title: 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.
authors.affiliation: Nuffield Department of Surgery, Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
authors.forename: S T
authors.initials: ST
authors.lastname: Bennett
authors.forename: A M
authors.initials: AM
authors.lastname: Lucassen
authors.forename: S C
authors.initials: SC
authors.lastname: Gough
authors.forename: E E
authors.initials: EE
authors.lastname: Powell
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
authors.forename: L E
authors.initials: LE
authors.lastname: Pritchard
authors.forename: M E
authors.initials: ME
authors.lastname: Merriman
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: M J
authors.initials: MJ
authors.lastname: Dronsfield
authors.forename: F
authors.initials: F
authors.lastname: Pociot
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018392:Genomic Imprinting; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; D007328:Insulin; D004247:DNA