More Complete Assessment of DNA Variation in Age-Related Macular Degeneration

这项提议建立在密歇根大学科学家之间积极和富有成效的合作基础上 和宾夕法尼亚大学。该研究小组为我们的研究和开发工作做出了一些贡献。 了解黄斑变性的遗传学和一系列的统计方法和分析 黄斑变性和其他疾病的基因组研究工具。年龄相关性黄斑 老年性黄斑变性（AMD）是一种进行性神经变性疾病，是老年人失明的主要原因。 老人黄斑变性引起的视力丧失目前是不可逆的。在过去的几年里， 我们对导致黄斑变性的分子机制的理解已经取得了进展 通过SNP基因分型研究，重点是一个容易获得的常见DNA序列类， 变体。在这里，我们建议使用DNA测序和基因分型技术的进步， 系统评价DNA序列变异在老年性黄斑病变易感性中的作用 退化我们的研究团队不仅包括临床专业知识和对黄斑病变的了解， 变性，而且在高通量遗传学和基因组学以及在开发和 尖端统计和计算方法的应用。通过深层外显子组 重测序和低通全基因组测序，我们建议在3000个基因组中表征遗传变异， 个体，并评估>20M遗传变异对疾病易感性的贡献，不仅包括 常见的SNPs，但也有罕见的SNPs，短插入缺失多态性和较大拷贝数的变异。 我们的方法应该产生新的黄斑变性易感基因位点，并提高我们对黄斑变性的理解。 在先前涉及的基因座中导致疾病易感性的分子机制。

This proposal builds on active and productive collaboration between scientists at the University of Michigan and at the University of Pennsylvania. The research team has made several contributions both to our understanding of the genetics of macular degeneration and to the array of statistical methods and analytical tools available for genomic studies of macular degeneration and other disorders. Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the major cause of blindness among the elderly. Loss of vision caused by macular degeneration is currently irreversible. In the past several years, great progress has been made in our understanding of the molecular mechanisms that lead to macular degeneration through SNP genotyping studies, which focus on an easily accessible class of common DNA sequence variants. Here, we propose to use advances in DNA sequencing and genotyping technology to more systematically evaluate the role of DNA sequence variation in susceptibility to age related macular degeneration. Our research team includes not only clinical expertise and understanding of macular degeneration but also expertise in high-throughput genetics and genomics and in the development and application of cutting edge statistical and computational methods. Through a combination of deep exome resequencing and low pass whole genome sequencing we propose to characterize genetic variation in 3,000 individuals and evaluate the contribution of >20M genetic variants to disease susceptibility, including not only common SNPs, but also rare SNPs, short insertion deletion polymorphisms, and larger copy number variants. Our approach should yield new susceptibility loci for macular degeneration and improve our understanding of the molecular mechanisms that contribute to disease susceptibility in previously implicated loci.