LINKAGE STUDIES OF AGE RELATED OCULAR DISORDERS

年龄相关性眼部疾病的关联研究

• 批准号: 2164601
• 负责人: BARBARA EDEN KLEIN
• 金额: $ 37.4万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2164601
• 关键词: cataract; epidemiology; eye disorder; eye disorder diagnosis; family genetics; genetic markers; human subject; lens; linkage mapping; macular degeneration; questionnaires; retina

This study is designed to investigate genetic factors in age-related eye disease. This will be done in the context of the Beaver Dam Eye Study a large population-based epidemiologic study of age-related eye disease in people 43-86 years of age (n=4,926). The specific diseases of interest are age-related maculopathy and age-related lens opacities, two of the most common causes of decreased vision in older Americans. Using standardized protocols, the presence and severity of these eye conditions were determined based on objective masked gradings of photographs of the retina and lens in the entire population five years ago. Sibships living within the community of Beaver Dam, Wisconsin were ascertained and their records linked for statistical analyses. Segregation analyses were performed using the S.A.G.E. program REG C. A recessively inherited gene could account for about 56% of the variability of the maculopathy score with recessive gene frequency of about 0.35. For nuclear sclerosis, a model of autosomal recessive inheritance accounted for 35% of the sample variability, with an estimated gene frequency of 0.42. For cortical opacity, transmission of a major effect was detected that was not completely one-locus mendelian. There appeared to be an effect of sex. A recessive gene frequency of 0.24 could account for 75% of the variability in males and 45% of the variability in females. The current proposal is to support linkage studies within this population in order to identify genetic loci that are related to these lesions. The Beaver Dam Eye Study population is currently being re-examined using the same protocols as five years ago. Buffy coat is being obtained from each participant. The current grant will entail further data gathering in the field to confirm the initial sibships and to identify other family members (especially cousins) in the community. Given special emphases to location where candidate genes are implicated, "positional cloning" which searches the whole genome for co-segregation with genetic markers that are not necessarily functionally related to the disease, will be used. Markers will be chosen that are approximately equally spaced so that a systematic "global search" is done. The results of this investigation will identify specific genetic patterns for age- related eye diseases and will permit a quantitative estimate of the relative importance of environmental exposures on these conditions. Findings from this study may provide further understanding of the pathogenesis of these diseases and may have public health implications if there are some segments of the population in which preventing environmental exposures may alter disease risk.

本研究旨在探讨年龄相关性眼病的遗传因素 疾病这将在比弗坝眼科研究的背景下进行， 中国老年性眼病流行病学研究 43-86岁的人（n= 4，926）。感兴趣的具体疾病是 年龄相关性黄斑病变和年龄相关性透镜混浊， 美国老年人视力下降的常见原因。 使用标准化 方案，这些眼部疾病的存在和严重程度是 基于视网膜照片的客观掩蔽分级确定 和透镜的数量。 居住在威斯康星州比弗坝社区的兄弟姐妹们 并将其记录连接起来进行统计分析。隔离 使用S.A.G.E.进行分析。程序REG C。一个recket 遗传基因可以解释约56%的变异性， 隐性基因频率约为0.35的黄斑病变评分。用于核 硬化症是一种常染色体隐性遗传模型，占35%， 样本变异性，估计基因频率为0.42。为 皮质混浊，检测到一个主要影响的传输， 完全的单位点孟德尔式似乎有性别的影响。一 隐性基因频率为0.24，可解释变异的75 在男性和45%的变异性在女性。 当前的提议是 支持在这一人群中的联系研究，以确定 与这些病变相关的基因位点。 比弗坝眼科研究人群目前正在重新检查， 和五年前一样的协议血沉棕黄层是从 每个参与者。目前的赠款将需要进一步收集数据， 该字段用于确认最初的兄弟姐妹关系并识别其他家庭 社区成员（尤其是堂兄弟）。 特别强调候选基因的位置， “定位克隆”，即寻找整个基因组的共分离 基因标记，不一定是功能相关的， 疾病，将被使用。将选择大约 等间隔，以便进行系统的“全局搜索”。结果 这项调查的结果将确定特定的年龄遗传模式- 相关眼病，并将允许定量估计 环境暴露对这些条件的相对重要性。 这项研究的结果可能会提供进一步的了解， 这些疾病的发病机制，并可能有公共卫生的影响，如果 在某些人群中， 环境暴露可改变疾病风险。