GENETICS OF AGE RELATED MACULAR DEGENERATION

年龄相关性黄斑变性的遗传学

• 批准号: 2888615
• 负责人: MICHAEL L KLEIN
• 金额: $ 32.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888615
• 关键词: aging; biopsy; clinical chemistry; clinical research; diagnosis design /evaluation; early diagnosis; eye disorder diagnosis; eye fundus photography; family genetics; gene expression; gene mutation; genetic mapping; genetic markers; genetic susceptibility; genotype; human genetic material tag; human subject; linkage mapping; macular degeneration; molecular pathology

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.

视网膜相关性黄斑变性（AMD）被认为是 在美国失明的原因。 影响了近150万人 美国老年人，并导致超过7%的 75岁以上的人。目前，没有建立 预防AMD的方法 唯一有效的治疗方法，激光 光凝术仅在小部分病例中成功。 虽然AMD的病因不明，但有相当多的证据表明， 说明这种疾病有很强的遗传因素进展 基因组筛选和分析方法使直接遗传 AMD的病因学、病理生理学和最终治疗方法 可行的 最近在其他复杂性状上取得的成功，这些性状与遗传学上的其他性状有相似之处。 以及与AMD的流行病学相似性，支持了这样一种观点， 鉴定导致AMD的遗传基因座是一种可实现的 目标. 该项目的长期目标是确定基因 负责AMD，开发诊断工具， 患者在发展疾病的风险，并了解其 分子病理生理学 这种理解将使 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 在一些受影响的家庭中与AMD共分离。 我们会委聘 参数和几种非参数连锁分析方法。 到 为了实现这些目标，我们建议：1）继续收集额外的 包含多个受影响的活体成员的运动神经元; 2）完全 AMD家族的全基因组筛选，从一组候选基因开始， 3）提示连锁的精细图谱位点，并进行详细的多重标记。 点参数和非参数连锁分析;以及4）细化 确定基因座，并开始研究，以确定特定的遗传 在这些家庭中负责AMD的缺陷。