title: Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains.
abstract: 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-naïve 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.
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. lcarr@iupui.edu
authors: Lucinda G
authors: LG
authors: Carr
authors: Mark W
authors: MW
authors: Kimpel
authors: Tiebing
authors: T
authors: Liang
authors: Jeanette N
authors: JN
authors: McClintick
authors: Kevin
authors: K
authors: McCall
authors: Melissa
authors: M
authors: Morse
authors: Howard J
authors: HJ
authors: Edenberg
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D020296:Animals, Congenic / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005819:Genetic Markers; D005838:Genotype; D008297:Male; D046228:Microarray Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar / Q000235:genetics
chemical_list: D005819:Genetic Markers