Genetic Determinants of Cataract

描述(申请人提供)：白内障是导致视力丧失的主要原因，占全球失明的45%。流行病学研究表明，白内障是一种涉及遗传和环境因素的多因素疾病。本研究的目的是提高对白内障分子遗传学基础的认识。该提案有三个具体目标。在特定的目标1中，我们将使用细胞转染和转基因小鼠技术来表征遗传性白内障新基因突变的致病作用。在特定的目标2中，我们将使用表达谱和突变谱技术来鉴定遗传性白内障的新基因。在具体目标3中，我们将使用定制的重新测序阵列来测试遗传性白内障和年龄相关性白内障的基因之间的关联。这些遗传学研究的结果将1)提供有关晶状体发育和老化的分子基础的新见解，2)有助于设计基于基因的白内障诊断和治疗方法，3)使人们能够更好地评估白内障发生的基因-基因和基因-环境相互作用。与公共健康相关：白内障困扰着超过2000万40岁以上的美国人，是眼科手术最常见的原因，占医疗保险视力预算的-60%。白内障也是儿童视力受损的一个重要原因。这项研究旨在识别和表征导致白内障在家庭中发生的遗传因素，并开发诊断、治疗甚至预防白内障的新方法。

DESCRIPTION (provided by applicant): Cataract is a leading cause of vision loss and accounts for -45% of blindness worldwide. Epidemiological studies have shown that cataract is a multi-factorial disease involving genetic and environmental factors. The goal of this study is to improve understanding of the molecular genetic basis of cataract. The proposal has three specific aims. In specific aim 1, we will use cell transfection and transgenic mouse techniques to characterize the pathogenic effects of a mutation in a novel gene for inherited cataract. In specific aim 2, we will use expression-profiling and mutation-profiling techniques to identify a novel gene for inherited cataract. In specific aim 3, we will use a custom re-sequencing array to test for association between genes for inherited cataract and age-related cataract. Results from these genetic studies will 1) provide new insights regarding the molecular basis of lens development and aging, 2) contribute to the design of gene-based diagnostics and therapeutics for cataract management, and 3) enable better evaluation of the gene-gene versus gene-environment interactions underlying cataract development. Public health relevance: Cataract afflicts more than 20 million Americans over age 40 and is the most common reason for eye surgery, accounting for -60% of the Medicare vision budget. Cataract is also a significant cause of visual impairment in childhood. This research aims to identify and characterize genetic factors that cause cataract to run in families and develop new ways to diagnose, treat and even prevent cataract.