"Our discovery is a first step towards developing new DNA tests for the condition"

Researchers at Genetics Expertise Centre discover risk factor for hereditary myiocardial disease in Dobermanns

More than half of all Dobermanns develop a myiocardial disorder that can ultimately lead to heart failure. The Faculty of Veterinary Medicine Genetics Expertise Centre is achieving great results with research on this hereditary condition in dogs, also known as dilating cardiomyopathy. Researchers at the centre are working closely with colleagues at UMC Utrecht who are studying the disease in humans. Dog owners can have their Dobermann screened for the condition at the Academic Veterinary Hospital's Cardiology Department. 

De familie Mollema en hun hond Shanti brengen een bezoek aan het Universitair Dierenziekenhuis. Mirte de Vries; coassistent Diergeneeskunde ontvangt hen op de polikamer van de afdeling Cardiologie.
The Mollema family and their dog Shanti visit the University Veterinary Hospital. Mirte de Vries; Veterinary Medicine resident welcomes them at the Cardiology Department outpatient room.

"Come on, girl," Jolanda Mollema encourages her dog Shanti on her way to the examination room. Shanti has been through a lot, she explains. "She had a twisted stomach and a leak in a lymphatic vessel, so she's been through a lot of surgery. I spent weeks sleeping on the sofa with Shanti next to me on a cushion on the floor. I'd see her head perk up every now and then and when she saw I was there, she'd go back to sleep." 

Staff at the University Clinic managed to treat Shanti effectively, and took an ultrasound to assess the Dobermann's current condition. After one last glance at her owner, Shanti decides to trust her. She allows herself to be led into the room where the specialist and assistants are patiently waiting for the dog and her owner.

Horror stories

The hereditary heart muscle disease known as 'dilating cardiomyopathy' (DCM) occurs in more than half of all Dobermanns. The heart muscle condition reduces muscle cells' ability to contract, increasing pressure in the left ventricle and dilating the myocardium. Dobermann enthusiasts have all heard the horror stories about dogs suddenly dropping dead as they're being walked. Shanti will hopefully be spared that fate – the ultrasound doesn't reveal any evidence of DCM.

The Genetics Expertise Centre has been researching the DNA variants that cause heart muscle disease for many years. Samples from healthy dogs play an important role in studies on the condition. As Shanti is undergoing the ultrasound, molecular geneticist Frank van Steenbeek is hard at work in the building next to the clinic. His colleagues at Veterinary Medicine jokingly refer to him as the 'Zoo keeper' because he keeps heart tissue slices from a wide variety of animal species in the laboratory. From a giraffe and an elephant, to an orca that washed up on Cadzand beach. The Dobermanns' blood samples arrive here by tube mail. The DNA is isolated from the blood sample and purified using a device known as the MagCore. So-called marker profiles are then extracted from the DNA and analysed with state-of-the-art software. Researcher Van Steenbeek: "We're comparing the DNA of dogs with this myocardial disease to that of healthy dogs in order to pinpoint the differences. Working with researchers from across Europe, we've made an important discovery: dogs with DCM have a specific DNA abnormality. The discovery was a really euphoric moment, especially since we also saw mutations in that same gene in human patients."

Cardioloog Giorgia Santarelli maakt een hartfilmpje bij de hond shanti van de familie Mollema. V.l.n.r: Mevrouw mollema; eigenaar, Martine de Ruijter Korver; poli assistent, Giorgia Santarelli, Cardioloog, Mirte de Vries; coassistent Diergeneeskunde, Bas van Nimwegen; Oncologisch Chirurg en Frank van Steenbeek, onderzoeker Expertise Centrum Genetica.
Cardiologist Giorgia Santarelli conducts an ECG scan of the Mollema family's dog Shanti. Including Ms Mollema and (on the front) Cardiologist Giorgia Santarelli and Frank van Steenbeek, researcher Expertise Centre Genetics.

Similar pathologies

Humans can also develop the myocardial condition, although it is more common in Doberman: the disease affects one in five hundred people. And, as with dogs, there is no cure for human patients either. However, humans do have the option of a heart transplant. The Faculty of Veterinary Medicine is conducting the DCM research in collaboration with UMC Utrecht. The similarities between many animal and human pathologies are sparking a growing number of collaborations between veterinary and human researchers. The partnership between the Faculty of Veterinary Medicine and UMC Utrecht is a case in point. "We're right next door to each other at Utrecht Science Park, which is definitely helpful," Van Steenbeek explains. "I also knew my colleague Magdalena Harakalova from UMC Utrecht because we did our PhD research together. The veterinary specialists at the University Clinic treat dogs and cats with a wide range of diseases on a daily basis. Almost every condition we see in our veterinary patients has a similar human variant. We hope we our knowledge of canine patients can be useful to our colleagues at UMC Utrecht. The collaboration also means we can – with the consent of our human patients – study the DNA of people with DCM. As it turns out, they show mutations in the same gene as the Dobermanns."

