Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Jul 1;164(1):333–338. doi: 10.1084/jem.164.1.333

An HLA-D region restriction fragment length polymorphism associated with celiac disease

PMCID: PMC2188220  PMID: 3014038

Abstract

This study is the first to describe a molecular marker that distinguishes the celiac disease HLA-D region haplotype from a serologically identical haplotype in unaffected controls. Using a DQ beta chain cDNA probe and the restriction endonuclease Rsa I, we have detected a polymorphic 4.0 kb fragment which, in DQw2 individuals, is associated with a 40-fold increased relative risk of developing celiac disease. This finding should permit the identification of the celiac disease susceptibility gene(s) in the HLA-D region and facilitate a more precise dissection of the molecular and immunogenetic mechanisms involved in the pathogenesis of that disease.

Full Text

The Full Text of this article is available as a PDF (448.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson M., Böhme J., Andersson G., Möller E., Thorsby E., Rask L., Peterson P. A. Genomic hybridization with class II transplantation antigen cDNA probes as a complementary technique in tissue typing. Hum Immunol. 1984 Oct;11(2):57–67. doi: 10.1016/0198-8859(84)90045-4. [DOI] [PubMed] [Google Scholar]
  2. Arnheim N., Strange C., Erlich H. Use of pooled DNA samples to detect linkage disequilibrium of polymorphic restriction fragments and human disease: studies of the HLA class II loci. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6970–6974. doi: 10.1073/pnas.82.20.6970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen D., Paul P., Le Gall I., Marcadet A., Font M. P., Cohen-Haguenauer O., Sayagh B., Cann H., Lalouel J. M., Dausset J. DNA polymorphism of HLA class I and class II regions. Immunol Rev. 1985 Jul;85:87–105. doi: 10.1111/j.1600-065x.1985.tb01131.x. [DOI] [PubMed] [Google Scholar]
  4. Cole S. G., Kagnoff M. F. Celiac disease. Annu Rev Nutr. 1985;5:241–266. doi: 10.1146/annurev.nu.05.070185.001325. [DOI] [PubMed] [Google Scholar]
  5. Corazza G. R., Tabacchi P., Frisoni M., Prati C., Gasbarrini G. DR and non-DR Ia allotypes are associated with susceptibility to coeliac disease. Gut. 1985 Nov;26(11):1210–1213. doi: 10.1136/gut.26.11.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Gustafsson K., Wiman K., Emmoth E., Larhammar D., Böhme J., Hyldig-Nielsen J. J., Ronne H., Peterson P. A., Rask L. Mutations and selection in the generation of class II histocompatibility antigen polymorphism. EMBO J. 1984 Jul;3(7):1655–1661. doi: 10.1002/j.1460-2075.1984.tb02026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Larhammar D., Schenning L., Gustafsson K., Wiman K., Claesson L., Rask L., Peterson P. A. Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3687–3691. doi: 10.1073/pnas.79.12.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Schenning L., Larhammar D., Bill P., Wiman K., Jonsson A. K., Rask L., Peterson P. A. Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains. EMBO J. 1984 Feb;3(2):447–452. doi: 10.1002/j.1460-2075.1984.tb01826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shanahan F., McKenna R., McCarthy C. F., Drury M. I. Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing. Q J Med. 1982 Summer;51(203):329–335. [PubMed] [Google Scholar]
  12. 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]
  13. Svejgaard A., Jersild C., Nielsen L. S., Bodmer W. F. HL-A antigens and disease. Statistical and genetical considerations. Tissue Antigens. 1974;4(2):95–105. doi: 10.1111/j.1399-0039.1974.tb00230.x. [DOI] [PubMed] [Google Scholar]
  14. Tosi R., Vismara D., Tanigaki N., Ferrara G. B., Cicimarra F., Buffolano W., Follo D., Auricchio S. Evidence that celiac disease is primarily associated with a DC locus allelic specificity. Clin Immunol Immunopathol. 1983 Sep;28(3):395–404. doi: 10.1016/0090-1229(83)90106-x. [DOI] [PubMed] [Google Scholar]
  15. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES