Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ
(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.
(Less)
- author
- Michelsen, B. and Lernmark, A. LU
- publishing date
- 1987-01-01
- 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 < 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.</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}}, }