Cys Asp Ile Lys Leu Ala Gly Asp Ser Phe Ile Val Ser Ser Glu 225 230 235 240 Phe Pro Val Arg Leu Ser Val Tyr Leu Glu Glu Glu Asp Ile Thr Glu 245 250 255 Glu Ala Ala Leu Ser Lys Lys Arg Ala Thr Lys Ala Lys Asn Thr Gly 260 265 270 Gln Arg Gly Leu Lys Met 275 <210> 345 <211> 317 <212> PRT <213> homo sapiens <400> 345 Met Gly Gly Val Ile Lys Ser Ile Phe Thr Phe Val Leu Ile Val Glu 1 5 10 15 Phe Ile Ile Gly Asn Leu Gly Asn Ser Phe Ile Ala Leu Val Asn Cys 20 25 30 Ile Asp Trp Val Lys Gly Arg Lys Ile Ser Ser Val Asp Arg Ile Leu 35 40 45 Thr Ala Leu Ala Ile Ser Arg Ile Ser Leu Val Trp Leu Ile Phe Gly 50 55 60 Ser Trp Cys Val Ser Val Phe Phe Pro Ala Leu Phe Ala Thr Glu Lys 65 70 75 80 Met Phe Arg Met Leu Thr Asn Ile Trp Thr Val Ile Asn His Phe Ser 85 90 95 Val Trp Leu Ala Thr Gly Leu Gly Thr Phe Tyr Phe Leu Lys Ile Ala 100 105 110 Asn Phe Ser Asn Ser Ile Phe Leu Tyr Leu Lys Trp Arg Val Lys Lys 115 120 125 Val Val Leu Val Leu Leu Leu Val Thr Ser Val Phe Leu Phe Leu Asn 130 135 140 Ile Ala Leu Ile Asn Ile His Ile Asn Ala Ser Ile Asn Gly Tyr Arg 145 150 155 160 Arg Asn Lys Thr Cys Ser Ser Asp Ser Ser Asn Phe Thr Arg Phe Ser 165 170 175 Ser Leu Ile Val Leu Thr Ser Thr Val Phe Ile Phe Ile Pro Phe Thr 180 185 190 Leu Ser Leu Ala Met Phe Leu Leu Leu Ile Phe Ser Met Trp Lys His 195 200 205 Arg Lys Lys Met Gln His Thr Val Lys Ile Ser Gly Asp Ala Ser Thr 210 215 220 Lys Ala His Arg Gly Val Lys Ser Val Ile Thr Phe Phe Leu Leu Tyr 225 230 235 240 Ala Ile Phe Ser Leu Ser Phe Phe Ile Ser Val Trp Thr Ser Glu Arg 245 250 255 Leu Glu Glu Asn Leu Ile Ile Leu Ser Gln Val Met Gly Met Ala Tyr 260 265 270 Pro Ser Cys His Ser Cys Val Leu Ile Leu Gly Asn Lys Lys Leu Arg 275 280 285 Gln Ala Ser Leu Ser Val Leu Leu Trp Leu Arg Tyr Met Phe Lys Asp 290 295 300 Gly Glu Pro Ser Gly His Lys Glu Phe Arg Glu Ser Ser 305 310 315 <210> 346 <211> 557 <212> PRT <213> homo sapiens <400> 346 Met Asp Gln Ser Arg Val Leu Leu Trp Val Lys Ala Glu Pro Phe Ile 1 5 10 15 Val Gly Ala Leu Gln Val Pro Pro Pro Ser Lys Phe Ser Leu His Tyr 20 25 30 Leu Arg Lys Ile Ser Thr Tyr Val Gln Ile Arg Ala Thr Glu Gly Ala 35 40 45 Tyr Pro Arg Leu Tyr Trp Ser Thr Trp Arg His Ile Ala Cys Gly Lys 50 55 60 Leu Gln Leu Ala Lys Asp Leu Ala Trp Leu Tyr Phe Glu Ile Phe Asp 65 70 75 80 Ser Leu Ser Met Lys Thr Pro Glu Glu Arg Leu Glu Trp Ser Glu Val 85 90 95 Leu Ser Asn Cys Met Ser Glu Glu Glu Val Glu Lys Gln Arg Asn Gln 100 105 110 Leu Ser Val Asp Thr Leu Gln Phe Leu Leu Phe Leu Tyr Ile Gln Gln 115 120 125 Leu Asn Lys Val Ser Leu Arg Thr Ser Leu Ile Gly Glu Glu Trp Pro 130 135 140 Ser Pro Arg Asn Lys Ser Gln Ser Pro Asp Leu Thr Glu Lys Ser Asn 145 150 155 160 Cys His Asn Lys Asn Trp Asn Asp Tyr Ser His Gln Ala Phe Val Tyr 165 170 175 Asp His Leu Ser Asp Leu Leu Glu Leu Leu Leu Asp Pro Lys Gln Leu 180 185 190 Thr Ala Ser Phe His Ser Thr His Ser Ser Leu Val Ser Arg Glu Ala 195 200 205 Val Val Ala Leu Ser Phe Leu Ile Glu Gly Thr Ile Ser Arg Ala Arg 210 215 220 Lys Ile Tyr Pro Leu His Glu Leu Ala Leu Trp Gln Pro Leu His Ala 225 230 235 240 Asp Ser Gly Phe Ser Lys Ile Ser Lys Thr Phe Ser Phe Tyr Lys Leu 245 250 255 Glu Thr Trp Leu Arg Ser Cys Leu Thr Gly Asn Pro Phe Gly Thr Ser 260 265 270 Ala Cys Leu Lys Ser Gly Lys Lys Leu Ala Trp Ala His Gln Val Glu 275 280 285 Gly Thr Thr Lys Arg Ala Lys Ile Ala Cys Asn Thr His Val Ala Pro 290 295 300 Arg Met His Arg Leu Val Val Met Ser Gln Val Tyr Lys Gln Thr Leu 305 310 315 320 Ala Lys Ser Ser Asp Thr Leu Ala Gly Ala His Val Lys Ile His Arg 325 330 335 Cys Asn Glu Ser Phe Ile Tyr Leu Leu Ser Pro Leu Arg Ser Val Thr 340 345 350 Ile Glu Lys Cys Arg Asn Ser Ile Phe Val Leu Gly Pro Val Gly Thr 355 360 365 Thr Leu His Leu His Ser Cys Asp Asn Val Lys Val Ile Ala Val Cys 370 375 380 His Arg Leu Ser Ile Ser Ser Thr Thr Gly Cys Ile Phe His Val Leu 385 390 395 400 Thr Pro Thr Arg Pro Leu Ile Leu Ser Gly Asn Gln Thr Val Thr Phe 405 410 415 Ala Pro Phe His Thr His Tyr Pro Met Leu Glu Asp His Met Ala Arg 420 425 430 Thr Gly Leu Ala Thr Val Pro Asn Tyr Trp Asp Asn Pro Met Val Val 435 440 445 Cys Arg Glu Asn Ser Asp Thr Arg Val Phe Gln Leu Leu Pro Pro Cys 450 455 460 Glu Phe Tyr Val Phe Ile Ile Pro Phe Glu Met Glu Gly Asp Thr Thr 465 470 475 480 Glu Ile Pro Gly Gly Leu Pro Ser Val Tyr Gln Lys Ala Leu Gly Gln 485 490 495 Arg Glu Gln Lys Ile Gln Ile Trp Gln Lys Thr Val Lys Glu Ala His 500 505 510 Leu Thr Lys Asp Gln Arg Lys Gln Phe Gln Val Leu Val Glu Asn Lys 515 520 525 Phe Tyr Glu Trp Leu Ile Asn Thr Gly His Arg Gln Gln Leu Asp Ser 530 535 540 Leu Val Pro Pro Ala Ala Gly Ser Lys Gln Ala Ala Gly 545 550 555 <210> 347 <211> 753 <212> PRT <213> homo sapiens <400> 347 Met Ala Ala Gly Ser Thr Thr Leu His Ala Val Glu Lys Leu Gln Val 1 5 10 15 Arg Leu Ala Thr Lys Thr Glu Pro Lys Lys Leu Glu Lys Tyr Leu Gln 20 25 30 Lys Leu Ser Ala Leu Pro Met Thr Ala Asp Ile Leu Ala Glu Thr Gly 35 40 45 Ile Arg Lys Thr Val Lys Arg Leu Arg Lys His Gln His Val Gly Asp 50 55 60 Phe Ala Arg Asp Leu Ala Ala Arg Trp Lys Lys Leu Val Leu Val Asp 65 70 75 80 Arg Asn Thr Arg Pro Gly Pro Gln Asp Pro Glu Glu Ser Ala Ser Arg 85 90 95 Gln Arg Phe Gly Glu Ala Leu Gln Asp Gln Glu Lys Ala Trp Gly Phe 100 105 110 Pro Glu Asn Ala Thr Ala Pro Arg Ser Pro Ser His Ser Pro Glu His 115 120 125 Arg Arg Thr Ala Arg Arg Thr Pro Pro Gly Gln Gln Arg Pro His Pro 130 135 140 Arg Ser His Ser Arg Glu Pro Arg Ala Glu Arg Lys Cys Pro Arg Ile 145 150 155 160 Ala Pro Ala Asp Ser Gly Arg Tyr Arg Ala Ser Pro Thr Arg Thr Ala 165 170 175 Pro Leu Arg Met Pro Glu Gly Pro Glu Pro Ala Ala Pro Gly Lys Gln 180 185 190 Pro Gly Arg Gly His Thr His Ala Ala Gln Gly Gly Pro Leu Leu Cys 195 200 205 Pro Gly Cys Gln Gly Gln Pro Gln Gly Lys Ala Val Val Ser His Ser 210 215 220 Lys Gly His Lys Ser Ser Arg Gln Glu Lys Arg Pro Leu Cys Ala Gln 225 230 235 240 Gly Asp Trp His Ser Pro Thr Leu Ile Arg Glu Lys Ser Cys Gly Ala 245 250 255 Cys Leu Arg Glu Glu Thr Pro Arg Met Pro Ser Trp Ala Ser Ala Arg 260 265 270 Asp Arg Gln Pro Ser Asp Phe Lys Thr Asp Lys Glu Gly Gly Gln Ala 275 280 285 Gly Ser Gly Gln Arg Val Pro Ala Leu Glu Glu Ala Pro Asp Ser His 290 295 300 Gln Lys Arg Pro Gln His Ser His Ser Asn Lys Lys Arg Pro Ser Leu 305 310 315 320 Asp Gly Arg Asp Pro Gly Asn Gly Thr His Gly Leu Ser Pro Glu Glu 325 330 335 Lys Glu Gln Leu Ser Asn Asp Arg Glu Thr Gln Glu Gly Lys Pro Pro 340 345 350 Thr Ala His Leu Asp Arg Thr Ser Val Ser Ser Leu Ser Glu Val Glu 355 360 365 Glu Val Asp Met Ala Glu Glu Phe Glu Gln Pro Thr Leu Ser Cys Glu 370 375 380 Lys Tyr Leu Thr Tyr Asp Gln Leu Arg Lys Gln Lys Lys Lys Thr Gly 385 390 395 400 Lys Ser Ala Thr Thr Ala Leu Gly Asp Lys Gln Arg Lys Ala Asn Glu 405 410 415 Ser Lys Gly Thr Arg Glu Ser Trp Asp Ser Ala Lys Lys Leu Pro Pro 420 425 430 Val Gln Glu Ser Gln Ser Glu Arg Leu Gln Ala Ala Gly Ala Asp Ser 435 440 445 Ala Gly Pro Lys Thr Val Pro Ser His Val Phe Ser Glu Leu Trp Asp 450 455 460 Leu Ser Glu Ala Trp Met Gln Ala Asn Tyr Asp Pro Leu Ser Asp Ser 465 470 475 480 Asp Ser Met Thr Ser Gln Ala Lys Pro Glu Ala Leu Ser Ser Pro Lys 485 490 495 Phe Arg Glu Glu Ala Ala Phe Pro Gly Arg Arg Val Asn Ala Lys Met 500 505 510 Pro Val Tyr Ser Gly Ser Arg Pro Ala Cys Gln Leu Gln Val Pro Thr 515 520 525 Leu Arg Gln Gln Cys Ala Gln Val Leu Arg Asn Asn Pro Asp Ala Leu 530 535 540 Ser Asp Val Gly Glu Val Pro Tyr Trp Val Leu Glu Pro Val Leu Glu 545 550 555 560 Gly Trp Arg Pro Asp Gln Leu Tyr Arg Arg Lys Lys Asp Asn His Ala 565 570 575 Leu Val Arg Glu Thr Asp Glu Leu Arg Arg Asn His Cys Phe Gln Asp 580 585 590 Phe Lys Glu Glu Lys Pro Gln Glu Asn Lys Thr Trp Arg Glu Gln Tyr 595 600 605 Leu Arg Leu Pro Asp Ala Pro Glu Gln Arg Leu Arg Val Met Thr Thr 610 615 620 Asn Ile Arg Ser Ala Arg Gly Asn Asn Pro Asn Gly Arg Glu Ala Lys 625 630 635 640 Met Ile Cys Phe Lys Ser Val Ala Lys Thr Pro Tyr Asp Thr Ser Arg 645 650 655 Arg Gln Glu Lys Ser Ala Gly Asp Ala Asp Pro Glu Asn Gly Glu Ile 660 665 670 Lys Pro Ala Ser Lys Pro Ala Gly Ser Ser His Thr Pro Ser Ser Gln 675 680 685 Ser Ser Ser Gly Gly Gly Arg Asp Ser Ser Ser Ser Ile Leu Arg Trp 690 695 700 Leu Pro Glu Lys Arg Ala Asn Pro Cys Leu Ser Ser Ser Asn Glu His 705 710 715 720 Ala Ala Pro Ala Ala Lys Thr Arg Lys Gln Ala Ala Lys Lys Val Ala 725 730 735 Pro Leu Met Ala Lys Ala Ile Arg Asp Tyr Lys Arg Arg Phe Ser Arg 740 745 750 Arg <210> 348 <211> 134 <212> PRT <213> homo sapiens <400> 348 Met Thr Glu Glu Pro Ile Lys Glu Ile Leu Gly Ala Pro Lys Ala His 1 5 10 15 Met Ala Ala Thr Met Glu Lys Ser Pro Lys Ser Glu Val Val Ile Thr 20 25 30 Thr Val Pro Leu Val Ser Glu Ile Gln Leu Met Ala Ala Thr Gly Gly 35 40 45 Thr Glu Leu Ser Cys Tyr Arg Cys Ile Ile Pro Phe Ala Val Val Val 50 55 60 Phe Ile Ala Gly Ile Val Val Thr Ala Val Ala Tyr Ser Phe Asn Ser 65 70 75 80 His Gly Ser Ile Ile Ser Ile Phe Gly Leu Val Val Leu Ser Ser Gly 85 90 95 Leu Phe Leu Leu Ala Ser Ser Ala Leu Cys Trp Lys Val Arg Gln Arg 100 105 110 Ser Lys Lys Ala Lys Arg Arg Glu Ser Gln Thr Ala Leu Val Ala Asn 115 120 125 Gln Arg Ser Leu Phe Ala 130 <210> 349 <211> 262 <212> PRT <213> homo sapiens <400> 349 Met Ala Trp Lys Ser Ser Val Ile Met Gln Met Gly Arg Phe Leu