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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Nov;82(21):7197–7201. doi: 10.1073/pnas.82.21.7197

Linkage map of three HLA-DR beta-chain genes: evidence for a recent duplication event.

P Rollini, B Mach, J Gorski
PMCID: PMC390816  PMID: 3933002

Abstract

The predominant class II, or Ia, antigen of the human major histocompatibility complex is HLA-DR. It consists of an alpha and a beta chain, the latter being responsible for the remarkable polymorphism of these Ia antigens. Studies with cloned genes had shown the existence of more than one DR beta-chain locus. We have isolated about 100 kilobases of the HLA-DR beta-chain gene region from a cosmid library generated from a consanguineous homozygous B-cell line of the DR3 haplotype. Three HLA-DR beta-chain genes have been characterized. They are arranged in a head-to-tail orientation. One of the genes lacks the region encoding the first domain of the DR beta chain. The two other genes are transcribed, as shown by RNA blot hybridization analysis. A striking restriction site homology has been found within the DR beta-chain gene cluster, suggesting a recent duplication event involving at least 25 kilobases of DNA. Moreover, the molecular map of DR beta chain genes cloned from B-cell lines of two other HLA-DR haplotypes shows extensive homology between alleles of a given DR beta-chain locus.

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Selected References

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  1. Auffray C., Kuo J., DeMars R., Strominger J. L. A minimum of four human class II alpha-chain genes are encoded in the HLA region of chromosome 6. Nature. 1983 Jul 14;304(5922):174–177. doi: 10.1038/304174a0. [DOI] [PubMed] [Google Scholar]
  2. Boss J. M., Strominger J. L. Cloning and sequence analysis of the human major histocompatibility complex gene DC-3 beta. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5199–5203. doi: 10.1073/pnas.81.16.5199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gorski J., Rollini P., Long E., Mach B. Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3934–3938. doi: 10.1073/pnas.81.13.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gorski J., Tosi R., Strubin M., Rabourdin-Combe C., Mach B. Serological and immunochemical analysis of the products of a single HLA DR-alpha and DR-beta chain gene expressed in a mouse cell line after DNA-mediated cotransformation reveals that the beta chain carries a known supertypic specificity. J Exp Med. 1985 Jul 1;162(1):105–116. doi: 10.1084/jem.162.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grosveld F. G., Lund T., Murray E. J., Mellor A. L., Dahl H. H., Flavell R. A. The construction of cosmid libraries which can be used to transform eukaryotic cells. Nucleic Acids Res. 1982 Nov 11;10(21):6715–6732. doi: 10.1093/nar/10.21.6715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hanahan D., Meselson M. Plasmid screening at high colony density. Gene. 1980 Jun;10(1):63–67. doi: 10.1016/0378-1119(80)90144-4. [DOI] [PubMed] [Google Scholar]
  7. Hohn B., Murray K. Packaging recombinant DNA molecules into bacteriophage particles in vitro. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3259–3263. doi: 10.1073/pnas.74.8.3259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kaufman J. F., Auffray C., Korman A. J., Shackelford D. A., Strominger J. The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1–13. doi: 10.1016/0092-8674(84)90068-0. [DOI] [PubMed] [Google Scholar]
  9. Larhammar D., Servenius B., Rask L., Peterson P. A. Characterization of an HLA DR beta pseudogene. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1475–1479. doi: 10.1073/pnas.82.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee J. S., Trowsdale J., Bodmer W. F. cDNA clones coding for the heavy chain of human HLA-DR antigen. Proc Natl Acad Sci U S A. 1982 Jan;79(2):545–549. doi: 10.1073/pnas.79.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Long E. O., Gorski J., Mach B. Structural relationship of the SB beta-chain gene to HLA-D-region genes and murine I-region genes. Nature. 1984 Jul 19;310(5974):233–235. doi: 10.1038/310233a0. [DOI] [PubMed] [Google Scholar]
