Genetic Variation in Age-related Macular Degeneration

描述(申请人提供)：老年性黄斑变性(AMD) 这是60岁以上人群后天视力受损的最常见原因。 AMD被认为是一种与以下两种因素相关的多因素障碍 环境和遗传因素。目前，还没有可靠的治疗选择 适用于AMD，但激光光凝疗法除外 可应用于一小部分患者的短期疗效。在……里面 尽管在破译孟德尔视网膜的遗传原因方面取得了巨大的成功 疾病，目前几乎对疾病的遗传决定因素一无所知。 AMD。此应用程序的基本假设是增加了 个别病例对AMD的易感性是多种缺陷共同作用的结果 在许多基因中，即来自特定的基因(S)。这项建议，来自一个新的 建立的眼病遗传学实验室，旨在 通过几种方法的组合来破译AMD的遗传原因。我们 计划：(1)大幅增加患者和控制组的数量 筛查DNA变异(每个样本约2000个)，包括两个零星的 和家族性病例；(2)利用半自动、高通量筛查 方法，包括用于基因分型的等位基因特异性微阵列；(3)使用 数据的等位基因关联分析的互补方法，例如 病例对照关联研究和传递不平衡检验； (4)大量衍生基因与表型变异相关 经统计分析，在AMD中。我们的初步经验表明 这一研究领域的进展只有在项目包括 上面列出的所有组件。基因、等位基因和 AMD复杂性状背后的基因类型和理解这些缺陷是如何 有助于黄斑变性的发展具有潜在的 改善受影响个人的生活质量。此外，它还将 能够在高危个体发展之前对其进行准确识别 这种障碍，并有可能改变或防止毁灭性的视觉 这种疾病在后代中的后果。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the most common cause of acquired visual impairment in people over the age 60. AMD is considered to be a multifactorial disorder associated both with environmental and genetic factors. Currently, no reliable treatment options are available for AMD with the exception of the laser photocoagulation therapy that can be applied to a small fraction of patients with short-term effects. In spite of great successes in deciphering the genetic cause of Mendelian retinal diseases, almost nothing is currently known about the genetic determinants of AMD. The underlying hypothesis of this application is that increased susceptibility to AMD in individual cases results from a combination of defects in many genes, i.e., from specific genotype(s). This proposal, from a newly established laboratory of genetics of eye diseases, is directed towards deciphering the genetic cause of AMD by a combination of several approaches. We plan to: (1) Substantially increase the cohorts of patients and controls to be screened for DNA variants (to about 2000 samples each), including both sporadic and familial cases; (2) Utilize semi-automated, high-throughput screening methods, including the allele-specific microarrays for genotyping; (3) Employ complementary methods of allelic association analyses of the data, such as the case-control association study and the transmission disequilibrium test (TDT); (4) Correlate the large numbers of derived genotypes with phenotypic variation in AMD by statistical analyses. Our preliminary experience indicates that progress in this area of research can only be achieved if a project includes all the components listed above. Identification of genes, alleles, and genotypes underlying the AMD complex trait and understanding how these defects contribute to the development of macular degeneration has the potential to improve the quality of life of the affected individuals. Further, it will enable the accurate identification of at-risk individuals before they develop the disorder, and has the potential to modify or prevent the devastating visual consequences of this disorder in future generations.