Leu 1 5 10 15 Leu Val Ile Leu Phe Leu Pro Arg Glu Met Thr Ser Ser Val Leu Thr 20 25 30 Val Asn Gly Lys Thr Glu Asn Tyr Ile Leu Asp Thr Thr Pro Gly Ser 35 40 45 Gln Ala Ser Leu Ile Cys Ala Val Gln Asn His Thr Arg Glu Glu Glu 50 55 60 Leu Leu Trp Tyr Arg Glu Glu Gly Arg Val Asp Leu Lys Ser Gly Asn 65 70 75 80 Lys Ile Asn Ser Ser Ser Val Cys Val Ser Ser Ile Ser Glu Asn Asp 85 90 95 Asn Gly Ile Ser Phe Thr Cys Arg Leu Gly Arg Asp Gln Ser Val Ser 100 105 110 Val Ser Val Val Leu Asn Val Thr Phe Pro Pro Leu Leu Ser Gly Asn 115 120 125 Asp Phe Gln Thr Val Glu Glu Gly Ser Asn Val Lys Leu Val Cys Asn 130 135 140 Val Lys Ala Asn Pro Gln Ala Gln Met Met Trp Tyr Lys Asn Ser Ser 145 150 155 160 Leu Leu Asp Leu Glu Lys Ser Arg His Gln Ile Gln Gln Thr Ser Glu 165 170 175 Ser Phe Gln Leu Ser Ile Thr Lys Val Glu Lys Pro Asp Asn Gly Thr 180 185 190 Tyr Ser Cys Ile Ala Lys Ser Ser Leu Lys Thr Glu Ser Leu Asp Phe 195 200 205 His Leu Ile Val Lys Asp Lys Thr Val Gly Val Pro Ile Glu Pro Ile 210 215 220 Ile Ala Ala Cys Val Val Ile Phe Leu Thr Leu Cys Phe Gly Leu Ile 225 230 235 240 Ala Arg Arg Lys Lys Ile Met Lys Leu Cys Met Lys Asp Lys Asp Pro 245 250 255 His Ser Glu Thr Ala Leu 260 <210> 350 <211> 344 <212> PRT <213> homo sapiens <400> 350 Met Gln Leu Glu Ile Lys Val Ala Leu Asn Phe Ile Ile Ser Tyr Leu 1 5 10 15 Tyr Asn Lys Leu Pro Arg Arg Arg Ala Asp Leu Phe Gly Glu Glu Leu 20 25 30 Glu Arg Leu Leu Lys Lys Lys Tyr Glu Gly His Trp Tyr Pro Glu Lys 35 40 45 Pro Leu Lys Gly Ser Gly Phe Arg Cys Val His Ile Gly Glu Met Val 50 55 60 Asp Pro Val Val Glu Leu Ala Ala Lys Arg Ser Gly Leu Ala Val Glu 65 70 75 80 Asp Val Arg Ala Asn Val Pro Glu Glu Leu Ser Val Trp Ile Asp Pro 85 90 95 Phe Glu Val Ser Tyr Gln Ile Gly Glu Lys Gly Ala Val Lys Val Leu 100 105 110 Tyr Leu Asp Asp Ser Glu Gly Cys Gly Ala Pro Glu Leu Asp Lys Glu 115 120 125 Ile Lys Ser Ser Phe Asn Pro Asp Ala Gln Val Phe Val Pro Ile Gly 130 135 140 Ser Gln Asp Ser Ser Leu Ser Asn Ser Pro Ser Pro Ser Phe Gly Gln 145 150 155 160 Ser Pro Ser Pro Thr Phe Ile Pro Arg Ser Ala Gln Pro Ile Thr Phe 165 170 175 Thr Thr Ala Ser Phe Ala Ala Thr Lys Phe Gly Ser Thr Lys Met Lys 180 185 190 Lys Gly Gly Gly Ala Ala Ser Gly Gly Gly Val Ala Ser Ser Gly Ala 195 200 205 Gly Gly Gln Gln Pro Pro Gln Gln Pro Arg Met Ala Arg Ser Pro Thr 210 215 220 Asn Ser Leu Leu Lys His Lys Ser Leu Ser Leu Ser Met His Ser Leu 225 230 235 240 Asn Phe Ile Thr Ala Asn Pro Ala Pro Gln Ser Gln Leu Ser Pro Asn 245 250 255 Ala Lys Glu Phe Val Tyr Asn Gly Gly Gly Ser Pro Ser Leu Phe Phe 260 265 270 Asp Ala Ala Asp Gly Gln Gly Ser Gly Thr Pro Gly Pro Phe Gly Gly 275 280 285 Ser Gly Ala Gly Thr Cys Asn Ser Ser Ser Phe Asp Met Ala Gln Val 290 295 300 Phe Gly Gly Gly Ala Asn Ser Leu Phe Leu Glu Lys Thr Pro Phe Val 305 310 315 320 Glu Gly Leu Ser Tyr Asn Leu Asn Thr Met Gln Tyr Pro Ser Gln Gln 325 330 335 Phe Gln Pro Val Val Leu Ala Asn 340 <210> 351 <211> 444 <212> PRT <213> homo sapiens <400> 351 Met Arg Glu Ile Val Leu Thr Gln Ile Gly Gln Cys Gly Asn Gln Ile 1 5 10 15 Gly Ala Lys Phe Trp Glu Val Ile Ser Asp Glu His Ala Ile Asp Ser 20 25 30 Ala Gly Thr Tyr His Gly Asp Ser His Leu Gln Leu Glu Arg Ile Asn 35 40 45 Val Tyr Tyr Asn Glu Ala Ser Gly Gly Arg Tyr Val Pro Arg Ala Val 50 55 60 Leu Val Asp Leu Glu Pro Gly Thr Met Asp Ser Val Arg Ser Gly Pro 65 70 75 80 Phe Gly Gln Val Phe Arg Pro Asp Asn Phe Ile Phe Gly Gln Cys Gly 85 90 95 Ala Gly Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala Glu Leu 100 105 110 Met Glu Ser Val Met Asp Val Val Arg Lys Glu Ala Glu Ser Cys Asp 115 120 125 Cys Leu Gln Gly Phe Gln Leu Thr His Ser Leu Gly Gly Gly Thr Gly 130 135 140 Ser Gly Met Gly Thr Leu Leu Leu Ser Lys Ile Arg Glu Glu Tyr Pro 145 150 155 160 Asp Arg Ile Ile Asn Thr Phe Ser Ile Leu Pro Ser Pro Lys Val Ser 165 170 175 Asp Thr Val Val Glu Pro Tyr Asn Ala Thr Leu Ser Val His Gln Leu 180 185 190 Ile Glu Asn Ala Asp Glu Thr Phe Cys Ile Asp Asn Glu Ala Leu Tyr 195 200 205 Asp Ile Cys Ser Lys Thr Leu Lys Leu Pro Thr Pro Thr Tyr Gly Asp 210 215 220 Leu Asn His Leu Val Ser Ala Thr Met Ser Gly Val Thr Thr Cys Leu 225 230 235 240 Arg Phe Pro Gly Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn 245 250 255 Met Val Pro Phe Pro Arg Leu His Phe Phe Met Pro Gly Phe Ala Pro 260 265 270 Leu Thr Ser Arg Gly Ser Gln Gln Tyr Arg Ala Leu Thr Val Ala Glu 275 280 285 Leu Thr Gln Gln Met Phe Asp Ala Lys Asn Met Met Ala Ala Cys Asp 290 295 300 Pro Arg His Gly Arg Tyr Leu Thr Ala Ala Ala Ile Phe Arg Gly Arg 305 310 315 320 Met Pro Met Arg Glu Val Asp Glu Gln Met Phe Asn Ile Gln Asp Lys 325 330 335 Asn Ser Ser Tyr Phe Ala Asp Trp Leu Pro Asn Asn Val Lys Thr Ala 340 345 350 Val Cys Asp Ile Pro Pro Arg Gly Leu Lys Met Ser Ala Thr Phe Ile 355 360 365 Gly Asn Asn Thr Ala Ile Gln Glu Leu Phe Lys Arg Val Ser Glu Gln 370 375 380 Phe Thr Ala Met Phe Arg Arg Lys Ala Phe Leu His Trp Tyr Thr Gly 385 390 395 400 Glu Gly Met Asp Glu Met Glu Phe Thr Glu Ala Glu Ser Asn Met Asn 405 410 415 Asp Leu Val Ser Glu Tyr Gln Gln Tyr Gln Asp Ala Thr Ala Glu Glu 420 425 430 Glu Glu Asp Glu Glu Tyr Ala Glu Glu Glu Val Ala 435 440 <210> 352 <211> 165 <212> PRT <213> homo sapiens <400> 352 Met Ala Pro Asn Ala Ser Cys Leu Cys Val His Val Arg Ser Glu Glu 1 5 10 15 Trp Asp Leu Met Thr Phe Asp Ala Asn Pro Tyr Asp Ser Val Lys Lys 20 25 30 Ile Lys Glu His Val Arg Ser Lys Thr Lys Val Pro Val Gln Asp Gln 35 40 45 Val Leu Leu Leu Gly Ser Lys Ile Leu Lys Pro Arg Arg Ser Leu Ser 50 55 60 Ser Tyr Gly Ile Asp Lys Glu Lys Thr Ile His Leu Thr Leu Lys Val 65 70 75 80 Val Lys Pro Ser Asp Glu Glu Leu Pro Leu Phe Leu Val Glu Ser Gly 85 90 95 Asp Glu Ala Lys Arg His Leu Leu Gln Val Arg Arg Ser Ser Ser Val 100 105 110 Ala Gln Val Lys Ala Met Ile Glu Thr Lys Thr Gly Ile Ile Pro Glu 115 120 125 Thr Gln Ile Val Thr Cys Asn Gly Lys Arg Leu Glu Asp Gly Lys Met 130 135 140 Met Ala Asp Tyr Gly Ile Arg Lys Gly Asn Leu Leu Phe Leu Ala Cys 145 150 155 160 Tyr Cys Ile Gly Gly 165 <210> 353 <211> 530 <212> PRT <213> homo sapiens <400> 353 Met Ser Leu Lys Trp Met Ser Val Phe Leu Leu Met Gln Leu Ser Cys 1 5 10 15 Tyr Phe Ser Ser Gly Ser Cys Gly Lys Val Leu Val Trp Pro Thr Glu 20 25 30 Tyr Ser His Trp Ile Asn Met Lys Thr Ile Leu Glu Glu Leu Val Gln 35 40 45 Arg Gly His Glu Val Ile Val Leu Thr Ser Ser Ala Ser Ile Leu Val 50 55 60 Asn Ala Ser Lys Ser Ser Ala Ile Lys Leu Glu Val Tyr Pro Thr Ser 65 70 75 80 Leu Thr Lys Asn Asp Leu Glu Asp Phe Phe Met Lys Met Phe Asp Arg 85 90 95 Trp Thr Tyr Ser Ile Ser Lys Asn Thr Phe Trp Ser Tyr Phe Ser Gln 100 105 110 Leu Gln Glu Leu Cys Trp Glu Tyr Ser Asp Tyr Asn Ile Lys Leu Cys 115 120 125 Glu Asp Ala Val Leu Asn Lys Lys Leu Met Arg Lys Leu Gln Glu Ser 130 135 140 Lys Phe Asp Val Leu Leu Ala Asp Ala Val Asn Pro Cys Gly Glu Leu 145 150 155 160 Leu Ala Glu Leu Leu Asn Ile Pro Phe Leu Tyr Ser Leu Arg Phe Ser 165 170 175 Val Gly Tyr Thr Val Glu Lys Asn Gly Gly Gly Phe Leu Phe Pro Pro 180 185 190 Ser Tyr Val Pro Val Val Met Ser Glu Leu Ser Asp Gln Met Ile Phe 195 200 205 Met Glu Arg Ile Lys Asn Met Ile Tyr Met Leu Tyr Phe Asp Phe Trp 210 215 220 Phe Gln Ala Tyr Asp Leu Lys Lys Trp Asp Gln Phe Tyr Ser Glu Val 225 230 235 240 Leu Gly Arg Pro Thr Thr Leu Phe Glu Thr Met Gly Lys Ala Glu Met 245 250 255 Trp Leu Ile Arg Thr Tyr Trp Asp Phe Glu Phe Pro Arg Pro Phe Leu 260 265 270 Pro Asn Val Asp Phe Val Gly Gly Leu His Cys Lys Pro Ala Lys Pro 275 280 285 Leu Pro Lys Glu Met Glu Glu Phe Val Gln Ser Ser Gly Glu Asn Gly 290 295 300 Ile Val Val Phe Ser Leu Gly Ser Met Ile Ser Asn Met Ser Glu Glu 305 310 315 320 Ser Ala Asn Met Ile Ala Ser Ala Leu Ala Gln Ile Pro Gln Lys Val 325 330 335 Leu Trp Arg Phe Asp Gly Lys Lys Pro Asn Thr Leu Gly Ser Asn Thr 340 345 350 Arg Leu Tyr Lys Trp Leu Pro Gln Asn Asp Leu Leu Gly His Pro Lys 355 360 365 Thr Lys Ala Phe Ile Thr His Gly Gly Thr Asn Gly Ile Tyr Glu Ala 370 375 380 Ile Tyr His Gly Ile Pro Met Val Gly Ile Pro Leu Phe Ala Asp Gln 385 390 395 400 His Asp Asn Ile Ala His Met Lys Ala Lys Gly Ala Ala Leu Ser Val 405 410 415 Asp Ile Arg Thr Met Ser Ser Arg Asp Leu Leu Asn Ala Leu Lys Ser 420 425 430 Val Ile Asn Asp Pro Ile Tyr Lys Glu Asn Ile Met Lys Leu Ser Arg 435 440 445 Ile His His Asp Gln Pro Val Lys Pro Leu Asp Arg Ala Val Phe Trp 450 455 460 Ile Glu Phe Val Met Arg His Lys Gly Ala Lys His Leu Arg Val Ala 465 470 475 480 Ala His Asn Leu Thr Trp Ile Gln Tyr His Ser Leu Asp Val Ile Ala 485 490 495 Phe Leu Leu Ala Cys Val Ala Thr Met Ile Phe Met Ile Thr Lys Cys 500 505 510 Cys Leu Phe Cys Phe Arg Lys Leu Ala Lys Thr Gly Lys Lys Lys Lys 515 520 525 Arg Asp 530 <210> 354 <211> 274 <212> PRT <213> homo sapiens <400> 354 Met Leu Ser Val Ala Ser Arg Ser Gly Pro Phe Ala Pro Val Leu Ser 1 5 10 15 Ala Thr Ser Arg Gly Val Ala Gly Ala Leu Arg Pro Leu Val Gln Ala 20 25 30 Thr Val Pro Ala Thr Pro Glu Gln Pro Val Leu Asp Leu Lys Arg Pro 35 40 45 Phe Leu Ser Arg Glu Ser Leu Ser Gly Gln Ala Val Arg Arg Pro Leu 50 55 60 Val Ala Ser Val Gly Leu Asn Val Pro Ala Ser Val Cys Tyr Ser His 65 70 75 80 Thr Asp Ile Lys Val Pro Asp Phe Ser Glu Tyr Arg Arg Leu Glu Val 85 90 95 Leu Asp Ser Thr