  12. Long E. O., Gorski J., Rollini P., Wake C. T., Strubin M., Rabourdin-Combe C., Mach B. Molecular analysis of the genes for human class II antigens of the major histocompatibility complex. Hum Immunol. 1983 Sep;8(1):113–121. doi: 10.1016/0198-8859(83)90089-7. [DOI] [PubMed] [Google Scholar]
  13. Long E. O., Wake C. T., Gorski J., Mach B. Complete sequence of an HLA-dR beta chain deduced from a cDNA clone and identification of multiple non-allelic DR beta chain genes. EMBO J. 1983;2(3):389–394. doi: 10.1002/j.1460-2075.1983.tb01435.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Long E. O., Wake C. T., Strubin M., Gross N., Accolla R. S., Carrel S., Mach B. Isolation of distinct cDNA clones encoding HLA-DR beta chains by use of an expression assay. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7465–7469. doi: 10.1073/pnas.79.23.7465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Okada K., Prentice H. L., Boss J. M., Levy D. J., Kappes D., Spies T., Raghupathy R., Mengler R. A., Auffray C., Strominger J. L. SB subregion of the human major histocompatibility complex: gene organization, allelic polymorphism and expression in transformed cells. EMBO J. 1985 Mar;4(3):739–748. doi: 10.1002/j.1460-2075.1985.tb03691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rabourdin-Combe C., Mach B. Expression of HLA-DR antigens at the surface of mouse L cells co-transfected with cloned human genes. Nature. 1983 Jun 23;303(5919):670–674. doi: 10.1038/303670a0. [DOI] [PubMed] [Google Scholar]
  17. Servenius B., Gustafsson K., Widmark E., Emmoth E., Andersson G., Larhammar D., Rask L., Peterson P. A. Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SB alpha (DP alpha) pseudogene. EMBO J. 1984 Dec 20;3(13):3209–3214. doi: 10.1002/j.1460-2075.1984.tb02280.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  19. Spielman R. S., Lee J., Bodmer W. F., Bodmer J. G., Trowsdale J. Six HLA-D region alpha-chain genes on human chromosome 6: polymorphisms and associations of DC alpha-related sequences with DR types. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3461–3465. doi: 10.1073/pnas.81.11.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steinmetz M., Hood L. Genes of the major histocompatibility complex in mouse and man. Science. 1983 Nov 18;222(4625):727–733. doi: 10.1126/science.6356354. [DOI] [PubMed] [Google Scholar]
  21. Steinmetz M., Minard K., Horvath S., McNicholas J., Srelinger J., Wake C., Long E., Mach B., Hood L. A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature. 1982 Nov 4;300(5887):35–42. doi: 10.1038/300035a0. [DOI] [PubMed] [Google Scholar]
  22. Tanigaki N., Tosi R. The genetic control of human Ia alloantigens: a three-loci model derived from the immunochemical analysis of 'supertypic' specificities. Immunol Rev. 1982;66:5–37. doi: 10.1111/j.1600-065x.1982.tb00432.x. [DOI] [PubMed] [Google Scholar]
  23. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Trowsdale J., Kelly A., Lee J., Carson S., Austin P., Travers P. Linkage map of two HLA-SB beta and two HLA-SB alpha-related genes: an intron in one of the SB beta genes contains a processed pseudogene. Cell. 1984 Aug;38(1):241–249. doi: 10.1016/0092-8674(84)90546-4. [DOI] [PubMed] [Google Scholar]
  25. Wake C. T., Long E. O., Mach B. Allelic polymorphism and complexity of the genes for HLA-DR beta-chains--direct analysis by DNA-DNA hybridization. Nature. 1982 Nov 25;300(5890):372–374. doi: 10.1038/300372a0. [DOI] [PubMed] [Google Scholar]
  26. Wake C. T., Long E. O., Strubin M., Gross N., Accolla R., Carrel S., Mach B. Isolation of cDNA clones encoding HLA-DR alpha chains. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6979–6983. doi: 10.1073/pnas.79.22.6979. [DOI] [PMC free article] [PubMed] [Google Scholar]

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