WO1997034928A1 - Methode d'evaluation des risques de voir se developper des affections psychotiques - Google Patents
Methode d'evaluation des risques de voir se developper des affections psychotiques Download PDFInfo
- Publication number
- WO1997034928A1 WO1997034928A1 PCT/GB1997/000681 GB9700681W WO9734928A1 WO 1997034928 A1 WO1997034928 A1 WO 1997034928A1 GB 9700681 W GB9700681 W GB 9700681W WO 9734928 A1 WO9734928 A1 WO 9734928A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vntr
- hsert
- psychotic disorder
- subject
- gene
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 53
- 208000028017 Psychotic disease Diseases 0.000 title claims abstract description 42
- 108700028369 Alleles Proteins 0.000 claims abstract description 60
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 30
- 238000012360 testing method Methods 0.000 claims abstract description 17
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 16
- 239000012472 biological sample Substances 0.000 claims abstract description 10
- 230000009261 transgenic effect Effects 0.000 claims abstract description 6
- 241001465754 Metazoa Species 0.000 claims abstract description 5
- 239000000523 sample Substances 0.000 claims description 13
- 238000007619 statistical method Methods 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 5
- 238000003556 assay Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 208000017194 Affective disease Diseases 0.000 claims description 3
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 239000012620 biological material Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000003176 neuroleptic agent Substances 0.000 claims 1
- 208000020401 Depressive disease Diseases 0.000 abstract description 10
- 201000003104 endogenous depression Diseases 0.000 abstract description 10
- 208000024714 major depressive disease Diseases 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 208000035475 disorder Diseases 0.000 abstract description 2
- 108020004414 DNA Proteins 0.000 description 35
- 208000028683 bipolar I disease Diseases 0.000 description 19
- 208000020925 Bipolar disease Diseases 0.000 description 18
- 208000025307 bipolar depression Diseases 0.000 description 17
- 238000003205 genotyping method Methods 0.000 description 7
- 239000003155 DNA primer Substances 0.000 description 6
- 101000631929 Homo sapiens Sodium-dependent serotonin transporter Proteins 0.000 description 4
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 4
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 4
- 102100028874 Sodium-dependent serotonin transporter Human genes 0.000 description 4
- 239000011543 agarose gel Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 4
- 229960005542 ethidium bromide Drugs 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 3
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 3
- 229960004170 clozapine Drugs 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000002751 oligonucleotide probe Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- 206010012374 Depressed mood Diseases 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000000698 schizophrenic effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 206010027951 Mood swings Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000007834 ligase chain reaction Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
Definitions
- Schizophrenia is a devastating psychiatric disease for which there is currently no cure, although advances are now being made in understanding its causes and controlling its symptoms. In general the age of onset is in late adolescence and it is a lifelong illness with a very poor prognosis. Subjects suffering from schizophrenia may exhibit positive symptoms, for example delusions and hallucinations, and /or negative symptoms such as withdrawal, isolation and demotivation leading ultimately to social decline and suicide. Early identification of subjects at risk of developing schizophrenia would enable early and if appropriate, prophylactic treatment to be given.
- the step of testing for and detecting the presence or absence of DNA encoding the 10- and or 12-repeat alleles may be carried out either directly or indirectly by any suitable means, such as by techniques well known in the art, and is preferably carried out ex vivo All generally involve the step of collecting a sample of biological material containing DNA from the subject, and then detecting which alleles the subject possesses from that sample.
- the detecting step may be carried out by collecting a biological sample containing DNA from the subject, and then determining the presence or absence of DNA comprising a 10- and/or 12-repeat allele in the biological sample.
- Any biological sample which contains the DNA of that subject may be employed, including tissue samples and blood samples, with blood cells being a particularly convenient source.
- the detecting step may include the step of detecting whether the subject is heterozygous or homozygous for the gene encoding a 10- and/or 12-repeat allele.
- Numerous different oligonucleotide probe assay formats are known which may be employed to carry out the present invention.
- the present invention has utility in enabling improvements in the clinical management of patients suffering from a psychotic disorder, such as schizophrenia, bipolar depression or unipolar depression.
- a psychotic disorder such as schizophrenia, bipolar depression or unipolar depression.
- the method used to detect the polymo ⁇ hism of the VNTR in the serotonin transporter hSERT was based on the method of Lesch et al. (J Neural Transm. 1994 95(2) 157-62) with the following modification: the oligonucleotide primers 5' gtcagtatcaacaggctgcgag 3' and 5' tgttcctagtcttacgccagtg 3' were used.
- the size of the DNA PCR products after the use of these oligonucleotide primers was determined by a standard method ie electrophoresis in an agarose gel next to DNA size standards and then staining of the DNA with ethidium bromide and visualisation of the DNA under an ultraviolet li *geh* t.
- the method used to detect the polymorphism of the VNTR in the serotonin transporter hSERT was based on the method of Lesch et al. (J Neural Transm. 1994 95(2) 157-62) with the following modification: the oligonucleotide primers 5' gtcagtatcacaggctgcgag 3' and 5' tgttcctagtcttacgccagtg 3' were used.
