Genomics and Molecular Biology Core

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The overall goal of the Genomics and Molecular Biology Core of this Indiana Alcohol Research Center (IARC) is to support both human and animal studies that pursue the genes underlying alcohol-seeking behavior, alcoholism, and related diseases. The services offered will be contributing to the goals of the IARC by supporting research projects involved in identifying the genetic determinants of alcohol ingestion and response to ethanol, goals of the IARC. The Core has developed genotyping assays for the human alcohol metabolizing enzymes, ADH1B, ADH1C, ALDH2, and ALDH1A1 and has determined the allele frequencies of these loci in many collaborative studies. The Core has expanded its human genotyping services to include high throughput genotyping using the Sequenom MassArray system. For the ADH cluster of genes, 63 SNPs covering all 7 genes across the ADH region will be genotyped, resulting in haplotypes that are used in association studies. Likewise, SNP panels have been developed to genotype SNPs covering the GABA receptors and the cholinergic receptor, muscarinic 2 (CHRM2). To identify genes that are differentially expressed between high alcohol drinking and low alcohol drinking animal models under various experimental conditions, the Core will continue to offer microarray technology. These findings will help us understand the biological mechanisms of alcohol drinking by pointing to CMS pathways that are differentially changed between high and low drinking models as a result of alcohol drinking. This technology will also be used to determine whether alcohol exposure during critical periods of development result in differential gene expression between embryos from C57BI/6 and DBA/2 mice which are differentially vulnerable to alcohol exposure. The Core will offer quantitative Real-Time PCR as a means to verify differential expression of key genes identified by microarray technology. A new service of the Core will be to provide genetic monitoring of the alcohol preferring and nonpreferring rat lines and strains. An overall increase in accuracy and cost savings result in having the genotyping and microarray analyses performed in a core laboratory rather than having independent facilities. The Core services benefit the Human Component, and Dr. Davidson's pilot projects and numerous existing and future collaborators by performing genotyping of various genes, the Animal Production Core for genetic monitoring of their rat lines and strains, and the Rat Research and Fetal Alcohol Syndrome Components for microarray analyses and confirmation studies to identify candidate genes for alcohol-related phenotypes. In addition, the Core interacts with and is dependent on the guidance of the Administration Core. The findings of the Core, identification of genes that determine vulnerability to alcoholism, will advance the understanding of alcohol-seeking behavior and provide information for developing treatments to prevent excessive alcohol consumption.