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Åke Lernmark

Principal investigator

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Susceptibility to insulin-dependent diabetes defined by restriction enzyme polymorphism of HLA-D region genomic DNA

Author

  • D. Owerbach
  • B. Hagglof
  • A. Lernmark
  • G. Holmgren

Summary, in English

DNA fragments complementary to cloned sequences encoding HLA-D region class II antigen α- and β-chains were determined by clotting with DNA from HLA-typed members of 22 complete families, 12 of which had a proband with insulin-dependent diabetes mellitus (IDDM). Analysis of genotypes showed that the DNA sequences were linked to HLA-DR and permitted confirmation of recombinations in two families. Digestion with the restriction enzymes BamHI, EcoRI, and Pstl and hybridization with an HLA-D region β-chain cDNA probe confirmed a BamHI 3.7 kilobase (kb) fragment present at low frequency among diabetic individuals and a BamHI 3.2 kb fragment that was also decreased among the diabetic subjects compared with siblings (P < 0.05) as well as nonrelated control siblings (P < 0.02) and their parents (P < 0.01). BamHI 12.0 kb (P < 0.05) and 5.8 kb (P < 0.02, P < 0.02), EcoRI 20 kb (P < 0.05, P < 0.02), and Psti 6.0 kb (P < 0.05) fragments were more frequent in diabetic individuals compared with nonrelated control siblings or their parents, respectively. Analysis of individual haplotypes revealed that HLA-DR4-containing chromosomes were heterogeneous among controls but that the diabetic individuals showed a similar pattern of restriction fragment length polymorphism. Genomic blotting of blood lymphocyte DNA with a cDNA clone encoding the chain of HLA-D region class II antigens permits detection of fragments that are strongly associated with IDDM.

Publishing year

1984-01-01

Language

English

Pages

958-965

Publication/Series

Diabetes

Volume

33

Issue

10

Document type

Journal article

Publisher

American Diabetes Association Inc.

Status

Published

ISBN/ISSN/Other

  • ISSN: 0012-1797