Purpose: This study was conducted to investigate the genetic component of three Chinese pedigrees originating from Hong Kong with autosomal dominant high myopia.
Methods: A whole-genome scan was performed by using microsatellite markers spanning the whole genome with an average spacing of 10 cM. Regions containing markers that yielded LOD scores >1.0 were further analyzed by fine mapping with additional microsatellite markers. Fine-scale mapping of the linkage region was performed by genotyping a set of gene-based SNP markers on a cohort of 94 high myopia cases and 94 control subjects.
Results: Two-point LOD scores >1 were observed at markers D5S630, D5S416, D7S510, D11S908, and D17S944. Additional microsatellite markers flanking D5S630 revealed a maximum two-point LOD score of 4.81 at D5S2505 at theta = 0.00. Haplotype analysis narrowed the linkage region to 5p15.33-p15.2 with a 17.45-cM interval. The coding sequences of five genes located within this region, IRX2, IRX1, POLS, CCT5, and CTNND2, were screened. No segregation of polymorphism with high myopia was found. Genotyping of 41 SNPs within this region in a Chinese cohort of 94 high myopia cases and 94 control subjects showed that the allele and genotype distributions of one SNP, rs370010, was different between cases and controls (genotype P = 0.01176, allele P = 0.00271 and trend P = 0.00375), but such association did not remain significant after false discovery rate (FDR) correction. This SNP is located within a hypothetical gene LOC442129.
Conclusions: A novel autosomal dominant high myopia locus was mapped on chromosome 5p15.33-p15.2 with an interval of 17.45 cM.