Confirmation of provisional quantitative trait loci for voluntary alcohol consumption: genetic analysis in chromosome substitution strains and F2 crosses derived from A/J and C57BL/6J progenitors

Abstract

Earlier research utilizing AXB/BXA recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice independently mapped provisional quantitative trait loci (QTL) for voluntary alcohol consumption (VAC) to common chromosomal regions. This study was designed to confirm QTL on chromosomes 2, 3, 5, 7, and 15 in an A/J (A)xC57Bl/6J (B6) F2 cross, and a panel of B6.A chromosome substitution strains (CSS). AxB6F2 mice, CSS, and A/J and C57BL/6J progenitors were tested for VAC. Previously identified QTL regions were targeted for genotyping in the AxB6F2 mice. Among the AxB6F2 mice, significant differences in VAC were associated with loci on chromosome 2 (peak marker D2Mit367) and chromosome 3 (D3Mit189). Additionally, a significant interaction was observed between loci on chromosome 15 (D15Mit245) and chromosome 2 (D2Mit367). A survey of the CSS panel provided further evidence for VAC QTLs on chromosomes 2 and 15. In the CSS panel, lower ethanol consumption was observed in those strains carrying the A/J 2 or 15 chromosome on a B6 background. This finding is consistent with the allelic influences observed in AxB6F2 mice in this study and those reported previously in the RI and RC strains of mice. Specifically, A/J alleles were associated with decreased ethanol consumption whereas C57BL/6J alleles were associated with increased ethanol consumption. The present results confirm previously reported QTL, on chromosomes 2 and 15 for VAC in RI and RC strains. Collectively, the regions on chromosomes 2 and 15 have now been replicated in at least three independent crosses derived from the A/J and C57BL/6J progenitors. The identification of potential candidate genes for the chromosome 15 QTL is discussed in the context of an in-silico analysis.