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<p>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 (<InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_5704_Article_IEq1.gif" Format="GIF" Height="15" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(\ge\)</EquationSource> </InlineEquation>&#xa0;10&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Joanna L. Kaplan,
  • Victor N. Rivas,
  • Jalena R. Wouters,
  • Michael W. Vandewege,
  • Samantha P. Harris,
  • Joshua A. Stern

摘要

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.