A Genome–Wide Screen for Pathological Myopia Suggests a Novel Locus on Chromosome 15q12–13

Abstract

Abstract: : Purpose: To map the gene locus of pathological myopia in 28 Chinese families. Methods: 28 families consented to participate our study. DNAs were available for 340 individuals from venous blood. 330 pairs of highly heterozygous microsatellite marker primers were selected for a genome–wide screen. We used multi–PCR to amplify these microsatellite markers, then carried out polyacrylamidedel electrophoresis on ABI 377 DNA sequencer. Genescan 2.0 and Genetyper 1.1 softwares were used to identify the genotype of every individual. Two–point linkage was calculated by LINKAGE package in an autosomal dominant mode with full penetrance at gene mutation frequency of 0.0133. Multipoint LOD scores were calcu1ated by use of GENEHUNTER program. Genetic distance between marker loci examined were determined on the basis of Genethon linkage map. Haplotype analysis was performed by software of Cyrillic 2.0 based on the lowest recombination principle. Results: Evidence of significant linkage was found on chromosome 15q in the MP1 family by two–point linkage analysis. The maximum LOD score was 1.76 with the markers D15S1010,D15S1007,D15S1042, at a recombination fraction of 0.00. Multipoint linkage analysis strongly supported existence of linkage on this region, with NPL score 5.16. Haplotype analysis refined this myopia locus to a 12–cM interval between D15S1019 and D15S146 on 15q12–13. No evidence of linkage was found at known myopia loci such as 18p11.31 and 12q21–23. Conclusions: Our study manifests there is a novel myopia locus on 15q12–13, which is the first myopia locus reported in China to date. 94 confirmed genes locate on this region, so it is necessary to sequence this region to find the virulence gene. This novel locus also demonstrates the high genetic heterogeneity of pathological myopia.

Keywords: myopia • gene mapping