Golden retrievers help scientists pinpoint a deadly heart mutation

“Man’s best friend” is proving to be helpful for studying a deadly heart mutation. A team at North Carolina State University identified a genetic mutation that’s a telltale sign of hypertrophic cardiomyopathy in golden retrievers. Although the disease itself is rare in dogs, the discovery may soon expand experts’ understanding of the life-threatening heart disease that’s far more common in other mammals—including pet owners.

What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy (HCM) affects approximately one in 500 people and is the result of genomic mutations. HCM thickens the heart’s left ventricular muscle, resulting in a significant reduction in oxygenated blood circulation. Although up to half of all cases show no obvious clinical signs, its complications including irregular heart rhythms, blood clotting, and even heart failure can turn fatal very suddenly for a smaller subset of patients. 

HCM is even more dangerous to other animal species. Cats have a one-in-seven chance of harboring the disease, a likelihood that increases to one-in-four for pig and rhesus macaque nuclear families. While previously considered rare in dogs, the authors of a recent study published in the journal Circulation: Genomic and Precision Medicine have pinpointed a genomic marker for canines.

“This is the first genetic variant to explain HCM outside of humans and cats. And while it is specific to golden retrievers, it’s the first variant to be described in any dog breed,” study co-author and veterinarian Victor Rivas said in a statement.

Surprising similarities between dogs and owners

The team focused on the whole genome sequences of three related golden retriever puppies under the age of two who all experienced sudden cardiac deaths. The data was then compared with relatives in their family tree, along with the sequences from over 2,500 unrelated canines across multiple breeds, as well as wolves and coyotes. Their analysis eventually highlighted a single variant present in the gene known as Cardiac Troponin-I, or TNNI3. And when it comes to humans, TNNI3 mutations are proven links between juvenile HCM and sudden death.

Further examinations revealed that the golden retriever TNNI3 mutation is autosomal recessive. This means that each parent must possess the same gene in order for the disease to present itself in offspring. Although the three puppies’ parents were cardiovascularly healthy, their copies of the mutation allowed it to manifest in the next generation.

Currently, the TNNI3 marker only applies to golden retrievers. However, the discovery is still a major moment in maintaining the popular breed’s overall health.

“The positive news is that by collaborating with the golden retriever community we may be able to ensure that HCM remains a very rare disease in dogs,” said Rivas.

Rivas also noted that the genomic variant overlap in humans and golden retrievers may lead to wider public health ramifications.

“The case similarities in humans and golden retrievers with these TNNI3 variants is remarkable and could lead to translational health studies that can shape our understanding of the disease mechanisms and ultimately benefit humans with similar mutations,” said Rivas.