Quantitative trait locus analysis: multiple cross and heterogeneous stock mapping.

Until well into the 1990s, both preclinical and clinical research focused on finding "the" gene for human diseases, including alcoholism. This focus was reinforced by the emergence of technologies to either inactivate (i.e., knock out) a gene or add extra copies of an existing gene in a living organism, which clearly demonstrated that over- or underexpressing a single gene could have a profound effect on behavior. However, a small but vocal group of scientists, including many alcohol researchers, argued that behaviors, including alcohol-related behaviors, were complex traits and therefore no one gene likely would have a large effect. This view was consistent with a large body of genetic research conducted in plants and fruit flies (e.g., Paterson et al. 1988) indicating that, for example, even a presumably simple characteristic, such as the size of a tomato, was determined by several genes. However, it was difficult to convince the scientific community that, in terms of its genetic determination, behavior was similar to the size of a tomato. Only with the advent of new genetic tools did it become possible to prove that many different genes contribute to complex behavioral characteristics.