Susceptibility Genes for Age-Related Maculopathy (ARM) on Chromosome 10q26

Abstract

Allelic variations in the genes PLEKHA1 and LOC387715 are identified herein as risk factor for Age Related Maculopathy (ARM). A method is therefore provided for identifying a risk of development of ARM in an individual that comprises identification of allelic variations in PLEKHA1 and/or LOC387715. Related apparatus, such as an array, are identified as being useful in implementing those methods.

1 - 33 . (canceled) 
     
     
         34 . A method of determining risk of developing Age-Related Maculopathy in a human subject comprising screening in the genome of the subject for the presence or absence of a risk haplotype characterized as including a thymine at base 270 of SEQ ID NO: 20 (rs10490924) from a sample obtained from the subject, the presence of said risk haplotype for one or both alleles being indicative of increased risk of developing Age-Related Maculopathy and the absence of said risk haplotype for both alleles being indicative of decreased risk of developing Age-Related Maculopathy. 
     
     
         35 . The method of  claim 34 , comprising examining base 270 of SEQ ID NO: 20 (rs10490924). 
     
     
         36 . The method of  claim 34 , comprising screening for the presence of a polymorphism in linkage disequilibrium with a thymine at base 270 of SEQ ID NO: 20 (rs10490924), wherein the polymorphism is indicative of the presence of said risk haplotype and with increased risk of developing Age-Related Maculopathy. 
     
     
         37 . The method of  claim 36 , wherein the polymorphism is located in PLEKHAI, PRSS11 or LOC387715. 
     
     
         38 . The method of  claim 36  in which the one or more polymorphisms is chosen from rs10490924, rs4146894, rs1045216, rs4405249, rs1882907, rs10490923, rs760336, rs763720, and rs1803403. 
     
     
         39 . The method of  claim 34 , in which the Age-Related Maculopathy is severe Age-Related Maculopathy. 
     
     
         40 . The method of  claim 34 , in which the patient has one or more symptoms of Age-related Maculopathy and the presence of said risk haplotype for one or both alleles indicates increased risk of developing end-stage Age-Related Maculopathy. 
     
     
         41 . The method of  claim 40 , in which the presence of said risk haplotype for one or both alleles indicates increased risk of developing one or both of geographic atrophy and choroidal neovascular membranes. 
     
     
         42 . The method of  claim 34 , in which the presence of said risk haplotype for one or both alleles indicates increased risk of developing end-stage Age-Related Maculopathy. 
     
     
         43 . The method of  claim 42 , in which the presence of said risk haplotype for one or both alleles indicates increased risk of developing one or both of geographic atrophy and choroidal neovascular membranes. 
     
     
         44 . A method of identifying a human subject having an increased risk of developing Age-Related Maculopathy comprising screening for the presence of a guanine or a thymine at base 270 of SEQ ID NO: 20 (rs10490924) in a nucleic acid of the subject by examination of allelic variation in the PLEKHA1/LOC387715/PRSS11 locus of Chromosome 10q26, wherein the presence of thymine-for one or both alleles indicates increased risk of developing Age-Related Maculopathy and the presence of guanine for both alleles indicates decreased risk of developing Age-Related Maculopathy.