SHORT-TERM SELECTIVE BREEDING AS A TOOL FOR QTL MAPPING - ETHANOL PREFERENCE DRINKING IN MICE

Short-term selective breeding starting from an F-2 intercross of two i nbred strains is a largely unexploited but potentially useful tool for quantitative trait locus (QTL) mapping. The selection lines can also serve as a valuable confirmation test of recombinant inbred (RI) QTL r esults when the same two progenitor strains are used. Starting from an F-2 from a C57BL/6J (B6) x DBA/2J (D2) cross (B6D2F2), this approach was used in a population of similar to 72 mice per generation bidirect ionally selected for two-bottle choice 10% ethanol (alcohol) preferenc e for four generations. The high-preference line diverged significantl y from the low line in the first generation with a realized heritabili ty of .32. By generation 4, the preference ratios in the high line wer e double those seen in the low line. Regions of the genome previously implicated by BXD RI QTL analysis as containing QTLs were searched usi ng microsatellite markers. The test for the presence of QTLs was based on the divergence of marker allele frequencies in the two oppositely selected lines significantly exceeding that expected from random (gene tic) drift and allele frequency estimation error. Combining the BXD an d two-way selection line results, the most probable QTL was found on c hromosome 3 (near the Adh1 locus; LOD similar to 2.9), other probable QTLs were found with LOD 2.4-2.6.