A genome-wide scan maps a novel high myopia locus to 5p15
A genome-wide scan maps a novel high myopia locus to 5p15
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DOI：
10.1167/iovs.07-1126
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Lam, Dennis S. C.
中科院分区：
文献类型：
--
作者：
Lam, Ching Yan;Tam, Pancy O. S.;Lam, Dennis S. C.
目的.本研究旨在探讨3个香港地区常染色体显性遗传高度近视家系的遗传组成。通过使用跨越整个基因组的微卫星标记进行全基因组扫描，平均间距为10 cM。通过用额外的微卫星标记进行精细作图，进一步分析含有产生LOD得分> 1.0的标记的区域。通过对94例高度近视患者和94例对照者的一组基因SNP标记进行基因分型，对连锁区域进行精细定位。在标记D5 S630、D5 S416、D 7S 510、D11 S908和D17 S944处观察到两点LOD评分> 1.0。D5 S630侧翼的其他微卫星标记显示，在θ = 0.00时，D5 S2505处的最大两点LOD评分为4.81。单倍型分析将连锁区域缩小到5p15.33p15.2，间隔为17.45 cM。筛选了位于该区域内的5个基因的编码序列，IRX 2、IRX 1、POLS、CCT 5和CTNND 2。对94例高度近视患者和94例对照者的41个SNPs进行基因分型，结果发现rs370010的等位基因和基因型分布在高度近视患者和对照者之间存在差异（基因型P = 0.01176，等位基因P = 0.00271和趋势P = 0.00375），但这种关联在错误发现率（FDR）校正后不再显著。该SNP位于假设基因LOC 442129内。在染色体5p15.33-p15.2上定位了一个新的常染色体显性遗传高度近视基因座，间距为17.45cM。
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 > 1.0 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 5p15.33p15.2 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.