High Capacity SNP Genotyping in Arsenic Induced Disease

描述(由申请人提供)： 众所周知，常见的多因素疾病的原因既有 起源于遗传和环境。流行病学研究(包括 调查人员？自己的国际调查)表明，消费 饮用无机砷含量高的水会导致健康状况良好 风险。目前的一个挑战是在一组 与环境相关的基因可能独立地赋予适度的风险， 但总体上包括高风险简档，使个人容易患上 砷暴露造成的不良健康后果。这样做的主要目标是 规划拨款是组成一个有能力满足这一要求的财团 当前的挑战。为了实现这一目标，本项目有3个具体的 目标。第一个具体目标是组织一个有凝聚力的 具有共同理解的多学科研究人员 开展分子生物学研究的方法学、问题和问题 流行病学研究。拟议的财团有来自4个国家的研究人员 院校：加州大学旧金山分校，加州大学 加州大学伯克利分校儿童？S医院奥克兰研究 美国国立卫生研究院国家癌症研究所(NCI)。第二个具体目标 是创建和执行一系列试验性研究，旨在调查 流行性出血热分子流行病学相关概念、假说和技术 暴露于砷的人群。这项研究包括三项这样的研究 应用：(1)确定最适宜的高产DNA SNP 研究个体间基因差异的技术，(2) 确定最合适的一组特定基因和SNPs 对接触砷的人群进行调查，以及(3)制定适当的 辨别和区分多项结果的优先顺序的方法 统计检验涉及使用SNP基因分型的流行病学研究。 在这些试点项目完成后，第三个具体目标是准备 并向NIH提交一份进行分子流行病学研究的详细建议 系统调查影响遗传因素的研究 印度人群对砷引起的皮肤损伤的易感性。 已经为这一人群采集了大约400份血液样本， 都被保存在冷冻仓库里。作为这项系统研究的结果，个人 特别是砷引起的影响的风险将被识别和研究 到加强监视筛查。此外，机械性信息 将为预防和治疗干预提供潜在的目标 接触人群(例如，营养素或药物)。

DESCRIPTION (provided by applicant): It is well known that the causes of common multifactorial diseases are both genetic and environmental in origin. Epidemiological studies (including the investigators? own international investigations) have shown that consuming drinking water with high levels of inorganic arsenic results in high health risk. A current challenge is to identify genetic polymorphisms in a set of environmentally-associated genes that may independently confer modest risk, but collectively comprise high risk profiles that predispose an individual to poor health consequences from arsenic exposure. The primary objective of this planning grant is to form a consortium with the capability to meet this current challenge. To accomplish this objective, this project has 3 specific aims. The first specific aim is to organize a cohesive group of multidisciplinary researchers with a shared mutual understanding of the methodologies, issues and problems involved in carrying out molecular epidemiology studies. The proposed consortium has researchers from 4 institutions: University of California San Francisco, University of California Berkeley (UC Berkeley), Children?s Hospital Oakland Research Institute and National Cancer Institute (NCI), NIH. The second specific aim is to create and perform a series of pilot studies designed to investigate concepts, hypotheses and technologies relevant to molecular epidemiology of arsenic-exposed populations. Three such studies are included in this application: (1) to determine the most feasible high output DNA SNP technology for investigating genotypic differences between individuals, (2) to identify the most appropriate set of specific genes and SNPs for investigations of arsenic-exposed populations, and (3) to develop appropriate methodologies for discriminating and prioritizing the results of the multiple statistical testing involved in epidemiology studies using SNP genotyping. After completion of these pilot projects, the third specific aim is to prepare and submit to NIH a detailed proposal to perform a molecular epidemiology study to systematically investigate genetic factors that influence susceptibility to arsenic-induced skin lesions in a population in India. About 400 blood samples for this population have already been collected and are held in frozen storage. As a result of this systematic study, individuals at particular risk for arsenic-induced effects will be identified and subject to intensified surveillance screening. In addition, mechanistic information will provide potential targets for preventive and curative interventions in exposed populations (e.g., nutrients or drugs).