CORE--BIOANALYTICAL

来自不同实验室的研究，包括超级基金调查人员的研究，已经确定人类群体对许多与毒理学相关的酶具有多态性。对于许多，但肯定不是所有的这些多态，已经确定了遗传相关性，在几个流行病学调查中，已经描述了生物转化基因的特定多态与疾病发生率之间的关联。生物监测越来越多地涉及评估个体的遗传/分子指数，目的是检测疾病易感性的可能标记，以及确定化学效应的近几个指标--例如因暴露于环境毒物而引起的基因表达谱的变化。支持分子研究的技术进步导致了复杂技术的发展，这些技术适用于广泛的实验问题。这些和其他令人信服的发现涉及生物转化基因和其他基因座内的遗传多态的影响，以及它们各自对化学引发的疾病状态的影响，构成了Superfund生物分析核心实验室的长期目标的基础-为Superfund研究人员提供服务设施，使其能够开发新的基因分析、高通量基因分析，并与环境相关疾病的发病率相关。八个单独的超级基金项目将利用生物分析核心，并将受益于集中服务。这些核心工作将侧重于广泛的分子生物学类型的生物标志物，这些标志物可能预测暴露于毒物、生理功能受损和/或对环境中发生的有毒物质的损害的异常敏感性，特别是那些通常存在于危险废物地点的有毒物质。在本提议的5年期间，Superfund生物分析核心实验室将提供以下服务：提取1,850个样本的DNA/RNA，分离750个单核细胞样本，开发5种新的基因分型分析方法，创建10种新的基因表达分析方法，制作1种新的基于DNA测序的分析方法，鉴定约17,000种基因类型，进行约8,000种基因表达分析，分析约4,000种DNA序列，并提供250个DNA测序凝胶以及约7,000个DNA测序凝胶通道。这一共享资源支持以具有成本效益和效率的方式实施这些分析，从而最大限度地使这些重要工具对最多的超级基金实验室有用。

Research from various laboratories, including those of Superfund investigators, has established that human populations, possess polymorphisms for many enzymes of toxicological relevance. For many, but certainly not all of these polymorphisms, genetic correlates have been identified, and in several epidemiologic investigations, associations have been described between particular polymorphisms in biotransformation genes and the incidence of disease. Biological monitoring increasingly involves assessment of genetic/molecular indices from individuals, for the purpose of detecting possible markers of disease susceptibility, as well as identification of nearly indicators of chemical effect-such as alterations in gene expression profiles due to exposure to environmental toxicants. Advances in technology supporting molecular research have led to the development of complex techniques which are applicable to a broad range of experimental problems. These and other compelling findings regarding the impact of genetic polymorphism within biotransformation genes and other gene loci, and their respective involvement to chemically-initiated disease states, form the basis of the long term objective of the Superfund Bioanalytical Core Laboratory-to provide a service facility for Superfund investigators enabling novel genetic assay development, high throughput genetic analysis, and correlates to environmentally-related disease incidence. Eight individual Superfund projects will utilize the Bioanalytical Core and will benefit from the centralized services. These Core efforts will focus on a wide range of molecular biology-type biomarkers that may be predictive of exposure to toxicants; impaired physiologic function; and/or unusual susceptibility to damage from toxic agents that occur in the environment, particularly those that are commonly present at hazardous waste sites. Over the 5 year duration of this proposal, the Superfund Bioanalytical Core Laboratory will provide the following services: DNA/RNA extraction of 1,850 samples, the isolation of 750 mononuclear cell samples, the development of 5 new genotyping assays, the creation of 10 new gene expression assays, the production of 1 novel DNA sequencing- based assay, the identification of approximately 17,000 genotypes, the execution of approximately 8,000 gene expression analyses, the analyses of approximately 4,000 DNA sequences,, and the provision of 250 DNA- sequencing gels are as well as approximately 7,000 DNA sequencing gel lanes. This shared resource supports implementation of these assays in a cost-effective and efficient manner and therefore maximizes the usefulness of these important tools for the largest number of Superfund laboratories.