Lys Ser Ser Arg Glu Ser Ser Glu Ala Arg Lys Gly 100 105 110 Phe Ser Tyr Leu Val Thr Gly Val Thr Thr Val Gly Val Ala Tyr Ala 115 120 125 Ala Lys Asn Ala Val Thr Gln Phe Val Ser Ser Met Ser Ala Ser Ala 130 135 140 Asp Val Leu Ala Leu Ala Lys Ile Glu Ile Lys Leu Ser Asp Ile Pro 145 150 155 160 Glu Gly Lys Asn Met Ala Phe Lys Trp Arg Gly Lys Pro Leu Phe Val 165 170 175 Arg His Arg Thr Gln Lys Glu Ile Glu Gln Glu Ala Ala Val Glu Leu 180 185 190 Ser Gln Leu Arg Asp Pro Gln His Asp Leu Asp Arg Val Lys Lys Pro 195 200 205 Glu Trp Val Ile Leu Ile Gly Val Cys Thr His Leu Gly Cys Val Pro 210 215 220 Ile Ala Asn Ala Gly Asp Phe Gly Gly Tyr Tyr Cys Pro Cys His Gly 225 230 235 240 Ser His Tyr Asp Ala Ser Gly Arg Ile Arg Leu Gly Pro Ala Pro Leu 245 250 255 Asn Leu Glu Val Pro Thr Tyr Glu Phe Thr Ser Asp Asp Met Val Ile 260 265 270 Val Gly <210> 355 <211> 513 <212> PRT <213> homo sapiens <400> 355 Met Thr Thr Gln Leu Pro Ala Tyr Val Ala Ile Leu Leu Phe Tyr Val 1 5 10 15 Ser Arg Ala Ser Cys Gln Asp Thr Phe Thr Ala Ala Val Tyr Glu His 20 25 30 Ala Ala Ile Leu Pro Asn Ala Thr Leu Thr Pro Val Ser Arg Glu Glu 35 40 45 Ala Leu Ala Leu Met Asn Arg Asn Leu Asp Ile Leu Glu Gly Ala Ile 50 55 60 Thr Ser Ala Ala Asp Gln Gly Ala His Ile Ile Val Thr Pro Glu Asp 65 70 75 80 Ala Ile Tyr Gly Trp Asn Phe Asn Arg Asp Ser Leu Tyr Pro Tyr Leu 85 90 95 Glu Asp Ile Pro Asp Pro Glu Val Asn Trp Ile Pro Cys Asn Asn Arg 100 105 110 Asn Arg Phe Gly Gln Thr Pro Val Gln Glu Arg Leu Ser Cys Leu Ala 115 120 125 Lys Asn Asn Ser Ile Tyr Val Val Ala Asn Ile Gly Asp Lys Lys Pro 130 135 140 Cys Asp Thr Ser Asp Pro Gln Cys Pro Pro Asp Gly Arg Tyr Gln Tyr 145 150 155 160 Asn Thr Asp Val Val Phe Asp Ser Gln Gly Lys Leu Val Ala Arg Tyr 165 170 175 His Lys Gln Asn Leu Phe Met Gly Glu Asn Gln Phe Asn Val Pro Lys 180 185 190 Glu Pro Glu Ile Val Thr Phe Asn Thr Thr Phe Gly Ser Phe Gly Ile 195 200 205 Phe Thr Cys Phe Asp Ile Leu Phe His Asp Pro Ala Val Thr Leu Val 210 215 220 Lys Asp Phe His Val Asp Thr Ile Val Phe Pro Thr Ala Trp Met Asn 225 230 235 240 Val Leu Pro His Leu Ser Ala Val Glu Phe His Ser Ala Trp Ala Met 245 250 255 Gly Met Arg Val Asn Phe Leu Ala Ser Asn Ile His Tyr Pro Ser Lys 260 265 270 Lys Met Thr Gly Ser Gly Ile Tyr Ala Pro Asn Ser Ser Arg Ala Phe 275 280 285 His Tyr Asp Met Lys Thr Glu Glu Gly Lys Leu Leu Leu Ser Gln Leu 290 295 300 Asp Ser His Pro Ser His Ser Ala Val Val Asn Trp Thr Ser Tyr Ala 305 310 315 320 Ser Ser Ile Glu Ala Leu Ser Ser Gly Asn Lys Glu Phe Lys Gly Thr 325 330 335 Val Phe Phe Asp Glu Phe Thr Phe Val Lys Leu Thr Gly Val Ala Gly 340 345 350 Asn Tyr Thr Val Cys Gln Lys Asp Leu Cys Cys His Leu Ser Tyr Lys 355 360 365 Met Ser Glu Asn Ile Pro Asn Glu Val Tyr Ala Leu Gly Ala Phe Asp 370 375 380 Gly Leu His Thr Val Glu Gly Arg Tyr Tyr Leu Gln Ile Cys Thr Leu 385 390 395 400 Leu Lys Cys Lys Thr Thr Asn Leu Asn Thr Cys Gly Asp Ser Ala Glu 405 410 415 Thr Ala Ser Thr Arg Phe Glu Met Phe Ser Leu Ser Gly Thr Phe Gly 420 425 430 Thr Gln Tyr Val Phe Pro Glu Val Leu Leu Ser Glu Asn Gln Leu Ala 435 440 445 Pro Gly Glu Phe Gln Val Ser Thr Asp Gly Arg Leu Phe Ser Leu Lys 450 455 460 Pro Thr Ser Gly Pro Val Leu Thr Val Thr Leu Phe Gly Arg Leu Tyr 465 470 475 480 Glu Lys Asp Trp Ala Ser Asn Ala Ser Ser Gly Leu Thr Ala Gln Ala 485 490 495 Arg Ile Ile Met Leu Ile Val Ile Ala Pro Ile Val Cys Ser Leu Ser 500 505 510 Trp <210> 356 <211> 502 <212> PRT <213> homo sapiens <400> 356 Met Ala Ala Pro Cys Glu Gly Gln Ala Phe Ala Val Gly Val Glu Lys 1 5 10 15 Asn Trp Gly Ala Val Val Arg Ser Pro Glu Gly Thr Pro Gln Lys Ile 20 25 30 Arg Gln Leu Ile Asp Glu Gly Ile Ala Pro Glu Glu Gly Gly Val Asp 35 40 45 Ala Lys Asp Thr Ser Ala Thr Ser Gln Ser Val Asn Gly Ser Pro Gln 50 55 60 Ala Glu Gln Pro Ser Leu Glu Ser Thr Ser Lys Glu Ala Phe Phe Ser 65 70 75 80 Arg Val Glu Thr Phe Ser Ser Leu Lys Trp Ala Gly Lys Pro Phe Glu 85 90 95 Leu Ser Pro Leu Val Cys Ala Lys Tyr Gly Trp Val Thr Val Glu Cys 100 105 110 Asp Met Leu Lys Cys Ser Ser Cys Gln Ala Phe Leu Cys Ala Ser Leu 115 120 125 Gln Pro Ala Phe Asp Phe Asp Arg Tyr Lys Gln Arg Cys Ala Glu Leu 130 135 140 Lys Lys Ala Leu Cys Thr Ala His Glu Lys Phe Cys Phe Trp Pro Asp 145 150 155 160 Ser Pro Ser Pro Asp Arg Phe Gly Met Leu Pro Leu Asp Glu Pro Ala 165 170 175 Ile Leu Val Ser Glu Phe Leu Asp Arg Phe Gln Ser Leu Cys His Leu 180 185 190 Asp Leu Gln Leu Pro Ser Leu Arg Pro Glu Asp Leu Lys Thr Met Cys 195 200 205 Leu Thr Glu Asp Lys Ile Ser Leu Leu Leu His Leu Leu Glu Asp Glu 210 215 220 Leu Asp His Arg Thr Asp Glu Arg Lys Thr Thr Ile Lys Leu Gly Ser 225 230 235 240 Asp Ile Gln Val His Val Thr Ala Cys Ile Leu Ser Val Cys Gly Trp 245 250 255 Ala Cys Ser Ser Ser Leu Glu Ser Met Gln Leu Ser Leu Ile Thr Cys 260 265 270 Ser Gln Cys Met Arg Lys Val Gly Leu Trp Gly Phe Gln Gln Ile Glu 275 280 285 Ser Ser Met Thr Asp Leu Asp Ala Ser Phe Gly Leu Thr Ser Ser Pro 290 295 300 Ile Pro Gly Leu Glu Gly Arg Pro Glu Arg Leu Pro Leu Val Pro Glu 305 310 315 320 Ser Pro Arg Arg Met Met Thr Arg Ser Gln Asp Ala Thr Phe Ser Pro 325 330 335 Gly Ser Glu Gln Ala Glu Lys Ser Pro Gly Pro Ile Val Ser Arg Thr 340 345 350 Arg Ser Trp Asp Ser Ser Ser Pro Val Asp Arg Pro Glu Pro Glu Ala 355 360 365 Ala Ser Pro Thr Thr Arg Thr Arg Pro Val Thr Arg Ser Met Gly Thr 370 375 380 Gly Asp Thr Pro Gly Leu Glu Val Pro Ser Ser Pro Leu Arg Lys Ala 385 390 395 400 Lys Arg Ala Arg Leu Cys Ser Ser Ser Ser Ser Asp Thr Ser Ser Arg 405 410 415 Ser Phe Phe Asp Pro Thr Ser Gln His Arg Asp Trp Cys Pro Trp Val 420 425 430 Asn Ile Thr Leu Gly Lys Glu Ser Arg Glu Asn Gly Gly Thr Glu Pro 435 440 445 Asp Ala Ser Ala Pro Ala Glu Pro Gly Trp Lys Ala Val Leu Thr Ile 450 455 460 Leu Leu Ala His Lys Gln Ser Ser Gln Pro Ala Glu Thr Asp Ser Met 465 470 475 480 Ser Leu Ser Glu Lys Ser Arg Lys Val Phe Arg Ile Phe Arg Gln Trp 485 490 495 Glu Ser Leu Cys Ser Cys 500 <210> 357 <211> 402 <212> PRT <213> homo sapiens <400> 357 Met Ala Ser Ile Ile Ala Arg Val Gly Asn Ser Arg Arg Leu Asn Ala 1 5 10 15 Pro Leu Pro Pro Trp Ala His Ser Met Leu Arg Ser Leu Gly Arg Ser 20 25 30 Leu Gly Pro Ile Met Ala Ser Met Ala Asp Arg Asn Met Lys Leu Phe 35 40 45 Ser Gly Arg Val Val Pro Ala Gln Gly Glu Glu Thr Phe Glu Asn Trp 50 55 60 Leu Thr Gln Val Asn Gly Val Leu Pro Asp Trp Asn Met Ser Glu Glu 65 70 75 80 Glu Lys Leu Lys Arg Leu Met Lys Thr Leu Arg Gly Pro Ala Arg Glu 85 90 95 Val Met Arg Val Leu Gln Ala Thr Asn Pro Asn Leu Ser Val Ala Asp 100 105 110 Phe Leu Arg Ala Met Lys Leu Val Phe Gly Glu Ser Glu Ser Ser Val 115 120 125 Thr Ala His Gly Lys Phe Phe Asn Thr Leu Gln Ala Gln Gly Glu Lys 130 135 140 Ala Ser Leu Tyr Val Ile Arg Leu Glu Val Gln Leu Gln Asn Ala Ile 145 150 155 160 Gln Ala Gly Ile Ile Ala Glu Lys Asp Ala Asn Arg Thr Arg Leu Gln 165 170 175 Gln Leu Leu Leu Gly Gly Glu Leu Ser Arg Asp Leu Arg Leu Arg Leu 180 185 190 Lys Asp Phe Leu Arg Met Tyr Ala Asn Glu Gln Glu Arg Leu Pro Asn 195 200 205 Phe Leu Glu Leu Ile Arg Met Val Arg Glu Glu Glu Asp Trp Asp Asp 210 215 220 Ala Phe Ile Lys Arg Lys Arg Pro Lys Arg Ser Glu Ser Met Val Glu 225 230 235 240 Arg Ala Val Ser Pro Val Ala Phe Gln Gly Ser Pro Pro Ile Val Ile 245 250 255 Gly Ser Ala Asp Cys Asn Val Ile Glu Ile Asp Asp Thr Leu Asp Asp 260 265 270 Ser Asp Glu Asp Val Ile Leu Val Glu Ser Gln Asp Pro Pro Leu Pro 275 280 285 Ser Trp Gly Ala Pro Pro Leu Arg Asp Arg Ala Arg Pro Gln Asp Glu 290 295 300 Val Leu Val Ile Asp Ser Pro His Asn Ser Arg Ala Gln Phe Pro Ser 305 310 315 320 Thr Ser Gly Gly Ser Gly Tyr Lys Asn Asn Gly Pro Gly Glu Met Arg 325 330 335 Arg Ala Arg Lys Arg Lys His Thr Ile Arg Cys Ser Tyr Cys Gly Glu 340 345 350 Glu Gly His Ser Lys Glu Thr Cys Asp Asn Glu Ser Asp Lys Ala Gln 355 360 365 Val Phe Glu Asn Leu Ile Ile Thr Leu Gln Glu Leu Thr His Thr Glu 370 375 380 Met Glu Arg Ser Arg Val Ala Pro Gly Glu Tyr Asn Asp Phe Ser Glu 385 390 395 400 Pro Leu <210> 358 <211> 451 <212> PRT <213> homo sapiens <400> 358 Met Ala Lys Leu Tyr Glu Ala Val Thr Phe Lys Asp Val Ala Val Ile 1 5 10 15 Phe Thr Glu Glu Glu Leu Gly Leu Leu Asp Pro Ala Gln Arg Lys Leu 20 25 30 Tyr Arg Asp Val Met Leu Glu Asn Phe Arg Asn Leu Leu Ser Val Gly 35 40 45 Gly Lys Ile Gln Thr Glu Met Glu Thr Val Pro Glu Ala Gly Thr His 50 55 60 Glu Glu Phe Ser Cys Lys Gln Ile Trp Glu Gln Ile Ala Ser Asp Leu 65 70 75 80 Thr Arg Ser Gln Asp Thr Thr Ile Ser Asn Ser Gln Leu Phe Glu Gln 85 90 95 Asp Asp Asn Pro Ser Gln Ile Lys Ala Arg Leu Ser Thr Val His Thr 100 105 110 Arg Glu Lys Pro Phe Gln Gly Glu Asn Cys Lys Gln Phe Phe Ser Asp 115 120 125 Val Ser Phe Phe Asp Leu Pro Gln Gln Leu Tyr Ser Gly Glu Lys Ser 130 135 140 His Thr Cys Asp Glu Cys Gly Lys Ser Phe Cys Tyr Ile Ser Ala Leu 145 150 155 160 His Ile His Gln Arg Val His Met Gly Val Lys Cys Tyr Lys Cys Asp 165 170 175 Val Cys Gly Lys Glu Phe Ser Gln Ser Ser Arg Leu Gln Thr His Gln 180 185 190 Arg Val His Thr Gly Glu Lys Pro Phe Lys Cys Glu Gln Cys Gly Lys 195 200 205 Gly Phe Arg Cys Arg Ser Ala Leu Lys Val His Cys Lys Leu His Met 210 215 220 Arg Glu Lys Pro Tyr Asn Cys Glu Lys Cys Gly Lys Ala Phe Met His 225 230 235 240 Asn Phe Gln Leu Gln Lys His His Arg