Nature Genetics
9, 284 - 292 (1995)
doi:10.1038/ng0395-284
Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locusS.T. Bennett1, A.M. Lucassen2, S.C.L. Gough1, E.E. Powell1, D.E. Undlien3, L.E. Pritchard1, M.E. Merriman1, Y. Kawaguchi1, M.J. Dronsfield1, 4, F. Pociot5, J. Nerup5, N. Bouzekri6, A. Cambon-Thomsen6, K.S. Rønningen3, A.H. Barnett4, S.C. Bain4
& J.A. Todd1
1Nuffield Department of Surgery, The Wellcome Trust Centre for Human Genetics, University of Oxford, Windmill Road, Oxford OX3 7BN, UK
2Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
3Institute of Transplantation Immunology, The National Hospital N-0027 Oslo, Norway
4Department of Medicine/Diabetes/Endocrinology, University of Birmingham, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK
5Steno Diabetes Center, DK-2820 Gentofte, Denmark
6CNRS UPR8291, Centre d'Immunopathologie et de génétique humaine, Hôdpital Purpan, 31300 Toulouse, France 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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