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Silent Mutations: What Your Pet’s DNA Isn’t Telling You
Episode 3811th December 2024 • Barking Mad • BSM Partners
00:00:00 00:31:49

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Pet health isn’t always an inside job—genetic makeup matters, but so do environmental factors like lifestyle and diet. In this episode of Barking Mad, we’re cracking the genetic code to explore how dogs’ DNA influences their heath—sometimes in unexpected ways. Join us as we discuss groundbreaking insights from veterinary experts and researchers who shed light on the genetic complexity of mixed-breed dogs and how genetic testing could revolutionize preventive pet care.

Helpful Links

BSM Partners’ Incidence paper: https://www.frontiersin.org/journals/animal-science/articles/10.3389/fanim.2022.846227/full

Genetic testing for dogs can help identify diseases and enable preventive care (from the Waltham Pet Care Institute): https://www.waltham.com/news-events/human-animal-interaction/genetic-testing-for-dogs-can-help-identify-diseases-and-enable-preventive-care

Learn more about EpiPaws: https://epipaws.com/

Tune in to our Pawing Through the Research episode here: https://bsmpartners.net/the-pet-industry-podcast/pawing-through-the-research-uncovering-the-fatal-flaws-of-dcm

Watch the full NBC News report on Flint, Michigan, 10 years after the community’s lead poisoning crisis first began: https://www.youtube.com/watch?v=k8LaMa7ZLIQ

Show Notes

00:00 – Inside the Episode

01:49 – How Genes Influence Health

05:27 – DNA, Diet, and DCM

07:20 – A One Health Approach

09:00 – Decoding DNA for Mixed Breeds

10:53 – The Vast Genetic Variance in the Canine Genome

12:15 – The Truth About Mixed Breeds’ Genes

15:40 – Genetic Testing: A Key Opportunity

17:19 – Genetics and Breeding Practices

20:09 – Understanding Epigenetics

20:47 – Where Do Our Genes Come From?

22:08 – What Other Factors Affect our Genes?

24:40 – Environmental Factors Impacting Gene Expression

28:38 – Using This Knowledge to Advance Pet Health

29:44 – Conclusion and Farewell

Transcripts

Stephanie Clark: Is your dog's health a gamble? We know family history is crucial in human medicine, but what about for our pets? The veterinary world is lagging, leaving your dog's health and, more specifically, their heart health, at risk. We're diving deep into the genetic code to uncover the secrets hidden in your dog's DNA. Scientists are unlocking the genetic secrets of heart disease in humans, and we're on a mission to do the same for dogs. It's time to rewrite the rules of canine care.

Join us as we delve into the cutting-edge science and remarkable snippets from veterinary and human cardiologists that may lead to a shake up in the future. When it comes to your dog, knowledge is power, and we're here to equip you with both.

Jordan Tyler: On today's episode, we're taking a One Health approach to genetic testing in pets and how this could revolutionize veterinary medicine diagnostics. The experts at BSM Partners are uniquely positioned to guide you through complex topics like genetics, so get ready for a fascinating conversation about how our health is influenced by more than just our genetic code.

Stephanie Clark: Welcome to Barking Mad, a podcast by BSM Partners. We're your hosts, Dr. Stephanie Clark.

Jordan Tyler: And I'm Jordan Tyler. So, genes—no, not the pants we all love at the start of fall weather, but the tiny genetic codes that can play a complex and multifaceted role in the development and influence of disease. The pesky family history intake sheet at the doctor's office is actually quite useful to doctors when determining the likelihood of developing medical conditions.

So Steph, I understand there are a few different ways genes can influence diseases.

Stephanie Clark

Exactly Jordan. So first there's genetic mutations. I like to think of this as Down syndrome. Shout out to my girl fierce pierce my homie with an extra chrome-y over there. And then we have gene environmental impact. This is impact of a particular gene variant that can be influenced by environmental exposure. Think of smoking can increase the risk of lung cancer in individuals with specific gene variations. And there's also complex, which is definitely complex. This can come from a combination of genetic and environmental factors, heart disease, cancer, diabetes, and that's just naming a few.

