Skip to main content
NCBI home page
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 May;82(10):3335–3339. doi: 10.1073/pnas.82.10.3335

A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus.

O Cohen-Haguenauer, E Robbins, C Massart, M Busson, I Deschamps, J Hors, J M Lalouel, J Dausset, D Cohen
PMCID: PMC397770  PMID: 2987920

Abstract

DNA restriction fragments of the genes encoding HLA class II-beta antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), were analyzed: (i) A DR Taq I 12.7-kilobase-pair fragment might be a marker for the extended haplotype HLA-B8, DR3. (ii) In controls, DR4 haplotypes are associated with two distinct clusters of DQ restriction fragments (DQR4 and DQR5). Almost all (94%) DR4 patients belong to the DQR4 and not to the DQR5 cluster. This suggests that, among HLA-DR4 haplotypes, only DQR4 haplotypes are involved in susceptibility to insulin-dependent diabetes mellitus. (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 X 10(-4). However, these results must be interpreted with caution, taking into account the high number of statistical tests performed.

Full text

PDF
3335

Images in this article

3338Image
on p.3338
3338Image
on p.3338

Selected References

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

  1. Alwine J. C., Kemp D. J., Parker B. A., Reiser J., Renart J., Stark G. R., Wahl G. M. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. Methods Enzymol. 1979;68:220–242. doi: 10.1016/0076-6879(79)68017-5. [DOI] [PubMed] [Google Scholar]
  2. Cohen D., Cohen O., Marcadet A., Massart C., Lathrop M., Deschamps I., Hors J., Schuller E., Dausset J. Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1774–1778. doi: 10.1073/pnas.81.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen D., Le Gall I., Marcadet A., Font M. P., Lalouel J. M., Dausset J. Clusters of HLA class II beta restriction fragments describe allelic series. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7870–7874. doi: 10.1073/pnas.81.24.7870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen D., Paul P., Font M. P., Cohen O., Sayagh B., Marcadet A., Busson M., Mahouy G., Cann H. M., Dausset J. Analysis of HLA class I genes with restriction endonuclease fragments: implications for polymorphism of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6289–6292. doi: 10.1073/pnas.80.20.6289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Owerbach D., Lernmark A., Platz P., Ryder L. P., Rask L., Peterson P. A., Ludvigsson J. HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals. Nature. 1983 Jun 30;303(5920):815–817. doi: 10.1038/303815a0. [DOI] [PubMed] [Google Scholar]
  8. Raum D., Awdeh Z., Yunis E. J., Alper C. A., Gabbay K. H. Extended major histocompatibility complex haplotypes in type I diabetes mellitus. J Clin Invest. 1984 Aug;74(2):449–454. doi: 10.1172/JCI111441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Roux-Dosseto M., Auffray C., Lillie J. W., Boss J. M., Cohen D., DeMars R., Mawas C., Seidman J. G., Strominger J. L. Genetic mapping of a human class II antigen beta-chain cDNA clone to the SB region of the HLA complex. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6036–6040. doi: 10.1073/pnas.80.19.6036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Svejgaard A., Platz P., Ryder L. P. HLA and disease 1982--a survey. Immunol Rev. 1983;70:193–218. doi: 10.1111/j.1600-065x.1983.tb00715.x. [DOI] [PubMed] [Google Scholar]
  12. Trowsdale J., Lee J., Carey J., Grosveld F., Bodmer J., Bodmer W. Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1972–1976. doi: 10.1073/pnas.80.7.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES