TY - JOUR
T1 - Candidate genes and their regulatory elements
T2 - Alcohol preference and tolerance
AU - Saba, Laura
AU - Bhave, Sanjiv V.
AU - Grahame, Nicholas
AU - Bice, Paula
AU - Lapadat, Razvan
AU - Belknap, John
AU - Hoffman, Paula L.
AU - Tabakoff, Boris
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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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U2 - 10.1007/s00335-005-0190-0
DO - 10.1007/s00335-005-0190-0
M3 - Article
C2 - 16783646
AN - SCOPUS:33745214657
SN - 0938-8990
VL - 17
SP - 669
EP - 688
JO - Mammalian Genome
JF - Mammalian Genome
IS - 6
ER -