Ile His Thr Gly Glu Lys Pro 245 250 255 Phe Lys Cys Glu Ile Cys Gly Lys Ser Phe Cys Leu Arg Ser Ser Leu 260 265 270 Asn Arg His Cys Met Val His Thr Ala Glu Lys Leu Tyr Lys Ser Glu 275 280 285 Lys Tyr Gly Arg Gly Phe Ile Asp Arg Leu Asp Leu His Lys His Gln 290 295 300 Met Ile His Met Gly Gln Lys Pro Tyr Asn Cys Lys Glu Cys Gly Lys 305 310 315 320 Ser Phe Lys Trp Ser Ser Tyr Leu Leu Val His Gln Arg Val His Thr 325 330 335 Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Gly Tyr Ile Ser 340 345 350 Lys Ser Gly Leu Asp Phe His His Arg Thr His Thr Gly Glu Arg Ser 355 360 365 Tyr Asn Cys Asp Asn Cys Gly Lys Ser Phe Arg His Ala Ser Ser Ile 370 375 380 Leu Asn His Lys Lys Leu His Cys Gln Arg Lys Pro Leu Lys Cys Glu 385 390 395 400 Asp Cys Gly Lys Arg Leu Val Cys Arg Ser Tyr Cys Lys Asp Gln Gln 405 410 415 Arg Asp His Ser Gly Glu Asn Pro Ser Lys Cys Glu Asp Cys Gly Lys 420 425 430 Arg Tyr Lys Arg Arg Leu Asn Leu Asp Ile Ile Leu Ser Leu Phe Leu 435 440 445 Asn Asp Ile 450 <210> 359 <211> 459 <212> PRT <213> homo sapiens <400> 359 Met Ala Ala Ser Gly Ala Val Glu Pro Gly Pro Pro Gly Ala Ala Val 1 5 10 15 Ala Pro Ser Pro Ala Pro Ala Pro Pro Pro Ala Pro Asp His Leu Phe 20 25 30 Arg Pro Ile Ser Ala Glu Asp Glu Glu Gln Gln Pro Thr Glu Ile Glu 35 40 45 Ser Leu Cys Met Asn Cys Tyr Cys Asn Gly Met Thr Arg Leu Leu Leu 50 55 60 Thr Lys Ile Pro Phe Phe Arg Glu Ile Ile Val Ser Ser Phe Ser Cys 65 70 75 80 Glu His Cys Gly Trp Asn Asn Thr Glu Ile Gln Ser Ala Gly Arg Ile 85 90 95 Gln Asp Gln Gly Val Arg Tyr Thr Leu Ser Val Arg Ala Leu Glu Asp 100 105 110 Met Asn Arg Glu Val Val Lys Thr Asp Ser Ala Ala Thr Arg Ile Pro 115 120 125 Glu Leu Asp Phe Glu Ile Pro Ala Phe Ser Gln Lys Gly Ala Leu Thr 130 135 140 Thr Val Glu Gly Leu Ile Thr Arg Ala Ile Ser Gly Leu Glu Gln Asp 145 150 155 160 Gln Pro Ala Arg Arg Ala Asn Lys Asp Ala Thr Ala Glu Arg Ile Asp 165 170 175 Glu Phe Ile Val Lys Leu Lys Glu Leu Lys Gln Val Ala Ser Pro Phe 180 185 190 Thr Leu Ile Ile Asp Asp Pro Ser Gly Asn Ser Phe Val Glu Asn Pro 195 200 205 His Ala Pro Gln Lys Asp Asp Ala Leu Val Ile Thr His Tyr Asn Arg 210 215 220 Thr Arg Gln Gln Glu Glu Met Leu Gly Leu Gln Glu Glu Ala Pro Ala 225 230 235 240 Glu Lys Pro Glu Glu Glu Asp Leu Arg Asn Glu Val Leu Gln Phe Ser 245 250 255 Thr Asn Cys Pro Glu Cys Asn Ala Pro Ala Gln Thr Asn Met Lys Leu 260 265 270 Val Gln Ile Pro His Phe Lys Glu Val Ile Ile Met Ala Thr Asn Cys 275 280 285 Glu Asn Cys Gly His Arg Thr Asn Glu Val Lys Ser Gly Gly Ala Val 290 295 300 Glu Pro Leu Gly Thr Arg Ile Thr Leu His Ile Thr Asp Ala Ser Asp 305 310 315 320 Met Thr Arg Asp Leu Leu Lys Ser Glu Thr Cys Ser Val Glu Ile Pro 325 330 335 Glu Leu Glu Phe Glu Leu Gly Met Ala Val Leu Gly Gly Lys Phe Thr 340 345 350 Thr Leu Glu Gly Leu Leu Lys Asp Ile Arg Glu Leu Val Thr Lys Asn 355 360 365 Pro Phe Thr Leu Gly Asp Ser Ser Asn Pro Gly Gln Thr Glu Arg Leu 370 375 380 Gln Glu Phe Ser Gln Lys Met Asp Gln Ile Ile Glu Gly Asn Met Lys 385 390 395 400 Ala His Phe Ile Met Asp Asp Pro Ala Gly Asn Ser Tyr Leu Gln Asn 405 410 415 Val Tyr Ala Pro Glu Asp Asp Pro Glu Met Lys Val Glu Arg Tyr Lys 420 425 430 Arg Thr Phe Asp Gln Asn Glu Glu Leu Gly Leu Asn Asp Met Lys Thr 435 440 445 Glu Gly Tyr Glu Ala Gly Leu Ala Pro Gln Arg 450 455 <210> 360 <211> 499 <212> PRT <213> homo sapiens <400> 360 Met Leu Ser Leu Ser Pro Ile Leu Leu Tyr Thr Cys Glu Met Phe Gln 1 5 10 15 Asp Pro Val Ala Phe Lys Asp Val Ala Val Asn Phe Thr Gln Glu Glu 20 25 30 Trp Ala Leu Leu Asp Ile Ser Gln Lys Asn Leu Tyr Arg Glu Val Met 35 40 45 Leu Glu Thr Phe Trp Asn Leu Thr Ser Ile Gly Lys Lys Trp Lys Asp 50 55 60 Gln Asn Ile Glu Tyr Glu Tyr Gln Asn Pro Arg Arg Asn Phe Arg Ser 65 70 75 80 Val Thr Glu Glu Lys Val Asn Glu Ile Lys Glu Asp Ser His Cys Gly 85 90 95 Glu Thr Phe Thr Pro Val Pro Asp Asp Arg Leu Asn Phe Gln Lys Lys 100 105 110 Lys Ala Ser Pro Glu Val Lys Ser Cys Asp Ser Phe Val Cys Glu Val 115 120 125 Gly Leu Gly Asn Ser Ser Ser Asn Met Asn Ile Arg Gly Asp Thr Gly 130 135 140 His Lys Ala Cys Glu Cys Gln Glu Tyr Gly Pro Lys Pro Trp Lys Ser 145 150 155 160 Gln Gln Pro Lys Lys Ala Phe Arg Tyr His Pro Ser Leu Arg Thr Gln 165 170 175 Glu Arg Asp His Thr Gly Lys Lys Pro Tyr Ala Cys Lys Glu Cys Gly 180 185 190 Lys Asn Ile Ile Tyr His Ser Ser Ile Gln Arg His Met Val Val His 195 200 205 Ser Gly Asp Gly Pro Tyr Lys Cys Lys Phe Cys Gly Lys Ala Phe His 210 215 220 Cys Leu Ser Leu Tyr Leu Ile His Glu Arg Thr His Thr Gly Glu Lys 225 230 235 240 Pro Tyr Glu Cys Lys Gln Cys Gly Lys Ser Phe Ser Tyr Ser Ala Thr 245 250 255 His Arg Ile His Glu Arg Thr His Ile Gly Glu Lys Pro Tyr Glu Cys 260 265 270 Gln Glu Cys Gly Lys Ala Phe His Ser Pro Arg Ser Cys His Arg His 275 280 285 Glu Arg Ser His Met Gly Glu Lys Ala Tyr Gln Cys Lys Glu Cys Gly 290 295 300 Lys Ala Phe Met Cys Pro Arg Tyr Val Arg Arg His Glu Arg Thr His 305 310 315 320 Ser Arg Lys Lys Leu Tyr Glu Cys Lys Gln Cys Gly Lys Ala Leu Ser 325 330 335 Ser Leu Thr Ser Phe Gln Thr His Ile Arg Met His Ser Gly Glu Arg 340 345 350 Pro Tyr Glu Cys Lys Thr Cys Gly Lys Gly Phe Tyr Ser Ala Lys Ser 355 360 365 Phe Gln Arg His Glu Lys Thr His Ser Gly Glu Lys Pro Tyr Lys Cys 370 375 380 Lys Gln Cys Gly Lys Ala Phe Thr Arg Ser Gly Ser Phe Arg Tyr His 385 390 395 400 Glu Arg Thr His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Gln Cys Gly 405 410 415 Lys Ala Phe Arg Ser Ala Pro Asn Leu Gln Leu His Gly Arg Thr His 420 425 430 Thr Gly Glu Lys Pro Tyr Gln Cys Lys Glu Cys Gly Lys Ala Phe Arg 435 440 445 Ser Ala Ser Gln Leu Arg Ile His Arg Arg Ile His Thr Gly Glu Lys 450 455 460 Pro Tyr Glu Cys Lys Lys Cys Gly Lys Ala Phe Arg Tyr Val Gln Asn 465 470 475 480 Phe Arg Phe His Glu Arg Thr Gln Thr His Lys Asn Ala Leu Trp Arg 485 490 495 Lys Thr Leu <210> 361 <211> 686 <212> PRT <213> homo sapiens <400> 361 Met Thr Glu Ser Gln Gly Thr Val Thr Phe Lys Asp Val Ala Ile Asp 1 5 10 15 Phe Thr Gln Glu Glu Trp Lys Arg Leu Asp Pro Ala Gln Arg Lys Leu 20 25 30 Tyr Arg Asn Val Met Leu Glu Asn Tyr Asn Asn Leu Ile Thr Val Gly 35 40 45 Tyr Pro Phe Thr Lys Pro Asp Val Ile Phe Lys Leu Glu Gln Glu Glu 50 55 60 Glu Pro Trp Val Met Glu Glu Glu Val Leu Arg Arg His Trp Gln Gly 65 70 75 80 Glu Ile Trp Gly Val Asp Glu His Gln Lys Asn Gln Asp Arg Leu Leu 85 90 95 Arg Gln Val Glu Val Lys Phe Gln Lys Thr Leu Thr Glu Glu Lys Gly 100 105 110 Asn Glu Cys Gln Lys Lys Phe Ala Asn Val Phe Pro Leu Asn Ser Asp 115 120 125 Phe Phe Pro Ser Arg His Asn Leu Tyr Glu Tyr Asp Leu Phe Gly Lys 130 135 140 Cys Leu Glu His Asn Phe Asp Cys His Asn Asn Val Lys Cys Leu Met 145 150 155 160 Arg Lys Glu His Cys Glu Tyr Asn Glu Pro Val Lys Ser Tyr Gly Asn 165 170 175 Ser Ser Ser His Phe Val Ile Thr Pro Phe Lys Cys Asn His Cys Gly 180 185 190 Lys Gly Phe Asn Gln Thr Leu Asp Leu Ile Arg His Leu Arg Ile His 195 200 205 Thr Gly Glu Lys Pro Tyr Glu Cys Ser Asn Cys Arg Lys Ala Phe Ser 210 215 220 His Lys Glu Lys Leu Ile Lys His Tyr Lys Ile His Ser Arg Glu Gln 225 230 235 240 Ser Tyr Lys Cys Asn Glu Cys Gly Lys Ala Phe Ile Lys Met Ser Asn 245 250 255 Leu Ile Arg His Gln Arg Ile His Thr Gly Glu Lys Pro Tyr Ala Cys 260 265 270 Lys Glu Cys Glu Lys Ser Phe Ser Gln Lys Ser Asn Leu Ile Asp His 275 280 285 Glu Lys Ile His Thr Gly Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly 290 295 300 Lys Ala Phe Ser Gln Lys Gln Ser Leu Ile Ala His Gln Lys Val His 305 310 315 320 Thr Gly Glu Lys Pro Tyr Ala Cys Asn Glu Cys Gly Lys Ala Phe Pro 325 330 335 Arg Ile Ala Ser Leu Ala Leu His Met Arg Ser His Thr Gly Glu Lys 340 345 350 Pro Tyr Lys Cys Asp Lys Cys Gly Lys Ala Phe Ser Gln Phe Ser Met 355 360 365 Leu Ile Ile His Val Arg Ile His Thr Gly Glu Lys Pro Tyr Glu Cys 370 375 380 Asn Glu Cys Gly Lys Ala Phe Ser Gln Ser Ser Ala Leu Thr Val His 385 390 395 400 Met Arg Ser His Thr Gly Glu Lys Pro Tyr Glu Cys Lys Glu Cys Arg 405 410 415 Lys Ala Phe Ser His Lys Lys Asn Phe Ile Thr His Gln Lys Ile His 420 425 430 Thr Arg Glu Lys Pro Tyr Glu Cys Asn Glu Cys Gly Lys Ala Phe Ile 435 440 445 Gln Met Ser Asn Leu Val Arg His Gln Arg Ile His Thr Gly Glu Lys 450 455 460 Pro Tyr Ile Cys Lys Glu Cys Gly Lys Ala Phe Ser Gln Lys Ser Asn 465 470 475 480 Leu Ile Ala His Glu Lys Ile His Ser Gly Glu Lys Pro Tyr Glu Cys 485 490 495 Asn Glu Cys Gly Lys Ala Phe Ser Gln Lys Gln Asn Phe Ile Thr His 500 505 510 Gln Lys Val His Thr Gly Glu Lys Pro Tyr Asp Cys Asn Glu Cys Gly 515 520 525 Lys Ala Phe Ser Gln Ile Ala Ser Leu Thr Leu His Leu Arg Ser His 530 535 540 Thr Gly Glu Lys Pro Tyr Glu Cys Asp Lys Cys Gly Lys Ala Phe Ser 545 550 555 560 Gln Cys Ser Leu Leu Asn Leu His Met Arg Ser His Thr Gly Glu Lys 565 570 575 Pro Tyr Val Cys Asn Glu Cys Gly Lys Ala Phe Ser Gln Arg Thr Ser 580 585 590 Leu Ile Val His Met Arg Gly His Thr Gly Glu Lys Pro Tyr Glu Cys 595 600 605 Asn Lys Cys Gly Lys Ala Phe Ser Gln Ser Ser Ser Leu Thr Ile His 610 615 620 Ile Arg Gly His Thr Gly Glu Lys Pro Phe Asp Cys Ser Lys Cys Gly 625 630 635 640 Lys Ala Phe Ser Gln Ile Ser Ser Leu Thr Leu His Met Arg Lys His 645 650 655 Thr Gly Glu Lys Pro Tyr His Cys Ile Glu Cys Gly Lys Ala Phe Ser 660 665 670 Gln Lys Ser His Leu Val Arg His Gln