Grant: Operating Grant - PA: Regional Partnership Program - Newfoundland and Labrador

Spondyloarthritis (SpA) represents a collection of chronic inflammatory conditions that primarily affect the spine, peripheral joints and exhibits several extra-articular features particularly psoriasis, inflammatory bowel disease and uveitis. The most common forms of SpA are ankylosing spondylitis (AS) and psoriatic arthritis (PsA). SpA constitutes a major health challenge because of its prevalence in Canada (affecting 400,00 Canadians), its propensity to affect young adults, and the necessity for lifelong medical management. Despite a high heritability for SpA, including identification of multiple genes via genome-wide association scans , only a fraction of the entire disease heritability is explained. Copy number variants, (CNVs) are a prominent source of variation in the human genome and are increasingly being associated with known genomic disorders, suggesting that they may underpin the pathogenesis of complex diseases. CNVs have not been comprehensively assessed in SpA. We hypothesize that CNVs represent highly penetrant genetic variation accounting for part of the missing heritability in SpA families that have multiple affected individuals. With the use of our custom two million probe microarray chip that we have developed, we will analyze 20 large informative SpA families with multiple affected members. CNVs identified from these families will then be tested in 900 individuals with SpA. By elucidating the entire genetic contribution of SpA ,including CNVs, this will hopefully lead to a better diagnostic tool and increased understanding of these disease so that the present challenges in managing SpA (substantial delay in diagnosis, inability to predict disease course and marked heterogeneity in treatment response) may be overcome.