Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota
Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota
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发表时间：
2007-02
期刊：
影响因子：
2.2
通讯作者：
Sudha Nallasamy;Prasuna C. Paluru;M. Devoto;N. Wasserman;Jie Zhou;T. Young
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作者：
Sudha Nallasamy;Prasuna C. Paluru;M. Devoto;N. Wasserman;Jie Zhou;T. Young
近视是一种常见的、复杂的疾病，严重的形式会导致失明，因为它增加了过早白内障、青光眼、视网膜脱离和黄斑变性的风险。常染色体显性（AD）非综合征性高度近视被定位于染色体18p11.31、12q21-23、17q21-23、7q36、2q37.1、7p15.3、15q12-13、3q26、4q12、8p23、4q22-q27、1p36和Xq23-q25。在这里，我们证明了在一个大的Hutterite家族中，AD非综合征性高度近视与染色体10q21.1上的一个位点相关的证据。方法对南达科他州一个huterite家族29名成员（7名患病）进行基因组DNA分型分析。患者的平均屈光不正为-7.04屈光。使用微卫星标记来排除与已知AD非综合征性高度近视位点以及综合征性高度近视位点的关联。然后使用382个标记进行基因组筛选，平均标记间距离为10 cM，然后在LOD评分为阳性的基因组所有区域进行精细点定位。使用SimWalk2软件进行基于AD和常染色体隐性（AR）模型的多点连锁，外显率为90%，疾病等位基因频率为0.001。结果AD模型在微卫星标记D10S1643处的多点LOD评分最高为3.22。精细点定位和单倍型分析确定了染色体10q21.1上2.67 cM的关键区域。单倍型分析显示两种不同的单倍型与高度近视分离，表明同一基因中发生了两种不同的突变。结论基于连锁和单倍型分析，我们已经确定了高度近视的推定近视位点。
Purpose Myopia is a common, complex disorder, and severe forms have implications for blindness due to increased risk of premature cataracts, glaucoma, retinal detachment, and macular degeneration. Autosomal dominant (AD) non-syndromic high-grade myopia has been mapped to chromosomes 18p11.31, 12q21-23, 17q21-23, 7q36, 2q37.1, 7p15.3, 15q12-13, 3q26, 4q12, 8p23, 4q22-q27, 1p36, and Xq23-q25. Here, we demonstrate evidence of linkage for AD non-syndromic high-grade myopia in a large Hutterite family to a locus on chromosome 10q21.1. Methods After clinical evaluation, genomic DNA was genotyped from 29 members of a Hutterite family from South Dakota (7 affected). The average refractive error of affected individuals was -7.04 diopters. Microsatellite markers were used to exclude linkage to the known AD nonsyndromic high-grade myopia loci as well as to syndromic high-grade myopia loci. A genome screen was then performed using 382 markers with an average inter-marker distance of 10 cM followed by fine-point mapping in all regions of the genome that gave positive LOD scores. SimWalk2 software was used for multipoint linkage based on AD and autosomal recessive (AR) models with a penetrance of 90% and a disease allele frequency of 0.001. Results A maximum multipoint LOD score of 3.22 was achieved under an AD model at microsatellite marker D10S1643. Fine point mapping and haplotype analysis defined a critical region of 2.67 cM on chromosome 10q21.1. Haplotype analysis demonstrated two distinct haplotypes segregating with high-grade myopia, indicative of two distinct mutations occurring in the same gene. Conclusions We have identified a presumptive myopia locus for high-grade myopia based on linkage and haplotype analysis.