Genome Explorations shall establish a 'proof of concept' correlational database that integrates genomic, transcriptional and proteomic information from mice in a format that will facilitate the study of alcoholism and alcohol-related organ damage. In Phase I, the contractor shall utilize genetically defined inbred mouse strains that differ in their functional tolerance to alcohol and establish an experimental ethanol treatment paradigm to examine changes in cerebellum. Building upon normative data sets already collected from these mice, transcriptome data from control and ethanol treated mice will be obtained using Affymetrix MG 430 2.0 expression arrays. Synaptic membrane fractions from cerebella and whole brain of one strain will also be analyzed by the LC/MS-based Multidimensional Protein Identification Technology (MudPIT) to generate proteome data reflective of each tissue. All generated data sets will be standardized and integrated into GenExQTL, a webbased and fully functional correlational database produced by Genome Explorations. Inclusion of the Phase I data will demonstrate the ability to functionally integrate transcriptome and proteome data into one correlational database. In Phase II, expansion of the data sets across an entire panel of recombinant inbred mouse strains will increase the precision of GenExQTL to map transcriptional, proteomic, and other higher order phenotypic traits to specific genes. This will enable NIAAA investigators to evaluate shared genetic modulation of thousands of traits and their joint control by upstream genetic polymorphisms and identify specific interconnected networks of genes and proteins that participate in alcohol-related illnesses.
