Candidate genes and their regulatory elements: Alcohol preference and tolerance

Laura Saba, Sanjiv V. Bhave, Nicholas Grahame, Paula Bice, Razvan Lapadat, John Belknap, Paula L. Hoffman, Boris Tabakoff

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)669-688
Number of pages20
JournalMammalian Genome
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Genetics

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    Saba, L., Bhave, S. V., Grahame, N., Bice, P., Lapadat, R., Belknap, J., Hoffman, P. L., & Tabakoff, B. (2006). Candidate genes and their regulatory elements: Alcohol preference and tolerance. Mammalian Genome, 17(6), 669-688. https://doi.org/10.1007/s00335-005-0190-0