India US Genetic Study of Ocular Quantitative Traits

描述（由申请人提供）：本探索性资助的主要目的是确定近亲谱系对数量性状定位的价值，并对常见眼部复杂疾病（如青光眼和黄斑变性）的重要危险因素进行选定的数量性状进行初步基因定位研究。长期目标是利用这种方法开发和支持基因型/表型数据库，使研究人员能够发现、评估和验证导致复杂人类眼病的数量性状的基因和生物标志物。开展该项目的一个主要动机是期望所获得的资源将为查明人类致盲疾病的重大风险因素提供新的机会。除了表型和基因型数据外，还将收集环境信息，以帮助研究基因与环境的相互作用。从每个研究参与者收集的血液样本中的DNA和血浆将被储存起来，用于未来的基因组、蛋白质和小分子分析，预计这些信息将导致识别一些复杂眼部疾病的遗传预测因子和生物标志物。这一提议的基本假设是，近亲谱系比没有近亲关系的家庭可以提供更多的信息来绘制负责数量性状的基因。初步研究表明，具有足够规模和结构的近亲系谱将比类似规模的核心家族集合提供更多的定量性状定位能力。这个试点项目的直接目标是使用大型近亲系谱进行初步分析，以验证它们对数量性状定位的有用性，并检查近交家庭中选定的数量性状的遗传。我们计划实现以下具体目标：1)识别和招募生活在印度南部的大型近亲系谱成员，2)测量所有参与个体的选定眼部数量性状，3)收集所有可用家庭成员的外周血样本并准备DNA和血浆样本，4)制定收集所有参与个体环境暴露信息的策略，5)执行初始SNP基因分型，6)执行初始数量性状位点定位。常见的年龄相关疾病，如黄斑变性、青光眼、白内障和糖尿病性视网膜病变，是世界上许多国家致盲的主要原因，随着世界范围内人口的老龄化，预计到2020年这些疾病的患病率将急剧增加。与年龄有关的疾病治疗费用高昂，威胁到老年人独立生活的能力，在一些国家还增加了死亡风险。该项目的目标是确定负责眼部数量性状的基因，这些性状是这些常见致盲疾病的主要危险因素。这些基因的鉴定将有助于确定这些疾病的潜在原因，这将导致新的治疗和诊断方法。

DESCRIPTION (provided by applicant): The primary objective of this exploratory grant is to determine the value of consanguineous pedigrees for quantitative trait mapping and to perform initial gene mapping studies for selected quantitative traits that are significant risk factors for common ocular complex disorders such as glaucoma, and macular degeneration. A long-term goal is to use this approach to develop and support a genotype/phenotype database that will enable investigators to discover, assess and validate genes and biomarkers responsible for quantitative traits that contribute to complex human ocular disease. A major motivation for the project is the expectation that the resources obtained will provide new opportunities for the identification of significant risk factors for blinding human disease. In addition to phenotypic and genotypic data, environmental information will be collected to aid studies of gene environment interactions. DNA and plasma from blood samples collected from each study participant will be stored for future genomic, protein and small molecule analysis with the anticipation that this information will lead to the identification of genetic predictors and biomarkers for some complex ocular disorders. The underlying hypothesis of this proposal is that consanguineous pedigrees can provide more information for mapping genes responsible for quantitative traits than families without consanguineous relationships. Preliminary studies have suggested that consanguineous pedigrees of sufficient size and structure will provide more power for quantitative trait mapping than a similarly sized collection of nuclear families. The immediate goals of this pilot project are to use large consanguineous pedigrees for initial analyses to verify their usefulness for quantitative trait mapping, and to examine the inheritance of selected quantitative traits in inbred families. We plan to accomplish the following specific aims: 1) Identify and enroll members from large consanguineous pedigrees living in southern India, 2) Measure selected ocular quantitative traits for all participating individuals, 3) Collect peripheral blood samples on all available family members and prepare DNA and plasma samples, 4) Develop strategies for collecting environmental exposure information on all participating individuals, 5) Perform initial SNP genotyping, and 6) Perform initial mapping of quantitative trait loci. Common age-related disorders such as macular degeneration, glaucoma, cataract, and diabetic retinopathy, are the leading causes of blindness in many countries throughout the world, and with the aging of the population world-wide, the prevalence of these disorders is expected to increase dramatically by the year 2020. Age-related diseases are costly to treat, threaten the ability of older adults to live independently and in some countries increase the risk of mortality. The goal of this project is to identify genes responsible for ocular quantitative traits that are major risk factors for these common blinding disorders. The identification of these genes will help define the underlying causes of these disorders which will lead to new methods of treatment and diagnosis.