Arg Ile His Thr His 675 680 685 <210> 362 <211> 525 <212> PRT <213> homo sapiens <400> 362 Met Gly Thr Ile Ser Leu Cys Ile Gly Val Cys Ala Phe Glu Gly Ala 1 5 10 15 Asn Thr Ser Thr Ser Phe Tyr Lys Leu Val Tyr Thr Ala Ile Leu Ser 20 25 30 Tyr Ser Ile Gln Asp Leu Leu Pro Glu Gln Asp Met Lys Asp Leu Cys 35 40 45 Gln Lys Val Thr Leu Thr Arg His Arg Ser Trp Gly Leu Asp Asn Leu 50 55 60 His Leu Val Lys Asp Trp Arg Thr Val Asn Glu Gly Lys Gly Gln Lys 65 70 75 80 Glu Tyr Cys Asn Arg Leu Thr Gln Cys Ser Ser Thr Lys Ser Lys Ile 85 90 95 Phe Gln Cys Ile Glu Cys Gly Arg Asn Phe Ser Trp Arg Ser Ile Leu 100 105 110 Thr Glu His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu 115 120 125 Glu Cys Gly Lys Val Phe Asn Arg Cys Ser Asn Leu Thr Lys His Lys 130 135 140 Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Asp Glu Cys Gly Lys 145 150 155 160 Val Phe Asn Trp Trp Ser Gln Leu Thr Asn His Lys Lys Ile His Thr 165 170 175 Gly Glu Lys Pro Tyr Lys Cys Asp Glu Cys Asp Lys Val Phe Asn Trp 180 185 190 Trp Ser Gln Leu Thr Ser His Lys Lys Ile His Ser Gly Glu Lys Pro 195 200 205 Tyr Pro Cys Glu Glu Cys Gly Lys Ala Phe Thr Gln Phe Ser Asn Leu 210 215 220 Thr Gln His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Lys 225 230 235 240 Glu Cys Cys Lys Ala Phe Asn Lys Phe Ser Asn Leu Thr Gln His Lys 245 250 255 Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Asn 260 265 270 Val Phe Asn Glu Cys Ser His Leu Thr Arg His Arg Arg Ile His Thr 275 280 285 Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ala Phe Thr Gln 290 295 300 Phe Ala Ser Leu Thr Arg His Lys Arg Ile His Thr Gly Glu Lys Pro 305 310 315 320 Tyr Gln Cys Glu Glu Cys Gly Lys Thr Phe Asn Arg Cys Ser His Leu 325 330 335 Ser Ser His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Glu 340 345 350 Glu Cys Gly Arg Thr Phe Thr Gln Phe Ser Asn Leu Thr Gln His Lys 355 360 365 Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Lys Glu Cys Gly Lys 370 375 380 Ala Phe Asn Lys Phe Ser Ser Leu Thr Gln His Arg Arg Ile His Thr 385 390 395 400 Gly Val Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Val Phe Lys Gln 405 410 415 Cys Ser His Leu Thr Ser His Lys Arg Ile His Thr Gly Glu Lys Pro 420 425 430 Tyr Lys Cys Lys Glu Cys Gly Lys Ala Phe Tyr Gln Ser Ser Ile Leu 435 440 445 Ser Lys His Lys Arg Ile His Thr Glu Glu Lys Pro Tyr Lys Cys Glu 450 455 460 Glu Cys Gly Lys Ala Phe Asn Gln Phe Ser Ser Leu Thr Arg His Lys 465 470 475 480 Arg Ile His Thr Gly Glu Lys Arg Tyr Lys Cys Lys Glu Cys Gly Lys 485 490 495 Gly Phe Tyr Gln Ser Ser Ile His Ser Lys Tyr Lys Arg Ile Tyr Thr 500 505 510 Gly Glu Glu Pro Asp Lys Cys Lys Lys Cys Gly Ser Leu 515 520 525 <210> 363 <211> 378 <212> PRT <213> homo sapiens <400> 363 Met Ile Ser Phe Gln Glu Ser Val Thr Phe Gln Asp Val Ala Val Asp 1 5 10 15 Phe Thr Ala Glu Glu Trp Gln Leu Leu Asp Cys Ala Glu Arg Thr Leu 20 25 30 Tyr Trp Asp Val Met Leu Glu Asn Tyr Arg Asn Leu Ile Ser Val Gly 35 40 45 Cys Pro Ile Thr Lys Thr Lys Val Ile Leu Lys Val Glu Gln Gly Gln 50 55 60 Glu Pro Trp Met Val Glu Gly Ala Asn Pro His Glu Ser Ser Pro Glu 65 70 75 80 Ser Asp Tyr Pro Leu Val Asp Glu Pro Gly Lys His Arg Glu Ser Lys 85 90 95 Asp Asn Phe Leu Lys Ser Val Leu Leu Thr Phe Asn Lys Ile Leu Thr 100 105 110 Met Glu Arg Ile His His Tyr Asn Met Ser Thr Ser Leu Asn Pro Met 115 120 125 Arg Lys Lys Ser Tyr Lys Ser Phe Glu Lys Cys Leu Pro Pro Asn Leu 130 135 140 Asp Leu Leu Lys Tyr Asn Arg Ser Tyr Thr Val Glu Asn Ala Tyr Glu 145 150 155 160 Cys Ser Glu Cys Gly Lys Ala Phe Lys Lys Lys Phe His Phe Ile Arg 165 170 175 His Glu Lys Asn His Thr Arg Lys Lys Pro Phe Glu Cys Asn Asp Cys 180 185 190 Gly Lys Ala Tyr Ser Arg Lys Ala His Leu Ala Thr His Gln Lys Ile 195 200 205 His Asn Gly Glu Arg Pro Phe Val Cys Asn Asp Cys Gly Lys Ala Phe 210 215 220 Met His Lys Ala Gln Leu Val Val His Gln Arg Leu His Thr Gly Glu 225 230 235 240 Lys Pro Tyr Glu Cys Ser Gln Cys Gly Lys Thr Phe Thr Trp Asn Ser 245 250 255 Ser Phe Asn Gln His Val Lys Ser His Thr Leu Glu Lys Ser Phe Glu 260 265 270 Cys Lys Glu Cys Gly Lys Thr Phe Arg Tyr Ser Ser Ser Leu Tyr Lys 275 280 285 His Ser Arg Phe His Thr Gly Glu Lys Pro Tyr Gln Cys Ile Ile Cys 290 295 300 Gly Lys Ala Phe Gly Asn Thr Ser Val Leu Val Thr His Gln Arg Ile 305 310 315 320 His Thr Gly Glu Lys Pro Tyr Ser Cys Ile Glu Cys Gly Lys Ala Phe 325 330 335 Ile Lys Lys Ser His Leu Leu Arg His Gln Ile Thr His Thr Gly Glu 340 345 350 Lys Pro Tyr Glu Cys Asn Arg Cys Gly Lys Ala Phe Ser Gln Lys Ser 355 360 365 Asn Leu Ile Val His Gln Lys Ile His Thr 370 375 <210> 364 <211> 495 <212> PRT <213> homo sapiens <400> 364 Met Ala Lys Arg Pro Gly Pro Pro Gly Ser Arg Glu Met Gly Leu Leu 1 5 10 15 Thr Phe Arg Asp Ile Ala Ile Glu Phe Ser Leu Ala Glu Trp Gln Cys 20 25 30 Leu Asp His Ala Gln Gln Asn Leu Tyr Arg Asp Val Met Leu Glu Asn 35 40 45 Tyr Arg Asn Leu Val Ser Leu Gly Ile Ala Val Ser Lys Pro Asp Leu 50 55 60 Ile Thr Cys Leu Glu Gln Asn Lys Glu Pro Gln Asn Ile Lys Arg Asn 65 70 75 80 Glu Met Val Ala Lys His Pro Val Thr Cys Ser His Phe Thr Gln Asp 85 90 95 Leu Gln Ser Glu Gln Gly Ile Lys Asp Ser Leu Gln Lys Val Ile Leu 100 105 110 Arg Arg Tyr Gly Lys Cys Gly Gln Glu Asp Leu Gln Val Lys Lys Cys 115 120 125 Cys Lys Ser Val Gly Glu Cys Glu Val His Lys Gly Gly Tyr Asn Tyr 130 135 140 Val Asn Gln Cys Leu Ser Ala Thr Gln Asn Lys Thr Phe Gln Thr His 145 150 155 160 Lys Cys Val Lys Val Phe Gly Lys Phe Ser Asn Ser Asn Arg His Lys 165 170 175 Thr Arg His Thr Gly Lys Lys His Phe Lys Cys Lys Asn Asp Gly Lys 180 185 190 Ser Phe Cys Met Leu Ser Arg Leu Asn Gln His Gln Ile Ile His Thr 195 200 205 Arg Glu Lys Ser Tyr Lys Cys Glu Glu Cys Gly Lys Ser Phe Asn Cys 210 215 220 Ser Ser Thr Leu Thr Arg His Lys Arg Ile His Thr Gly Glu Lys Pro 225 230 235 240 Tyr Arg Cys Glu Glu Cys Gly Lys Ala Phe Ser Trp Ser Ala Ser Leu 245 250 255 Thr Lys His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Thr Cys Glu 260 265 270 Glu Arg Gly Lys Val Phe Ser Arg Ser Thr Leu Thr Asn Tyr Lys Arg 275 280 285 Ile His Thr Gly Glu Lys Pro Tyr Thr Cys Glu Glu Cys Gly Lys Ala 290 295 300 Phe Ser Arg Ser Ser Thr Leu Thr Asn His Lys Arg Ile His Thr Gly 305 310 315 320 Glu Arg Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ala Phe Ser Leu Ser 325 330 335 Ser Thr Leu Lys Lys His Lys Ile Val His Thr Gly Glu Lys Leu Tyr 340 345 350 Thr Cys Glu Glu Cys Gly Lys Ala Phe Thr Phe Ser Ser Thr Leu Asn 355 360 365 Thr His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Thr Cys Glu Glu 370 375 380 Cys Gly Lys Ala Phe Ser Leu Pro Ser Thr Phe Thr Tyr His Lys Arg 385 390 395 400 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ala 405 410 415 Phe Asn Cys Ser Ser Thr Leu Lys Lys His Lys Ile Ile His Thr Gly 420 425 430 Glu Lys Leu Tyr Lys Cys Lys Glu Cys Gly Lys Ala Phe Thr Phe Ser 435 440 445 Ser Thr Leu Asn Thr His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr 450 455 460 Lys Cys Glu Glu Cys Asp Gln Thr Phe Lys Trp His Ser Ser Leu Ala 465 470 475 480 Asn His Lys Asn Met His Thr Gly Glu Lys Pro Tyr Lys Tyr Glu 485 490 495 <210> 365 <211> 478 <212> PRT <213> homo sapiens <400> 365 Met Glu Leu Leu Thr Phe Lys Asp Val Ala Ile Glu Phe Ser Pro Glu 1 5 10 15 Glu Trp Lys Cys Leu Asp Ile Ser Gln Gln Asn Leu Tyr Arg Asp Val 20 25 30 Met Leu Glu Asn Tyr Arg Asn Leu Val Ser Leu Gly Val Thr Ile Ser 35 40 45 Asn Pro Asp Leu Val Thr Ser Leu Glu Gln Arg Lys Glu Pro Tyr Asn 50 55 60 Leu Lys Ile His Glu Thr Ala Ala Arg Pro Pro Ala Val Cys Ser His 65 70 75 80 Phe Thr Gln Asn Leu Trp Thr Val Gln Gly Ile Glu Asp Ser Phe His 85 90 95 Lys Leu Ile Pro Lys Gly His Glu Lys Arg Gly His Glu Asn Leu Arg 100 105 110 Lys Thr Cys Lys Ser Ile Asn Glu Cys Lys Val Gln Lys Gly Gly Tyr 115 120 125 Asn Arg Ile Asn Gln Cys Leu Leu Thr Thr Gln Lys Lys Thr Ile Gln 130 135 140 Ser Asn Ile Cys Val Lys Val Phe His Lys Phe Ser Asn Ser Asn Lys 145 150 155 160 Asp Lys Ile Arg Tyr Thr Gly Asp Lys Thr Phe Lys Cys Lys Glu Cys 165 170 175 Gly Lys Ser Phe His Val Leu Ser Arg Leu Thr Gln His Lys Arg Ile 180 185 190 His Thr Gly Glu Asn Pro Tyr Thr Cys Glu Glu Cys Gly Lys Ala Phe 195 200 205 Asn Trp Ser Ser Ile Leu Thr Lys His Lys Arg Ile His Ala Arg Glu 210 215 220 Lys Phe Tyr Lys Cys Glu Glu Cys Gly Lys Gly Phe Thr Arg Ser Ser 225 230 235 240 His Leu Thr Lys His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Ile 245 250 255 Cys Glu Lys Cys Gly Lys Ala Phe Asn Gln Ser Ser Thr Leu Asn Leu 260 265 270 His Lys Arg Ile His Ser Ala Gln Lys Tyr Tyr Lys Cys Glu Glu Cys 275 280 285 Gly Lys Ala Phe Lys Trp Ser Ser Ser Leu Asn Glu His Lys Arg Ile 290 295 300 His Ala Gly Glu Lys Pro Phe Ser Cys Glu Glu Cys Gly Asn Val Phe 305 310 315 320 Thr Thr Ser Ser Asp Phe Ala Lys His Lys Arg Ile His Thr Gly Glu 325 330 335 Lys Pro Tyr Lys Cys Glu Glu Cys Gly Lys Ser Phe Asn Arg Ser Thr 340 345 350 Thr Leu Thr Thr His Lys Arg Ile His Thr Gly Glu Lys Pro Tyr Thr 355 360 365 Cys Glu Glu Cys Gly Lys Ala Phe Asn Trp Ser Ser Thr Leu Asn Val 370 375 380 His Lys Arg Ile His Ser Gly Lys Asn Pro Tyr Lys Cys Glu Asp Cys 385 390 395 400 Gly Lys Ala Phe Lys Val Phe Ala Asn Leu His Asn Arg Lys Lys Ile 