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Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy

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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
  • | 2 Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27607.
  • | 3 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
  • | 5 Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27607.
  • | 6 Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
  • | 7 Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27607.
  • | 8 Department of Statistics, North Carolina State University, Raleigh, NC 27607.
  • | 9 Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27607.
  • | 10 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
  • | 11 Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC 27607.

Abstract

OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM).

ANIMALS 8 dogs with and 5 dogs without DCM.

PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM.

RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.

Supplementary Materials

    • Supplementary Tables (PDF 108 kb)

Contributor Notes

Address correspondence to Dr. Friedenberg (steven_friedenberg@ncsu.edu).