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Researchers have discovered the first genetic mutation associated with hypertrophic cardiomyopathy (HCM) and sudden death in golden retrievers. The work could lead to increased early detection and disease prevention for the breed while further shaping our understanding of the disease in humans. The study appears in .

HCM is a cardiac disease that most commonly affects humans and cats but was previously considered rare in dogs. In HCM, the left ventricular muscle thickens, affecting the heart's ability to deliver oxygenated blood to the body. The disease can lead to abnormal blood clotting, irregular heart rhythms and heart failure, although in up to 50% of cases, individuals with the disorder show no clinical signs. HCM affects approximately one in 500 humans and one in seven cats, representing one of the top causes of sudden death in both populations.

In the study, the research team looked at the whole genome sequences for three related golden retriever puppies less than two years of age who all suffered sudden cardiac deaths. Genetic sequences were compared to other dogs within the puppies' family tree, sequences from over 2,500 unrelated dogs of various breeds, and sequences from wolves and coyotes.

Bioinformatic analysis and sequential filter steps led the team to identify a single genetic variant located in a gene called Cardiac Troponin-I, or TNNI3.

"In humans, TNNI3 mutations are associated with juvenile HCM and sudden death," says Victor Rivas, DVM student and Ph.D. graduate at North Carolina State University. "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." Rivas is first author of the study.

The researchers also found that the mutation is autosomal recessive, which means that two copies of the gene—one from each parent—must be present for the disease to occur. In the case of the affected puppies, both parents were cardiovascularly normal, but each carried a copy of the mutation.

The researchers hope that this information can be used to prevent the spread of the TNNI3 variant—and thereby HCM—through the breed. Golden retriever owners who may be interested in breeding can have genotype testing performed for this mutation to determine whether their animal is a carrier.

"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," Rivas says.

"Additionally, 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."