ENVIRONMENTAL GENETICS

环境遗传学

• 批准号: 2154917
• 负责人: Daniel W. Nebert
• 金额: $ 126.53万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-15 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2154917
• 关键词: environmental adaptation; environmental toxicology; genetic polymorphism; population genetics

A new Center on Environmental Genetics is proposed by the University of Cincinnati. The focus of this Center will be to investigate the impact of genetic diversity on the response of the individual, or populations, to toxic environmental agents. The Center will include a multidisciplinary approach, from "the molecule to the human," devoted to application of molecular biology and genetics to environmental research. The fundamental strategy of the Center is to understand variation in response to toxic agents due to the underlying interindividual differences in genetic predisposition. Basic research may include everything from microbes and lower eukaryotes to mammals and human material. Center research will take advantage of the usefulness of genetic variants, i.e. genetically different subpopulations, resistant versus sensitive groups, and/or interindividual and intraspecies differences. It is clear that interindividual genetic differences can lead to dramatic dissimilarities in the response to a wide variety of environmental substances. An appreciation of these differences, and an understanding of the underlying mechanisms, are critical in the evaluation of risk of adverse health effects caused by toxic environmental agents. Individual variation often reflects allelic differences in genes encoding proteins involved in critical life functions such as receptors, drug metabolism, ion channels, multidrug resistance glycoprotein pumps, second-messenger pathways, DNA repair, and chelation of metals. The elucidation of these functions that can influence interindividual response to toxic agents, and the evaluation of their genetic diversity in the population, will be the central focus of the Center. The identification of these underlying causes of genetic differences in response to toxic agents is an important key to understanding the basic mechanisms of toxicity and provides the basis for both preventing adverse health effects and exploring opportunities for interventions in the disease process. The four Research Cores of the new Center represent existing strengths and interactions among scientists within the University of Cincinnati Medical Center that are relevant to genetics. The central focus of the Ecogenetics Research Core is the identification and characterization of genetic polymorphisms that affect the metabolism, and therefore the toxicity, of foreign chemicals. The other Research Cores--Reproductive & Developmental Toxicology, Genetic Toxicology, and Oxidative Stress Toxicology--are focused on three specific areas of toxicology of major importance. These Research Cores investigate specific toxic effects of environmental agents with an emphasis on the use of genetic techniques. The role of environmental substances in causing infertility, in utero toxicity, and birth defects is an important public health issue. The impact of environmental agents on the structure of genetic material itself, leading to mutations and cancer, is an area of vital importance. Oxidative stress is an emerging area of importance which may underlie many diverse toxic effects of environmental agents in biological systems. This new Center will be unique among NIEHS Centers and will provide. an important. resource to the environmental research community.

大学提出了一个新的环境遗传学中心 辛辛那提。 该中心的重点是调查影响 对个人或人群反应的遗传多样性 对有毒环境代理商。 中心将包括一个 多学科的方法，从“分子到人” 分子生物学和遗传学在环境研究中的应用。 该中心的基本策略是了解 由于基本间个体而引起的对有毒药物的反应 遗传倾向的差异。 基础研究可能包括 从微生物和较低的真核生物到哺乳动物和人类的一切 材料。 中心研究将利用 遗传变异，即遗传不同的亚群，抗性 相对于敏感组，以及/或个体间和内在 差异。 显然，个体间的遗传差异可以 导致对各种各样的响应的显着差异 环境物质。 对这些差异的欣赏，以及 对基本机制的理解至关重要 评估由有毒造成的不良健康影响的风险 环境代理。 个体变化通常反映等位基因 编码涉及关键生命的蛋白质的基因差异 功能，例如受体，药物代谢，离子通道，多药 抗性糖蛋白泵，第二门途径，DNA修复和 金属的螯合。 阐明这些功能可以 影响对有毒剂的个体反应，并评估 他们在人口中的遗传多样性将成为 中心。 鉴定这些遗传的基本原因 对有毒剂的响应差异是重要的关键 了解毒性的基本机制，并为 两者都可以防止不利的健康影响以及探索机会 疾病过程中的干预措施。 新中心的四个研究核心代表现有优势 辛辛那提大学科学家之间的互动 与遗传学相关的医疗中心。 核心重点 生态学研究核心是鉴定和表征 影响新陈代谢的遗传多态性，因此 毒性，外国化学物质。 其他研究核心 - 生产性和 发育毒理学，遗传毒理学和氧化应激 毒理学 - 专注于主要的三个特定领域 重要性。 这些研究核心研究了 环境药物强调使用遗传技术。 环境物质在导致不育症的作用，在子宫内 毒性和先天缺陷是一个重要的公共卫生问题。 这 环境药物对遗传物质结构的影响 自身导致突变和癌症是一个至关重要的领域。 氧化应激是一个重要的领域，可能是 环境药物在生物系统中的许多不同毒性作用。 这个新中心将在NIEHS中心之间是独一无二的，并将提供。一个 重要的。为环境研究社区提供资源。