Skip to main content
Log in

Genomic organization of a polymorphic duplicated region centromeric of HLA-B

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The region between tumor necrosis factor (TNF) and HLA-B in the central major histocompatibility complex (MHC) is polymorphic and associated with several autoimmune diseases. The polymorphisms are haplospecific or haplotypic and retained within the same MHC ancestral haplotype (AH). We have cloned this region from four AHs into λ bacteriophage and found that a highly polymorphic region in the TNF-HLA-B interval is duplicated. Clones from this region isolated from three MHC AHs show two populations. The regions, designated CL1 and CL2, have different sizes of Bam HI fragments carrying the duplicated sequences. These fragments correspond to those seen after Bam HI restriction fragment length polymorphism (RFLP) analysis of genomic DNA from the same cell lines. Pulsed field gel electrophoresis analysis shows that both CL1 and CL2 are in the central MHC and are about 16 kilobases apart. DNA cloning and RFLP analysis demostrate that the Cl region is highly polymorphic but retained within an MHC AH. Polymorphism and duplication are common characteristics of the genes found in the MHC and therefore the CL sequences have the potential to be interesting in this respect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abraham L. J., ChinDu, D., Zahedi, K., Dawkins, R. L., and Whitehead, A. S.: Haplotypic polymorphism of the TNFB gene. Immunogenetics 33: 50–53, 1991

    Google Scholar 

  • Abraham, L. J., Leelayuwat, C., Grimsley, G., Degli-Esposti, M. A., Mann, A., Zhang, W. J., Christiansen, F. T., and Dawkins, R. L.: Sequence differences between HLA B and TNF distinguish different MHC ancestral haplotypes. Tissue Antigens, in press 1992.

  • Chimini, G., Boretto, J., Marguet, D., Lanau, F., Lauguin, G., and Pontarotti. P.: Molecular analysis of the human MHC class I region using yeast artificial chromosome clones. Immunogenetics 32: 419–426, 1990

    Google Scholar 

  • Ciccone, E., Colonna, M., Viale, O., Pende, D., Di Donato, C., Reinharz, D., Amoroso, A., Jeannet, M., Guardiola, J., Moretta, A., Spies, T., Strominger, J., and Moretta, L.: Susceptibility or resistance to lysis by alloreactive natural killer cells is governed by a gene in the human major histocompatibility complex between BF and HLA-B. Proc Natl Acad Sci USA 87: 9794–9797, 1990

    Google Scholar 

  • Dawkins, R. L., Leaver, A., Cameron, P. U., Martin, E., Kay, P. H., and Christiansen, F. T.: Some disease-associated ancestral haplotypes carry a polymorphism of TNF. Hum Immunol 26: 91–97, 1989

    Google Scholar 

  • Dawkins, R. L., Zhang, W. J., Degli-Esposti, M. A., Abraham, L., McCann, V., and Christiansen, F. T.: Studies of MHC haplotypes by pulsed field electrophories. In L. C. harrison and B. D. Tait (eds): Clinical Endocrinology and Metabolism, pp. 285–297, Bailliere Tindall, London, 1991 UK

    Google Scholar 

  • Degli-Esposti, M. A., Andreas, A., Christiansen, F. T., Albert, E., and Dawkins, R. L.: An approach to the localization of the susceptibility gene for generalized myasthenia gravis by mapping recombinant ancestral haplotypes. immunogenetics 35: 355–364, 1992

    Google Scholar 

  • French, M. A. H. and Dawkins, R. L.: Central MHC genes, IgA deficiency and autoimmune disease. Immunol Today 11: 271–274, 1990

    Google Scholar 

  • Inoko, H. and Trowsdale, J.: Linkage of TNF genes to the HLA-B locus. Nucleic Acids Res 15(21): 8957–8963, 1987

    Google Scholar 

  • Kendall, E., Sargent, C. A., and Campbell, R. D.: Human major histocompatibility complex C4 loci. Nucleic Acids Res 18(24): 7251–7257, 1990

    Google Scholar 

  • Maniatis, T., Fritsch, E. F., and Sambrook, L.: Molecular Cloning. A Laboratory Manual, Cold Spring Harbour Laboratory Press, Cold Spring Harbor, 1982

    Google Scholar 

  • Milner, C. M. and Campbell, R. D.: Structure and expression of the three MHC-linked HSp70 genes. Immunogenetics 32: 242–251, 1990

    CAS  PubMed  Google Scholar 

  • Pennica, D., Nedwin, G. E., Hayflick, J. S., Seeburg, P. H., Derynck, R., Kohr, W. J., Aggarwal, B. B. and Goedell, D. V.: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312: 724–729, 1984

    Google Scholar 

  • Sargent, C. A., Dunham, I., and Campbell, R. D.: Identification of multiple HTF-island associated genes in the human major histocompatibility complex class III region. EMBO J 8: 2305–2312, 1989a

    Google Scholar 

  • Sargent, C. A., Dunham, I., Trowsdale, J., and Campbell, R. D.: Human major histocompatibility complex cotains genes for the major heat shock protein HSP70. Proc Natl Acad Sci USA 86: 1968–1972, 1989b

    Google Scholar 

  • Spies, T., Blanck, G., Bresnahan, M., Sands, J., and Strominger, J. L.: A new cluster of genes within the human major histocompatibility complex Science 243: 214–217, 1989a

    Google Scholar 

  • Spies, T., Bresnahan, M., and Strominger, J. L.: Human major histocompatibility complex contains a minimum of 19 genes between the compatibility cluster and HLA-B. Proc Natl Acad Sci USA 86: 8955–8958, 1989b

    Google Scholar 

  • Tokunaga, K., Saueracker, G., Kay, P. H., Christiansen, F. T., Anand, R., and Dawkins, R. L.: Extensive deletions and insertions in different MHC supratypes detected by pulsed field gel electrophoresis. J Exp Med 168: 933–940, 1988

    Google Scholar 

  • Wu, X., Zhang, W. J., Witt, C. S., Abraham, L. J., Christiansen, F. T., and Dawkins, R. L.: Haplospecific polymorphism between HLA B and TNF. Hum Immunol, in press, 1992

  • Zhang, W. J., Degli-Esposti, M. A., Cobain, T. J., Cameron, P. U., Christiansen, F. T., and Dawkins, R. L.: Differences in gene copy number carried by different MHC ancestral haplotypes: quantitation after physical separation of haplotypes by Pulsed Field Gel Electrophoresis. J Exp Med 171: 2101–2114, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leelayuwat, C., Abraham, L.J., Tabarias, H. et al. Genomic organization of a polymorphic duplicated region centromeric of HLA-B . Immunogenetics 36, 208–212 (1992). https://doi.org/10.1007/BF00215049

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00215049

Keywords

Navigation