Quantitative trait locus (QTL) mapping in mice

Complex traits, such as the human disease alcoholism, are influenced by multiple genetic and environmental factors. Animals can be used to model certain components of this disease. However, even the apparently simplified traits modeled in animals are found to be under the influence of multiple genes, each of relatively small effect. Thus, the distributions of these traits in genetically heterogeneous populations tend to be continuous, rather than displaying simple Mendelian inheritance patterns. The genomic loci that influence the quantitative variability in these traits are termed quantitative trait loci (QTL).*The identification of the genes influencing such quantitative traits can be approached using QTL mapping methods that were originally developed by plant geneticists (see Lynch and Walsh, 1998). Initial efforts may be directed at localizing an influential gene (a QTL) to a chromosome or a chromosomal segment. Additional experiments may then be performed, using stringent statistical criteria, to confirm the presence of the QTL. Finer mapping methods are then used to narrow the chromosomal region in which the QTL resides, with the ultimate goal of identifying the causative gene or regulatory element. Single gene mutants, gene expression analyses and sequence information can be used at each stage to provide evidence that a candidate gene is the QTL (Figure 1.1).