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-seekingbehavior, alcoholism, and related diseases. The services offered will be contributing to the goals of the IARCby supporting research projects involved in identifying the genetic determinants of alcohol ingestion andresponse to ethanol, goals of the IARC. The Core has developed genotyping assays for the human alcoholmetabolizing enzymes, ADH1B, ADH1C, ALDH2, and ALDH1A1 and has determined the allele frequenciesof these loci in many collaborative studies. The Core has expanded its human genotyping services to includehigh throughput genotyping using the Sequenom MassArray system. For the ADH cluster of genes, 63 SNPscovering all 7 genes across the ADH region will be genotyped, resulting in haplotypes that are used inassociation studies. Likewise, SNP panels have been developed to genotype SNPs covering the GABAreceptors and the cholinergic receptor, muscarinic 2 (CHRM2). To identify genes that are differentiallyexpressed between high alcohol drinking and low alcohol drinking animal models under various experimentalconditions, the Core will continue to offer microarray technology. These findings will help us understand thebiological mechanisms of alcohol drinking by pointing to CMS pathways that are differentially changedbetween high and low drinking models as a result of alcohol drinking. This technology will also be used todetermine whether alcohol exposure during critical periods of development result in differential geneexpression between embryos from C57BI/6 and DBA/2 mice which are differentially vulnerable to alcoholexposure. The Core will offer quantitative Real-Time PCR as a means to verify differential expression of keygenes identified by microarray technology. A new service of the Core will be to provide genetic monitoring ofthe alcohol preferring and nonpreferring rat lines and strains. An overall increase in accuracy and costsavings result in having the genotyping and microarray analyses performed in a core laboratory rather thanhaving independent facilities. The Core services benefit the Human Component, and Dr. Davidson's pilotprojects and numerous existing and future collaborators by performing genotyping of various genes, theAnimal Production Core for genetic monitoring of their rat lines and strains, and the Rat Research and FetalAlcohol Syndrome Components for microarray analyses and confirmation studies to identify candidate genesfor alcohol-related phenotypes. In addition, the Core interacts with and is dependent on the guidance of theAdministration Core. The findings of the Core, identification of genes that determine vulnerability toalcoholism, will advance the understanding of alcohol-seeking behavior and provide information fordeveloping treatments to prevent excessive alcohol consumption.
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