Mammalian Genome

, Volume 17, Issue 6, pp 669–688 | Cite as

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 TabakoffEmail author


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.


Quantitative Trait Locus Transcription Factor Binding Site Quantitative Trait Locus Analysis Recombinant Inbred Identify Candidate Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.

Supplementary material

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Supplementary material


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Laura Saba
    • 1
  • Sanjiv V. Bhave
    • 1
  • Nicholas Grahame
    • 3
  • Paula Bice
    • 4
  • Razvan Lapadat
    • 1
  • John Belknap
    • 2
  • Paula L. Hoffman
    • 1
  • Boris Tabakoff
    • 1
    • 5
    Email author
  1. 1.Department of PharmacologyUniversity of Colorado at Denver and Health Sciences CenterAuroraUSA
  2. 2.Research Service R&D-5VA Medical CenterPortlandUSA
  3. 3.Department of PsychologyIndiana University School of MedicineIndianapolisUSA
  4. 4.Department of MedicineIndiana UniversityIndianapolisUSA
  5. 5.Department of PharmacologyBoris TabakoffAuroraUSA

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