Gene map of the extended human MHC

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 definiti...

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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
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Abstract	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 .
AbstractList	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/journal/v5/n12/poster/MHCmap. 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. 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 . 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.
Audience	Academic
Author	Lush, Michael J Wright, Mathew W Ziegler, Andreas Horton, Roger Khodiyar, Varsha K Beck, Stephan Rand, Vikki Povey, Sue Trowsdale, John Wain, Hester M Bruford, Elspeth A Wilming, Laurens Lovering, Ruth C Talbot, C. Conover
Author_xml	– sequence: 1 givenname: Stephan surname: Beck fullname: Beck, Stephan organization: Wellcome Trust Sanger Institute, Genome Campus, Hinxton – sequence: 2 givenname: Roger surname: Horton fullname: Horton, Roger organization: Wellcome Trust Sanger Institute, Genome Campus, Hinxton – sequence: 3 givenname: Laurens surname: Wilming fullname: Wilming, Laurens organization: Wellcome Trust Sanger Institute, Genome Campus, Hinxton – sequence: 4 givenname: Vikki surname: Rand fullname: Rand, Vikki organization: Wellcome Trust Sanger Institute, Genome Campus, Hinxton – sequence: 5 givenname: Ruth C surname: Lovering fullname: Lovering, Ruth C organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 6 givenname: Elspeth A surname: Bruford fullname: Bruford, Elspeth A organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 7 givenname: Varsha K surname: Khodiyar fullname: Khodiyar, Varsha K organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 8 givenname: Michael J surname: Lush fullname: Lush, Michael J organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 9 givenname: Sue surname: Povey fullname: Povey, Sue organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 10 givenname: C. Conover surname: Talbot fullname: Talbot, C. Conover organization: HUGO Gene Nomenclature Committee, The Johns Hopkins School of Medicine, Institute of Genetic Medicine, The Johns Hopkins University – sequence: 11 givenname: Mathew W surname: Wright fullname: Wright, Mathew W organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 12 givenname: Hester M surname: Wain fullname: Wain, Hester M organization: HUGO Gene Nomenclature Committee, Department of Biology, University College London – sequence: 13 givenname: John surname: Trowsdale fullname: Trowsdale, John organization: University of Cambridge, Department of Pathology, Immunology Division – sequence: 14 givenname: Andreas surname: Ziegler fullname: Ziegler, Andreas organization: Institut für Immungenetik, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Humboldt-Universität zu Berlin
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Snippet	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 —... The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in...
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SubjectTerms	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
Title	Gene map of the extended human MHC
URI	http://dx.doi.org/10.1038/nrg1489 https://link.springer.com/article/10.1038/nrg1489 https://www.ncbi.nlm.nih.gov/pubmed/15573121 https://www.proquest.com/docview/223753488 https://search.proquest.com/docview/17750792 https://search.proquest.com/docview/67141692
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