Genes are not so black and white, though; they provide a blueprint, but environmental factors and lifestyle choices can significantly influence disease development. For instance, someone with a genetic predisposition for a certain type of cancer may never develop the disease if they live a healthy lifestyle. This is similar to the newer phrase, epigenetics, which is the study of how environmental factors and behavior can cause changes in the way genes work. It doesn't necessarily alter the genetic code, but it works like a light switch by turning on and off the gene expression.

Jordan Tyler: Yeah, that's fascinating. I'm already like, have so many questions, but what are some examples that you've seen in real life, either, you know, in people or in pets?

Stephanie Clark: Obesity is a really good example. We can all relate. We all know what obesity is. But what if I said genes can influence how our body stores and uses fat. So, if we eat candy all day and sit on the couch binging reality TV, it can actually affect our ability to metabolize and how we store fat. These abilities, or lack thereof, can be passed down to our children, increasing their likelihood of developing obesity, but it can be mitigated if that child is active and eats healthy.

The truth is, we're still scratching the surface when it comes to understanding canine genetics, and feline genetics are even more of a mystery. From the cradle to the grave, genes influence everything from breed specific disorders to the silent killers lurking beneath the surfaces. We're diving deep into the world of genetics to uncover how these tiny building blocks shape the lives of our pets and how we can use this knowledge to protect them.

Jordan Tyler: Yeah, absolutely. I like the way that you said that, from cradle to grave, because it's not just the genes that you were born with, but, you know, the genes that you're stuck with, but also the things that you choose to do, the environmental factors that really play into how those genes express themselves in good ways and in bad.

Stephanie Clark: I tell you what, after doing a little bit of research for this episode, it definitely makes me think about how my behaviors can affect my kids health.

Jordan Tyler: Yeah, kind of reiterates there are so many different factors that contribute to health. So, in past episodes, you may have heard us reference DCM or dilated cardiomyopathy as a perfect storm, and this whole conversation about genetics is exactly why.

So, a mixed breed dog might carry genetic mutations for a cardiovascular disease and be totally fine their whole life, but then they could be exposed to an environmental factor or factors that actually turn that gene on and then develop DCM. So genetic testing, family genealogy, and family history are super common questions that are asked during doctor visits, because there are hundreds of genes linked to various cardiac conditions and specific heart diseases like cardiomyopathy. Over 1,000 different genetic variants have been identified, but only a fraction of a fraction of a fraction has actually been identified in dogs.

Stephanie Clark: Isn't that scary?

Jordan Tyler: It is scary. It's like the infographic, where you zoom out on yourself, and then it's the earth, and then it's like the whole solar system. And you're just like, “Oh no, we're all ants.”

Stephanie Clark: And your problem is, like, the golf ball.

Jordan Tyler: Yeah. So, so far, we know that there are specific genes in certain breeds, like in Dobermans, Great Danes, and Boxers, that have the mutations that predispose them to dilated cardiomyopathy. And the veterinary community has also identified specific genes, but when you take that a step further, they've also identified environmental factors that can interact with those genes and lead to a potentially increased risk of developing the disease.

So, we mentioned the One Health approach to genetics earlier. This approach can help lead us to a deeper understanding of genetic variants in dogs that may have already been identified in humans. So, for example, dogs and humans have shared genetic diseases such as cystic fibrosis, also immune disorders and heart conditions. So, you know, why wouldn't there be more genes to identify in dogs related to DCM? Let's hear from Dr. Bradley quest, a veterinarian and Principal of Veterinary Services at BSM Partners, about just how complex this issue truly is.