405 410 415 His Thr Gly Glu Lys Pro Tyr Ile Cys Lys Gln Cys Gly Lys Ala Phe 420 425 430 Lys Gln Ser Ser His Leu Asn Lys His Lys Lys Ile His Thr Val Asp 435 440 445 Lys Pro Tyr Lys Cys Lys Glu Cys Gly Lys Ala Phe Lys Gln Tyr Ser 450 455 460 Asn Leu Pro Gln His Lys Arg Thr His Thr Gly Gly Lys Phe 465 470 475 <210> 366 <211> 936 <212> PRT <213> homo sapiens <400> 366 Met Arg Pro Arg Ser Gly Gly Arg Pro Gly Ala Thr Gly Arg Arg Arg 1 5 10 15 Arg Arg Leu Arg Arg Arg Pro Arg Gly Leu Arg Cys Ser Arg Leu Pro 20 25 30 Pro Pro Pro Pro Leu Pro Leu Leu Leu Gly Leu Leu Leu Ala Ala Ala 35 40 45 Gly Pro Gly Ala Ala Arg Ala Lys Glu Thr Ala Phe Val Glu Val Val 50 55 60 Leu Phe Glu Ser Ser Pro Ser Gly Asp Tyr Thr Thr Tyr Thr Thr Gly 65 70 75 80 Leu Thr Gly Arg Phe Ser Arg Ala Gly Ala Thr Leu Ser Ala Glu Gly 85 90 95 Glu Ile Val Gln Met His Pro Leu Gly Leu Cys Asn Asn Asn Asp Glu 100 105 110 Glu Asp Leu Tyr Glu Tyr Gly Trp Val Gly Val Val Lys Leu Glu Gln 115 120 125 Pro Glu Leu Asp Pro Lys Pro Cys Leu Thr Val Leu Gly Lys Ala Lys 130 135 140 Arg Ala Val Gln Arg Gly Ala Thr Ala Val Ile Phe Asp Val Ser Glu 145 150 155 160 Asn Pro Glu Ala Ile Asp Gln Leu Asn Gln Gly Ser Glu Asp Pro Leu 165 170 175 Lys Arg Pro Val Val Tyr Val Lys Gly Ala Asp Ala Ile Lys Leu Met 180 185 190 Asn Ile Val Asn Lys Gln Lys Val Ala Arg Ala Arg Ile Gln His Arg 195 200 205 Pro Pro Arg Gln Pro Thr Glu Tyr Phe Asp Met Gly Ile Phe Leu Ala 210 215 220 Phe Phe Val Val Val Ser Leu Val Cys Leu Ile Leu Leu Val Lys Ile 225 230 235 240 Lys Leu Lys Gln Arg Arg Ser Gln Asn Ser Met Asn Arg Leu Ala Val 245 250 255 Gln Ala Leu Glu Lys Met Glu Thr Arg Lys Phe Asn Ser Lys Ser Lys 260 265 270 Gly Arg Arg Glu Gly Ser Cys Gly Ala Leu Asp Thr Leu Ser Ser Ser 275 280 285 Ser Thr Ser Asp Cys Ala Ile Cys Leu Glu Lys Tyr Ile Asp Gly Glu 290 295 300 Glu Leu Arg Val Ile Pro Cys Thr His Arg Phe His Arg Lys Cys Val 305 310 315 320 Asp Pro Trp Leu Leu Gln His His Thr Cys Pro His Cys Arg His Asn 325 330 335 Ile Ile Glu Gln Lys Gly Asn Pro Ser Ala Val Cys Val Glu Thr Ser 340 345 350 Asn Leu Ser Arg Gly Arg Gln Gln Arg Val Thr Leu Pro Val His Tyr 355 360 365 Pro Gly Arg Val His Arg Thr Asn Ala Ile Pro Ala Tyr Pro Thr Arg 370 375 380 Thr Ser Met Asp Ser His Gly Asn Pro Val Thr Leu Leu Thr Met Asp 385 390 395 400 Arg His Gly Glu Gln Ser Leu Tyr Ser Pro Gln Thr Pro Ala Tyr Ile 405 410 415 Arg Ser Tyr Pro Pro Leu His Leu Asp His Ser Leu Ala Ala His Arg 420 425 430 Cys Gly Leu Glu His Arg Ala Tyr Ser Pro Ala His Pro Phe Arg Arg 435 440 445 Pro Lys Leu Ser Gly Arg Ser Phe Ser Lys Ala Ala Cys Phe Ser Gln 450 455 460 Tyr Glu Thr Met Tyr Gln His Tyr Tyr Phe Gln Gly Leu Ser Tyr Pro 465 470 475 480 Glu Gln Glu Gly Gln Ser Pro Pro Ser Leu Ala Pro Arg Gly Pro Ala 485 490 495 Arg Ala Phe Pro Pro Ser Gly Ser Gly Ser Leu Leu Phe Pro Thr Val 500 505 510 Val His Val Ala Pro Pro Ser His Leu Glu Ser Gly Ser Thr Ser Ser 515 520 525 Phe Ser Cys Tyr His Gly His Arg Ser Val Cys Ser Gly Tyr Leu Ala 530 535 540 Asp Cys Pro Gly Ser Asp Ser Ser Ser Ser Ser Ser Ser Gly Gln Cys 545 550 555 560 His Cys Ser Ser Ser Asp Ser Val Val Asp Cys Thr Glu Val Ser Asn 565 570 575 Gln Gly Val Tyr Gly Ser Cys Ser Thr Phe Arg Ser Ser Leu Ser Ser 580 585 590 Asp Tyr Asp Pro Phe Ile Tyr Arg Ser Arg Ser Pro Cys Arg Ala Ser 595 600 605 Glu Ala Gly Gly Ser Gly Ser Ser Gly Arg Gly Pro Ala Leu Cys Phe 610 615 620 Glu Gly Ser Pro Pro Pro Glu Glu Leu Pro Ala Val His Ser His Gly 625 630 635 640 Ala Gly Arg Gly Glu Pro Trp Pro Gly Pro Ala Ser Pro Ser Gly Asp 645 650 655 Gln Val Ser Thr Cys Ser Leu Glu Met Asn Tyr Ser Ser Asn Ser Ser 660 665 670 Leu Glu His Arg Gly Pro Asn Ser Ser Thr Ser Glu Val Gly Leu Glu 675 680 685 Ala Ser Pro Gly Ala Ala Pro Asp Leu Arg Arg Thr Trp Lys Gly Gly 690 695 700 His Glu Leu Pro Ser Cys Ala Cys Cys Cys Glu Pro Gln Pro Ser Pro 705 710 715 720 Ala Gly Pro Ser Ala Gly Ala Ala Gly Ser Ser Thr Leu Phe Leu Gly 725 730 735 Pro His Leu Tyr Glu Gly Ser Gly Pro Ala Gly Gly Glu Pro Gln Ser 740 745 750 Gly Ser Ser Gln Gly Leu Tyr Gly Leu His Pro Asp His Leu Pro Arg 755 760 765 Thr Asp Gly Val Lys Tyr Glu Gly Leu Pro Cys Cys Phe Tyr Glu Glu 770 775 780 Lys Gln Val Ala Arg Gly Gly Gly Gly Gly Ser Gly Cys Tyr Thr Glu 785 790 795 800 Asp Tyr Ser Val Ser Val Gln Tyr Thr Leu Thr Glu Glu Pro Pro Pro 805 810 815 Gly Cys Tyr Pro Gly Ala Arg Asp Leu Ser Gln Arg Ile Pro Ile Ile 820 825 830 Pro Glu Asp Val Asp Cys Asp Leu Gly Leu Pro Ser Asp Cys Gln Gly 835 840 845 Thr His Ser Leu Gly Ser Trp Gly Gly Thr Arg Gly Pro Asp Thr Pro 850 855 860 Arg Pro His Arg Gly Leu Gly Ala Thr Arg Glu Glu Glu Arg Ala Leu 865 870 875 880 Cys Cys Gln Ala Arg Ala Leu Leu Arg Pro Gly Cys Pro Pro Glu Glu 885 890 895 Ala Gly Ala Val Arg Ala Asn Phe Pro Ser Ala Leu Gln Asp Thr Gln 900 905 910 Glu Ser Ser Thr Thr Ala Thr Glu Ala Ala Gly Pro Arg Ser His Ser 915 920 925 Ala Asp Ser Ser Ser Pro Gly Ala 930 935 <210> 367 <211> 852 <212> PRT <213> homo sapiens <400> 367 Met Met Ala Lys Ser Ala Leu Arg Glu Asn Gly Thr Asn Ser Glu Thr 1 5 10 15 Phe Arg Gln Arg Phe Arg Arg Phe His Tyr Gln Glu Val Ala Gly Pro 20 25 30 Arg Glu Ala Phe Ser Gln Leu Trp Glu Leu Cys Cys Arg Trp Leu Arg 35 40 45 Pro Glu Val Arg Thr Lys Glu Gln Ile Val Glu Leu Leu Val Leu Glu 50 55 60 Gln Phe Leu Thr Val Leu Pro Gly Glu Ile Gln Asn Trp Val Gln Glu 65 70 75 80 Gln Cys Pro Glu Asn Gly Glu Glu Ala Val Thr Leu Val Glu Asp Leu 85 90 95 Glu Arg Glu Pro Gly Arg Pro Arg Ser Ser Val Thr Val Ser Val Lys 100 105 110 Gly Gln Glu Val Arg Leu Glu Lys Met Thr Pro Pro Lys Ser Ser Gln 115 120 125 Glu Leu Leu Ser Val Arg Gln Glu Ser Val Glu Pro Gln Pro Arg Gly 130 135 140 Val Pro Lys Lys Glu Arg Ala Arg Ser Pro Asp Leu Gly Pro Gln Glu 145 150 155 160 Gln Met Asn Pro Lys Glu Lys Leu Lys Pro Phe Gln Arg Ser Gly Leu 165 170 175 Pro Phe Pro Lys Ser Gly Val Val Ser Arg Leu Glu Gln Gly Glu Pro 180 185 190 Trp Ile Pro Asp Leu Leu Gly Ser Lys Glu Lys Glu Leu Pro Ser Gly 195 200 205 Ser His Ile Gly Asp Arg Arg Val His Ala Asp Leu Leu Pro Ser Lys 210 215 220 Lys Asp Arg Arg Ser Trp Val Glu Gln Asp His Trp Ser Phe Glu Asp 225 230 235 240 Glu Lys Val Ala Gly Val His Trp Gly Tyr Glu Glu Thr Arg Thr Leu 245 250 255 Leu Ala Ile Leu Ser Gln Thr Glu Phe Tyr Glu Ala Leu Arg Asn Cys 260 265 270 His Arg Asn Ser Gln Val Tyr Gly Ala Val Ala Glu Arg Leu Arg Glu 275 280 285 Tyr Gly Phe Leu Arg Thr Leu Glu Gln Cys Arg Thr Lys Phe Lys Gly 290 295 300 Leu Gln Lys Ser Tyr Arg Lys Val Lys Ser Gly His Pro Pro Glu Thr 305 310 315 320 Cys Pro Phe Phe Glu Glu Met Glu Ala Leu Met Ser Ala Gln Val Ile 325 330 335 Ala Leu Pro Ser Asn Gly Leu Glu Ala Ala Ala Ser His Ser Gly Leu 340 345 350 Val Gly Ser Asp Ala Glu Thr Glu Glu Pro Gly Gln Arg Gly Trp Gln 355 360 365 His Glu Glu Gly Ala Glu Glu Ala Val Ala Gln Glu Ser Asp Ser Asp 370 375 380 Asp Met Asp Leu Glu Ala Thr Pro Gln Asp Pro Asn Ser Ala Ala Pro 385 390 395 400 Val Val Phe Arg Ser Pro Gly Gly Val His Trp Gly Tyr Glu Glu Thr 405 410 415 Lys Thr Tyr Leu Ala Ile Leu Ser Glu Thr Gln Phe Tyr Glu Ala Leu 420 425 430 Arg Asn Cys His Arg Asn Ser Gln Leu Tyr Gly Ala Val Ala Glu Arg 435 440 445 Leu Trp Glu Tyr Gly Phe Leu Arg Thr Pro Glu Gln Cys Arg Thr Lys 450 455 460 Phe Lys Ser Leu Gln Thr Ser Tyr Arg Lys Val Lys Asn Gly Gln Ala 465 470 475 480 Pro Glu Thr Cys Pro Phe Phe Glu Glu Met Asp Ala Leu Val Ser Val 485 490 495 Arg Val Ala Ala Pro Pro Asn Asp Gly Gln Glu Glu Thr Ala Ser Cys 500 505 510 Pro Val Gln Gly Thr Ser Glu Ala Glu Ala Gln Lys Gln Ala Glu Glu 515 520 525 Ala Asp Glu Ala Thr Glu Glu Asp Ser Asp Asp Asp Glu Glu Asp Thr 530 535 540 Glu Ile Pro Pro Gly Ala Val Ile Thr Arg Ala Pro Val Leu Phe Gln 545 550 555 560 Ser Pro Arg Gly Phe Glu Ala Gly Phe Glu Asn Glu Asp Asn Ser Lys 565 570 575 Arg Asp Ile Ser Glu Glu Val Gln Leu His Arg Thr Leu Leu Ala Arg 580 585 590 Ser Glu Arg Lys Ile Pro Arg Tyr Leu His Gln Gly Lys Gly Asn Glu 595 600 605 Ser Asp Cys Arg Ser Gly Arg Gln Trp Ala Lys Thr Ser Gly Glu Lys 610 615 620 Arg Gly Lys Leu Thr Leu Pro Glu Lys Ser Leu Ser Glu Val Leu Ser 625 630 635 640 Gln Gln Arg Pro Cys Leu Gly Glu Arg Pro Tyr Lys Tyr Leu Lys Tyr 645 650 655 Ser Lys Ser Phe Gly Pro Asn Ser Leu Leu Met His Gln Val Ser His 660 665 670 Gln Val Glu Asn Pro Tyr Lys Cys Ala Asp Cys Gly Lys Ser Phe Ser 675 680 685 Arg Ser Ala Arg Leu Ile Arg His Arg Arg Ile His Thr Gly Glu Lys 690 695 700 Pro Tyr Lys Cys Leu Asp Cys Gly Lys Ser Phe Arg Asp Ser Ser Asn 705 710 715 720 Phe Ile Thr His Arg Arg Ile His Thr Gly Glu Lys Pro Tyr Gln Cys 725 730 735 Gly Glu Cys Gly Lys Cys Phe Asn Gln Ser Ser Ser Leu Ile Ile His 740 745 750 Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Gln Cys Glu Glu Cys Gly 755 760 765 Lys Ser Phe Asn Asn Ser Ser His Phe Ser Ala His Arg Arg Ile His 770 775 780 Thr Gly Glu Arg Pro His Val Cys Pro Asp Cys Gly Lys Ser Phe Ser 785 790 795 800 Lys Ser Ser Asp Leu Arg Ala His His Arg Thr His Thr Gly Glu Lys 805 810 815 Pro Tyr Gly Cys His Asp Cys Gly Lys Cys Phe Ser Lys Ser Ser Ala 820 825 830 Leu Asn Lys His Gly Glu Ile His Ala Arg Glu Lys Leu Leu Thr Gln 835 840 845 Ser Ala Pro Lys 850

