Genetic Variation in Age-related Macular Degeneration

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是 这是导致60岁以上人群获得性视力障碍的最常见原因。 AMD被认为是一种多因素疾病， 环境和遗传因素。目前，没有可靠的治疗方案， 可用于AMD，但激光光凝疗法除外， 可以应用于一小部分短期有效的患者。在 尽管在破译孟德尔视网膜病变的遗传原因方面取得了巨大的成功， 疾病，目前几乎没有什么是已知的遗传决定因素， AMD.本申请的基本假设是， 个体病例中对AMD的易感性是由以下缺陷的组合引起的： 在许多基因中，即，从特定的基因型。这一建议，从一个新的 建立了眼科疾病遗传学实验室，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）大幅增加患者和对照组， 筛选DNA变异（每个样本约2000个），包括散发性 和家族性病例;（2）利用半自动化，高通量筛选 方法，包括等位基因特异性基因分型芯片;（3）采用 数据的等位基因关联分析的补充方法，例如 病例对照关联研究和传递不平衡检验; (4)将大量衍生的基因型与表型变异相关联 AMD的发病率进行统计分析。我们的初步经验表明， 只有当一个项目包括以下内容时，才能在这一研究领域取得进展： 上面列出的所有组件。基因、等位基因和 基因型潜在的AMD复杂的特点，并了解这些缺陷如何 黄斑变性的发生发展有可能 改善受影响个人的生活质量。此外，它将 在风险个体发展之前， 疾病，并有可能修改或防止破坏性的视觉 这种疾病对后代的影响。

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.