Authors J. Novo Matos (1), A. Psifidi (1,2), D.J. Connolly (1), L. Wilkie (1), R. Piercy (1), V. Luis Fuentes (1)
Affiliations 1. Royal Veterinary College, London, UK, 2. The Roslin Institute, University of Edinburgh, UK
Presentation Type Poster
Abstract
Hypertrophic cardiomyopathy (HCM) is a common heritable myocardial disease in cats. In humans, HCM is typically caused by mutations in cardiac sarcomere protein genes and occasionally in non-sarcomeric genes. In cats only 2 causative mutations for HCM have been identified so far; both in the sarcomeric gene MYBPC3. We hypothesised that HCM in cats is associated with mutations in the same genes as in human HCM. To investigate this, we performed targeted re-sequencing of 18 genes known to cause HCM in humans in a group of 48 cats (25 cases and 23 breed-matched controls) of 8 different breeds. Variant discovery was performed using the GATK tools for best practice. Allelic/genotypic frequencies at each single nucleotide polymorphism (SNP) locus with a likely high, moderate, or modifier functional impact were compared between cases and controls using the Chi-squared and T-tests. Using this re-sequencing data we also performed genome-wide association (GWAS) and selective sweep (Fst) analyses using the PLINK and GEMMA algorithms. A mixed model that accounted for age, weight and breed, and included the genomic relationship matrix among individuals as a random effect was implemented. Significance level was set at P< 0.05 and a Bonferroni correction for multiple testing was performed. More than 9,000 SNPs and insertions and deletions (INDELs) were detected in 15 out of the 18 genes. 10 SNPs located in the TNNT2, TPM1, ACTN, PDLIM3 and CSRP3 genes had a significantly higher frequency in cases compared to controls. The GWAS detected one SNP with a genome-wide significant association with HCM located within the TNNT2 gene and several others with a suggestive significant association. Fst results supported GWAS results with the highest Fst peak also spanning the TNNT2 gene. These results suggest an association of HCM with TNNT2 and other candidate genes across feline breeds. These results should be validated in a larger population.