Identification of QTLs influencing alcohol preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) mouse lines.

摘要

The High- and Low-Alcohol Preferring (HAP1/LAP1 and HAP2/LAP2) mouse lines were developed by selective breeding for differences in alcohol preference. They represent the only extant selectively bred mouse lines developed for this alcohol phenotype. Therefore, they provide a unique resource for QTL detection and mapping. Importantly, neither of the replicate lines is inbred and therefore, novel study designs can be employed to detect loci contributing to alcohol preference. Two independent studies, with very different approaches, were conducted in the HAP and LAP replicate lines. In Study 1, microsatellite markers were genotyped in the replicate HAP1/LAP1 and HAP2/LAP2 mice in QTL regions nominated by other mouse RI and F2 studies in order to detect divergence of allele frequencies in the two oppositely selected lines. Significant differences in allele frequencies were observed in the HAP1/LAP1 mice with markers on chromosome 9 (p<0.01). In the HAP2/LAP2 mice, significant differences in allele frequencies were identified on chromosomes 2 and 9 (p<0.01). In Study 2, a genome-wide screen was performed in a sample of 432 HAP1xLAP1 F2 animals and a QTL on chromosome 9 (LOD=5.04) was found which met criteria for genome wide significance (p<0.001). Gender specific analyses supported a greater effect of the QTL among female mice (LOD=5.19; p<0.0008) than male mice (LOD=1.19). This study provides additional evidence and confirmation that specific regions on chromosomes 9 and perhaps 2 are important for alcohol preference.