Candidate Genes for Primary Open Angle Glaucoma

描述（由申请人提供）：青光眼是导致青光眼的主要原因之一。 在美国，有超过1500万人失明。视力丧失 是由视神经变性引起的，通常伴有升高的 眼压这种疾病有很大的遗传成分，但 涉及的具体基因尚不清楚。目前的治疗方法主要针对 通过降低眼内压来减缓视力丧失，但没有解决 疾病的分子基础。这个项目的目标是调查 小梁网中的差异基因表达，以确定 影响液体排出的基因，进而影响眼内压。我们 假设小梁网组织的异常功能， 原发性开角型青光眼（POAG）患者与改变的 基因表达的模式。我们将使用基因序列分析 表达（SAGE），以分析小梁网的转录模式， POAG患者以及年轻（20-40岁）和年龄匹配（50-70岁）的患者 对照表达水平显著上调或下调的基因 将作为POAG的候选基因进行研究。我们 还将研究表达水平随时间显著变化的基因， 正常人的年龄。这些基因将被定位，提供一个很好的 资源为未来的疾病基因的位置克隆，影响 小梁网然后将测试候选基因与 POAG通过基于家族的关联分析。这双屏幕差分 受影响组织中的表达以及与疾病意愿的统计学关联 提供了一个强有力的机制，以确定候选人的敏感性 基因.最有希望的候选人将在 在分子水平上检测突变和多态性。的 POAG易感基因的鉴定可为POAG的治疗提供依据。 诊断测试，并导致POAG的早期检测和大大改善 对数百万患有这种使人衰弱的疾病的患者的预后。

DESCRIPTION (provided by applicant): Glaucoma is one of the leading causes of blindness in America, and affects over 15 million individuals. Loss of vision is caused by degeneration of the optic nerve, often accompanied by elevated intraocular pressure. There is a large genetic component to this disease, but the specific genes involved are not yet known. Current treatments are aimed at slowing vision loss by reducing intraocular pressure, but do not address the molecular basis of the disease. The goal of this project is to investigate differential gene expression in the trabecular meshwork, in order to identify genes that affect the drainage of fluid, and in turn, intraocular pressure. We hypothesize that the abnormal functioning of trabecular meshwork tissue in patients with primary open angle glaucoma (POAG) is associated with altered patterns of gene expression in this tissue. We will use Serial Analysis of Gene Expression (SAGE) to profile transcription patterns in trabecular meshwork from POAG patients as well as from young (20-40 years) and age-matched (50-70 years) controls. Genes whose expression levels are significantly up- or down-regulated in affected individuals will be investigated as candidate genes for POAG. We will also investigate genes whose expression levels changes significantly with age in normal individuals. These genes will be mapped, providing an excellent resource for future positional cloning of disease genes that affect the trabecular meshwork. Candidate genes will then be tested for association with POAG by family-based association analysis. This double screen-differential expression in affected tissue and statistical association with disease-will provide a powerful mechanism for the identification of candidate susceptibility genes. The most promising candidates will then be characterized at the molecular level and screened for mutations and polymorphisms. The identification of POAG susceptibility genes could provide the basis for diagnostic tests and lead to earlier detection of POAG and a greatly improved prognosis for the millions of patients affected with this debilitating disease.