- the size of the DNA PCR products after the use of these oligonucleotide primers was determined by a standard method ie electrophoresis in an agarose gel next to DNA size standards and then staining of the DNA with ethidium bromide and visualisation of the DNA under an ultraviolet light.
- Genotyping for VNTR polymorphism was carried out using blood samples obtained from individuals diagnosed as suffering from unipolar and/or bipolar depression (DSM IV). Genotyping was also carried out on a control group of patients not suffering from unipolar and/or bipolar depression.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU19336/97A AU1933697A (en) | 1996-03-15 | 1997-03-12 | Method for assessing risk to develop psychotic disease |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9605494.5 | 1996-03-15 | ||
GBGB9605493.7A GB9605493D0 (en) | 1996-03-15 | 1996-03-15 | Novel method |
GBGB9605494.5A GB9605494D0 (en) | 1996-03-15 | 1996-03-15 | Novel method |
GB9605493.7 | 1996-03-15 | ||
GB9607526.2 | 1996-04-11 | ||
GBGB9607526.2A GB9607526D0 (en) | 1996-04-11 | 1996-04-11 | Novel method |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997034928A1 true WO1997034928A1 (fr) | 1997-09-25 |
Family
ID=27268182
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1997/000681 WO1997034928A1 (fr) | 1996-03-15 | 1997-03-12 | Methode d'evaluation des risques de voir se developper des affections psychotiques |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU1933697A (fr) |
WO (1) | WO1997034928A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056947A1 (fr) * | 1997-06-10 | 1998-12-17 | The Garvan Institute Of Medical Research | Methodes permettant de diagnostiquer et d'evaluer une predisposition aux troubles bipolaires de l'humeur |
EP1353549A2 (fr) * | 2000-06-01 | 2003-10-22 | PHARMACIA & UPJOHN COMPANY | Souris heterozygotes pour le gene wfs1 en tant que modeles de souris pour la depression |
WO2009036513A1 (fr) * | 2007-09-21 | 2009-03-26 | Murdoch Childrens Research Institute | Protocoles de diagnostic et thérapeutique |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993008261A1 (fr) * | 1991-10-22 | 1993-04-29 | Emory University | Adn complementaire codant un transporteur de serotonine |
WO1997011175A1 (fr) * | 1995-09-23 | 1997-03-27 | Medical Research Council | Depistage de troubles lies au dysfonctionnement serotoninergique |
-
1997
- 1997-03-12 AU AU19336/97A patent/AU1933697A/en not_active Abandoned
- 1997-03-12 WO PCT/GB1997/000681 patent/WO1997034928A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993008261A1 (fr) * | 1991-10-22 | 1993-04-29 | Emory University | Adn complementaire codant un transporteur de serotonine |
WO1997011175A1 (fr) * | 1995-09-23 | 1997-03-27 | Medical Research Council | Depistage de troubles lies au dysfonctionnement serotoninergique |
Non-Patent Citations (4)
Title |
---|
ALAN D OGILVLE ET AL,: "Polymorphism in serotonin transporter gene associated with susceptibility to major depression", THE LANCET, vol. 347, March 1996 (1996-03-01), XP000615491, DOI: doi:10.1016/S0140-6736(96)90079-3 * |
DAVID A. COLLIER ET AL,: "The serotonin transporter is a potential susceptibility factor for bipolar affective disorder", GENETICS OF NERVOUS SYSTEM DISEASE, vol. 7, no. 10, July 1996 (1996-07-01), XP000613721 * |
Dialog Information Services, File 34, SciSearch, Dialog accession no. 15628040, Quinn JP et al: "Structure of a variable number tandem repeat of the serotonin transporter gene and association with affective disorder", Psychiatric Genetics, 1996, V6, N4 (WIN), p177-181 * |
K.-P. LESCH ET AL,: "Organization of the human serotonin transporter gene", J NEURAL TRANSM, VOLUME, vol. 95, 1994, XP000613887, DOI: doi:10.1007/BF01276434 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056947A1 (fr) * | 1997-06-10 | 1998-12-17 | The Garvan Institute Of Medical Research | Methodes permettant de diagnostiquer et d'evaluer une predisposition aux troubles bipolaires de l'humeur |
US6274352B1 (en) | 1997-06-10 | 2001-08-14 | Garvan Institute Of Medical Research | Methods for diagnosing and assessing a predisposition to bipolar affective disorder |
EP1353549A2 (fr) * | 2000-06-01 | 2003-10-22 | PHARMACIA & UPJOHN COMPANY | Souris heterozygotes pour le gene wfs1 en tant que modeles de souris pour la depression |
WO2009036513A1 (fr) * | 2007-09-21 | 2009-03-26 | Murdoch Childrens Research Institute | Protocoles de diagnostic et thérapeutique |
Also Published As
Publication number | Publication date |
---|---|
AU1933697A (en) | 1997-10-10 |
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