Abstract
Identification of genes underlying complex traits has been difficult, but combined application of novel methods and mouse models provides new hope. Rare monogenic syndromes, and candidate gene and biochemical approaches are sometimes useful, but each of these approaches also has limitations. Some problems that prevent identification and isolation of genes underlying complex disease can be avoided by the use of whole genome mapping of mouse crosses or of human families. Mice have many advantages for the study of complex disease, including an extensive genetic map. A generic method has recently been developed and applied for detection of quantitative trait loci (QTLs) using whole genome maps of mouse crosses. Availability of more than 200 congenic strains provides another incentive for studies in mice. Congenic strains provide a rich, but previously unexploited, resource for the rapid identification of genes causing complex diseases. A congenic mouse strain is genetically identical to a background strain, except for a small chromosomal region derived from a donor strain. Thus, comparison of a phenotype in a congenic strain with the phenotype in its background strain allows study of the effects of single genes derived from the donor strain, isolated from the effects of other donor strain genes. Application of all or several techniques to complex disease studies in mice and in humans may lead to the identification and understanding of complex diseases whose etiology is currently unknown.