Quantitative trait loci (QTLs) are DNA regions that may contain one or more genes related to the development of a certain quantitative trait. Mapping of QTLs in animal models of alcohol-related phenotypes has identified multiple genomic areas that potentially contain candidate genes for these phenotypes. (For more information on QTL mapping, see the article in this issue by Grisel, pp. 169–174.) The methods of identifying these candidate genes and any potential functional variants are essentially the same as those used in humans. Once functional variants are found, however, any positive association between a variant and the trait of interest must be interpreted with caution. For example, because of the way mouse strains are bred, mice who have a trait (analogous to human cases) and mice who do not have that trait (analogous to controls) may possess different alleles at a particular gene even if that gene is unrelated to the disease (or trait) under consideration. The gene that actually confers the risk for the disease or trait under investigation may be located near the gene showing the allelic polymorphism, but may be difficult to identify positively using association methods alone.
