Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus
Abstract
The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5. By 'cross-match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself. Other polymorphisms were systematically excluded as primary disease determinants. Transmission of IDDM2 may be influenced by parent-of-origin phenomena. Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR. Allelic variation at VNTRs may play an important general role in human disease.
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Linkage analysis of sibling pairs affected by type 1 diabetes identified an area on chromosome 11p15 that was subsequently mapped to a region upstream of the insulin gene as associated with type 1 diabetes.
“In the 1990s, linkage analysis of sibling pairs affected by type 1 diabetes identified an area on chromosome 11p15 (ref. 49) that was subsequently mapped to a region upstream of the insulin gene50–52 as associated with type 1 diabetes.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [50]
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- Authors
- Bennett, S. T., Lucassen, A. M., Gough, S. C. L., Powell, E. E., Undlien, D. E., Pritchard, L. E., Merriman, M. E., Kawaguchi, Y., Dronsfield, M. J., Pociot, F., Nerup, J., Bouzekri, N., Cambon-Thomsen, A., Rønningen, K. S., Barnett, A. H., Bain, S. C., & Todd, J. A.
- Affiliations
- Centre for Human Genetics (GB)
- John Radcliffe Hospital (GB)
- Oslo University Hospital (NO)
- Centre National de la Recherche Scientifique (FR)
- Heartlands Hospital (GB)
- ORCID
- Venue
- Nature Genetics
- Published
- 1995-03
- Volume
- 9
- Issue
- 3
- Pages
- 284-292
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2034957838
- Cited by
- 746
- References
- 1
- Citations by year
- 2025: 7 · 2024: 6 · 2023: 10 · 2022: 4 · 2021: 14 · 2020: 6 · 2019: 12 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 16 · 2014: 14 · 2013: 28 · 2012: 22
- FWCI
- 29.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- type 1 diabetes, insulin gene, minisatellites, variable number tandem repeats, chromosome 11p15.5, genetic susceptibility, haplotype analysis, association mapping, parent-of-origin effects, biallelic expression, insulin gene transcription, allelic variation
- MeSH terms
- Adult, Alleles, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 11, Diabetes Mellitus, Type 1, DNA, DNA, Satellite, Female, Haplotypes, Humans, Insulin, Male, Molecular Sequence Data, Polymorphism, Restriction Fragment Length, Linkage Disequilibrium, Gene Expression, Polymerase Chain Reaction, DNA Primers, Genomic Imprinting, Minisatellite Repeats
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