Over the last 10-15 years rapid progress has been made in the study of ethanol related traits including alcoholism and behavioral responses to ethanol in both humans and animal models. Refined genetic strategies and high-throughput molecular technologies such as large-scale genotyping and DNA microarrays have identified a relatively large number of chromosomal locations and candidate genes contributing to the genetic risk for alcoholism and ethanol response behaviors. At present, integrating and making the combined wealth of results easily accessible and interpretable presents significant challenges for researchers. In this application, we propose to construct such a unique and important ethanol response gene resource (ERGR). We will first collect and curate all the available data sets for ethanol response genes including those generated by the groups at VCU and publicly available. Examples of these internal and external data include human linkage scan and association studies, mouse ethanol QTL, microarray data, high throughput literature searches, and candidate genes in other organisms (e.g. rat, fly, worm). The collected data will be integrated via a data management system and updated routinely by computer programs. Many analyses will be performed for the identification of susceptibility genes and their features, including comparative genomics, gene network, Gene Ontology term, and gene expression analyses. We will also develop scoring algorithms for prioritizing candidate genes and implement tools for customization of gene prioritization. Finally, we will design and implement a user-friendly web-based platform. This platform will provide (1) simultaneous access to the data collected and annotated and to certain public genomic databases and (2) tools for statistical analysis and data presentation. The overall goal is to provide a comprehensive ethanol response gene resource to NIAAA research community and to facilitate understanding the mechanism(s) of action for individual genes in alcoholism and identify potential targets for novel new interventions in alcoholism. Public Health Relevance: The proposed project will collect, curate, and analyze all the available data sets for ethanol response genes and prioritize the candidate genes for future investigation. A user-friendly web-based ethanol response gene database system will be constructed for NIAAA research community.
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