GENETIC DETERMINANTS OF CATARACT

白内障的遗传决定因素

基本信息

批准号：
8449087
负责人：
Alan Shiels
金额：
$ 46.62万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8449087
关键词：
12q 12q24.11 Accounting Adolescent Adult Age Aging Amblyopia Anterior Bioinformatics Blindness Candidate Disease Gene Cataract Centromere Childhood Chromosome Mapping Chromosomes, Human, Pair 9 Complex Counseling Crystalline Lens Cytogenetics Data Development Diagnosis Dideoxy Chain Termination DNA Sequencing Disease Environmental Risk Factor Eye Development Family Foundations Genes Genetic Genetic Determinism Genomics Glaucoma Goals Human Human Chromosomes Hybrids Inherited Investigation Lead Link Maps Medical Molecular Molecular Genetics Mutant Strains Mice Mutation Nature Ocular Hypertension Ocular Motility Disorders Operative Surgical Procedures Pathologic Nystagmus Pathway interactions Play Population Postoperative Period Research Retinal Detachment Risk Role Strabismus Surgical Management Techniques Uveitis Vision Visual impairment age related base congenital cataract cost deep sequencing early onset gene discovery genetic risk factor infancy insight lens lens transparency mouse model mutant next generation novel prevent public health relevance

项目摘要

Project Summary The crystalline lens plays a central role in vertebrate anterior eye development and refractive vision. Loss of lens transparency, or cataract(s), is a clinically important cause of low vision that despite surgical treatment remains a leading cause (~40%) of blindness worldwide. Typically, cataract is acquired with aging (>40 yrs) as a multi-factorial or complex disorder involving environmental and genetic risk factors. In addition, cataract may be inherited as a Mendelian disorder usually with juvenile-onset, and many mouse models of human cataract have been described. While several environmental risk factors have been established for age-related cataract, little is known about the nature and precise role of genetic factors that are estimated to account for ~50% of the risk. However, there is increasing evidence that genes underlying inherited forms of cataract are also involved in age-related cataract. The overall goal of this research is to advance understanding of the molecular mechanisms/pathways that lead to cataract. Specifically, we propose to identify novel genes for inherited forms of cataract in humans, and to identify the causative gene in a mouse model of human age-related cataract using a combination of molecular genetic and genomic techniques. Results from these studies will provide new insights about the molecular basis of lens development, aging and cataractogenesis, and ultimately may contribute to the discovery of non-surgical means to delay, reverse or even prevent cataract formation.

项目摘要结晶镜在脊椎动物前眼发育和屈光视觉中起着核心作用。损失镜头透明度或白内障是低视力的临床重要原因，尽管手术治疗仍然是全球失明的主要原因（约40％）。通常，白内障是用衰老（> 40年）获得的涉及环境和遗传危险因素的多因素或复杂疾病。此外，白内障可能通常以少年发作和许多人类白内障的老鼠模型遗传为孟德尔疾病已经描述了。尽管已经建立了与年龄相关白内障的几个环境危险因素，但关于遗传因素的性质和精确作用，估计约占约50％的遗传因素的性质和精确作用。风险。但是，有越来越多的证据表明，遗传形式的白内障基因也涉及与年龄有关的白内障。这项研究的总体目标是提高对分子的理解导致白内障的机制/途径。具体而言，我们建议识别遗传形式的新基因人类的白内障，并鉴定与人类年龄相关白内障的小鼠模型中的病因基因结合分子遗传技术和基因组技术。这些研究的结果将提供新的关于晶状体发育，衰老和白内障发生的分子基础的见解，最终可能有助于发现非手术手段延迟，逆转甚至防止白内障形成。