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.
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