Quantitative trait loci and psychopharmacology

Abstract

Unlike simple Mendelian characteristics, individual differences in behavior, including behavioral responses to drugs, are generally distributed continuously, show substantial non-genetic as well as genetic influence, and appear to be influenced by many genes rather than one or two major genes. For these reasons, application of techniques of molecular biology to identify DNA sequences responsible for behavioral variation requires strategies that can detect genes that account for small amounts of variation, so-called quantitative trait loci (QTL). One such strategy involves analyses of association using recombinant inbred (RI) strains of mice. The RI QTL approach is especially valuable when researchers use the same RI series, such as BXD, which has 26 strains and more than 300 mapped genetic markers. Even when the progenitor inbred strains do not differ and when the strain distribution pattern of the RI strains is continuous, the approach can be used to identify and map QTL and estimate the extent to which the QTL account for genetic variance for a particular phenotype. A multivariate extension of this approach can assess genetic correlations among measures as well as the QTL underpinnings of these genetic correlations. The cumulative and integrative nature of such a program of research is the major benefit of the RI QTL approach for molecular genetic analysis of psychopharmacological processes, their physiological infrastructure, and their interface with other biological and behavioural systems.