Gene map of the extended human MHC

• Published in: Nature reviews. Genetics Vol. 5; no. 12; pp. 889 - 899
• Main Authors: Beck, Stephan, Horton, Roger, Wilming, Laurens, Rand, Vikki, Lovering, Ruth C, Bruford, Elspeth A, Khodiyar, Varsha K, Lush, Michael J, Povey, Sue, Talbot, C. Conover, Wright, Mathew W, Wain, Hester M, Trowsdale, John, Ziegler, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2004; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Annotations; Antigens; Autoimmune Diseases - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 6; Classical genetics, quantitative genetics, hybrids; Disease; Fundamental and applied biological sciences. Psychology; Gene Function; Gene loci; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genomes; Haplotypes; Human Genetics; Humans; Immunity; Leukocytes; Major Histocompatibility Complex; Methods, theories and miscellaneous; Multigene Family; Polymorphism, Genetic; Proteins; review-article; RNA, Transfer - genetics; Transfer RNA; Transplants & implants; United Kingdom > UK; Genetic mapping; Human
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg1489

Key Points The gene map for the extended major histocompatibility complex (xMHC) comprises 421 loci (excluding RNA genes) in a sequence length of 7.6 Mb — extending the previous gene map of the classical MHC, which was 3.6 Mb long and contained 224 loci. All 421 xMHC loci have been assigned definitive and approved gene symbols. About 50% of the xMHC gene loci are present in clusters or superclusters that are not restricted only to immune genes. The two largest clusters, comprising histone and tRNA genes are the largest of their type in the genome. Transcription hotspot analysis indicates that it is just as likely that the classical MHC is hitch-hiking with gene clusters of the xMHC as the reverse. About 22% of the expressed xMHC genes show a higher than average number of non-synonymous coding polymorphisms. About 28% of the xMHC genes can be associated with immune system function. About 10% of the xMHC genes are currently known to be disease-causing or disease-associated. About 20% of the xMHC genes have putative paralogues elsewhere in the genome, indicating considerable potential for functional redundancy. The gene map of the xMHC provides an invaluable resource for the study of the most important genetic region of the human genome in relation to infectious, inflammatory and autoimmune diseases. The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in adaptive and innate immunity. Decades of biomedical research have revealed many MHC genes that are duplicated, polymorphic and associated with more diseases than any other region of the human genome. The recent completion of several large-scale studies offers the opportunity to assimilate the latest data into an integrated gene map of the extended human MHC. Here, we present this map and review its content in relation to paralogy, polymorphism, immune function and disease. The gene map of the xMHC is also available as a poster, which accompanies this issue and is available at http://www.nature.com/nrg/posters/mhcmap/index.html .