Genome-wide microsatellite mapping of multi-factorial ocular diseases.

人类基因组计划的完成引起了全世界对筛选与疾病易感性相关的基因组多态性的兴趣。为此，有必要采用有效的方法，通过多态性标记系统、快速、准确地探测整个基因组，以识别具有疾病相关多态性的特定基因。微卫星（Microsatellite， MS）是一种由2 - 6个核苷酸（重复单元）组成的重复序列，散布在整个人类基因组中。多发性硬化在重复单元数上具有高度的遗传多态性，有望成为评价疾病易感性的关联分析的良好标记。MS的平均等位基因数为10个（远多于SNP）， MS的平均连锁不平衡长度为100kb（远多于SNP）。因此，定位疾病易感基因的最佳方法是首先通过MS全基因组关联定位将候选疾病基因区域缩小到100 kb，然后通过常规SNP分析从这100 kb候选区域中鉴定疾病基因。我们以100kb的间隔在人类基因组中收集并定位了3万多个MS标记，并开始了全基因组的MS筛选，以鉴定高血压、糖尿病、开角型青光眼（OAG）、类固醇型青光眼（类固醇易感基因）、白塞特糖尿病、开角型青光眼（OAG）、类固醇型青光眼（类固醇易感基因）、白塞特病、高度近视、视网膜格变性、年龄相关性黄斑变性（AMD）、圆锥角膜、白内障和结节病。因此，到目前为止，我们已经发现了50到100个可能有高血压易感基因的病灶。SNP分析正在进行中，最终达到单一疾病基因。我们正在继续进行其他疾病的MS筛选、作图和鉴定，表明我们基于MS的策略对于疾病的全基因组作图是非常有效的，特别是具有多因子基础的复杂或常见疾病。少

The completion of the human genome project has led to worldwide interest in screening for genomic polymorphisms associated with disease susceptibility. For this to be accomplished, it is necessary to adopt efficient methods that probe the entire genome systematically, rapidly and accurately by polymorphic markers to identify specific genes with disease associated polymorphisms. Microsatellite (MS) is a repeated sequence consisting of generally two to six nucleotides (repeated unit), scattering throughout the human genome. MS characterized by a high degree of genetic polymorphisms in its number of repeated unit is expected to be an excellent marker in association analysis for evaluating disease susceptibility. The average number of alleles in MS is 10 (much more than that of SNP) and the average length of linkage disequilibrium of MS is 100kb (much longer than that of SNP). The best way to map the disease susceptibility gene, therefore, is first to narrow down candidate disease gene reg … More ions to 100 kb by genome-wide association mapping with MS, and then next to identify disease gene from these 100 kb candidate regions by conventional SNP analysis. We have collected and localized more than 30,000 MS markers in the human genome at 100 kb intervals and started pan genomic (genomewide) MS screening for identification of pathogenic genes of several diseases including hypertension, diabetes mellitus, open angle glaucoma (OAG), steroid glaucoma (steroid susceptibility gene), Behcet's diabetes mellitus, open angle glaucoma (OAG), steroid glaucoma (steroid susceptibility gene), Behcet's disease, high myopia, retinal lattice degeneration, age related macular degeneration (AMD), keratoconus, cataract, and sarcoidosis. Accordingly, we have so far found fifty to a hundred foci that may have hypertension susceptible genes. SNP analyses are under way to finally reach single disease genes. We are continuing MS screening, mapping and identification for the other diseases, demonstrating that our MS based strategy is quite efficient for genomewide mapping of diseases, especially complex or common diseases with multi-factorial basis. Less