Genetics of Adult-Onset POAG

描述(由申请人提供)： 青光眼是一种影响全球数百万人的致盲疾病；原发性开角型青光眼(POAG)是最常见的形式(70%-90%)。超过14个POAG基因座已经被定位，但只有4个基因被识别出来。我们的实验室已经定位了三个POAG基因座，并在最近确定了GLC1F的致病基因。这项提议的长期目标是阐明POAG基因是如何导致青光眼的。我们的工作假设是，每个青光眼位点代表POAG分级中的一个特定疾病实体，因此将呈现不同的结果，例如高眼压、疾病快速发作或视神经典型缺陷。在这项建议中，我们试图确定剩下的两个基因座，GLC1C和GLC1G的基因。我们的特异性目标是：7.特异性目的1.鉴定GLC1G基因并测定POAG人群中突变的发生率7.特异性目的2.鉴定GLC1C基因并测定POAG人群中突变的发生率。7特定目的3.研究GLC1C和GLC1G基因在正常眼和青光眼患者眼前段、小梁细胞和视神经中的表达。完成这些特定的目标将增加我们对导致青光眼的基因的了解。潜在地，GLC1C或GLC1G基因可能比先前发现的基因影响更大比例的POAG人群。然而，即使它们只影响4-8%的青光眼人群，识别这些基因仍然是重要的，因为这些基因影响的途径。对这些途径的研究将使人们更好地了解青光眼的原因，并最终在此基础上找到更好的治疗方法。

DESCRIPTION (provided by applicant): Glaucoma is a blinding disease affecting millions of people around the world; primary open angle glaucoma (POAG) is the most common form (70-90%). Over 14 POAG loci have been mapped but only 4 of these genes have been identified. Our lab has mapped three of the POAG loci and just recently identified the causative gene for GLC1F. The long-term goal of this proposal is to elucidate how POAG genes cause glaucoma. Our working hypothesis is that each glaucoma locus represents a specific disease entity within the POAG hierarchy and thus, will present with distinct findings, e.g. high intraocular pressure, fast onset of disease or characteristic defects in the optic nerve. In this proposal we seek to identify the genes for the two remaining loci, GLC1C and GLC1G. Our specific aims are: 7 Specific Aim 1. Identify the GLC1G gene and determine the incidence of mutations in POAG populations 7 Specific Aim 2. Identify the GLC1C gene and determine the incidence of mutations in POAG populations. 7 Specific Aim 3. Characterize expression of the GLC1C and GLC1G gene in the anterior segment of the eye, trabecular meshwork cells, and optic nerve of normal and glaucomatous eyes. Completion of these specific aims will increase our knowledge of the genes that cause glaucoma. Potentially either the GLC1C or GLC1G gene may impact a larger proportion of the POAG population than previously identified genes. However, even if they affect only 4-8% of the glaucoma population, identification of these genes will still be of importance because of the pathways that these genes impact. Research into these pathways will lead to a better understanding of what causes glaucoma and ultimately to better treatments based upon this knowledge.