RGD Reference Report - Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains. - Rat Genome Database

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Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains.

Authors: Carr, LG  Kimpel, MW  Liang, T  McClintick, JN  McCall, K  Morse, M  Edenberg, HJ 
Citation: Carr LG, etal., Alcohol Clin Exp Res. 2007 Apr 19;.
RGD ID: 1624272
Pubmed: PMID:17451403   (View Abstract at PubMed)
PMCID: PMC4455872   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1530-0277.2007.00397.x   (Journal Full-text)

Background: A highly significant quantitative trait locus (QTL) on chromosome 4 that influenced alcohol preference was identified by analyzing crosses between the iP and iNP rats. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol consumption compared with the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might contribute to the differences in alcohol consumption between the alcohol-naive congenic and background strains. Methods: RNA from 5 brain regions from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray to look for both cis-regulated and trans-regulated genes. Expression levels were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time polymerase chain reaction. Five individual brain regions (nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum) were analyzed to detect differential expression of genes within the introgressed QTL interval, as well as genes outside that region. To increase the power to detect differentially expressed genes, combined analyses (averaging data from the 5 discrete brain regions of each animal) were also carried out. Results: Analyses within individual brain regions that focused on genes within the QTL interval detected differential expression in all 5 brain regions; a total of 35 genes were detected in at least 1 region, ranging from 6 genes in the nucleus accumbens to 22 in the frontal cortex. Analysis of the whole genome detected very few differentially expressed genes outside the QTL. Combined analysis across brain regions was more powerful. Analysis focused on the genes within the QTL interval confirmed 19 of the genes detected in individual regions and detected 15 additional genes. Whole genome analysis detected 1 differentially expressed gene outside the interval. Conclusions: Cis-regulated candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying a QTL for alcohol preference.



Objects referenced in this article
QTL Alc22 Alcohol consumption QTL 22 Rattus norvegicus
Strain Iusm:NP alcohol-nonpreferring Rattus norvegicus
Strain Iusm:P alcohol-preferring Rattus norvegicus
Strain NP.P-(D4Rat119-D4Rat55)/Iusm null Rattus norvegicus

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