Establishing a robust genetic sequencing and gene expression data library in cardiovascularly healthy cats

Abstract

Abstract Cardiovascular disease is a leading cause of increased morbidity and mortality in cats, with hypertrophic cardiomyopathy (HCM) significantly overrepresented. While feline HCM is hereditary, the genetic etiology of disease remains poorly understood. Establishing a cohort of well-phenotyped and -genotyped healthy control cats is essential to fuel future genetic/pharmacogenetic discoveries. We sought to construct a robust genetic sequencing and gene expression library from cardiovascularly healthy cats using whole genome sequencing (WGS) and RNA sequencing (RNA-Seq). Fifty-four client-owned cats ( $$\ge$$  10 years) were screened, of which 18 cats (cohort 1) were prospectively enrolled after being deemed cardiovascularly healthy by clinicopathology, biochemistry, and echocardiography. DNA isolated from blood samples was submitted for paired-end WGS at ~ 30X coverage. Standard pipelines were employed for variant calling across sequenced cats. A second cohort of 15 purpose-bred cats were euthanized for non-cardiac reasons. Flash-frozen left ventricular (LV), interventricular septum (IVS), and left atrium (LA) tissues from 11, 14, and 13 cats, respectively, were submitted for stranded mature RNA-Seq at 50 million reads/sample. Gene variants and expression profiling were catalogued for both meticulously selected cohorts. Transcriptomic and WGS data libraries were generated to serve as an open-access resource in future investigations of feline cardiovascular precision medicine.