GENETICS OF AGE RELATED MACULAR DEGENERATION

老年性黄斑变性(AMD)是公认的 在美国导致失明的原因。它影响了近150万人 美国老年人并导致超过7%的人失明 75岁以上的个人。目前，还没有建立起 预防AMD的方法。唯一被证明有效的治疗方法是激光 光凝，只在一小部分病例中成功。 虽然AMD的病因尚不清楚，但有相当多的证据表明 暗示这种疾病有很强的遗传成分。最新进展 基因组筛选和分析方法使直接的基因 老年性黄斑变性的病因、病理生理学及最终治疗探讨 可行。最近在其他复杂性状上的成功，这些性状具有相同的基因 以及与AMD的流行病学相似性，支持了这样的观点 识别与AMD有关的遗传基因座是一种可行的方法 进球。 这个项目的长期目标是识别基因 负责AMD，开发诊断工具以确定 有可能罹患该病的患者，并了解其 分子病理生理学。这项谅解将使 制定预防措施和改进方法 治疗。 这项研究计划的直接目标是绘制遗传基因座图。 在一些受影响的家庭中与AMD共分离。我们将聘用 包括参数和几种非参数连杆分析方法。至 为了实现这些目标，我们建议：1)继续征收额外的 包含多个受影响的活体成员的家族；2)完整 AMD家族全基因组筛查，从一组候选基因开始 3)精细作图提示连锁，并进行详细的多基因定位 点参数和非参数联动分析；4)细化 确定基因座并开始研究以确定特定的基因 缺陷是这些家庭中AMD的主要原因。

Age-related macular degeneration (AMD) is recognized as the leading cause of blindness in the United States. It affects nearly 1.5 million older Americans and causes loss of vision in more than 7 percent of individuals over 75 years of age. Currently, there are no established means of preventing AMD. The only proven effective treatment, laser photocoagulation, is successful in only a small proportion of cases. While the etiology of AMD is unknown, there is considerable evidence implicating a strong genetic component for the disease. Advances in genomic screening and analysis methodologies make a direct genetic approach to the etiology, pathophysiology, and ultimate therapy of AMD viable. Recent successes with other complex traits, which share genetic and epidemiological similarities with AMD, support the idea that identification of genetic loci responsible for AMD is an achievable goal. The long-term objectives of this project are to identify genes responsible for AMD, develop diagnostic tools to identify patients at risk of developing the disease, and to understand its molecular pathophysiology. This understanding will allow the development of preventive measures and improved methods of treatment. The immediate goal of this research proposal is to map genetic loci cosegregating with AMD in a number of affected families. We will employ both parametric and several nonparametric linkage analysis methods. To achieve these goals, we propose to: 1) Continue to collect additional kindreds containing multiple affected living members; 2) Complete genome-wide screening of AMD families, beginning with a set of candidate loci; 3) Fine-map loci suggestive of linkage and conduct detailed multi- point parametric and nonparametric linkage analysis; and 4) Refine identified loci and begin studies to identify the specific genetic defects responsible for AMD in these families.