Genetics of Adult-Onset POAG

描述（由申请人提供）： 青光眼是一种致盲性疾病，影响全世界数百万人;原发性开角型青光眼（POAG）是最常见的形式（70-90%）。超过14个POAG位点已被定位，但只有4个这些基因已被确定。我们的实验室已经绘制了三个POAG基因座，最近刚刚确定了GLC 1F的致病基因。这项提案的长期目标是阐明POAG基因如何导致青光眼。我们的工作假设是，每个青光眼位点代表POAG等级中的特定疾病实体，因此将呈现不同的发现，例如高眼内压、疾病的快速发作或视神经中的特征性缺陷。在这个建议中，我们试图确定剩下的两个基因座，GLC 1C和GLC 1G的基因。我们的具体目标是：7具体目标1。鉴定GLC 1G基因并确定POAG人群中突变的发生率7特异性目的2.鉴定GLC 1C基因并确定POAG人群中突变的发生率。7具体目标3表征正常和青光眼眼前节、小梁网细胞和视神经中GLC 1C和GLC 1G基因的表达。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，GLC 1C或GLC 1G基因可能比先前鉴定的基因影响更大比例的POAG群体。然而，即使它们只影响4-8%的青光眼人群，由于这些基因影响的途径，鉴定这些基因仍然很重要。对这些途径的研究将有助于更好地了解青光眼的病因，并最终基于这些知识提供更好的治疗方法。

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.