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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
. 1983 Apr;80(7):1972–1976. doi: 10.1073/pnas.80.7.1972

Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes.

J Trowsdale, J Lee, J Carey, F Grosveld, J Bodmer, W Bodmer
PMCID: PMC393734  PMID: 6300884

Abstract

Three sets of cosmid clones--containing the HLA-DR alpha chain gene and two additional related genes--were isolated from human genomic DNA libraries by using a cDNA probe for the HLA-DR alpha chain. Southern blot analysis using DNA from somatic cell hybrids indicated that all of the clones mapped to chromosome 6. Partial sequence analysis showed that the two additional related genes were highly homologous to each other, and to the HLA-DR alpha chain, in parts of the exon that encoded the alpha 2 domain but were more divergent in intron sequences. One of the genes corresponds to the HLA-DR-related DC series. DNA probes made from this gene revealed marked restriction enzyme polymorphism when hybridized to genomic DNA from HLA-DR typed homozygous cell lines. The patterns obtained from a number of homozygous and heterozygous cell lines correlated with the HLA-DR crossreactive serotypes and also indicated that there is a further sequence in the haploid human genome that is closely homologous with the DC alpha chain sequence. One family was studied and showed the expected HLA-DR-associated inheritance of restriction enzyme patterns. No polymorphism has yet been demonstrated in restriction enzyme fragments that include the other cloned sequence, which may correspond to the SB alpha chain gene or to a novel HLA-DR-related gene. These experiments indicate that there are at least three sequences in the human genome related, but not identical, to the HLA-DR alpha chain gene.

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Selected References

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  1. Auffray C., Korman A. J., Roux-Dosseto M., Bono R., Strominger J. L. cDNA clone for the heavy chain of the human B cell alloantigen DC1: strong sequence homology to the HLA-DR heavy chain. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6337–6341. doi: 10.1073/pnas.79.20.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bodmer W. F., Bodmer J. G. Evolution and function of the HLA system. Br Med Bull. 1978 Sep;34(3):309–316. doi: 10.1093/oxfordjournals.bmb.a071518. [DOI] [PubMed] [Google Scholar]
  3. Bodmer W. F. Evolutionary significance of the HL-A system. Nature. 1972 May 19;237(5351):139–passim. doi: 10.1038/237139a0. [DOI] [PubMed] [Google Scholar]
  4. Bono M. R., Strominger J. L. Direct evidence of homology between human DC-1 antigen and murine I-A molecules. Nature. 1982 Oct 28;299(5886):836–840. doi: 10.1038/299836a0. [DOI] [PubMed] [Google Scholar]
  5. De Kretser T. A., Crumpton M. J., Bodmer J. G., Bodmer W. F. Two-dimensional gel analysis of the polypeptides precipitated by a polymorphic HLA-DR1,2,w6 monoclonal antibody: evidence for a third locus. Eur J Immunol. 1982 Jul;12(7):600–606. doi: 10.1002/eji.1830120713. [DOI] [PubMed] [Google Scholar]
  6. Goodfellow P. N., Banting G., Trowsdale J., Chambers S., Solomon E. Introduction of a human X-6 translocation chromosome into a mouse teratocarcinoma: investigation of control of HLA-A, B, C expression. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1190–1194. doi: 10.1073/pnas.79.4.1190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Hurley C. K., Shaw S., Nadler L., Schlossman S., Capra J. D. Alpha and beta chains of SB and DR antigens are structurally distinct. J Exp Med. 1982 Nov 1;156(5):1557–1562. doi: 10.1084/jem.156.5.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kavathas P., DeMars R., Bach F. H., Shaw S. SB: a new HLA-linked human histocompatibility gene defined using HLA-mutant cell lines. Nature. 1981 Oct 29;293(5835):747–749. doi: 10.1038/293747a0. [DOI] [PubMed] [Google Scholar]
  10. Korman A. J., Auffray C., Schamboeck A., Strominger J. L. The amino acid sequence and gene organization of the heavy chain of the HLA-DR antigen: homology to immunoglobulins. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6013–6017. doi: 10.1073/pnas.79.19.6013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Larhammar D., Gustafsson K., Claesson L., Bill P., Wiman K., Schenning L., Sundelin J., Widmark E., Peterson P. A., Rask L. Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins. Cell. 1982 Aug;30(1):153–161. doi: 10.1016/0092-8674(82)90021-6. [DOI] [PubMed] [Google Scholar]
  12. Larhammar D., Wiman K., Schenning L., Claesson L., Gustafsson K., Peterson P. A., Rask L. Evolutionary relationship between HLA-DR antigen beta-chains, HLA-A, B, C antigen subunits and immunoglobulin chains. Scand J Immunol. 1981 Dec;14(6):617–622. doi: 10.1111/j.1365-3083.1981.tb00603.x. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Lee J. S., Trowsdale J., Travers P. J., Carey J., Grosveld F., Jenkins J., Bodmer W. F. Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization of the corresponding gene. Nature. 1982 Oct 21;299(5885):750–752. doi: 10.1038/299750a0. [DOI] [PubMed] [Google Scholar]
  15. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shackelford D. A., Mann D. L., van Rood J. J., Ferrara G. B., Strominger J. L. Human B-cell alloantigens DC1, MT1, and LB12 are identical to each other but distinct from the HLA-DR antigen. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4566–4570. doi: 10.1073/pnas.78.7.4566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shaw S., Kavathas P., Pollack M. S., Charmot D., Mawas C. Family studies define a new histocompatibility locus, SB, between HLA-DR and GLO. Nature. 1981 Oct 29;293(5835):745–747. doi: 10.1038/293745a0. [DOI] [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. Tosi R., Tanigaki N., Centis D., Ferrara G. B., Pressman D. Immunological dissection of human Ia molecules. J Exp Med. 1978 Dec 1;148(6):1592–1611. doi: 10.1084/jem.148.6.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]

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