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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 PDF

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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
Application number
PCT/GB1997/000681
Other languages
English (en)
Inventor
David Andrew Collier
Maria Jesus Arranz
Original Assignee
Smithkline Beecham Plc
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 GBGB9605493.7A external-priority patent/GB9605493D0/en
Priority claimed from GBGB9605494.5A external-priority patent/GB9605494D0/en
Priority claimed from GBGB9607526.2A external-priority patent/GB9607526D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to AU19336/97A priority Critical patent/AU1933697A/en
Publication of WO1997034928A1 publication Critical patent/WO1997034928A1/fr

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals 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.

Landscapes

  • 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

L'invention porte sur une méthode utilisable lorsqu'il s'agit d'évaluer si un patient risque ou non de développer un trouble d'ordre psychotique, une schizophrénie, un trouble affectif bipolaire ou une dépression unipolaire, par exemple. La méthode consiste à rechercher la présence ou l'absence d'ADN codant les allèles à 10 répétitions et/ou à 12 répétitions de l'intron 2 VNTR sur le gène hSERT dans un échantillon biologique prélevé sur ce patient. Cette invention concerne également une lignée cellulaire et un animal transgénique exprimant les 10 et/ou 12 répétitions.
PCT/GB1997/000681 1996-03-15 1997-03-12 Methode d'evaluation des risques de voir se developper des affections psychotiques WO1997034928A1 (fr)

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
GBGB9605493.7A GB9605493D0 (en) 1996-03-15 1996-03-15 Novel method
GB9605494.5 1996-03-15
GB9605493.7 1996-03-15
GBGB9605494.5A GB9605494D0 (en) 1996-03-15 1996-03-15 Novel method
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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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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