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Candidate genes and their regulatory elements: alcohol preference and tolerance

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Abstract

QTL analysis of behavioral traits and mouse brain gene expression studies were combined to identify candidate genes involved in the traits of alcohol preference and acute functional alcohol tolerance. The systematic application of normalization and statistical analysis of differential gene expression, behavioral and expression QTL location, and informatics methodologies resulted in identification of 8 candidate genes for the trait of alcohol preference and 22 candidate genes for acute functional tolerance. Pathway analysis, combined with clustering by ontology, indicated the importance of transcriptional regulation and DNA and protein binding elements in the acute functional tolerance trait, and protein kinases and intracellular signal transduction elements in the alcohol preference trait. A rudimentary search for transcription control elements that could indicate coregulation of the panels of candidate genes produced modest results, implicating SMAD-3 in the regulation of four of the eight candidate genes for alcohol preference. However, the realization of the many caveats related to transcription factor binding site analysis, and attempts to correlate between transcription factor binding and function, forestalled any definitive global analysis of transcriptional control of differentially expressed candidate genes.

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Acknowledgments

The authors acknowledge the financial support of the National Institute on Alcohol Abuse and Alcoholism and particularly the Integrative Neuroscience Initiative on Alcoholism; Lohocla Research Corporation and the Banbury Fund.

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Authors and Affiliations

  1. Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado, 80045, USA

    Laura Saba, Sanjiv V. Bhave, Razvan Lapadat, Paula L. Hoffman & Boris Tabakoff

  2. Research Service R&D-5, VA Medical Center, Portland, Oregon, 97239, USA

    John Belknap

  3. Department of Psychology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA

    Nicholas Grahame

  4. Department of Medicine, Indiana University, Indianapolis, Indiana, 46202, USA

    Paula Bice

  5. Department of Pharmacology, Boris Tabakoff, Mail Stop 8303, Building RCl, 12801 East 17th Avenue, Room L18-6104, PO Box 6511, Aurora, CO, 80045, USA

    Boris Tabakoff

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  1. Laura Saba
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Correspondence to Boris Tabakoff.

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Saba, L., Bhave, S.V., Grahame, N. et al. Candidate genes and their regulatory elements: alcohol preference and tolerance. Mamm Genome 17, 669–688 (2006). https://doi.org/10.1007/s00335-005-0190-0

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