Researchers identify gene associated with deadly heart disease in golden retrievers
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.
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.”
The study appears in Circulation: Genomic and Precision Medicine. Other NC State contributors were Michael Vandewege, Ronald Li, Sandra Losa, Meghan Leber, Panchan Sitthicharoenchai, and Joshua Stern. Dayna Goldsmith, Jennifer Davies and Carolyn Legge of the University of Calgary; Kim Hawkes of Pulse Veterinary Cardiology and Sarah Revell of Highview Animal Clinic also contributed to the work.
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Note to editors: An abstract follows.
“Novel Cardiac Troponin-I Missense Variant (c.593C>T) Is Associated With Familial Hypertrophic Cardiomyopathy in Golden Retrievers”
DOI: 10.1161/CIRCGEN.125.005096
Authors: Victor Rivas, Michael Vandewege, Ronald Li, Sandra Losa, Meghan Leber, Panchan Sitthicharoenchai, Joshua Stern, North Carolina State University; Dayna Goldsmith, Jennifer Davies, Carolyn Legge, University of Calgary; Kim Hawkes, Pulse Veterinary Cardiology; Sarah Revell, Highview Animal Clinic
Published: Aug. 22, 2025 in Circulation: Genomic and Precision Medicine
Abstract:
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a naturally occurring cardiac disorder afflicting humans, cats, rhesus macaques, pigs, and rarely dogs. The disease is characterized by maladaptive left ventricular wall thickening. Over 1500 sarcomere-coding mutations explain HCM in humans, whereas only 3 have been reported in cat breeds. To date, no mutations have been described in dogs. HCM in a nuclear family of Golden Retrievers was identified following the sudden cardiac death of 3 related puppies <2 years of age from 2 dam-offspring repeat matings. METHODS: Whole-genome sequencing on the 3 affected puppies, along with nuclear family members (ie, sire, dam, 4 unaffected littermates, 4 unaffected half-siblings), and 1 distantly related, geriatric, cardiovascularly normal Golden Retriever was performed (n=14). Candidate variant genotyping was performed in an unphenotyped cohort of dogs (n=2771) and an expanded population of phenotyped, unrelated Golden Retrievers (n=45). Left ventricular tissue immunofluorescence staining was subsequently performed to investigate incorporation and expression of mutant protein within the cardiac sarcomere of HCM-affected cases. RESULTS: Gross and histopathologic evaluations of the HCM-affected puppies revealed hallmark features of the disease, including cardiomyocyte hypertrophy, interstitial fibrosis, and left-sided congestive heart failure. Segregation analysis of called variants, performed under assumptions of an autosomal-recessive mode of inheritance, identified a single segregating c.593C>T missense variant in TNNI3 (Cardiac Troponin-I). This variant was not observed in the unphenotyped (n=2771) nor in the phenotyped, unrelated cohort of dogs (n=45). Immunofluorescence staining of left ventricular tissues did not reveal obvious aberrant protein localization and expression at the sarcomeric level, suggesting the molecular pathogenesis of the TNNI3 variant is not related to abnormal protein incorporation within the sarcomere.
CONCLUSIONS: This variant represents the first-ever reported HCM-associated variant in any canine species, and its identification holds promise for establishing translational models, genetic screening, and early disease prevention within the breed.
Journal
Circulation Genomic and Precision Medicine
Method of Research
Data/statistical analysis
Subject of Research
Animal tissue samples
Article Title
Novel Cardiac Troponin-I Missense Variant (c.593C>T) Is Associated With Familial Hypertrophic Cardiomyopathy in Golden Retrievers
A diagnostic system developed for identifying ADHD-suspected dogs
Hungarian ethologists developed the first diagnostic system to detect ADHD-like symptoms in family dogs, based on human ADHD principles.
Eötvös Loránd University
In a groundbreaking study with international significance, Hungarian ethologists have developed the first diagnostic system capable of screening family dogs with suspected ADHD, following the diagnostic principles of human ADHD (Attention-Deficit/Hyperactivity Disorder). The research, conducted at the Department of Ethology, Eötvös Loránd University (ELTE), has been published in the prestigious journal Scientific Reports.
The study aimed to create an objective and standardised tool to identify dogs showing behaviours associated with ADHD, such as inattention, hyperactivity, impulsivity, and functional impairment. The new system may support both scientific research and veterinary practice, since there is currently no universally accepted method for screening dogs with ADHD-like symptoms – despite increasing reports from owners about such behavioural problems.
The study involved 1872 family dogs and their owners. Researchers used the previously validated “Dog ADHD and Functionality Rating Scale” (DAFRS), which evaluates dog behaviour from two perspectives. The first part measures the presence of symptoms (inattention, hyperactivity, impulsivity), while the second assesses the extent to which these behaviours interfere with the dog’s daily functioning – for example, everyday interactions with the owner or learning.
“In human diagnostics, the presence of symptoms such as inattention, hyperactivity, or impulsivity alone does not necessarily indicate ADHD. A key element is functional impairment – that is, whether these symptoms have a negative impact on everyday life,” explained Dr. Nóra Bunford, clinical psychologist and human ADHD researcher.
The researchers first examined how many dogs showed behavioural problems associated with ADHD symptoms, which also negatively affected everyday life. A dog was considered functionally impaired if owners reported at least four out of seven items with moderate or greater problem severity in any of the ADHD-related domains (inattention, hyperactivity, impulsivity). This criterion applied to 116 dogs (6.2% of the sample).
Subsequently, the team combined the functional impairment data with the ADHD symptom total scores. They established a final criterion: dogs were classified as at-risk if they scored at least 26 points on the ADHD symptom scale and showed noticeable problems in at least one functional area. These two criteria together applied to 79 dogs (4.2% of the sample).
“This prevalence rate is surprisingly similar to what has been reported in adults with ADHD, while the prevalence is somewhat higher in children and adolescents. At the same time, it is important to note that certain factors may influence our results: for instance, some owners may fail to recognise symptoms or their severity, while others – those particularly interested in dog behaviour – may be more likely to participate and report more symptoms,” emphasised Dr. Márta Gácsi, lead researcher of the study.
“It is crucial to stress that the questionnaire alone is not sufficient for diagnosis. Our team has developed this diagnostic system step by step: the development of the questionnaire was the first step. In addition, we have designed a simple behaviour test that can objectively assess a dog’s inattention, excessive activity and impulsivity levels, complementing the - often subjective - reports provided by owners,” added Dr. Barbara Csibra, first author of the study.
“A final diagnosis should be based on multiple sources: the owner-rated questionnaire, a short behavioural test, and expert consultation. When possible, we also include input from the dog’s trainer. This multi-faceted approach helps rule out other behavioural problems that may cause similar symptoms and reduces the chance of misdiagnosis,” noted Dr. Márta Gácsi.
“Our goal is to establish a reliable diagnostic system that enables more accurate identification of at-risk dogs. This way, we can improve the well-being of both dogs and their owners, facilitating harmonious daily interactions, as recognising such behavioural issues helps guide appropriate treatment or training decisions,” highlighted Dr. Barbara Csibra.
Recommended Literature
The full diagnostic study is available here: https://www.nature.com/articles/s41598-025-09988-8
More on the previously developed dog ADHD questionnaire: https://www.nature.com/articles/s41598-024-51924-9
Details on the dg ADHD behavior test can be found here: https://www.mdpi.com/2076-2615/14/13/1841
Journal
Scientific Reports
Article Title
Development of a human analogue ADHD diagnostic system for family dogs.
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