WO2001082774A2 - Methods and compositions for the diagnosis of schizophrenia - Google Patents

Methods and compositions for the diagnosis of schizophrenia Download PDF

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Publication number
WO2001082774A2
WO2001082774A2 PCT/US2001/013044 US0113044W WO0182774A2 WO 2001082774 A2 WO2001082774 A2 WO 2001082774A2 US 0113044 W US0113044 W US 0113044W WO 0182774 A2 WO0182774 A2 WO 0182774A2
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WO
WIPO (PCT)
Prior art keywords
allele
determining
scz
patient
dna
Prior art date
Application number
PCT/US2001/013044
Other languages
French (fr)
Other versions
WO2001082774A3 (en
Inventor
Linda M. Brzustowicz
Anne S. Bassett
Original Assignee
Rutgers, The State University Of New Jersey
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
Application filed by Rutgers, The State University Of New Jersey filed Critical Rutgers, The State University Of New Jersey
Priority to AU2001257164A priority Critical patent/AU2001257164A1/en
Publication of WO2001082774A2 publication Critical patent/WO2001082774A2/en
Publication of WO2001082774A3 publication Critical patent/WO2001082774A3/en

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    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention maps a gene (SCZ) associated with schizophrenia to the q22 region of chromosome 1. The invention exploits this discovery to provide methods of diagnosing schizophrenia and schizophrenia susceptibility, methods of screening for the SCZ gene, and libraries of cloned segments including the SCZ gene.

Claims

What is claimed is:
1. A method of diagnosing susceptibility to schizophrenia in a patient, the method comprising: determining the presence or absence of an allele of a polymorphic marker in the DNA of the patient, wherein the polymorphic marker is within a segment of chromosome lq22 bordered by D1S2705 and D1S1679 and is linked to a DNA segment (SCZ) having a variant form associated with a phenotype of schizophrenia, and said allele is in phase with the variant form of SCZ, whereby the presence of said allele in the patient indicates susceptibility to schizophrenia .
2. The method of claim 1, wherein the polymorphic • marker is AP0A2, FcERlG, FcGR2A, B426K24T, or D1S2675.
3. The method of claim 1, wherein the polymorphic marker is within 4 cM of the B426K24T marker.
4. The method of claim 1, wherein the polymorphic marker is between B426K24T and D1S2675.
5. The method of claim 1, wherein the allele is in linkage disequilibrium with the DNA segment.
6. The method of claim 1, further comprising the step of establishing that the allele is in phase with the variant form of the DNA segment.
7. The method of claim 6, wherein the establishing step comprises determining the presence or absence of the allele in first and second degree relatives of the patient, the first and second degree relative each being of known phenotype for schizophrenia, at least one of the
70 relatives having a phenotype of schizophrenia and being informative for the allele.
8. The method of claim 7, further comprising the step of determining the phenotypes of relatives .
9. The method of claim 8, wherein the phenotypes of the relatives are determined by the DSM-IIIR criteria of Table 1 and Table 2.
10. The method of claim 9 , wherein one of the relatives is a parent or, sibling of the patient.
11. The method of claim 1, further comprising the step of determining the presence or absence of an allele of a second polymorphic marker in the patient.
12. The method of claim 1, wherein the presence or absence of the allele is determined by amplifying a segment of DNA within chromosome lq22 that spans the polymorphic marker.
13. The method of claim 12, further comprising the step of determining the size of the amplified segment.
14. The method of claim 12, further comprising the step of determining the sequence of the amplified segment .
15. The method of claim 12, further comprising the step of determining the presence or absence of a restriction enzyme site within the amplified segment.
16. The method of claim 1, wherein the presence or absence of the allele is determined by contacting the DNA
71 from the patient with an oligonucleotide probe capable of hybridizing to the allele under stringent conditions; and determining whether hybridization has occurred thereby indicating the presence of the allele.
17. The method of claim 16, further comprising the step of isolating a sample of DNA from the patient.
18. The method of claim 17, wherein the DNA is genomic and the sample is obtained from saliva, blood or buccal mucosal cells .
19. A method for determining the presence of an alteration in the SCZ promoter sequence, said alteration being associated with a schizophrenic condition, said method comprising: a) providing a nucleic acid molecule comprising SEQ ID NO : 1 ; b) isolating the corresponding sequence from a test subject suspected of having an alteration in the SCZ promoter; c) forming a heteroduplex between the sequence of step a) and step b) ; and d) assessing said duplex for the presence of an alteration selected from the group consisting of a mismatch, an insertion and a deletion.
20. A method for assessing a test compound for SCZ protein modulating activity, comprising: a) providing a purified SCZ protein having SEQ
ID NO: 2; b) contacting said SCZ protein with an agent suspected on modulating SCZ protein activity; c) determining the extent of said SCZ modulation by said test compound, if any.
72
PCT/US2001/013044 2000-04-21 2001-04-23 Methods and compositions for the diagnosis of schizophrenia WO2001082774A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001257164A AU2001257164A1 (en) 2000-04-21 2001-04-23 Methods and compositions for the diagnosis of schizophrenia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19899000P 2000-04-21 2000-04-21
US60/198,990 2000-04-21

Publications (2)

Publication Number Publication Date
WO2001082774A2 true WO2001082774A2 (en) 2001-11-08
WO2001082774A3 WO2001082774A3 (en) 2002-05-02

Family

ID=22735750

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/013044 WO2001082774A2 (en) 2000-04-21 2001-04-23 Methods and compositions for the diagnosis of schizophrenia

Country Status (2)

Country Link
AU (1) AU2001257164A1 (en)
WO (1) WO2001082774A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004081197A2 (en) * 2003-03-12 2004-09-23 Incyte Corporation Immune response associated proteins
JP2012502000A (en) * 2008-09-05 2012-01-26 ズップレモル ゲゼルシャフト ミット ベシュレンクテル ハフツング Substances and methods for the treatment of B cell mediated multiple sclerosis

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BRZUSTOWICZ L.A. ET AL.: 'Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-22' SCIENCE vol. 288, no. 5466, 28 April 2000, pages 678 - 682, XP002949636 *
GOODMAN A.B.: 'Medical conditions in ashkenazi schizophrenic pedigrees' SCHIZOPHRENIA BULLETIN vol. 20, no. 3, 1994, pages 507 - 517, XP002949639 *
PULVER A.E. ET AL.: 'Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes' MOLECULAR PSYCHIATRY vol. 5, no. 6, November 2000, pages 650 - 653, XP002949638 *
WITTEKINDT O. ET AL.: 'The human small conductance calcium-regulated potassium channel gene (hSKCa3) contains two CAG repeats in Exon 1, is on chromosome 1q21.3 and shows a possible association with schizophrenia' NEUROGENETICS vol. 1, no. 4, August 1998, pages 259 - 265, XP002949637 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004081197A2 (en) * 2003-03-12 2004-09-23 Incyte Corporation Immune response associated proteins
WO2004081197A3 (en) * 2003-03-12 2007-03-29 Incyte Corp Immune response associated proteins
JP2012502000A (en) * 2008-09-05 2012-01-26 ズップレモル ゲゼルシャフト ミット ベシュレンクテル ハフツング Substances and methods for the treatment of B cell mediated multiple sclerosis

Also Published As

Publication number Publication date
AU2001257164A1 (en) 2001-11-12
WO2001082774A3 (en) 2002-05-02

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