Genetic linkage study of high-grade myopia in a Hutteritepopulation from South Dakota

[摘要] Purpose: Myopia is a common, complex disorder, and severe forms haveimplications for blindness due to increased risk of premature cataracts,glaucoma, retinal detachment, and macular degeneration. Autosomaldominant (AD) non-syndromic high-grade myopia has been mapped tochromosomes 18p11.31, 12q21-23, 17q21-23, 7q36, 2q37.1, 7p15.3,15q12-13, 3q26, 4q12, 8p23, 4q22-q27, 1p36, and Xq23-q25. Here, wedemonstrate evidence of linkage for AD non-syndromic high-grade myopiain a large Hutterite family to a locus on chromosome 10q21.1.Methods: After clinical evaluation, genomic DNA was genotyped from29 members of a Hutterite family from South Dakota (7 affected). Theaverage refractive error of affected individuals was -7.04 diopters.Microsatellite markers were used to exclude linkage to the known ADnonsyndromic high-grade myopia loci as well as to syndromic high-grademyopia loci. A genome screen was then performed using 382 markers withan average inter-marker distance of 10 cM followed by fine-point mappingin all regions of the genome that gave positive LOD scores. SimWalk2software was used for multipoint linkage based on AD and autosomalrecessive (AR) models with a penetrance of 90% and a disease allelefrequency of 0.001.Results: A maximum multipoint LOD score of 3.22 was achieved underan AD model at microsatellite marker D10S1643. Fine point mappingand haplotype analysis defined a critical region of 2.67 cM onchromosome 10q21.1. Haplotype analysis demonstrated two distincthaplotypes segregating with high-grade myopia, indicative of twodistinct mutations occurring in the same gene.Conclusions: We have identified a presumptive myopia locus forhigh-grade myopia based on linkage and haplotype analysis.

[学科分类] 生物化学/生物物理