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.
MeSH Terms
DNA Restriction Enzymes
Diabetes Mellitus, Type 1/genetics,immunology
Genes
HLA-DR Antigens
Histocompatibility Antigens Class II/genetics
Humans
Polymorphism, Genetic
Statistics as Topic
Chemicals
HLA-DR Antigens
Histocompatibility Antigens Class II
DNA Restriction Enzymes
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Cohen-Haguenauer O
Robbins E
Massart C
Busson M
Deschamps I
Hors J
Lalouel J M
Dausset J
Cohen D
References (13)
13 references, click to expand
-
Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper.
Methods Enzymol. 1979;68:220-42
PMID: 94421
-
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):3687-91
PMID: 6954511
-
Allelic polymorphism and complexity of the genes for HLA-DR beta-chains--direct analysis by DNA-DNA hybridization.
Nature. 1982 Nov 25;300(5890):372-4
PMID: 6292729
-
HLA and disease 1982--a survey.
Immunol Rev. 1983;70:193-218
PMID: 6339368
-
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):1972-6
PMID: 6300884
-
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):815-7
PMID: 6306468
-
Detection of specific sequences among DNA fragments separated by gel electrophoresis.
J Mol Biol. 1975 Nov 5;98(3):503-17
PMID: 1195397
-
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):6289-92
PMID: 6312451
-
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):1774-8
PMID: 6324215
-
Mutations and selection in the generation of class II histocompatibility antigen polymorphism.
EMBO J. 1984 Jul;3(7):1655-61
PMID: 6589154
-
Extended major histocompatibility complex haplotypes in type I diabetes mellitus.
J Clin Invest. 1984 Aug;74(2):449-54
PMID: 6746903
-
Clusters of HLA class II beta restriction fragments describe allelic series.
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7870-4
PMID: 6096865
-
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):6036-40
PMID: 6310612