Fine Mapping of Genes for Age-Related Maculopathy

描述（由申请人提供）：黄斑变性是西方世界影响老龄化人口的主要致盲原因。年龄相关性黄斑变性分子基础的复杂性现在开始通过多个基因组扫描鉴定致病位点来阐明。本提案描述了对两个基因组扫描的后续研究，一个是基于社区的研究（海狸坝眼研究），第二个是来自视网膜诊所的样本（家庭年龄相关黄斑病变研究），由我们小组进行。在家庭年龄相关性黄斑病变研究中，我们有证据表明染色体15q21上有一个主要位点（GATA50C03多点P = 1.98 x 10[7]；经验P < 10[-5]；单点P = 3.6 x 10[-7]）。在我们之前对Beaver Dam Eye研究样本的ARMD基因组扫描中，该位点作为弱连锁信号存在（D15S659多点P=0.047），这代表了我们的结果的重复。在目前的提案中，我们将通过对15q上的区域进行精细映射来跟进我们最初的结果。我们提出了分层战略

DESCRIPTION (provided by applicant): Macular degeneration is a leading cause of blindness in the Western World that affects the aging population. The complexity of the molecular basis of age-related macular degeneration is now beginning to be elucidated with the identification of disease-causing loci through multiple genome scans. This proposal describes a follow-up to two genome scans, one on a community based study (The Beaver Dam Eye Study) and the second in sample obtained from a Retinal Clinic (The Family Age Related Maculopathy Study) conducted by our group. We have evidence of a major locus on chromosome 15q21 (GATA50C03 multipoint P = 1.98 x 10[7]; empirical P < 10[-5]; singlepoint P = 3.6 x 10[-7]) in the Family Age Related Maculopathy Study. This locus was present as a weak linkage signal in our previous ARMD genome scan in the Beaver Dam Eye Study sample (D15S659 multipoint P=0.047), which represents a replication of our results. In the current proposal we will follow up our initial results by fine mapping the region on 15q. We have presented a tiered strategy to perform fine mapping, including validating our results in a sample of cases and controls from the Age-Related Eye Disease Study. We also propose to map other loci that demonstrated positive linkage signals in our genome scan. The cloning of genes for the heritable forms of macular degeneration will increase our understanding of the basic pathogenesis of the disease process. Further, since we propose to examine a case control sample, we will be able to obtain initial estimates of attributable risk due to a particular gene in the population.