Genomic Wide Linkage of Familial Myopia and evidence for a locus on chromosome 22

Abstract

Abstract: : Purpose: To identify regions of the human genome containing genes responsible for nonsyndromic myopia using Ashkenazi Jewish pedigrees from the Myopia Family Study. Methods:Cycloplegic and manifest refraction were measured and individuals with –1.00 D or worse in each meridian of both eyes were classified as myopic (affected). Six markers each on previously assigned regions on chromosomes 12 and 18 regions were genotyped on a subset of 38 families. Genome–wide scan using 390 microsatellite markers was performed on the total number of 44 families (410 individuals). Parametric and nonparametric linkage analyses were conducted to determine what loci are important in these families with less severe, clinical forms of myopia. Results: There was no strong evidence of linkage to chromosomes 18p and 12q: all two point and multipoint heterogeneity LOD scores were less than 1.0 and non–parametric linkage p–values were greater than 0.01 for each region. Genome–wide linkage analysis yielded positive multipoint heterogeneity LOD scores (HLOD greater than 3.2) to a region on chromosome 22 and suggestive linkage (multipoint HLOD greater than 1.0) on chromosomes 11, 14 and 17. Conclusions: Significant evidence of linkage of myopia was not found to chromosome 18p and 12q loci. We did find significant evidence of linkage on chromosome 22.

Keywords: genetics • myopia • linkage analysis