Pathogenic Variants Screening in Seventeen Candidate Genes on 2p15 for Association with Ankylosing Spondylitis in a Han Chinese Population Running title: Genes on 2p15 for Association with Ankylosing Spondylitis

Ankylosing spondylitis (AS) is an inflammatory autoimmune and polygenic complex disease. Several studies in different races revealed that chromosome 2p15 is a susceptibility locus of AS. More importantly, chromosome 2p15 region contributed the highest contribution to AS heritability besides HLA-B27, but the specific mechanism was unclear. This project planned to fine-map 2p15 region by NimbleGen Sequence Capture technology combined with new-generation Solexa high-throughput sequencing technology base on 100 cases and 100 matched controls, then the susceptibility variation will be verified in the independent large sample size (3000 subjects). Based on the above results, we try to clarify the mechanisms of susceptibility genes/loci through two steps, first, by the bioinformatics function prediction, we will build the cell model if both the overexpression and low expression, second, the expression and functional studies of susceptibility loci were demonstrated by multiple molecular biology functional experiments, such as flow cytometry, Dual-Luciferase reporter gene assays, Chromatin Immunoprecipitation(ChIP), Electrophoretic mobility shift assay(EMSA), western blotting and so on. New evidence based on a comprehensive understanding of the 2p15 mediated AS-related pathogenic mechanisms, could provide great value in academic study and application to early screening and prevention of AS.