Indiana University School of Medicine, Department of Medicine, IB424G, 975 West Walnut Street, Indianapolis, IN 46202, USA.
Genome Biol. 2010;11(2):R11. doi: 10.1186/gb-2010-11-2-r11. Epub 2010 Feb 3.
Selectively 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. Alcohol consumption scores of reciprocal chromosome 4 congenic strains NP.P and P.NP correlated with the introgressed interval. 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.
Within the QTL region, 104 cis-regulated probe sets were differentially expressed in more than one region, and an additional 53 were differentially expressed in a single region. Fewer trans-regulated probe sets were detected, and most differed in only one region. Analysis of the average expression values across the 5 brain regions yielded 141 differentially expressed cis-regulated probe sets and 206 trans-regulated probe sets. Comparing the present results from inbred alcohol-preferring vs. congenic P.NP rats to earlier results from the reciprocal congenic NP.P vs. inbred alcohol-nonpreferring rats demonstrated that 74 cis-regulated probe sets were differentially expressed in the same direction and with a consistent magnitude of difference in at least one brain region.
Cis-regulated candidate genes for alcohol consumption that lie within the chromosome 4 QTL were identified and confirmed by consistent results in two independent experiments with reciprocal congenic rats. These genes are strong candidates for affecting alcohol preference in the inbred alcohol-preferring and inbred alcohol-nonpreferring rats.
经选择性繁殖的酒精偏好（P）和酒精非偏好（NP）大鼠在酒精偏好方面存在很大差异，部分原因是 4 号染色体上存在一个高度显著的数量性状基因座（QTL）。NP.P 和 P.NP 回交染色体 4 近交系大鼠的酒精消耗评分与渐渗间隔相关。本研究的目的是通过比较五个脑区的基因表达来确定可能影响酒精消耗的候选基因：杏仁核、伏隔核、海马体、尾壳核和前额皮质。
在 QTL 区域内，104 个顺式调控探针集在一个以上区域中差异表达，另外 53 个探针集在单个区域中差异表达。检测到的反式调控探针集较少，大多数仅在一个区域中不同。对 5 个脑区的平均表达值进行分析，得到 141 个差异表达的顺式调控探针集和 206 个差异表达的反式调控探针集。将本研究中近交酒精偏好大鼠与同基因 P.NP 近交系大鼠的结果与之前来自反向同基因 NP.P 与近交酒精非偏好大鼠的结果进行比较，显示 74 个顺式调控探针集在至少一个脑区以相同的方向和一致的差异幅度差异表达。
在两个独立的、具有反向同基因大鼠的实验中，通过一致的结果，确定并证实了位于 4 号染色体 QTL 内的酒精消耗的顺式调控候选基因。这些基因是影响近交酒精偏好和近交酒精非偏好大鼠酒精偏好的强有力候选基因。