Bradley Quest: A lot of breeds we know are genetically predisposed to developing doesn't mean like all dogs in a certain breed will develop DCM, but we know it can play a really big part. You know the word multifactorial, I know we've used it. A lot of people use it, it gets thrown around. But I really, think it really, really fits kind of, sometimes the perfect storm type of scenario. You know, you might have a dog that may or may not be genetically predisposed. Maybe he had, you know, a viral infection. Maybe he's a breed that has a different amino acid requirement. And I think a lot of these things together in some individuals, you can see conditions like a DCM phenotype. And, you know, we may not be able to explain it all right now, hopefully someday we will. But what we try to do is do controlled research to try to flush out, you know, if we can identify causes of conditions like that.

Stephanie Clark: So, with genetics playing a larger part than previously thought, it makes you wonder if the dogs that made up the FDA’s reporting on DCM were actually DNA tested. I think of the times that you know, I've gone into the shelter, whether to help out or volunteer or even adopt, and you always see that the dog is labeled “Lab,” but you know well and good that that dog is probably a fraction of a Lab, if it even has lab in it. The same as being true with these breeds in clinics. We are assuming breeds based on look, but not confirming with the test. This is extremely important, as we cannot just rule out mixed dogs as non-predisposed dogs.

Jordan Tyler: Yeah, absolutely. And that's funny that you mentioned the, you know, every dog being classified as a Lab, because we literally just went through this with our newest puppy, and we ended up getting him DNA tested. And Lab was, like, his like, third most predominant breed.

Stephanie Clark: With like 10%?

Jordan Tyler: It was like a good, it was like 25 percent or so. But like, when we first rescued him and we took him to the vet for the first time, they were like, “Oh yeah, no, he's a Lab. He's 100% Lab, nothing other than Lab.” We were like, how crazy would that be that we just, like, picked up a pure breed dog on off the side of the road. So, we were like, let's just get him tested.

Stephanie Clark: That's what happened with Anny. She was a quote unquote dachshund mix, and we got her genetically tested because I was just super curious. I've never seen a meatball dog like this before, and she was 12 and a half percent dachshund. She was like, 50% AmStaff, so way off. You can't judge a book by its cover, and you can't judge a dog by its looks. Maybe?

Jordan Tyler: Yeah, let's massage that a little bit. But I like it. I like where it's going.

So, BSM Partners actually saw this coming back to trying to figure out what breed of dogs we’re actually dealing with here, they saw in their incident study with mixed breed dogs having an increased rate of DCM reported in some hospitals. But is it accurate to lump all mixed breed dogs into the same category? You know, it almost would be like grouping Americans based on, you know, like, what region they live in in the United States. There are similarities between the human genome and the canine genome, but the genetic differences between breeds are so much more vast compared to the genetic differences between like, different races of people.

So, you know, while there might be like a cultural norm or like a way of speaking, you know, you say soda, I say pop, there will always be exceptions to this rule, and if you paint with a broad brush, it would actually overlook a lot of really critical considerations in genetic diversity. As it turns out, the human genome is actually more consistent across like ethnicities and races than the genomes of different dog breeds. So, you can almost think of it as like humans are all like kind of the same breed, whereas there are hundreds of dog breeds, each of which are actually pretty distinct from each other.

And recently, the Waltham Institute released a paper confirming that mixed breed dogs can't actually be grouped together, because they can still carry genetic predispositions for diseases. We'll be sure to link that report in the show notes for this episode.

Stephanie Clark: And so going on to that further, it actually took some readers by surprise when that paper came out, because this was classified as atypical, the breeds that we're discussing. But it's important to know that research has supported that mixed breeds are just as likely to develop a disease as a purebred dog.

Jordan Tyler: Interestingly, when we sat down with Dr. Andria Beal from EpiPaws, she shared her genetic insight on this.

Andria Beal: I like to think of them as being less prone to some of the diseases that we see. Each breed has its own predisposition due to its genetics. When you have that mixed breed, you're going to have more of just like a general survey, almost, I would say, representation with that mixed breed. I definitely think that by having a big, large group of mixed breeds, that you get the mixed bag effect and see like for the general population, does this cause something or not?

Stephanie Clark: Wow, we can really see how pet owners are confused. Like, what is it? Are mixed breed dogs less prone to diseases than pure bred dogs? Or does it not matter? Does it even matter? If there's a genetic predisposition to a disease attached to that gene, surely that can be transferred regardless.

