Major Histocompatibility Complex: Disease Associations

Human major histocompatibility complex (MHC) alleles can be used as markers for a wide variety of autoimmune and other disorders. The interpretation of and possible bases for these associations can be considered in relation to conserved extended MHC haplotypes (CEHs). The latter are fixed stretches of up to several million base pairs of genomic deoxyribonucleic acid (DNA). CEHs constitute at least a third of normal European Caucasian MHC haplotypes and contribute most of the MHC disease susceptibility genetic markers. Whereas this has facilitated the detection of MHC gene-disease association, it paradoxically makes the identification of true susceptibility genetic loci (as distinguished from genetic markers) more difficult. It is likely that the great majority of true susceptibility genes for MHC-associated diseases are yet to be discovered. It may take new methods and new approaches to identify the true MHC susceptibility genes and their relation to many of the polygenic MHC-associated diseases.