The Major Histocompatibility Complex

The major histocompatibility complex (MHC) is an approximately four-megabase segment of DNA on the short arm of chromosome 6. It is a dense genomic region that includes many genes involved in the immune response, whether innate or adaptive. It has been determined to be the single region in the whole genome, of equivalent size, that includes the largest number of single nucleotide polymorphisms (SNPs) associated with close to 500 traits and/or diseases. It includes the human leukocyte antigen (HLA) genes that play a key role in antigen-specific adaptive immune responses. These genes are extremely polymorphic—indeed, the most polymorphic in the human genome. The genomic organization of the MHC is very complex and, despite the recent technological advances using next-generation sequencing technologies, remains the least characterized part of the genome. It is marked by a high degree of linkage disequilibrium, most likely reflecting the functional interconnectivity of the many genes included in this region. Many of the genes of the MHC play important roles in a number of clinical settings. These include transplantation, autoimmunity, cancer, vaccine development, and pharmacogenomics. Recent findings suggest that noncoding genomic regions within the MHC also harbor functional elements involved in numerous biological processes.