Genetic markers of schizophrenia spectrum disorders in the sulfotransferase 4a (sult4a) gene

• US 7,892,735 B2
• Filed: 12/30/2005
• Issued: 02/22/2011
• Est. Priority Date: 12/30/2004
• Status: Expired due to Fees

• Current Assignee: University of Louisville
• Original Assignee: University of Louisville
• Inventors: Condra, Jodi Ann, Massey, Amy Tabb, Brennan, Mark David, Neibergs, Holly
• Primary Examiner(s): Bausch; Sarae
• Application Number:
  US11/323,061
• Publication Number:
  US 20060177851A1
• Time in Patent Office: 1,880 Days
• Field of Search: None
• US Class Current: 435/6.14
• 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 method of determining if a subject is at risk for developing schizophrenia (SZ), schizotypal personality disorder (SPD), or schizoaffective disorder (SD).

Claims

1. A method of determining a human subject'"'"'s risk of developing schizophrenia (SZ), the method comprising detecting the presence of a haplotype in a sample from the subject, wherein the haplotype comprises:

(i) an A allele at rs138060;

(ii) a C allele at rs138097; and

(iii) a G allele at rs138110,

wherein the presence of the haplotype indicates that the subject has an increased risk of developing the disorder.

2. The method of claim 1, wherein the haplotype further comprises an allele at microsatellite marker D22s1749e comprising more than 207 nucleotides.

3. The method of claim 1, wherein detecting the presence of a haplotype comprises:

obtaining a sample comprising DNA from the subject; and

determining the identity, presence or absence of the polymorphisms in the sample.

4. The method of claim 1, wherein detecting the presence of a haplotype comprises reviewing a subject'"'"'s medical history, wherein the medical history includes information regarding the polymorphisms.

5. The method of claim 3, wherein the sample is obtained from the subject by a health care provider.

6. The method of claim 3, wherein the sample is provided by the subject without the assistance of a health care provider.

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

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

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

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

11. The method of claim 10, 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.

12. The method of claim 11, wherein the subject has one or more of a grandparent, parent, uncle or aunt, sibling, or child who has or had SZ.

13. The method of claim 11, wherein the genetically based phenotypic is eye tracking dysfunction.

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

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

16. The method of claim 15, wherein the treatment is a pharmacological or psychosocial treatment for SZ.

17. The method of claim 1, further comprising using the information to select a subject population for a clinical trial.

18. The method of claim 1, further comprising using the information to stratify a subject population in a clinical trial.

19. The method of claim 1, further comprising using the information to stratify subjects that respond to a treatment from those who do not respond to a treatment, or subjects that have negative side effects from those who do not have negative side effects.

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

detecting the presence of a test haplotype in a sample from the subject, wherein the test haplotype comprises;

(i) an A allele at rs138060;

(ii) a C allele at rs138097; and

(iii) a G allele at rs138110,

obtaining a reference haplotype comprising reference markers that correspond to the polymorphisms; and

comparing the test haplotype to the reference haplotype, wherein sharing of a haplotype between the test haplotype and a reference haplotype is indicative of whether there is an increased likelihood that the subject will develop schizophrenia (SZ);

determining whether the subject has an increased risk of developing SZ based on the presence of a haplotype associated with 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 20, wherein the clinical trial is of a treatment for SZ.

22. The method of claim 20, wherein the haplotype further includes an allele at microsatellite marker D22s1749e comprising more than 207 nucleotides.