Abstract: Background – Cardiovascular disease is a leading cause of increased morbidity and mortality in cats, with hypertrophic cardiomyopathy (HCM) significantly overrepresented. While HCM is hereditary, the genetic etiology of disease remains poorly understood in the cat. Establishing a cohort of well-phenotyped and -genotyped control cats is essential to fuel future genetic/pharmacogenetic discoveries.Objectives – Develop a robust genetic sequencing and gene expression library from cardiovascularly healthy cats using whole genome sequencing (WGS) and RNA sequencing (RNA-Seq).Animals – Fifty-four apparently healthy client-owned cats (≥10 years of age) and 14 purpose-bred or client-owned cats euthanized for non-cardiac related causes.Methods – Blood samples from prospectively enrolled cats (Cohort1) were used to isolate DNA and subsequently submitted for paired-end WGS at ~30X coverage. Standard variant calling pipelines were employed for variant calling across sequenced cats. Immediately flash-frozen left ventricular (LV), interventricular septum (IVS), and left atrium (LA) tissue samples (Cohort2) were collected and submitted for stranded mature RNA-Seq at 50 million reads/sample. All geriatric cats in this study were deemed true cardiovascularly healthy representatives of their species on clinicopathology, biochemistry, and echocardiography.Results – Of 54 cats screened in Cohort1, 19 cats were successfully enrolled. In Cohort2, flash-frozen LV, IVS, and LA tissue from 11, 14, and 12 cats, respectively, underwent RNA-Seq. Gene variants and expression profiling were catalogued for both meticulously selected cohorts. Conclusions – Libraries of transcriptomic and WGS data in cardiovascularly normal cats were generated to serve as an open-access resource in future investigations of feline cardiovascular medicine.
Learning Objectives:
Upon completion, participant will be able to understand the applications of and differences between whole genome sequencing and RNA sequencing.
Upon completion, participant will be able to understand how to create a well-phenotyped control group for whole genome sequencing and RNA sequencing.
Upon completion, participant will be able to understand the potential for using the generated transcriptome and WGS data for future investigations in feline cardiovascular medicine.
