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: 6681052
• 负责人: Mary K Wirtz
• 金额: $ 57.42万
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681052
• 关键词: Europe; adult human (21+); disease /disorder onset; family genetics; functional /structural genomics; genetic polymorphism; genetic screening; genotype; glaucoma; high performance liquid chromatography; human population genetics; human subject; linkage mapping; optic nerve; polymerase chain reaction; sensory neuropathy; trabecular meshwork

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，这是世界上导致失明的主要原因之一。事实证明，早期发现 POAG 并进行治疗是阻止失明的最成功方法之一。 POAG 的原因很多，涉及环境和遗传决定因素。多种形式的 POAG 已被证明是由特定基因缺陷引起的。我们的实验室正在致力于 GLC1C 和 GLC1F POAG 基因的鉴定。希腊北部伊庇鲁斯的一个孤立小区域可能掌握着识别 POAG GLC1C 基因的重要钥匙。来自伊庇鲁斯的一个大家族有超过 12 名 POAG 患者携带 GLC1C 基因。我们认为 GLC1C 是该地区主要的 POAG 基因，这是基于过去两个世纪中该地区人口与外界很少或没有互动的隔离。如果是这样，对患有 POAG 的 Epirian 家族和个体进行单倍型分析，将鉴定出创始者染色体，并应显着减小用于搜索 POAG 基因的 GLC1C 区域的大小。类似的策略将用于分析美国和澳大利亚的 POAG 家族，这些家族显示出与 GLC1C 或 GLC1F 关联的积极证据。 GLC1C 和 GLC1F 创始人单倍型的鉴定可用作检测携带 GLC1C 或 GLC1F 基因的 POAG 个体的筛选工具。虽然筛选工具很重要，但 GLC1C 和 GLC1F 基因的鉴定是我们的最终目标。通过单倍型分析细化的 GLC1C 和 GLC1F 区域内包含的候选基因的突变分析将是该提案的主要目标。该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。 GLC1C 和 GLC1F POAG 基因的鉴定和表征将为治疗和/或预防 POAG 引起的失明研究开辟新途径。