Assistant Professor of Cardiology UC Davis School of Veterinary Medicine Davis, CA, United States
Abstract: Background– The genetics of feline hypertrophic cardiomyopathy are poorly understood and limited genetic discoveries remain breed or family specific. Hypothesis/Objectives– We aimed to identify novel causative or disease modifying variants in a large cohort of cats reflective of the general cat population. In a second cohort, we sought to characterize transcriptomic differences between HCM-affected cats and healthy controls. Animals– Cohort1 consisted of 109 HCM-affected and 29 control cats ≥10 years old. Cohort2 consisted of 27 HCM-affected and 15 control cats euthanized for cardiac or non-cardiac-related causes, respectively. Methods– DNA was isolated from blood samples and submitted for paired-end WGS at ~30X coverage (cohort1). Standard pipelines were employed for variant calling across sequenced cats. In cohort2, immediately flash-frozen left ventricular (LV), interventricular septal (IVS) and left atrial (LA) tissues were submitted for stranded mature RNA-sequencing at 50 million reads/sample. Results– No single or combination of variants of high, moderate or modifying impact were identified in genome wide analysis to cause or modify disease severity of HCM. Several rare high and moderate impact variants in genes associated with human HCM were detected in diseased cats. A total of 70, 111, and 57 DEGs were upregulated and 8, 52, and 130 DEGs were downregulated in LVPW, IVS, and LA tissue, respectively, in HCM-affected cats compared to controls. Conclusions– Similar to humans, the genetic etiology of feline HCM remains unknown in a high proportion of cases. Transcriptomics revealed molecular signatures that may help identify novel HCM biomarkers or drug targets in future investigations.
