Methods and Compositions For Diagnosis of Age-Related Macular Degeneration

• US 20110117557A1
• Filed: 02/23/2009
• Published: 05/19/2011
• Est. Priority Date: 02/21/2008
• Status: Abandoned Application

• Current Assignee: University of Miami, Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Pericak-Vance, Margaret A., Canter, Jeffrey A., Spencer, Kylee M., Haines, Jonathan L.
• Application Number:
  US12/934,027
• Publication Number:
  US 20110117557A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G01N 2800/164 Retinal disorders, e.g. retinopathy

Abstract

The invention generally concerns methods and compositions for screening individuals for susceptibility to age-related macular degeneration (AMD). In particular, association with the various markers including complement factor H, LOC387717/ARMS2, C2/CFB, C3 and VEGF, indicates that a subject is at risk of AMD.

Claims

1. A method of screening an individual for susceptibility to age-related macular degeneration (AMD) comprising assessing (a) the individual'"'"'s structure and/or function of a Complement factor H(CHF) protein;

(b) the individual'"'"'s structure at LOC387715/ARMS2; and

(c) the interaction between the individual'"'"'s structure at LOC387715/ARMS2 and the individual'"'"'s smoking history.

2. The method of claim 1, wherein (a) comprises assessing the structure of a CFH-encoding nucleic acid from said individual.

3. The method of claim 2, wherein assessing comprises determining the CFH-encoding nucleic acid sequence for all or a portion of a CFH-encoding RNA.

4. The method of claim 3, wherein assessing comprises determining the portion of the CFH-encoding nucleic acid sequence corresponding to position Y402.

5. The method of claim 4, further comprising amplifying all or part of said individual'"'"'s CFH-encoding nucleic acid.

6. The method of claim 5, wherein amplifying comprises polymerase chain reaction (PCR).

7. The method of claim 3, wherein determining the sequence CFH-encoding nucleic acid sequence comprises determining the sequence of a nucleic acid that is in linkage disequilibrium with position Y402.

8. The method of any of claim 7, wherein determining the sequence comprises differential hybridization.

9. The method of claim 1, wherein (a) comprises assessing the function of a CFH protein from said individual.

10. The method of claim 1, wherein (b) comprises assessing the presence or absence of a T allele at rs10490924.

11. The method of claim 10, wherein assessing comprises sequencing of rs10490924.

12. The method of claim 11, further comprising amplifying all or part of said individual'"'"'s nucleic acid at rs10490924.

13. The method of claim 12, wherein amplifying comprises polymerase chain reaction (PCR).

14. The method of claim 10, wherein assessing comprises determining the sequence of a nucleic acid that is in linkage disequilibrium with rs10490924.

15. The method of any of claim 10, wherein assessing comprises differential hybridization.

16. The method of claim 1, wherein (c) comprises a product of the codes for individual susceptibility factors.

17. The method of claim 1, further comprising assessing genetic variation in said individual'"'"'s mtDNA.

18. The method of claim 17, wherein assessing comprises determining the mtDNA sequence at positions corresponding to the MTND1*LHON4216C and/or MTND2*LHON4917G alleles.

19. The method of claim 18, wherein determining the sequence of said individual'"'"'s mtDNA comprises sequencing of all or a portion of a corresponding RNA.

20. The method of claim 19, further comprising amplifying all or part of said individual'"'"'s mtDNA.

21. The method of claim 20, wherein amplifying all or part of said individual'"'"'s mtDNA comprises polymerase chain reaction (PCR).

22. The method of claim 18, wherein determining the sequence of said individual'"'"'s mtDNA at positions corresponding to the MTND1*LHON4216C and/or MTND2*LHON4917G alleles by determining the sequence of a mitochondrial RNA that comprises a polymorphism that is in linkage disequilibrium with the MTND1*LHON4216C and/or MTND2*LHON4917G alleles.

23. The method of claim 22, further comprising amplifying all or part of said individual'"'"'s mtDNA.

24. The method of claim 23, wherein amplifying all or part of said individual'"'"'s mtDNA comprises polymerase chain reaction (PCR).

25. The method of claim 18, wherein assessing the presence or absence of the MTND1*LHON4216C and/or MTND2*LHON4917G alleles comprises assessing the presence or absence of the MTND1*LHON4216C and/or MTND2*LHON4917G alleles in said individual'"'"'s maternal blood relative'"'"'s mtDNA.

26. The method of claim 18, wherein assessing the presence or absence of the MTND1*LHON4216C and/or MTND2*LHON4917G alleles comprises differential hybridization.

27. The method of claim 1, further comprising assessing genetic variation in said individual'"'"'s C2/CFB gene cluster.

28. The method of claim 1, further comprising assessing genetic variation in said individual'"'"'s C3 gene locus.

29. The method of claim 1, further comprising assessing genetic variation in said individual'"'"'s VEGF gene locus.

30. The method of claim 1, wherein said AMD is wet AMD.

31. The method of claim 1, wherein said AMD is dry AMD.

32. A method for determining the need for prophylactic treatment for age-related macular degeneration (AMD) comprising assessing (a) the individual'"'"'s structure and/or function of a Complement factor H(CHF) protein;

(b) the individual'"'"'s structure at LOC387715/ARMS2; and

(c) the interaction between the individual'"'"'s structure at LOC387715/ARMS2 and the individual'"'"'s smoking history.

33. The method of claim 32, further comprising assessing genetic variation in said individual'"'"'s mtDNA.

34. The method of claim 32, further comprising assessing genetic variation in said individual'"'"'s C2/CFB gene cluster, genetic variation in said individual'"'"'s C3 gene locus, and/or genetic variation in said individual'"'"'s VEGF gene locus.

35. A kit comprising, in a suitable container means, at least one nucleic acid for determining:

(i) the presence or absence of one or more of (a) a T allele at rs10490924 or (b) a mutation in the Complement H gene; and

(ii) the structure at LOC387715/ARMS2.

36. The kit of claim 35, further comprising (iii) a nucleic acid for determining the presence or absence of the MTND1*LHON4216C allele and/or at least one nucleic acid for determining the presence or absence of the MTND2*LHON4917G allele;

(iv) a nucleic acid for determining a sequence with a C3 gene locus;

(v) a nucleic acid for determining a sequence with a C2/CFB gene cluster; and

/or (vi) a nucleic acid for determining a sequence within an VEGF gene locus.