Human and veterinary experts forming a joint research team is a unique development.

Learning from each other

Less than a kilometre from Van Steenbeek's lab, Harakalova is hard at work at UMC Utrecht. A human cardiogenetics researcher, she explains that she and Van Steenbeek share a kind of 'scientific telepathy'. "That's because we received the same kind of training. We don't need to take notes or email each other, we just instinctively how to approach things. As Harakalova emphasises, she isn't just learning from her colleague's results with Dobermanns at Veterinary Medicine: it's a two-way street. "We learn from each other and there's really no hierarchy. I'm actually surprised that veterinary and human researchers aren't collaborating more often on cardiology research. The fact that we've researching cardiogenetics as part of a single research team is actually unique, even at a global level. We're also getting great results. For example, the discovery of the gene in Dobermanns will allows us to do targeted screenings of people suffering from this hereditary myocardial disease. That could help those patients to understand the root cause of their disease, which can then lead to more accurate diagnoses, better treatments or therapies for people with DCM."

Cardioloog Giorgia Santarelli maakt een hartfilmpje bij de hond shanti van de familie Mollema.
Cardiologist Giorgia Santarelli conducts an ECG scan of the Mollema family's dog Shanti.

Screening Dobermanns

Back at the University Clinic, Shanti is sitting on the treatment table waiting for her ultrasound. "That's exciting isn't it, sweetie?" Owner Mollema gently strokes the Dobermann's nose. "She loves to cuddle, always wants to sit on your lap. When I go to the toilet, she pushes the door open with her paw because she wants to be there with me. I jokingly say she's my shadow sometimes." Dobermanns need to be screened for dilating cardiomyopathy. That involves an ultrasound examination and an ECG. The European Society of Veterinary Cardiology recommends regular screening once a dog reaches the age of three. Van Steenbeek explains why this is so important for dog owners and their pets. "Once we know a dog has DCM, we can keep a closer eye on it and give it the right medication. We still don't have a cure, but it does allow for a better – and in some cases longer – life."

The researchers believe they will be able to do more for Dobermanns with DCM in future. Finding the abnormal gene is an important first step in that process. Van Steenbeek: “The next step will be to develop a genetic test. That will allow us to determine whether a dog has the variant by taking some blood or cheek swabs. You could then say: we won't breed these two dogs, because there's a high risk their offspring will be born with a dilated myocardium. If every breeder in the Netherlands were to use the test in the near future, we might be able to eliminate DCM altogether." Developing a genetic test doesn't have to involve a lengthy process, Van Steenbeek believes. "After all, we know which part of the DNA we need to focus on. The test could be available as early as 2023."

Our team is working to make sure your DNA no longer determines your heart health.

Swiping on Tinder with a DNA passport

In the case of humans, genetic testing doesn't necessarily offer an equally effective solution. In humans, we know DCM can be caused by a far greater number of mutations. After all, humans are less homogeneous than a pedigree dog breed like Dobermanns. There are also some ethical dilemmas. "Will people be swiping on Tinder with a DNA passport at some point? Do we want to consciously select genetically desirable partners to have children with? That obviously raises all sorts of ethical issues. You might be able to get to the point where there are no more people with genetic diseases, but do we really want to create some kind of 'super-human'? And wouldn't we rather just fall in love with whoever we happen to fall in love with? Fortunately, we can also tackle these diseases without reproducing on the basis of genetics. Our joint research could eventually contribute to new medications for this human myocardial disease. "Our team is working to make sure your DNA no longer determines your heart health." We'd love to find a way of eliminating DCM at an early stage. Once you know that a human or animal has the mutation, you can then ?focus on the heart? and minimise the effects. That means you can address the problem without having to eliminate the actual mutation."

Good news about Shanti

Shanti cheerfully saunters out of the examination room and into the consulting room. Her owner looks on affectionately, but glances up tensely when the vet walks in. Thankfully, the news is reassuring: "It's looking good". You can see the sense of relief on Mollema's face. Shanti appears to be recovering well. And her owner already knew the Dobermann wasn't suffering from DCM. While there's no guarantee Shanti will never develop DCM, early diagnosis through regular screening could help ensure a longer and more pleasant life if she ever does. Thanks to the Genetics Expertise Centre, Dobermanns with DCM will probably have even more treatment options in future. For now, though, owner Mollema will get to enjoy more time with her dog. Shanti cheerfully bounds out of the University Clinic.

For more information on the University Veterinary Hospital's research and various screenings, visit: www.diergeneeskunde.nl/onderzoek (In Dutch)

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