GENETICS OF AGE RELATED MACULAR DEGENERATION

年龄相关性黄斑变性的遗传学

• 批准号: 6384743
• 负责人: MICHAEL L KLEIN
• 金额: $ 34.6万
• 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/6384743
• 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.

年龄相关性黄斑变性（AMD）被认为是主要的 在美国是导致失明的原因。 影响近150万人 导致 7% 以上的美国人失明 75 岁以上的个人。目前，还没有设立 预防 AMD 的方法。 唯一被证明有效的治疗方法是激光 光凝术仅在一小部分病例中取得成功。 虽然 AMD 的病因尚不清楚，但有大量证据 暗示该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。 最近在其他具有共同遗传特征的复杂性状方面取得了成功 以及与 AMD 的流行病学相似性，支持以下观点： 鉴定导致 AMD 的基因位点是可以实现的 目标。 该项目的长期目标是识别基因 负责AMD，开发诊断工具来识别 患者有患该疾病的风险，并了解其情况 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。 该研究计划的直接目标是绘制遗传位点图谱 在许多受影响的家庭中与 AMD 共同隔离。 我们将聘用 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 包含多名受影响的活着成员的亲属； 2) 完成 AMD 家族的全基因组筛选，从一组候选者开始 基因座； 3) 精细绘制暗示连锁的位点并进行详细的多重分析 点参数和非参数连锁分析； 4) 精炼 确定基因座并开始研究以确定特定的遗传 这些家族中导致 AMD 的缺陷。