Claims (36)

  1. 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 가능성(likelihood)을 평가하는 데 사용되는 지표(indicator)를 결정하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 적어도 부분적으로 가리키는 것인 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  2. 대상체에 존재하는 종양의 악성(malignancy)을 평가하는 데 사용되는 지표를 결정하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 종양의 악성을 적어도 부분적으로 가리키는 것인 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  3. 대상체에서 암 재발 가능성을 예측하는 데 사용되는 지표를 결정하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계; 및
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 암이 재발하는 가능성을 적어도 부분적으로 가리키는 것인 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  4. 대상체에서 저산소증을 감소시키는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계;
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및
    (3) 지표가 대상체에서 저산소증의 존재의 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  5. 대상체에서 저산소증 질환(예를 들어 저산소증 암)을 치료하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계;
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및
    (3) 지표가 대상체에서 저산소증 질환의 존재의 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  6. 대상체에서 저산소증 종양의 악성을 감소시키는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계;
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및
    (3) 지표가, 종양이 저산소증이라는 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  7. 대상체에서 저산소증 종양을 치료하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계;
    (2) 바이오마커 값(들)을 사용하여 지표를 결정하는 단계; 및
    (3) 지표가, 종양이 저산소증이라는 가능성을 적어도 부분적으로 가리킨다는 것을 기초로, 유효량의 G9a 길항제를 대상체에게 투여하는 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  8. 제5항 내지 제7항 중 어느 한 항에 있어서,
    대상체에게 보조 치료(ancillary treatment)가 투여되는, 방법.
  9. 제8항에 있어서,
    보조 치료가 화학 요법 및/또는 방사선 요법인, 방법.
  10. 제1항 내지 제9항 중 어느 한 항에 있어서,
    지표가 적어도 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20(및 이들 사이의 모든 정수)개의 저산소증 바이오마커에 대한 바이오마커 값을 포함하는 것인, 방법.
  11. 제1항 내지 제10항 중 어느 한 항에 있어서,
    시료가 생물학적 시료인, 방법.
  12. 제11항에 있어서,
    생물학적 시료가 종양 세포를 포함하는, 방법.
  13. 제1항 내지 제12항 중 어느 한 항에 있어서,
    적어도 하나의 저산소증 바이오마커가
    (a) 서열번호 1-10 중 임의의 하나에 표시된 서열, 또는 이의 보체와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 동일성을 공유하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물;
    (b) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물;
    (c) 서열번호 202-211에 표시된 서열 중 적어도 일부와 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 폴리펩타이드를 인코딩하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물;
    (d) 중간 또는 높은 엄격성 조건 하에, (a), (b), (c)의 서열 또는 이의 보체에 혼성화하는 뉴클레오타이드 서열을 포함하는 폴리뉴클레오타이드 발현 생성물;
    (e) 서열번호 202-211 중 임의의 하나에 표시된 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물; 및
    (f) 서열번호 202-211 중 임의의 하나에 표시된 서열과 적어도 70%(또는 적어도 71% 내지 적어도 99% 및 이들 사이의 모든 정수 퍼센트) 서열 유사성 또는 동일성을 공유하는 아미노산 서열을 포함하는 폴리펩타이드 발현 생성물
    로 구성된 군으로부터 선택되는, 방법.
  14. 제1항 내지 제13항 중 어느 한 항에 있어서,
    바이오마커 값이 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커의 농도를 적어도 부분적으로 가리키는 것인, 방법.
  15. 제1항 내지 제13항 중 어느 한 항에 있어서,
    바이오마커 값이 대상체로부터 수득된 시료에서 적어도 하나의 저산소증 바이오마커의 유전자 발현의 수준을 적어도 부분적으로 가리키는 것인, 방법.
  16. 제1항 내지 제13항 중 어느 한 항에 있어서,
    바이오마커 값이 바이오마커의 풍부도(abundance)를 포함하는 것인, 방법.
  17. 제1항 내지 제16항 중 어느 한 항에 있어서,
    적어도 하나의 저산소증 바이오마커의 수준이 정상적인(즉, 비-저산소증) 질환의 존재와 연관이 있는 바이오마커의 수준에 비해 감소되고, 이로써 지표가 저산소증을 적어도 부분적으로 가리키는 것으로 결정되는, 방법.
  18. 제1항 내지 제16항 중 어느 한 항에 있어서,
    적어도 하나의 저산소증 바이오마커의 수준이 정상적인(즉, 비-저산소증) 질환의 존재와 연관이 있는 바이오마커의 수준과 대략 동일하고, 지표가 정상산소증(normoxia)을 적어도 부분적으로 가리키는 것으로 결정되는, 방법.
  19. 대상체에서 저산소증 질환(예를 들어 저산소증 암)의 존재 또는 부재의 가능성을 평가하는 데 사용되는 지표를 결정하는 방법으로서, 상기 방법은:
    (1) 대상체로부터 수득된 시료에서 적어도 하나의 그룹 1 저산소증 바이오마커(예를 들어 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10개의 저산소증 바이오마커)에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 단계;
    (2) 그룹 2 저산소증 바이오마커에 대해 측정되거나 파생되는 바이오마커 값을 결정하는 단계로서, 여기서, 그룹 2 저산소증 바이오마커는 G9a인 단계; 및
    (3) 바이오마커 값을 사용하여 지표를 결정하는 단계로서, 여기서, 지표는 대상체에서 저산소증 질환의 존재 또는 부재의 가능성을 적어도 부분적으로 가리키는 것인 단계
    를 포함하거나, 구성되거나, 본질적으로 구성되는 방법.
  20. 제19항에 있어서,
    상기 방법은 조합 기능을 적어도 하나의 그룹 1 저산소증 바이오마커 값(들) 및 그룹 2 저산소증 바이오마커에 적용하는 단계를 추가로 포함하는, 방법.
  21. 제19항 또는 제20항에 있어서,
    지표가 그룹 1 저산소증 바이오마커 및 그룹 2 저산소증 바이오마커 상에 기록된 바이오마커 값의 비(ratio)인, 방법.
  22. 제1항 내지 제21항 중 어느 한 항에 있어서,
    바이오마커 값(들)이 현미경, 유세포분석, 면역검정법, 질량 분광법, 시퀀싱 플랫폼, 어레이 및 혼성화 플랫폼, 또는 이들의 조합을 사용하여 측정되는, 방법.
  23. 저산소증의 가능성을 평가하는 데 사용되는 지표를 결정하기 위한 조성물로서, 상기 조성물은 적어도 하나의 cDNA, 및 상기 cDNA에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하거나, 구성되거나, 본질적으로 구성되며, 여기서, 적어도 하나의 cDNA는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는, 조성물.
  24. 적어도 하나의 cDNA, 및 상기 cDNA에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하거나, 구성되거나, 본질적으로 구성되는 복합체로서, 여기서, 적어도 하나의 cDNA는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는, 복합체.
  25. 제23항 또는 제24항에 있어서,
    2개 이상의 cDNA, 및 상기 cDNA 중 개별적인 하나에 혼성화하는 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브를 포함하는, 조성물 또는 복합체.
  26. 제25항에 있어서,
    조성물 또는 복합체가 세포 또는 세포 집단(population)으로부터 파생되는 mRNA에 상응하는 cDNA의 집단을 포함하는, 조성물 또는 복합체.
  27. 제26항에 있어서,
    세포가 종양 세포인, 조성물 또는 복합체.
  28. 제23항 내지 제27항 중 어느 한 항에 있어서,
    적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브가 cDNA 중 개별적인 하나에 혼성화하는, 조성물 또는 복합체.
  29. 제23항 내지 제28항 중 어느 한 항에 있어서,
    조성물 또는 복합체가 cDNA를 검출하기 위한 표지된 시약을 추가로 포함하는, 조성물 또는 복합체.
  30. 제29항에 있어서,
    표지된 시약이 표지된 상기 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브인, 조성물 또는 복합체.
  31. 제30항에 있어서,
    표지된 시약이 표지된 상기 cDNA인, 조성물 또는 복합체.
  32. 제23항 내지 제31항 중 어느 한 항에 있어서,
    적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브가 고밀도 어레이 이외의 형태로 존재하는, 조성물 또는 복합체.
  33. 대상체에서 저산소증의 가능성을 가리키는 지표를 결정하기 위한 키트로서,
    상기 키트는:
    (a) 저산소증 바이오마커의 정량화를 허용하는 적어도 하나의 시약으로서, 여기서, 적어도 하나의 저산소증 바이오마커는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는 시약; 및 선택적으로
    (b) 적어도 하나의 시약을 사용하기 위한 설명서
    를 포함하는, 키트.
  34. 적어도 하나(즉, 2, 3, 4, 5, 6, 7, 8, 9, 10, 또는 10개 초과)의 cDNA, 및 각각의 제각기 cDNA에 대해 상기 cDNA의 반대쪽 상보 가닥에 혼성화하는 2개의 올리고뉴클레오타이드 프라이머, 및 상기 cDNA에 혼성화하는 올리고뉴클레오타이드 프로브를 포함하거나, 구성되거나, 본질적으로 구성되는 조성물로서, 여기서, 적어도 하나의 cDNA는 ARNTL, CD1C, HHEX, KLRG1, MMP16, FGFR2, GATA2, CEACAM7, OGN 및 AGTR1로부터 선택되는, 조성물.
  35. 제34항에 있어서,
    조성물이 cDNA를 검출하기 위한 표지된 시약을 추가로 포함하는, 조성물.
  36. 제34항에 있어서,
    표지된 시약이 표지된 적어도 하나의 올리고뉴클레오타이드 프라이머 또는 프로브인, 조성물.
KR1020197027295A 2017-02-23 2018-02-23 질환 진단용 바이오마커 Ceased KR20190126812A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AU2017900607 2017-02-23
AU2017900607A AU2017900607A0 (en) 2017-02-23 Biomarkers for diagnosing conditions
PCT/AU2018/050156 WO2018152585A1 (en) 2017-02-23 2018-02-23 "biomarkers for diagnosing conditions"

