title: Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping.
abstract: The CD3 gene region on chromosome 11q23 has been implicated in susceptibility to type 1 (insulin-dependent) diabetes mellitus. Using semi-automated fluorescence-based technology, we have undertaken association and linkage analysis of a dinucleotide microsatellite in the CD3 delta (CD3D) gene. We have also performed a large case-control analysis of a restriction fragment length polymorphism (RFLP) in the CD3 epsilon (CD3E) gene, 26 kb from CD3D. We found no evidence for the previously reported association between the 8 kb allele of the RFLP and disease in a UK dataset of 403 diabetic patients and 446 nondiabetic controls. Furthermore, the use of the transmission/disequilibrium test (TDT) showed no evidence of linkage or association to type 1 diabetes at either marker locus. We conclude that the CD3 gene region does not contribute significantly to IDDM susceptibility. We have successfully applied semi-automated, fluorescence-based technology to undertake association analysis on the CD3D microsatellite. Moreover, by analysing 94 other dinucleotide repeat markers, we conclude that fluorescence-based methodology can generally be applied to large-scale, semi-automated association studies with most microsatellite markers.
authors.affiliation: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, UK.
authors.forename: L E
authors.initials: LE
authors.lastname: Pritchard
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: P W
authors.initials: PW
authors.lastname: Reed
authors.forename: J B
authors.initials: JB
authors.lastname: Copeman
authors.forename: J L
authors.initials: JL
authors.lastname: Davies
authors.forename: A H
authors.initials: AH
authors.lastname: Barnett
authors.forename: S C
authors.initials: SC
authors.lastname: Bain
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015415:Biomarkers; D017252:CD3 Complex / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005069:Evaluation Studies as Topic; D005192:Family Health; D005260:Female; D005453:Fluorescence; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008722:Methods; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015415:Biomarkers; D017252:CD3 Complex