GENOTYPIC SELECTION PROVIDES EXPERIMENTAL CONFIRMATION FOR AN ALCOHOL-CONSUMPTION QUANTITATIVE TRAIT LOCUS IN MOUSE

Quantitative genetic research has produced a wealth of basic informati on concerning genetic influence on alcohol-related processes. Recent d evelopments in quantitative trait locus (QTL) methodology were promptl y applied to the task of individuating polygenes affecting alcohol-rel ated attributes in animal models and a body of reliable data is gradua lly coming into focus as a result of replication and convergence of ev idence from a variety of methods. A key issue in QTL research is the n eed to distinguish true positive results from the false positive resul ts that are inherent in analytical procedures requiring large numbers of significance tests. One school of thought holds that stringent sign ificance levels should be imposed;(1,2) another suggests more modest c riteria for QTL nomination, with subsequent confirmation trials with i ndependent samples.(3-5) Recombinant inbred strains(6,7) and various t ypes of intercrosses(8,9) have been used in correlational designs, bot h for nomination and confirmation studies. Alternative experimental pr ocedures include knockout preparations(10) and short-term phenotypic s elective breeding.(11) We present here results from a third experiment al method-that of marker-based genotypic selection-in evaluation of tw o nominated QTLs for alcohol acceptance in mice.