Publications (1)

Publication Number Publication Date
KR20190126812A true KR20190126812A (ko) 2019-11-12

Family

ID=63253478

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020197027295A Ceased KR20190126812A (ko) 2017-02-23 2018-02-23 질환 진단용 바이오마커

Country Status (5)

Country Link
US (1) US20200239937A1 (ko)
EP (1) EP3585909A4 (ko)
KR (1) KR20190126812A (ko)
AU (1) AU2018223224A1 (ko)
WO (1) WO2018152585A1 (ko)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113222966B (zh) * 2018-06-07 2023-01-10 深圳迈瑞生物医疗电子股份有限公司 基于超声影像设备的图像分析方法及超声影像设备
CN111477276B (zh) * 2020-04-02 2020-12-15 上海之江生物科技股份有限公司 微生物的种特异共有序列的获得方法、装置及应用
US20250210193A1 (en) * 2022-03-16 2025-06-26 The Regents Of The University Of California Methods and systems for microbial tumor hypoxia diagnostics and theranostics

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2001292802A1 (en) * 2000-09-19 2002-04-02 Dana-Farber Cancer Institute Inc. Genetic markers for tumors
WO2005098037A1 (en) * 2003-03-07 2005-10-20 Arcturus Bioscience, Inc. Breast cancer signatures
WO2006124022A1 (en) * 2005-05-13 2006-11-23 Vanandel Research Institute Microarray gene expression profiling in subtypes of clear cell renal cell carcinoma
US20100105564A1 (en) * 2006-09-15 2010-04-29 Mcgill University Stroma Derived Predictor of Breast Cancer
WO2010065940A1 (en) * 2008-12-04 2010-06-10 The Regents Of The University Of California Materials and methods for determining diagnosis and prognosis of prostate cancer
KR101142588B1 (ko) * 2009-05-26 2012-05-10 서울대학교산학협력단 렙틴 메틸화를 통해 저산소 반응을 음성 조절하는 메틸전달효소를 포함하는 암 치료용 조성물
EP2472263A1 (en) * 2011-01-03 2012-07-04 Commissariat À L'Énergie Atomique Et Aux Énergies Alternatives Methods for the prognostic assessment of breast cancer
CN103492590A (zh) * 2011-02-22 2014-01-01 卡里斯生命科学卢森堡控股有限责任公司 循环生物标志物
WO2013075059A1 (en) * 2011-11-18 2013-05-23 Vanderbilt University Markers of triple-negative breast cancer and uses thereof
KR101849409B1 (ko) * 2011-12-31 2018-06-01 서울대학교산학협력단 폰틴의 메틸화 정도를 이용한 항암제 스크리닝 방법
US20170107577A1 (en) * 2014-03-11 2017-04-20 The Council Of The Queensland Institute Of Medical Research Determining Cancer Aggressiveness, Prognosis and Responsiveness to Treatment
WO2016057705A1 (en) * 2014-10-08 2016-04-14 Novartis Ag Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof

Also Published As

Publication number Publication date
EP3585909A1 (en) 2020-01-01
AU2018223224A1 (en) 2019-09-12
WO2018152585A1 (en) 2018-08-30
EP3585909A4 (en) 2020-12-23
US20200239937A1 (en) 2020-07-30

Similar Documents

Publication Publication Date Title
AU2017267184B2 (en) Method for assessing a prognosis and predicting the response of patients with malignant diseases to immunotherapy
AU2015334842B2 (en) Medical prognosis and prediction of treatment response using multiple cellular signaling pathway activities
KR102252561B1 (ko) Ｃ/ｅｂｐ 알파 짧은 활성화 ｒｎａ 조성물 및 사용 방법
KR101778036B1 (ko) 전립선암 마커로서의 포스포디에스테라제 4ｄ7
KR101234281B1 (ko) 염색체 안정화에 관한 유전자를 표적으로 하는 암세포 특이적 아포토시스 유도제
KR102110469B1 (ko) 악성의 호르몬 민감성 전립선 암에 대한 마커로서의 포스포디에스테라제 4ｄ7
KR102149483B1 (ko) 예측변수 인자들을 이용하여 동정된 환자 부분 모집단에서 암 치료를 위한 마시티닙의 용도
KR20180093902A (ko) 태아와 임신 여성간에 상이하게 메틸화된 디엔에이 영역을 이용한 태아 염색체 이수성의 검출
CN107223159A (zh) 源自特定细胞类型的dna的检测及相关方法
CA2936612A1 (en) Atf6 polymorphisms associated with myocardial infarction, method of detection and uses thereof
KR20220024184A (ko) 대장암의 검출
KR20220025749A (ko) 대장암의 검출
KR20220054401A (ko) 감염의 숙주 rna 바이오마커의 신속한 조기-검출 및 인간의 covid-19 코로나바이러스 감염의 조기 식별을 위한 시스템, 방법 및 조성물
CN101258249A (zh) 检测黑素瘤的方法和试剂
KR20040065524A (ko) 백혈병을 검사 및 치료하는 방법
KR20210144822A (ko) Ube3a-ats를 조절하기 위한 화합물 및 방법
KR20060045950A (ko) 혈액학적 악성종양에 대한 예후
AU2018360287B2 (en) Method for determining the response of a malignant disease to an immunotherapy
KR20190126812A (ko) 질환 진단용 바이오마커
JP2003259877A (ja) 肝線維症疾患マーカーおよびその利用
TW202227102A (zh) 治療脂肪肝病之方法
KR102001153B1 (ko) 유방암 예후 예측용 조성물 및 방법
CN100516876C (zh) 用于诊断肾细胞癌(rcc)和其他实体瘤的方法
KR20170116009A (ko) 전립선암의 진단을 위한 신규한 rna-바이오마커 시그니처
KR102642320B1 (ko) 항암제에 대한 내성 진단용 조성물

Legal Events

Date Code Title Description
PA0105 International application

Patent event date: 20190918

Patent event code: PA01051R01D

Comment text: International Patent Application

PG1501 Laying open of application
A201 Request for examination
PA0201 Request for examination

Patent event code: PA02012R01D

Patent event date: 20210222

Comment text: Request for Examination of Application

E902 Notification of reason for refusal
PE0902 Notice of grounds for rejection

Comment text: Notification of reason for refusal

Patent event date: 20230105

Patent event code: PE09021S01D

E601 Decision to refuse application
PE0601 Decision on rejection of patent

Patent event date: 20230816

Comment text: Decision to Refuse Application

Patent event code: PE06012S01D

Patent event date: 20230105

Comment text: Notification of reason for refusal

Patent event code: PE06011S01I