The biology of DEXI a novel candidate gene in autoimmune disease. (360G-Wellcome-096398_Z_11_Z)

The autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis (MS) have a strong genetic basis, and recent genome-wide association studies have revealed many shared genetic risk variants, including the 16p13 region. Within this region, we have identified the DEXI gene, of unknown function and with no paralogue elsewhere in the genome as the most likely causal variant in autoimmune disease risk. The T1D and MS associated SNPs in the 16p13 region are eQTLs for DEXI expression in 2 independe nt monocyte data sets, and we have also shown their physical association with the DEXI promotor region by chromosome conformation capture. My future goal is to understand the biology of DEXI and its role in autoimmune disease pathogenesis. Key goals: 1. To evaluate changes in DEXI expression by qPCR in different stimulation conditions using cell lines, human monocytes and CD4+ cells 2. To develop a monoclonal antibody to DEXI to allow localisation of the protein within cells, quantificatio n of protein and to assist with the identification of binding partners of DEXI 3. To examine changes in immune cell gene-expression profiles by microarrray following over-expression and knockdown of the DEXI gene 4. To make recombinant DEXI and identify binding partners of this protein