HLA-DRA promoter polymorphism and diversity generation within the immune system
Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we...
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| Veröffentlicht in: | Human genetics 1997-06, Vol.99 (6), p.801-805 |
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| container_title | Human genetics |
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| creator | SCHWIEBERT, L. M HUGHES, A MONOS, D. S ONO, S. J |
| description | Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we sequenced the non-coding promoter region of the HLA-DRA gene from several Epstein-Barr virus-transformed B cell lines and compared the extent of polymorphism found in this region with the known polymorphism of the HLA-DQB promoter. Our results indicate that the HLA-DRA promoter displays a low level of polymorphism while the promoter of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes. |
| doi_str_mv | 10.1007/s004390050452 |
| format | Article |
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Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes.</description><identifier>ISSN: 0340-6717</identifier><identifier>EISSN: 1432-1203</identifier><identifier>DOI: 10.1007/s004390050452</identifier><identifier>PMID: 9187677</identifier><identifier>CODEN: HUGEDQ</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Alleles ; Biological and medical sciences ; Cell Line ; Classical genetics, quantitative genetics, hybrids ; Epstein-Barr virus ; Evolution, Molecular ; Fundamental and applied biological sciences. Psychology ; Genetic Linkage ; Genetic Variation ; Genetics of eukaryotes. 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Our results indicate that the HLA-DRA promoter displays a low level of polymorphism while the promoter of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes.</description><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Epstein-Barr virus</subject><subject>Evolution, Molecular</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Linkage</subject><subject>Genetic Variation</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>HLA-DQ Antigens - genetics</subject><subject>HLA-DQ beta-Chains</subject><subject>HLA-DR alpha-Chains</subject><subject>HLA-DR Antigens - genetics</subject><subject>Human</subject><subject>Humans</subject><subject>Polymorphism, Genetic</subject><subject>Promoter Regions, Genetic</subject><subject>Sequence Alignment</subject><subject>Sequence Analysis, DNA</subject><issn>0340-6717</issn><issn>1432-1203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAUhYMoOj6WLoUsxF315tU0y2F8jDAgiK5LJr11Ik07Jq0y_97KDIIrV5fL-Th8HELOGVwzAH2TAKQwAAqk4ntkwqTgGeMg9skEhIQs10wfkeOU3gGYMlwdkkPDCp1rPSFP88U0u32e0nXsQtdjpOuu2YQurlc-BWrbilb-E2Py_Ya-YYvR9r5r6ZfvV76l_QqpD2FokaZN6jGckoPaNgnPdveEvN7fvczm2eLp4XE2XWROyKLPrLaycEbL0ZYZvmTCVrk2ttK1VapGsFBwRCmWxWhvzPjn4FAXvHJOWBQn5GrbO3p_DJj6MvjksGlsi92QSm1AKcHVvyDLodAjN4LZFnSxSyliXa6jDzZuSgblz9Lln6VH_mJXPCwDVr_0btoxv9zlNjnb1NG2zqdfjOdaykKIb2QqhRE</recordid><startdate>19970601</startdate><enddate>19970601</enddate><creator>SCHWIEBERT, L. 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Biological and molecular evolution</topic><topic>HLA-DQ Antigens - genetics</topic><topic>HLA-DQ beta-Chains</topic><topic>HLA-DR alpha-Chains</topic><topic>HLA-DR Antigens - genetics</topic><topic>Human</topic><topic>Humans</topic><topic>Polymorphism, Genetic</topic><topic>Promoter Regions, Genetic</topic><topic>Sequence Alignment</topic><topic>Sequence Analysis, DNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHWIEBERT, L. M</creatorcontrib><creatorcontrib>HUGHES, A</creatorcontrib><creatorcontrib>MONOS, D. S</creatorcontrib><creatorcontrib>ONO, S. 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J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA-DRA promoter polymorphism and diversity generation within the immune system</atitle><jtitle>Human genetics</jtitle><addtitle>Hum Genet</addtitle><date>1997-06-01</date><risdate>1997</risdate><volume>99</volume><issue>6</issue><spage>801</spage><epage>805</epage><pages>801-805</pages><issn>0340-6717</issn><eissn>1432-1203</eissn><coden>HUGEDQ</coden><abstract>Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we sequenced the non-coding promoter region of the HLA-DRA gene from several Epstein-Barr virus-transformed B cell lines and compared the extent of polymorphism found in this region with the known polymorphism of the HLA-DQB promoter. Our results indicate that the HLA-DRA promoter displays a low level of polymorphism while the promoter of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><cop>New York, NY</cop><pub>Springer</pub><pmid>9187677</pmid><doi>10.1007/s004390050452</doi><tpages>5</tpages></addata></record> |
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| ispartof | Human genetics, 1997-06, Vol.99 (6), p.801-805 |
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| language | eng |
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| subjects | Alleles Biological and medical sciences Cell Line Classical genetics, quantitative genetics, hybrids Epstein-Barr virus Evolution, Molecular Fundamental and applied biological sciences. Psychology Genetic Linkage Genetic Variation Genetics of eukaryotes. Biological and molecular evolution HLA-DQ Antigens - genetics HLA-DQ beta-Chains HLA-DR alpha-Chains HLA-DR Antigens - genetics Human Humans Polymorphism, Genetic Promoter Regions, Genetic Sequence Alignment Sequence Analysis, DNA |
| title | HLA-DRA promoter polymorphism and diversity generation within the immune system |
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