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是 遗传和环境的起源。流行病学研究（包括 调查员？国际调查显示，消费 饮用高水平的无机砷的水会导致高健康 风险目前的挑战是在一组基因组中鉴定遗传多态性。 与环境相关的基因，可能独立地赋予适度的风险， 但是共同地包括使个体倾向于 砷暴露对健康的不良影响。本研究的主要目的 规划补助金的目的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，该项目有3个具体的 目标。第一个具体目标是组织一个有凝聚力的小组， 多学科研究人员，共同了解 开展分子生物学研究所涉及的方法、问题和难题 流行病学研究。拟议中的联盟拥有来自4个国家的研究人员， 院校：加州大学旧金山分校弗朗西斯科 加州伯克利（UC Berkeley），儿童？奥克兰研究医院 研究所和国家癌症研究所（NCI），NIH。第二个具体目标 是创建和执行一系列旨在调查 分子流行病学相关的概念、假设和技术 砷暴露人群。其中包括三项此类研究。 应用：（1）确定最可行的高产量DNA SNP 研究个体间基因型差异的技术，（2） 确定最合适的一组特定基因和SNP， 调查砷暴露人群，（3）制定适当的 区分和优先考虑多重 使用SNP基因分型的流行病学研究中涉及的统计测试。 这些试点项目完成后，第三个具体目标是准备 并向国家卫生研究院提交一份详细的建议， 研究系统地调查遗传因素，影响 印度人群中砷诱发皮肤病变的易感性。 已经为这一人群采集了大约400份血液样本， 都被冷冻保存由于这项系统的研究，个人 特别是砷引起的影响的风险将被确定和主题 加强监控筛查此外，机械信息 将为预防和治疗干预提供潜在目标， 暴露人群（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).