Genetics and Autoimmunity: Non-MHC Genes

This chapter focuses on the contribution of non-major histocompatiblity complex (MHC) genes to the genetic susceptibility to autoimmune diseases. Several non-MHC immune regulatory genes have been shown to be susceptibility genes for autoimmunity. As expected, these genes are not specific for one autoimmune disease but predispose to several autoimmune conditions. However, some variability does exist with certain immune regulatory genes showing a much stronger association with some autoimmune conditions than with others. For example, the (cytotoxic T-lymphocyte antigen-4) CTLA-4 gene shows the strongest association with Graves' disease and a much weaker association with Hashimoto's disease and T1D. Furthermore, whole genome screening is a powerful genetic tool with which to identify loci or genetic regions that might be linked with disease. When a locus, which is linked with disease, is identified, the region can be fine mapped and the gene identified. This strategy has been used successfully in a number of complex diseases, most notably in the mapping and identification of NOD2 as a susceptibility gene for Crohn's disease.