Jordan Tyler: Yeah. And like you said, this has been shown in research. And it also kind of begs the question, so during COVID, people adopted dogs like it was going out of style. The populations of shelters were going way down because people were adopting so much, and a lot of dogs that you rescue from a shelter are going to be mixed breed dogs. And so, you know, when you have an influx of mixed breed dogs, and you understand that their genetic code is it's kind of a grab bag, right?

When BSM Partners was looking at this, the research was really focused on, you know, bringing in dogs of different sizes. So, there were small dogs, there were medium sized dogs, and there were pure bred dogs and there were mixed breed dogs. They did that because in the FDA communications, the mixed breeds were really predominant in a lot of these reports that they were seeing related to increased cases of DCM. And so, it was super important for BSM to control that factor. Even though we may not fully understand a dog's genome, you know, this is kind of taking steps toward that.

Stephanie Clark: I think you bring up really good points, because the FDA, in their communication, they mentioned mixed breeds are coming to the forefront, and they labeled these dogs as atypical, like they're not your typical purebred dogs that you see with heart disease. But let's think about this, if mixed breed dog adoption is going up, and mixed breed dogs are at the same risk or the same likelihood of getting those mutations transferred down, wouldn't we see an increase in mixed breed dogs because we're adopting more?

So, I mean, I think you're spot on, and research is definitely showing that mixed breed dogs are going up in popularity. But also with the FDA report, we saw an over representation of Labs, and going back even to a fraction of a fraction of a fraction of the genes that we've identified, are we missing a gene in Labs?

So there's, like, lots of questions that we can still ask. And again, we're just scratching the surface here with genes and veterinary medicine, but it goes back to that perfect storm. We can't just say, “Oh, it's the food. There you go.” There's so many environmental factors—there's breeding factors, there's genetic predisposition and epigenetics playing a factor in all of this. You know, I always think, if you bring in a mixed dog to a vet clinic, should one of the tests that is recommended be a genetic test so you know what you're dealing with? Are they predisposed to any genetic mutations, or do they have a potential risk factor that we should maybe watch?

Jordan Tyler: Yeah. I mean, it sounds like an excellent opportunity. And if it's something that we haven't been looking at before, and something that we just don't to this day know a whole lot about, in my brain, that lights up as, like, “Figure this out! Figure this out!” You know, it's like a huge red flag. But that's a really good point, because it's, you know, genetic testing has become like a market too. And so it's like, hmm, at one point, do we determine that genetic testing is actually more of a necessity to help a dog live its best life, or a cat, for that matter?

And then it also brings up like, so we saw all this happening in the US, but Europe, which, you know, the European market, the pet food market I mean, is heavily influenced by what happens in in the American pet food market. And so, you would think that there would be maybe, like, if not as much of a perceived spike in canine DCM cases, you think there would be, like, at least a blip, and people would be like, “Hey, what's this?” But nobody really saw that. And I just think it's really interesting.

We shared in a previous episode that breeding standards in Europe could have something to do with that.

When it comes to comparing breeding practices in the European Union to those in the United States, Europe is more comprehensive. The EU has stricter regulations on animal breeding and selling. In Europe, breeders are legally required to have proven competency, and they must follow specific practices for welfare, as well as for biosecurity.

Also, European breeders are restricted on breeding that could be harmful to the pet, such as inbreeding or breeding for extreme physical traits. Think of all those smush face dogs out there that can have trouble breathing. This is a no-no in Europe.

Additionally, European breeders are required to conduct genetic screening tests before breeding a dog, and this is to identify “carriers,” or dogs who aren't affected by a disease but carry the mutated gene for it, and could therefore pass it on to their pups. Breeders and sellers in the European Union must also adhere to some level of traceability to keep track of where animals are going and where they came from, and this actually includes providing the genetic screening results to prospective new owners. So, lots of stop gaps here to try and reduce genetic predisposition to certain diseases in dogs.

