Abstract
Transcriptional profiling of specific regions of inbred rat brains reveals genes associated with alcohol preference in a known QTL locus on chromosome 4
Highlights
Bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ greatly in alcohol preference, in part due to a highly significant quantitative trait locus (QTL) on chromosome 4
Cis-regulated genes Because alcohol preference in the congenic strains correlated with the strain origin of the introgressed region, our primary hypothesis was that the genes in that region contributing to the phenotype would differ in expression as a result of cis-acting elements
Of the probe sets differentially expressed in the introgressed region of chromosome 4, many are located within the 95% confidence interval of the QTL (54.8 to 105 million bases (Mb)). (Figure 2) The number of differentially expressed probe sets (false discovery rate (FDR) ≤ 0.25) within the QTL was similar in each of the 5 brain regions, ranging from 72 in the nucleus accumbens to 89 in the hippocampus (Table 1). most probe sets significant in any one brain region were significant in multiple regions; 104 of the 157 cis-regulated probe sets showed differential expression in more than one brain
Summary
Bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ greatly in alcohol preference, in part due to a highly significant quantitative trait locus (QTL) on chromosome 4. The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in five brain regions of alcohol-naïve inbred alcohol-preferring and P.NP congenic rats: amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex. Selected strains of rodents that differ in voluntary alcohol consumption have been valuable tools to aid in dissecting the genetic components of alcoholism [35,36,37,38]. Inbred alcohol-preferring (iP) and -nonpreferring (iNP) strains were established; these inbred strains maintain highly divergent alcohol consumption scores [41]. Due to the physiological and genetic similarity between humans and rats, iP and iNP rats can be studied to identify important genetic factors that might influence predisposition to alcoholism in humans
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