Classical and Neoclassical Approaches to the Genetic Analysis of Alcohol‐Related Phenotypes

Theoretical descriptions are given for two breeding methods in animal genetics that might be of use In alcohol research. These methods are marker‐based selection and marker‐based development of congenic strains, both using DNA markers such as polymerase chain reaction‐detectable polymorphisms as the criteria for breeding. Such designs would utilize these markers as Indicators of adjacent Quantitative Trait Loci (QTL) that are influential on alcohol‐related phenotypes. Issues in the logic and implementation of these methods, such as proximity of the markers and the QTL allele, are explored. A third method, development of congenic strains with phenotypic screening, is also described. This method is currently being used to create two sets of congenic lines on a C57BL/6 inbred mouse background. The criterion phenotype is locomotor activation to 1.5 g/kg (ip) ethanol. Data are reported on the success of transferring the activation phenotype from two strains, DBA/2Abg and MOLD/Rk‐Abg, onto the nonactivated C57BL/6Abg background. The value of these methods in alcohol research is outlined with regard to both identification of relevant genes and for their use as tools in basic research on mechanism of alcohol action.