We really expand on this in a previous episode titled, “Pawing Through the Research,” in which Dr. Stephanie and I sit down with the BSM Partners Research Team to discuss the literature review they published on DCM. We’ll link that episode in the show notes if you’d like to hear more.

Stephanie Clark: And like you were saying, Jordan, how can we do better to help reduce the passing of mutations to offsprings? You know, that's what the EU is doing right now. They're doing genetic testing. Is that something that we should be doing here? Could that potentially help our overall health of our pets?

Jordan Tyler: Yeah, I think genetic testing is a huge opportunity. I also think, you know, the rapid advancements in science that are happening around genetics will trickle down to our dogs. We just need to make it a priority. And I think that epigenetics, you know, the kind of the rise of awareness of epigenetics is also a really interesting opportunity to really study not only genes like gene mutations, but like, what factors cause those types of mutations?

Stephanie Clark: I always thought, before this episode and doing a lot of research and then doing the DCM research, that your genes are your genes, and they define you, and you are set for life, but the fact that we can actually, like, turn off and on genes, like you may have a genetic predisposition for cardiovascular disease.

So when I was doing some research for this, I was looking at where our genes come from, like paternal maternal side, and our cardiovascular genes come from our paternal grandparents, and so when I take a look at this for my kid, Esther, it looks like she doesn't have a great outlook, like cardiovascular disease is very prominent on the paternal grandparent side. However, that doesn't mean she's going to get heart disease when she grows up, like we can teach her how to live a healthy, active lifestyle and eat decent food. So, it's kind of like we have, like, a renewal on life.

However, I think we're pretty much set in stone when it comes to her sense of humor, so that comes from the paternal grandma, and we've seen it, and I don't think we could do anything to turn that gene off, nor would I want to. But I mean, for a three-year-old, she calls herself a trickster, and it's funny, because you can see a lot of similarities when you start tracing back.

Jordan Tyler: That's so cool. I never knew that. And actually, as you were saying that, I was thinking back to my dad's mom, and was just like, “Oh, wow, yeah, yeah, that tracks.” Totally.

Stephanie Clark: For better or for worse.

Jordan Tyler: For better or worse, absolutely, yeah. So, we've talked a lot about some of the different factors that can impact genetics. We talked a ton about epigenetics and a little bit about breeding practices and what we know today, but what other things might be able to affect gene expression? And coming back to Dr. Andria Beal of EpiPaws, she actually has some interesting insights on this. So, let's hear again from her.

Andria Beal: A lot of it is creating a baseline and understanding how different lifestyles produce different patterns in the epigenetics, having everything in that data set, from the different microbiome, what was their lifestyle, as far as exercise went, what was the food that they ate? Were there other stressors in their life? Do they have other genes that contribute to whether they have more stress or not?

So, it is complicated, and everything's cross talking, right? So, I guess the answer is, actually being able to have a baseline for an individual would help us a lot with understanding why that individual, although they had no predisposition to heart disease, but they still got heart disease. What was the contributing factor? And I think there's still a lot of questions out there about how disease develops, and it could be something else. A lot of diseases are part of the aging pathway, really. So, age is playing a role, and that aging process is playing a role in certain diseases developing. And that's something we want to get at, is how each of the environmental factors, whether it's food or it could be something else, is going to contribute to the aging process and then those downstream diseases developing.

Stephanie Clark: So, I really want to highlight on what Andria says. So many outside factors that can affect our genes, and we're talking about the microbiome and our gut. So essentially, our gut health can depict our future health, you know, exercise or lifestyle. Again, going back to my daughter and cardiovascular disease, even the types of food we eat, stressors—so, people who stress more can actually turn on some unfavorable genes—aging and obesity—so, we know with pets that obesity can lead to secondary diseases and open a slew of other things that maybe they would have been totally fine with if they were ideal body weight.

