Pharmacogenetic Epidemiology of Birth Defects and Cancer

描述（由申请人提供）： 目前的建议是基于这样的前提，即遗传结构的 许多常见疾病只能通过“基因组”方法来定义， 结合高通量技术，并考虑高阶效应 (i.e.,涉及多个基因和/或环境暴露的相互作用）。 拟议活动的动机是调查人员希望 将他们目前的分子流行病学方法整合到研究中， 出生缺陷和癌症，并扩大他们的努力，包括基因组 药物作为这些风险因素的研究方法 条件 这些活动将以方法问题为基础， 药理学试剂（例如，叶酸拮抗剂）和遗传途径（例如， 叶酸-同型半胱氨酸代谢轴），这是常见的出生缺陷， 癌 成功扩大研究工作，纳入基因组学方法 将需要来自多个学科的专业知识，而传统上没有 被很好地融合。 因此，拟议项目的资金将用于 在宾夕法尼亚大学医学院（PENN）建立一个 拥有科学专业知识和技术资源的研究团队 需要采取基因组方法来研究疾病病因。 该团队开发的工具和资源将为 未来的“基于基因组”的药物研究作为风险因素， 出生缺陷和癌症。 此外，由于许多工具和资源 既不是疾病，也不是暴露， 具体来说，这个团队的工作也将有助于促进，在宾夕法尼亚州，基因组 对许多其他环境引起的疾病的研究。

DESCRIPTION (provided by applicant): The current proposal is based on the premise that the genetic architecture of many common diseases will only be defined by a "genomic" approach that incorporates high throughput technologies and considers higher order effects (i.e., interactions involving multiple genes and/or environmental exposures). The proposed activities are motivated by the desires of the investigators to integrate their current molecular epidemiological approaches to the study of birth defects and cancer, and to expand their efforts to encompass a genomic approach to the study of pharmacological agents as risk factors for these conditions. These activities will build on methodological issues, pharmacological agents (e.g., folate antagonists) and genetic pathways (e.g., folate-homocysteine metabolic axis) that are common to birth defects and cancer. The successful expansion of research efforts to encompass a genomics approach will require expertise from multiple disciplines which traditionally have not been well integrated. Hence, funding for the proposed project will be used to establish, at the University of Pennsylvania School of Medicine (PENN), a research team that has the scientific expertise and technological resources required to undertake a genomic approach to the study of disease etiology. The tools and resources developed by this team will provide the foundation for future "genome-based" studies of pharmacological agents as risk factors for birth defects and cancer. In addition, since many of the tools and resources that are required of a genomic approach are neither disease- nor exposure- specific, the work of this team will also serve to foster, at PENN, genomic research on many additional environmentally-induced diseases.