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Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ

Michelsen, B. and Lernmark, A. LU orcid (1987) In Journal of Clinical Investigation 79(4). p.1144-1152
Abstract

A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ β-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ β-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA-DR3/4 controls but in 0 of 13 DR-identical IDDM patients. All IDDM patients (13 of 13) had BamHI fragments of 12 and 4 kb, detected in 9 of 17 controls (P < 0.02). The simple restriction fragment length polymorphism pattern of the IVS 1 probe was exploited by comparing 113 IDDM patients with 177 healthy controls to show increased prevalences in IDDM of... (More)

A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ β-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ β-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA-DR3/4 controls but in 0 of 13 DR-identical IDDM patients. All IDDM patients (13 of 13) had BamHI fragments of 12 and 4 kb, detected in 9 of 17 controls (P < 0.02). The simple restriction fragment length polymorphism pattern of the IVS 1 probe was exploited by comparing 113 IDDM patients with 177 healthy controls to show increased prevalences in IDDM of the 12-kb (P < 0.0001) and 4-kb (P < 0.0001) fragments. In IDDM patients younger than 20 yr at onset, 98% were 12- and/or 4-kb positive, compared with 63% of controls (P < 0.0001), giving a relative risk of 91.8 for individuals with both fragments. The 12-kb fragment was linked to HLA-DR4, and the 4-kb fragment to HLA-DR3. Both serologic markers were split and a non-DR3/non-DR4 IDDM patient was 4-kb positive. HLA-DQ seems therefore closer, than HLA-DR, to an IDDM susceptibility gene.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
79
issue
4
pages
1144 - 1152
publisher
The American Society for Clinical Investigation
external identifiers
  • scopus:0023274081
  • pmid:2881947
ISSN
0021-9738
DOI
10.1172/JCI112931
language
English
LU publication?
no
id
cf605d53-662f-485f-b8e6-db2b925d915c
date added to LUP
2019-09-16 12:29:33
date last changed
2024-03-13 07:59:24
@article{cf605d53-662f-485f-b8e6-db2b925d915c,
  abstract     = {{<p>A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ β-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ β-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA-DR3/4 controls but in 0 of 13 DR-identical IDDM patients. All IDDM patients (13 of 13) had BamHI fragments of 12 and 4 kb, detected in 9 of 17 controls (P &lt; 0.02). The simple restriction fragment length polymorphism pattern of the IVS 1 probe was exploited by comparing 113 IDDM patients with 177 healthy controls to show increased prevalences in IDDM of the 12-kb (P &lt; 0.0001) and 4-kb (P &lt; 0.0001) fragments. In IDDM patients younger than 20 yr at onset, 98% were 12- and/or 4-kb positive, compared with 63% of controls (P &lt; 0.0001), giving a relative risk of 91.8 for individuals with both fragments. The 12-kb fragment was linked to HLA-DR4, and the 4-kb fragment to HLA-DR3. Both serologic markers were split and a non-DR3/non-DR4 IDDM patient was 4-kb positive. HLA-DQ seems therefore closer, than HLA-DR, to an IDDM susceptibility gene.</p>}},
  author       = {{Michelsen, B. and Lernmark, A.}},
  issn         = {{0021-9738}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{1144--1152}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ}},
  url          = {{http://dx.doi.org/10.1172/JCI112931}},
  doi          = {{10.1172/JCI112931}},
  volume       = {{79}},
  year         = {{1987}},
}