Same genes behind heart muscle disorders in dogs and humans

We have identified new genetic factors of dilated cardiomyopathy, a disease that enlarges the heart muscle, in dogs and humans. This research helps us understand the genetic risk factors related to fatal diseases of the heart muscle and the mechanisms underlying the disease and offers new tools for their prevention.

Cardiomyopathy can be caused by a variety of factors, but genetics play a significant role. Although dozens of genes underlying cardiomyopathy in humans have been identified, the hereditary nature and genetic background of the disease in dogs have remained unclear.

Various research data collected over decades on more than 500 Dobermanns from across Europe were combined for the purposes of the research. The dogs in the study cohort were categorised into five different groups: dogs with only dilated cardiomyopathy; dogs with only arrhythmia; dogs with dilated cardiomyopathy and arrhythmia; dogs with congestive heart failure and healthy dogs aged at least six years as a control subcohort.

With the help of genetic mapping, two adjacent gene loci in chromosome 5 were associated with dilated cardiomyopathy. Among the numerous genes in the loci, two, namely RNF207 and PRKAA2, were found to demonstrate structural variation which could have a detrimental effect on the functioning of the genes and cause heart failure. The genes we identified are only associated with a dilated heart and affected cardiac function. Arrhythmia appeared to be a genetically distinct disease.

The significance of the gene discovery in dogs was investigated in human patients who had been diagnosed with dilated cardiomyopathy using Dutch, English (UK Biobank) and Finnish (FinnGen) cohorts. Fifteen potentially harmful and predisposing variants in the same RNF207 and PRKAA2 genes, which had been identified in dogs, were discovered in humans. The identical genetic background suggests that, to a degree, similar problems with the functioning of the heart muscle lead to dilated cardiomyopathy in both humans and dogs. A deeper understanding of the pathogenetic mechanisms is important, and Dobermanns represent a natural model organism for further research.

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human
Niskanen JE, Ohlsson Å, Ljungvall I, Drögemüller M, Ernst RF, Dooijes D, van Deutekom HWM, van Tintelen PJ, Snijders Blok CJB, van Vugt M, van Setten J, Asselbergs FW, Domanjko Petrič A, Salonen M, Hörtenhuber M, DoGA consortium, Pyle WG, Donner J, Postma AV, Leeb T, Andersson G, Hytönen MK, Häggström J, Wiberg M, Friederich J, Eberhard J, Harakalova M, van Steenbeek FG, Wess G, Lohi H. Genome Medicine.