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FOXP3 is a lineage-specific transcription factor that is required for regulatory T cell development and function. In this study, we determined the crystal structure of the FOXP3 forkhead domain bound to DNA. The structure reveals that FOXP3 can form a stable domain-swapped dimer to bridge DNA in the absence of cofactors, suggesting that FOXP3 may play a role in long-range gene interactions. To ...

In order to model the effect of PTPN22 on rheumatoid arthritis (RA), we determined the combination of single-nucleotide-polymorphisms (SNPs) showing the strongest association with RA. Three SNPs (rs2476601-rs12730735-rs11102685) were selected for which we estimated the genotypic relative risks (GRRs) of the corresponding genotypes. On the basis of these GRRs we defined four at-risk genotypic cl...

The genes PTPN22 and HLA-DRB1 have been found by a number of studies to confer an increased risk for rheumatoid arthritis (RA), which indicates that both genes play an important role in RA etiology. It is believed that they not only have strong association with RA individually, but also interact with other related genes that have not been found to have predisposing RA mutations. In this paper, ...

Rheumatoid arthritis is inherited in a complex manner. So far several single susceptibility genes, such as PTPN22, STAT4, and TRAF1-C5, have been identified. However, it is presumed that some genes may interact to have a significant effect on the disease, while each of them only plays a modest role. We propose a new combinatorial association test to detect the gene-gene interaction in the rheum...

LYP, the protein product of the protein tyrosine phosphatase gene PTPN22 located on human chromosome 1p13.2, is involved in downregulation of T cell signaling through its interaction with C-terminal Src tyrosine kinase (Csk) (Cloutier and Veillette, 1996), by phosphorylation of regulatory tyrosines on the Src family kinase Lck (Cloutier and Veillette, 1999). A missense mutation of this gene (C1...

autoimmune disease with an annual incidence of 10.5/100,000 in Asian Indians [1]. It is characterized by T cell-mediated destruction of pancreatic beta cells influenced by multiple genetic factors, such as HLA-II locus on chromosome 6p21.3 [2], insulin gene on 11p15.5 [3] and the CTLA4 locus on 2q33 [4], all of these are involved in T cell activation, immune homeostasis and development of T cel...

LYP, the protein product of the protein tyrosine phosphatase gene PTPN22 located on human chromosome 1p13.2, is involved in downregulation of T cell signaling through its interaction with C-terminal Src tyrosine kinase (Csk) (Cloutier and Veillette, 1996), by phosphorylation of regulatory tyrosines on the Src family kinase Lck (Cloutier and Veillette, 1999). A missense mutation of this gene (C1...