Genetics of complex diseases: from mouse to man and back

Identification of genes underlying complex (non-Mendelian) traits, which include diseases such as IBD, has been an important and difficult problem in genetics. However, new tools and methods have brought on a new era in the genetic analysis of complex traits. While identification of the genes underlying common diseases will never be easy, we believe that general approaches to analysis of common diseases are practical now. An outline of the approaches to analysis of complex diseases is given in Fig. 1. The numbers shown for each step correspond to the six sections of this chapter: 1. The role of rare monogenic syndromes in the analysis of complex diseases. 2. Candidate gene and biochemical approaches to complex diseases. 3. Complete linkage maps in humans and animal models. 4. Positional cloning of genes underlying complex diseases in animal models. 5. Testing hypotheses by genetic modifications in animals. 6. Testing whether genes identified in animal models also cause human complex disease.