Genetics of Adult-Onset Primary Open-Angle Glaucoma

描述(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是世界上导致失明的主要原因之一。及早发现和治疗POAG已被证明是防止失明的最成功的方法之一。引起开角型青光眼的原因很多，既有环境因素，也有遗传因素。几种形式的POAG已被证明是由特定的基因缺陷引起的。我们实验室正在进行GLC1C和GLC1F POAG基因的鉴定。希腊北部一个孤立的小口袋伊皮鲁斯可能是鉴定POAG GLC1C基因的重要关键。来自伊皮鲁斯的一个大家庭，有超过12个患有POAG的人，携带GLC1C基因。我们认为GLC1C是该地区主要的POAG基因，因为在过去的两个世纪里，该地区的种群与外界几乎没有或几乎没有相互作用。如果是这样的话，对患有POAG的Epirian家族和个人的单倍型分析将识别出一条创始人染色体，并将显著减少要搜索的POAG基因的GLC1C区域的大小。类似的策略将被用来分析美国和澳大利亚的POAG家庭，这些家庭显示出与GLC1C或GLC1F连锁的积极证据。GLC1C和GLC1F单倍型的鉴定可作为检测携带GLC1C或GLC1F基因的POAG个体的筛查工具。虽然筛查工具很重要，但鉴定GLC1C和GLC1F基因是我们的最终目标。通过单倍型分析对GLC1C和GLC1F区域中包含的候选基因进行突变分析将是该建议的主要目标，该建议的最后目的将是分析我们的希腊和美国POAG家族以及随机的POAG个体，以寻找已知的POAG基因MYOC和OPTN的突变。GLC1C和GLC1F POAG基因的鉴定和鉴定将为治疗和/或预防POAG所致失明的研究指明新的途径。

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.