An overview of the genetic analysis of complex diseases, with reference totype I diabetes

Despite extensive efforts by many groups, progress in the mapping of comple x diseases has been exceedingly slow, only a few genes and some genetic reg ions having been identified. The general picture is one of difficulty in lo cating disease genes and in the replication of linkages. This results from the role in disease of a large number of genes, many with a relatively mino r effect and many involving common genetic variation. A multi-strategy appr oach to the mapping of complex diseases is required: no single method is su fficient or optimal. The role of human leukocyte antigens in type 1 diabete s has been known for nearly 30 years, and the associations, linkage and gen etic contribution to disease are all strong, but all the human leukocyte an tigen region genes involved in the disease process have not yet been identi fied. The methods used in study of this component to type 1 diabetes are a model for all complex diseases.