Identification of quantitative trait loci influencing alcohol consumption in the high alcohol drinking and low alcohol drinkingt rat lines

Selective breeding has been employed to develop high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to disc ourage inbreeding (Li rr al, 1993). To identify quantitative trait loci (QT Ls) contributing to alcohol consumption, reciprocal HAD and LAD matings in conjunction with Fl intercrosses were used to create 459 F2 progeny. Using selective genotyping of 151 FZ progeny with extreme alcohol consumption sco res and a novel least squares method developed by Haley et al (1994), five chromosomal regions (1,5,10,12, and 16) were identified with lod scores gre ater than 2.0. Genotyping of the entire sample of 459 F2 progeny produced m aximum lod scores of 3.5 on chromosome 5, 2.4 on chromosome 10, 4.7 on chro mosome 12 and 2.9 on chromosome 16. The evidence of linkage to chromosome I diminished substantially to a maximum lod score of 0.5 when all F2 progeny were genotyped. This study is the first genome-wide study for QTLs underly ing alcohol consumption that has employed noninbred lines. Further localiza tion of these QTLs will likely provide insight and candidate genes for the study of human alcoholism.