Genetic determinants of cataract

白内障的遗传决定因素

• 批准号: 6763198
• 负责人: Alan Shiels
• 金额: $ 34.43万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6763198
• 关键词: autosomal dominant trait; biotechnology; cataract; clinical research; computer data analysis; congenital eye disorder; crystallins; electrophysiology; family genetics; gene environment interaction; gene expression; gene mutation; genetic polymorphism; genetic susceptibility; genotype; human genetic material tag; linkage disequilibriums; linkage mapping; molecular cloning; nucleic acid amplification techniques; nucleic acid sequence; pathologic process; polymerase chain reaction; transfection

DESCRIPTION (provided by applicant): Cataract is the leading cause of vision loss (accounting for ~45% of blindness worldwide) and represents the most common reason for eye surgery. A long-term goal of our research is to map, identify and characterize common and novel genetic determinants of cataract. In Specific Aim 1 of this proposal, genetic linkage analysis with microsatellite markers and DNA amplification/sequencing techniques will be used to map and identify genetic mutations underlying autosomal dominant cataract in four or more pedigrees from the St. Louis population. In Specific Aim 2, DNA amplification and sequencing techniques will be used to characterize the nature, pattern and frequency of nucleotide variation in genes linked with autosomal dominant cataract. In Specific Aim 3, linkage disequilibrium analysis and DNA amplification/sequencing techniques will be used to test for association between genes for hereditary cataract and age-related cataract. In Specific Aim 4, DNA expression methods, analytical biochemical techniques and molecular cell biology techniques will be used to characterize the functional consequences of mutations in the genes for alphaA-crystallin and betaB1-crystallin that are associated with autosomal dominant cataract linked to chromosomes 21q and 22q, respectively. Results from these studies will lead to 1. A molecular basis for understanding the pathogenetic mechanisms of cataract development, 2. The design of DNA-based diagnostics and therapeutics for cataract that are targeted to the underlying defects and 3. Better evaluation of environmental risk factors for cataract, thereby enabling genetically susceptible individuals to choose a lifestyle that delays or even prevents cataract onset.

描述（由申请人提供）：白内障是视力丧失的主要原因（约占全球失明的 45%），也是眼科手术最常见的原因。我们研究的长期目标是绘制、识别和表征白内障的常见和新颖的遗传决定因素。在该提案的具体目标 1 中，将使用微卫星标记的遗传连锁分析和 DNA 扩增/测序技术来绘制和鉴定来自圣路易斯人群的四个或更多家系中常染色体显性白内障的基因突变。在具体目标 2 中，DNA 扩增和测序技术将用于表征与常染色体显性白内障相关的基因中核苷酸变异的性质、模式和频率。在具体目标 3 中，连锁不平衡分析和 DNA 扩增/测序技术将用于测试遗传性白内障和年龄相关性白内障基因之间的关联。在具体目标 4 中，将使用 DNA 表达方法、分析生化技术和分子细胞生物学技术来表征与 21q 和 21 号染色体相关的常染色体显性白内障相关的 αA-晶状体蛋白和 βB1-晶状体蛋白基因突变的功能后果。分别为22q。这些研究的结果将带来： 1. 了解白内障发展发病机制的分子基础，2. 针对潜在缺陷设计基于 DNA 的白内障诊断和治疗方法，以及 3. 更好地评估环境风险因素从而使遗传易感人群能够选择延缓甚至预防白内障发病的生活方式。