Abstract
BackgroundType 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. Decay accelerating factor (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a candidate for autoimmune disease susceptibility based on its role in restricting complement activation and evidence that DAF expression modulates the phenotype of mice models for autoimmune disease. In this study, we adopt a linkage disequilibrium (LD) mapping approach to test for an association between the DAF gene and T1D.ResultsInitially, we used HapMap II genotype data to examine LD across the DAF region. Additional resequencing was required, identifying 16 novel polymorphisms. Combining both datasets, a LD mapping approach was adopted to test for association with T1D. Seven tag SNPs were selected and genotyped in case-control (3,523 cases and 3,817 controls) and family (725 families) collections.ConclusionWe obtained no evidence of association between T1D and the DAF region in two independent collections. In addition, we assessed the impact of using only HapMap II genotypes for the selection of tag SNPs and, based on this study, found that HapMap II genotypes may require additional SNP discovery for comprehensive LD mapping of some genes in common disease.
Highlights
Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells
DAF resequencing As we were concerned about adopting a linkage disequilibrium (LD) mapping approach given the HapMap SNP density[27], we resequenced DAF in 32 Centre d'Etude du Polymorphisme Humain (CEPH) individuals, selected from the 60 CEPH individuals used by the HapMap project, to increase the SNP density across the region
The relatively small number of common polymorphisms found in both datasets is not unexpected, as HapMap II SNPs were selected to provide an even coverage in terms of distance across the genome, whereas the resequencing is focused on regions of interest and extracts all common polymorphisms present in these individuals
Summary
Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. T1D is characterised as a common autoimmune disease, mainly resulting from a T-cell mediated destruction of pancreatic beta cells that leaves patients completely dependent on exogenous insulin to regulate their blood glucose level. D' = 1 blue bright red LFDigumraep1for human DAF region on Chromosome 1q32 LD map for human DAF region on Chromosome 1q32. All markers with the MAF of less than 0.05 or with insufficient genotyping data were excluded in the LD measurement. A. LD map with 21 markers genotyped in 60 individuals obtained from HapMap II. B. LD map with 22 markers identified by resequencing with 32 CEPH's individuals. LD map with 38 markers, a combined dataset of both HapMap II and in-house resequencing data with 32 CEPH's individuals
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