POSTER ABSTRACTS
#39 Genetic susceptibility of the Cavalier King Charles Spaniel to Canine Myxomatous Mitral Valve Disease Marsha Wallace1,2 , J Wilshaw2, A Boswood2, MJ Hezzell3*, LJ Davison1,2* * Co-senior Authors mwallace@well.ox.ac.uk 1Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, 2Department of Clinical Science & Services, Royal Veterinary College, University of London, Hertfordshire, UK, 3Bristol Veterinary School, University of Bristol, Bristol, UK. The Cavalier King Charles Spaniel (CKCS) is highly predisposed to myxomatous mitral valve disease (MMVD), with almost all dogs affected by 11 years of age. MMVD-associated congestive heart failure (CHF) develops in <50% dogs, with a variable age of onset. The aim of this study was to identify genetic variants associated with MMVD in CKCS, and variants associated with early CHF onset. Whole-genome sequencing (WGS) was undertaken of 12 CKCS with MMVD and selected for either severe (early onset CHF) or mild (non-cardiac death without CHF) heart disease phenotypes. Additional unpublished WGS data from 48 dogs across 7 breeds and data from public databases were available for comparison. A multi-species annotation-focused bioinformatics workflow was used to identify and prioritize variants at high frequency in CKCS with plausible roles in MMVD, as well as variants associated with severe compared to mild MMVD phenotype within the CKCS breed. Targeted high-throughput sequencing of ~2,000 prioritized variants was undertaken on an addi- tional cohort of 49 CKCS with MMVD, 21 dogs with MMVD from other breeds, and 113 dogs without MMVD. This led to further prioritization and a final round of targeted sequencing on 60 CKCS with MMVD (32 severe, 28 mild MMVD). We identified >100 variants of potential importance in CKCS MMVD and associated CHF. Notably, many significant variants were located in genes and biological pathways with potential for future therapeutic intervention, including e.g. calcium signaling, cell adhesion, inflammation, and wound healing.
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