LINKAGE STUDIES OF AGE RELATED OCULAR DISORDERS

这项研究旨在调查年龄相关眼睛的遗传因素。 疾病。这将在海狸水坝眼睛研究的背景下进行 年老年性眼病的大规模人群流行病学研究 年龄43-86岁(n=4,926)。令人感兴趣的具体疾病有 老年性黄斑病变和老年性晶状体混浊是最常见的两种 美国老年人视力下降的常见原因。使用标准化的 协议，这些眼病的出现和严重程度是 基于视网膜照片的客观掩蔽分级来确定 以及五年前在整个人口中使用的透镜。 居住在威斯康星州海狸大坝社区内的兄弟姐妹 已查明并将他们的记录联系起来，以供统计分析。隔离 使用S.A.G.E.程序REG C.A逐次进行分析 遗传基因可能解释了大约56%的变异 黄斑病变评分与隐性基因频率约为0.35。对于核能 硬化症是常染色体隐性遗传的一种模式，占35% 样本变异较大，估计基因频率为0.42。为 皮质混浊，传导的主要影响是检测不到 完全是单轨迹孟德尔式的。这似乎是性的影响。一个 0.24的隐性基因频率可以解释75%的变异 男性有45%的变异性，女性有45%。目前的建议是 支持这一人群中的连锁研究，以便确定 与这些损伤相关的遗传基因。 目前正在使用以下方法重新检查海狸大坝眼科研究人群 和五年前一样的协议。黄褐色的大衣是从 每一位参与者。目前的拨款将需要进一步收集数据 用于确认初始兄弟姐妹关系和标识其他家族的字段 社区中的成员(尤其是表亲)。 由于特别强调候选基因所涉及的位置， 在全基因组中搜索共分离的“位置克隆” 这些遗传标记在功能上不一定与 疾病，将被使用。标记将被选择为大约 等间距，以便进行系统的“全局搜索”。结果是 将确定特定的年龄遗传模式- 相关的眼部疾病，并将允许对 环境暴露对这些条件的相对重要性。 这项研究的发现可能会提供对 这些疾病的发病机制，并可能在以下情况下影响公共卫生 在人口的某些部分中，预防 环境暴露可能会改变疾病风险。

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.