And adding to this in the incidence paper, we saw that in the different areas of the US, there was different prevalences, and so it really makes you wonder, is the environmental factors in that particular region adding to the increased risk of DCM, or maybe other diseases? Unfortunately, we don't know enough right now, but that's definitely something we should start thinking about in the future. And so, understanding this in animal health could be a complete game changer to the pet industry, not only veterinary medicine, but also pet food wise. Should we be feeding dogs for their specific breed? But also, maybe for specific regions that they're living in? Like, how mind blowing?

Jordan Tyler: Super mind blowing, yeah, and it makes me think of Flint, Michigan, you know, being exposed to lead in water. And I found this clip from NBC News, who published an update to this story, actually, seven months ago.

th,:

Jordan Tyler: We know that exposure to lead negatively impacts all sorts of systems in the body including neurodevelopment, renal and digestive health. This exposure prompts epigenetic changes to the DNA of people living in that community, and those changes can have what’s been described as “transgenerational” meaning epigenetic changes can occur not only to the person exposed to led, but also in later generations. Like, those mutations are being passed down. One example of this impact is an increased risk for neurodegenerative diseases like Alzheimer’s.

So, that's like a super hyper local issue that’s going to impact the people living in that community for generations, and it's because of an environmental factor that is altering their genetics. It's just crazy to think about.

Stephanie Clark: Well, I wonder, like in my hometown, we have a refinery, and my grandpa passed away from a brain tumor. He worked at the refinery for many, many, many years, and then it came out that a lot of people who had worked there had brain tumors and unfortunately passed away. But I wonder if we actually took an incidence level of how many dogs and cats are diagnosed with cancer in this area to, I don't know, a different area, or maybe a coastal area, would we see the same? I don't know.

Jordan Tyler: Seriously mind blowing. Just thinking about how, using this train of thought, two dogs can eat the same exact diet for 15 years and have completely different health outcomes. This really brings things back to the One Health approach we discussed earlier, and begs the question—are we truly leveraging all the genetic data we have across all of human and veterinary medicine to make the best health decisions for our companions? Just really interesting to think about all the nuance that goes into it.

So, how does this affect taking care of a dog with a known genetic mutation? Or maybe a dog that doesn't have a genetic mutation but could have a risk for one or is living a lifestyle or experiencing an environmental risk?

Stephanie Clark: If people are concerned, you know, my best recommendation would be to get your dog DNA tested and sit down with your vet and go over those results. Is there something that could be an issue down the road? Is everything fine? And then, of course, you know, monitoring your dog's health parameters, you know, over time, if you're concerned so with like heart disease, you know, making sure that your dog's heart is healthy, listening to it, making sure that your dog isn't becoming extremely exhausted when you take them around for a walk.

And so even though this is still very new in veterinary medicine, and we've only scratched the surface, as pet owners we can still keep tabs and we can still take care of our pets.

Jordan Tyler: When it comes to your dog's genetic makeup, there's more than meets the eye. Whether you have a purebred or a mixed-breed rescue on your hands, the genetic lottery affects them all, and a myriad of environmental and lifestyle factors can be just as important for influencing gene expression as our hard-coded DNA.

As we've highlighted today, being a mixed breed doesn't mean your dog is immune to genetic health risks, and in fact, they could be carrying genetic predispositions from multiple breed lines. But this reality check isn't meant to sound the alarm. Rather, it's a call to action for both veterinary professionals and pet owners to take a more proactive approach to our pets’ health all the way down to the genetic level. The ability to identify genetic predispositions early on could transform how we approach preventive care, nutrition and treatment plans for our four-legged family members, and by better understanding the interplay of genetics, disease, diet and other factors, we can hopefully avoid catastrophic misunderstandings like DCM in the future.

Thank you for tuning in to another episode of barking mad. If you want to learn more about BSM partners, please visit us at bsmpartners.net. Don't forget to subscribe on your favorite, leading podcast platform to stay current on the latest pet industry trends and conversations. We'd also like to thank our dedicated team: Ada-Miette Thomas, Neeley Bowden, Kait Wright, and Dr. Katy Miller, and an extra thank you to Lee Ann Hagerty and Michael Johnson in support of this episode. See you next time!

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