Skip to main content
SpringerLink
Log in

Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing β-cells of the pancreas1,2. Family and population studies indicate that predisposition is probably polygenic3. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3,4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR–DQ haplotypes, whose frequencies vary between races4–6. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rossini, A. A., Mordes, J. P. & Like, A. A. A. Rev. Immun. 3, 289–320 (1985).

    Article  CAS  Google Scholar 

  2. Wicker, L. S., Miller, B. J., Chai, A., Terada, M. & Mullen, Y. J. exp. Med. 167, 1801–1810 (1988).

    Article  CAS  Google Scholar 

  3. Thomson, G. et al. Am. J. hum Genet. 43, 799–816 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Tiwari, J. L. & Terasaki, P. I. in HLA and Disease Associations (eds Tiwari, J. I. & Terasaki, P. I.) 185–210 (Springer, Berlin, 1985).

    Google Scholar 

  5. Gregersen, P. K. et al. J. Immun. 141, 1365–1368 (1988).

    CAS  PubMed  Google Scholar 

  6. Fletcher, J. A. et al. Diabetologia, 31, 864–870 (1988).

    CAS  PubMed  Google Scholar 

  7. Todd, J. A., Bell, J. I. & McDevitt, H. O. Nature 329, 599–604 (1987).

    Article  ADS  CAS  Google Scholar 

  8. Germain, R. H. & Malissen, B. A. Rev. Immun. 4, 281–315 (1986).

    Article  CAS  Google Scholar 

  9. Babbitt, B., Allen, P., Matsueda, G., Haber, E. & Unanue, E. Nature 317, 359–361 (1985).

    Article  ADS  CAS  Google Scholar 

  10. Brown, J. H. et al. Nature 332, 845–850 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Pullen, A. M., Marrack, P. & Kappler, J. W. Nature 335, 796–801 (1988).

    Article  ADS  CAS  Google Scholar 

  12. Mickelson, E. M., Nepom, G. T., Nisperos, B. & Hansen, J. A. Hum. Immun. 21, 63–73 (1988).

    Article  CAS  Google Scholar 

  13. Lundin, K. E. A., Gaudernack, G., Qvigstad, E., Sollid, L. M. & Thorsby, E. Hum. Immun. 22, 235–246 (1988).

    Article  CAS  Google Scholar 

  14. Horn, G. T., Bugawan,T, L., Long, C. & Erlich, H. A. Proc. natn. Acad. Sci. U.S.A. 85, 6012–6016 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Sterkers, G. et al. Proc. natn. Acad. Sci. U.S.A. 85, 6473–6477 (1988).

    Article  ADS  CAS  Google Scholar 

  16. Morel, P., Dorman, J., Todd, J. A., McDevitt, H. O. & Trucco, M. Proc. natn. Acad. Sci. U.S.A. 85, 8111–8115 (1988).

    Article  ADS  CAS  Google Scholar 

  17. Klitz, W. Nature 333, 402–403 (1988).

    Article  CAS  Google Scholar 

  18. Todd, J. A., Bell, J. I. & McDevitt, H. O. Nature 333, 710 (1988).

    Article  ADS  CAS  Google Scholar 

  19. Karr, R. W. et al. J. Immun. 137, 2886–2890 (1986).

    CAS  PubMed  Google Scholar 

  20. Bell, J. I. et al. Proc. natn. Acad. Sci. U.S.A 84, 6234–6238 (1987).

    Article  ADS  CAS  Google Scholar 

  21. Moriuchi, J., Moriuchi, T. & Silver, J. Proc. natn. Acad. Sci. U.S.A. 82, 3420–3424 (1985).

    Article  ADS  CAS  Google Scholar 

  22. Saiki, R. H. et al. Science 239, 487–491 (1988).

    Article  ADS  CAS  Google Scholar 

  23. Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B. & Erlich, H. A. Nature 324, 163–166 (1986).

    Article  ADS  CAS  Google Scholar 

  24. Scharf, S. J., Horn, G. T. & Erlich, H. A. Science 233, 1076–1078 (1986).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuffield Department of Surgery and Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

    J. A. Todd

  2. Department of Immunology, University of Birmingham, B15 2TJ, UK

    C. Mijovic & A. R. Bradwell

  3. Department of Medicine, University of Birmingham & East Birmingham Hospital, B9 5ST, UK

    J. Fletcher, D. Jenkins & A. H. Barnett

Authors
  1. J. A. Todd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Mijovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Fletcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. R. Bradwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. H. Barnett
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Todd, J., Mijovic, C., Fletcher, J. et al. Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping. Nature 338, 587–589 (1989). https://doi.org/10.1038/338587a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/338587a0

  • Springer Nature Limited

This article is cited by

Search

Navigation