Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus - PubMed (original) (raw)
Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus
S T Bennett et al. Nat Genet. 1995 Mar.
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.
Comment in
- Insulin expression: is VNTR allele 698 really anomalous?
McGinnis RE, Spielman RS. McGinnis RE, et al. Nat Genet. 1995 Aug;10(4):378-80. doi: 10.1038/ng0895-378. Nat Genet. 1995. PMID: 7670485 No abstract available.
Similar articles
- The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes.
Pugliese A, Zeller M, Fernandez A Jr, Zalcberg LJ, Bartlett RJ, Ricordi C, Pietropaolo M, Eisenbarth GS, Bennett ST, Patel DD. Pugliese A, et al. Nat Genet. 1997 Mar;15(3):293-7. doi: 10.1038/ng0397-293. Nat Genet. 1997. PMID: 9054945 - Imprinted and genotype-specific expression of genes at the IDDM2 locus in pancreas and leucocytes.
Vafiadis P, Bennett ST, Colle E, Grabs R, Goodyer CG, Polychronakos C. Vafiadis P, et al. J Autoimmun. 1996 Jun;9(3):397-403. doi: 10.1006/jaut.1996.0054. J Autoimmun. 1996. PMID: 8816977 - Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus.
Vafiadis P, Bennett ST, Todd JA, Nadeau J, Grabs R, Goodyer CG, Wickramasinghe S, Colle E, Polychronakos C. Vafiadis P, et al. Nat Genet. 1997 Mar;15(3):289-92. doi: 10.1038/ng0397-289. Nat Genet. 1997. PMID: 9054944 - Human type 1 diabetes and the insulin gene: principles of mapping polygenes.
Bennett ST, Todd JA. Bennett ST, et al. Annu Rev Genet. 1996;30:343-70. doi: 10.1146/annurev.genet.30.1.343. Annu Rev Genet. 1996. PMID: 8982458 Review. - Genetic analysis of type 1 diabetes using whole genome approaches.
Todd JA. Todd JA. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8560-5. doi: 10.1073/pnas.92.19.8560. Proc Natl Acad Sci U S A. 1995. PMID: 7567975 Free PMC article. Review.
Cited by
- Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.
Guneri D, Alexandrou E, El Omari K, Dvořáková Z, Chikhale RV, Pike DTS, Waudby CA, Morris CJ, Haider S, Parkinson GN, Waller ZAE. Guneri D, et al. Nat Commun. 2024 Aug 20;15(1):7119. doi: 10.1038/s41467-024-50553-0. Nat Commun. 2024. PMID: 39164244 Free PMC article. - Decoding the immune dance: Unraveling the interplay between beta cells and type 1 diabetes.
Roy S, Pokharel P, Piganelli JD. Roy S, et al. Mol Metab. 2024 Oct;88:101998. doi: 10.1016/j.molmet.2024.101998. Epub 2024 Jul 26. Mol Metab. 2024. PMID: 39069156 Free PMC article. Review. - Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.
Robertson CC, Elgamal RM, Henry-Kanarek BA, Arvan P, Chen S, Dhawan S, Eizirik DL, Kaddis JS, Vahedi G, Parker SCJ, Gaulton KJ, Soleimanpour SA. Robertson CC, et al. Mol Metab. 2024 Aug;86:101973. doi: 10.1016/j.molmet.2024.101973. Epub 2024 Jun 22. Mol Metab. 2024. PMID: 38914291 Free PMC article. Review. - Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions.
Ansari MA, Chauhan W, Shoaib S, Alyahya SA, Ali M, Ashraf H, Alomary MN, Al-Suhaimi EA. Ansari MA, et al. Int J Obes (Lond). 2023 Dec;47(12):1179-1199. doi: 10.1038/s41366-023-01369-3. Epub 2023 Sep 11. Int J Obes (Lond). 2023. PMID: 37696926 Review. - Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.
Berumen J, Orozco L, Gallardo-Rincón H, Juárez-Torres E, Barrera E, Cruz-López M, Benuto RE, Ramos-Martinez E, Marin-Madina M, Alvarado-Silva A, Valladares-Salgado A, Peralta-Romero JJ, García-Ortiz H, Martinez-Juarez LA, Montoya A, Alvarez-Hernández DA, Alegre-Diaz J, Kuri-Morales P, Tapia-Conyer R. Berumen J, et al. J Endocrinol Invest. 2024 Mar;47(3):571-583. doi: 10.1007/s40618-023-02175-4. Epub 2023 Aug 25. J Endocrinol Invest. 2024. PMID: 37624484 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical