Candidate genes and their regulatory elements: alcohol preference and tolerance.
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.
Saba
Laura
L
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, 12801 East 17th Avenue, Aurora, CO 80045, USA.
Bhave
Sanjiv V
SV
Grahame
Nicholas
N
Bice
Paula
P
Lapadat
Razvan
R
Belknap
John
J
Hoffman
Paula L
PL
Tabakoff
Boris
B
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D004361:Drug Tolerance / Q000235:genetics*; D005809:Genes, Regulator; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000235:genetics