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

Owerbach, D. ; Hagglof, B. ; Lernmark, A. LU orcid and Holmgren, G. (1984) In Diabetes 33(10). p.958-965
Abstract

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... (More)

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.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
in
Diabetes
volume
33
issue
10
pages
8 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:6090247
  • scopus:0021200433
ISSN
0012-1797
DOI
10.2337/diab.33.10.958
language
English
LU publication?
no
id
5c173074-7468-40f2-9ba2-ee93c2e0d837
date added to LUP
2019-09-16 12:43:27
date last changed
2024-03-13 08:13:54
@article{5c173074-7468-40f2-9ba2-ee93c2e0d837,
  abstract     = {{<p>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 &lt; 0.05) as well as nonrelated control siblings (P &lt; 0.02) and their parents (P &lt; 0.01). BamHI 12.0 kb (P &lt; 0.05) and 5.8 kb (P &lt; 0.02, P &lt; 0.02), EcoRI 20 kb (P &lt; 0.05, P &lt; 0.02), and Psti 6.0 kb (P &lt; 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.</p>}},
  author       = {{Owerbach, D. and Hagglof, B. and Lernmark, A. and Holmgren, G.}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{10}},
  pages        = {{958--965}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Susceptibility to insulin-dependent diabetes defined by restriction enzyme polymorphism of HLA-D region genomic DNA}},
  url          = {{http://dx.doi.org/10.2337/diab.33.10.958}},
  doi          = {{10.2337/diab.33.10.958}},
  volume       = {{33}},
  year         = {{1984}},
}