Genetics of Adult-Onset Primary Open-Angle Glaucoma

成人发病的原发性开角型青光眼的遗传学

• 批准号: 7269890
• 负责人: Mary K Wirtz
• 金额: $ 50.71万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269890
• 关键词: Adult; Blindness; Candidate Disease Gene; Chromosomes; Defect; Early Diagnosis; Family; Functional disorder; Genes; Genetic; Genetic Determinism; Goals; Greece; Greek; Haplotypes; Incidence; Individual; Lead; Maps; Mutation; Northwestern United States; Population; Prevention; Primary Open Angle Glaucoma; Research; Screening procedure; base; insight; size; tool

DESCRIPTION (provided by applicant): Our long-term objective is to successfully intervene in the progression of primary open-angle glaucoma (POAG), one of the leading causes of blindness in the world. Early detection of POAG and treatment has proven to be one of the most successful ways to stop blindness from ensuing. The causes of POAG are numerous involving both environmental and genetic determinants. Several forms of POAG have been shown to result from a specific gene defect. Our lab is pursuing the identification of the GLC1C and GLC1F POAG genes. A small isolated pocket of Northern Greece, Epirus, may hold an important key to identifying the POAG GLC1C gene. A large family from Epirus with over 12 individuals with POAG carries the GLC1C gene. We propose that GLC1C is the major POAG gene in this region based on the isolation of the population with little or no interaction with outside populations over the last two centuries. If so, haplotype analysis of Epirian families and individuals with POAG, will identify a founder chromosome and should dramatically reduce the size of the GLC1C region to be searched for the POAG gene. A similar strategy will be used to analyze US and Australian POAG families that show positive evidence for linkage to GLC1C or GLC1F. Identification of a GLC1C and a GLC1F founder haplotype could be used as a screening tool for detecting POAG individuals carrying either the GLC1C or GLC1F gene. While screening tools are important, identification of the GLC1C and GLC1F genes is our ultimate goal. Mutational analysis of candidate genes contained within the GLC1C and GLC1F regions refined by haplotype analysis will be a major goal of this proposal, The last aim of this proposal will be to analyze our Greek and US POAG families and random POAG individuals for mutations in the known POAG genes, MYOC and OPTN. Identification and characterization of the GLC1C and GLC1F POAG genes will point the way to new avenues for research for treatment and/or prevention of blindness resulting from POAG.

描述（由申请人提供）：我们的长期目标是成功干预原发性开角型青光眼（POAG）的进展，POAG是世界上主要的致盲原因之一。POAG的早期发现和治疗已被证明是阻止失明的最成功的方法之一。POAG的病因众多，涉及环境和遗传因素。POAG的几种形式已被证明是由特定的基因缺陷引起的。我们的实验室正在进行GLC 1C和GLC 1F POAG基因的鉴定。希腊北方伊庇鲁斯的一个小的孤立的口袋，可能持有一个重要的关键，以确定POAG GLC 1C基因。来自伊庇鲁斯的一个大家族，有超过12名POAG患者携带GLC 1C基因。我们建议，GLC 1C是主要的POAG基因在该地区的基础上隔离的人口很少或没有互动与外界人口在过去的两个世纪。如果是这样的话，单倍型分析Epirian家族和个人与POAG，将确定一个创始人染色体，并应显着减少的大小GLC 1C区域搜索POAG基因。将使用类似的策略分析显示与GLC 1C或GLC 1F相关的阳性证据的美国和澳大利亚POAG家族。GLC 1C和GLC 1F创始者单倍型的鉴定可用作检测携带GLC 1C或GLC 1F基因的POAG个体的筛查工具。虽然筛选工具很重要，但GLC 1C和GLC 1F基因的鉴定是我们的最终目标。通过单倍型分析细化的GLC 1C和GLC 1F区域内包含的候选基因的突变分析将是本提案的主要目标。本提案的最后一个目标是分析我们的希腊和美国POAG家族和随机POAG个体中已知POAG基因MYOC和OPTN的突变。GLC 1C和GLC 1F POAG基因的鉴定和表征将为治疗和/或预防POAG导致的失明的研究指明新的途径。