Microsatellite Markers of Schizophrenia

• US 20110143341A1
• Filed: 01/26/2011
• Published: 06/16/2011
• Est. Priority Date: 12/30/2004
• Status: Abandoned Application

• Current Assignee: University of Louisville
• Original Assignee: University of Louisville
• Inventors: Condra, Jodi Ann, Massey, Amy Tabb, Brennan, Mark David, Neibergs, Holly
• Application Number:
  US13/014,455
• Publication Number:
  US 20110143341A1
• Time in Patent Office: Days
• US Class Current: 435/6.1
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The invention includes methods of determining if a subject is at risk for developing schizophrenia (SZ).

Claims

1. A method of determining a human subject'"'"'s risk of developing schizophrenia (SZ), the method comprising:

obtaining a sample comprising DNA from the subject;

determining the identity of both alleles of rs1573726 in the sample;

comparing the identity of the rs1573726 alleles in the subject to the alleles of rs1573726 in;

(i) a relative of the subject who is affected with SZ, and

(ii) a relative of the subject who is not affected with SZ,

wherein the presence of an allele at rs1573726 in the subject that is the same as an allele in the relative who is affected with SZ, and is not the same as the allele in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ.

2. The method of claim 1, further comprising determining the identity of both alleles of one or more of rs135221, rs763126, rs848768, rs2269523, rs738615, rs738596, rs738598, rs138844, or rs135819 in the subject, thereby determining a subject haplotype, and comparing the subject haplotype to

(i) a haplotype in a relative of the subject who is affected with SZ, and

(ii) a haplotype in a relative of the subject who is not affected with SZ,

wherein the presence of a haplotype in the subject that is the same as the haplotype in the relative who is affected with SZ, and is not the same as the haplotype in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ.

3. The method of claim 1, further comprising:

obtaining a sample comprising DNA from a relative of the subject who is affected with SZ, and determining the genotype of rs1573726 in the sample; and

obtaining a sample comprising DNA from a relative of the subject who is not affected with SZ, and determining the identity of both alleles of rs1573726 in the sample.

4. The method of claim 1, wherein the relative is a parent or sibling.

5. The method of claim 1, wherein determining the identity of both alleles comprises:

obtaining a sample comprising DNA from the subject; and

determining the identity of both alleles at rs1573726 in the sample.

6. The method of claim 1, wherein the sample is obtained from the subject by a health care provider.

7. The method of claim 1, wherein the sample is provided by the subject without the assistance of a health care provider.

8. The method of claim 1, further comprising determining the presence or absence of one or more additional markers associated with schizophrenia.

9. The method of claim 1, wherein the subject is a patient having, or at risk of, schizophrenia.

10. The method of claim 1, wherein the subject is suffering from early, intermediate or aggressive schizophrenia.

11. The method of claim 1, wherein the subject has one or more risk factors associated with SZ.

12. The method of claim 11, wherein the risk factors associated with SZ include one or more of:

a relative afflicted with schizophrenia, a genetically based phenotypic trait associated with risk for SZ;

deficits in working memory; and

mixed-handedness, particularly in females.

13. The method of claim 12, wherein the subject has one or more of a grandparent, parent, uncle or aunt, sibling, or child who has or had SZ.

14. The method of claim 12, wherein the genetically based phenotypic is eye tracking dysfunction.

15. The method of claim 1, wherein the subject is a child, fetus, or embryo, and one of the relatives of the subject has SZ.

16. The method of claim 1, further comprising administering a treatment to a subject identified as being at increased risk for developing SZ.

17. The method of claim 16, wherein the treatment is a pharmacological or psychosocial treatment for SZ.

18. The method of claim 1, further comprising stratifying a subject population for a clinical trial based on the genotype of rs1573726.

19. A method of selecting a human subject for inclusion or exclusion in a clinical trial, the method comprising:

obtaining a sample comprising DNA from the subject;

determining the identity of both alleles of rs1573726 in the sample;

comparing the identity of the alleles at rs1573726 in the subject to the alleles of rs1573726 in;

(i) a relative of the subject who is affected with SZ, and

(ii) a relative of the subject who is not affected with SZ,

wherein the presence of an rs1573726 allele in the subject that is the same as the allele in the relative who is affected with SZ, and is not the same as an allele in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ; and

including or excluding the subject if the genotype indicates that the subject has an increased risk of developing SZ.

20. The method of claim 19, further comprising determining the identity of both alleles of one or more of rs135221, rs763126, rs848768, rs2269523, rs738615, rs738596, rs738598, rs138844, or rs135819, thereby providing a subject haplotype, and comparing the subject haplotype to:

(i) a haplotype in a relative of the subject who is affected with SZ, and

(ii) a haplotype in a relative of the subject who is not affected with SZ,

wherein the presence of a haplotype in the subject that is the same as the haplotype in the relative who is affected with SZ, and is not the same as the haplotype in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ; and

including or excluding the subject if the haplotype indicates that the subject has an increased risk of developing SZ.

21. The method of claim 19, wherein the clinical trial is of a treatment for SZ.