Genomic regulatory sequence analysis for alcohol-related phenotypes

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DESCRIPTION (provided by applicant): The development of alcoholism related traits is believed to be caused by both genetic and environmental factors, in addition to their interactions. Genetic variations associated with alcoholism related traits can affect several different mechanisms, including gene expression regulation. The goal of this work is to study mammalian model systems to identify genomic regulatory sequences that contribute to transcriptional changes in alcohol-related behaviors. Genome-wide exploration of regulatory sequences is difficult in mammals because of the small and degenerate nature of these elements and because of the complexity and size of mammalian genomes. Therefore, the proposed study will rely on evidence from multiple different data sources to help narrow the search for regulatory sequences. First, high-throughput gene expression data in addition to genotypic data on recombinant inbred strains will be analyzed to identify genes that show common regulatory patterns and are correlated with alcohol related phenotypes. Then, common sequences shared in the upstream and downstream regions of these genes will be identified as potential regulatory elements. Second, gene expression experiments on rat selected lines will be performed so that they can be compared with existing mouse studies on alcohol preference. To improve the search for potential regulatory elements, only common expression patterns and sequences shared between orthologous genes in the two rodent studies will be considered. This project is designed as a mentored research opportunity for the candidate to apply her prior experience and training in computational approaches for studying transcription regulation to alcohol research. The candidate will use the award period to develop the background and skills in pharmacology, mammalian systems and genomics necessary for this endeavor. The outcome of this project is to develop large scale bioinformatics methods for analyzing gene expression studies, genetic data and genomic sequences in model systems of alcohol related traits. The resulting methods and data will be made available to the alcohol research community at large.