ANALYSIS OF THE CD3 GENE REGION AND TYPE-1 DIABETES - APPLICATION OF FLUORESCENCE-BASED TECHNOLOGY TO LINKAGE DISEQUILIBRIUM MAPPING

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.