Tack Box Talk
Tack Box Talk
Genetics Part 2: The story of fragile foals and muscle disorders
Dr. Samantha Brooks, of the University of Florida, returns to discuss three new genetic diseases. We cover polysaccharide storage myopathy, the gene that impacts height in Thoroughbreds and fragile foal syndrome in warmbloods. We learn that genetic tests can do more than just help in breeding decisions.
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Kris Hiney: Welcome to Extension horse's tack box talk series horse stories with a purpose. I'm your host, Doctor Kris Hiney, with Oklahoma State University, and today we're delighted to have a returning guest, doctor Samantha Brooks, from the University of Florida, who's back to chat about more genetics with us. So welcome back, Doctor Brooks.
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Samantha Brooks: Hi, thanks. I'm I'm glad to be back. It's always a lot of fun.
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Kris Hiney: So I invited you back because even when I listened back to the podcast we had said that we were going to talk about 3 main things, and then we completely just went off into a new direction. So we never got around to the 3 main things that person might need to know, or this might be helpful. So maybe you should tell us what those 3 things are. I will write them down, and I will do a better job of like not chasing the squirrel.
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Samantha Brooks: Right. Yes, we we had. We had a little bit of a plastic bag moment. There, I will put my blinkers on, and we'll we'll stay. We'll stay focused. But I feel like I don't remember if you raise the question or I, it's a question I often get when talking out there to horse folks is like, oh, all this genomic stuff! It sounds really fancy.
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Samantha Brooks: But can you give me an example of how it really would make a difference in my day-to-day
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Samantha Brooks: in a way that I keep my horses, and I'm you know I've got to got to rise to the occasion on this one.
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Samantha Brooks: So I've tried to pick out 3 key examples of how our genetic tests
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Samantha Brooks: can be
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Samantha Brooks: useful for folks who are not just horse breeders
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Samantha Brooks: and need to more effectively or efficiently
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Samantha Brooks: manage the horses they have in their program, like nobody around here these days. That I, at least nobody I hang out with
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Samantha Brooks: has extra money
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Samantha Brooks: to be inefficient necessarily, in the way they're keeping their horses right. I feel like we all have to work a little smarter rather than a little harder these days. And so I tried to find just nice key examples of ways that genomics can help us to do that.
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Kris Hiney: Awesome.
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Samantha Brooks: So I'm gonna give you the list so you can write it down.
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Kris Hiney: Okay, I'm ready. And then I'm I might have a few other ones that I'm gonna ask you about. But I'm gonna definitely stick to the 3 to start with.
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Samantha Brooks: Okay. So I tried to pick examples from different aspects of horse industry. So I'm going to start with stock horses, and I'll give an example of the pssm, one
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Samantha Brooks: allele test.
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Samantha Brooks: And then I'm gonna actually move to thoroughbreds and some other breeds. But so I'll talk about a locus that's important for confirmation. And
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Samantha Brooks: a couple other things
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Samantha Brooks: spoiler alert. I'm not going to tell you which ones.
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Kris Hiney: Okay. I'll stay.
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Samantha Brooks: And the 3rd thing, I'm gonna go solidly dive right into the sport horse world. And I'm gonna talk about the Ffs Allele.
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Kris Hiney: FSS, or SIS.
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Samantha Brooks: FFS.
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Kris Hiney: Fox, Fox, Sam.
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Samantha Brooks: That's right. Fragile fall syndrome.
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Kris Hiney: Okay. Okay, okay, all right. As a non sport horse person. That's not my jam. So. But I am excited. So Pss. 1, 1.
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Kris Hiney: I had one of those. It was not fun, let me tell you.
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Kris Hiney: so I think this one is super important, and because probably the majority of our horse owner, population, our stock horse. I think this one is super important. So tell us why this one is something that everybody needs to know about.
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Kris Hiney: and then I'm going to ask you some other questions.
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Samantha Brooks: Okay. Great. So PSSM. 1, it stands for Polysaccharide storage, myopathy number one, because it comes in a couple of different varieties. But one is the the version that we have known about the longest. And to really give you the reader's digest version, it changes the way that your horse stores, sugars in their muscles.
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Samantha Brooks: We store sugars in our muscles, horses. It's a key part of metabolism, but these horses have a change in an enzyme that structures those stored carbohydrates a little bit differently, and actually makes it a bit harder for the horse to utilize those carbohydrates back out of the muscle.
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Samantha Brooks: Now, most of us might become aware of this because they have a problem potentially, or they've been asked to do some mandatory testing
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Samantha Brooks: the downside is is that it is. It's sort of a semi.
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Samantha Brooks: I'll call it.
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Samantha Brooks: I'll I'll have to be creative in my we'll call it a little bit additive a little bit co-dominant in that. Horses with one copy do show signs, and horses with 2 copies do tend to be more severe. Right? So did you have a horse with one copy, or with 2.
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Kris Hiney: So I will be honest. This was oh, goodness! When I started, I think I got this mare 2,002, 2,003, and it was just well known that her lineage had it so. I never did the genetic testing. But we you knew right. They all the relatives did this.
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Kris Hiney: but she was severely affected. So whether she had one copy, 2 copy, or had mh, 2, that's another one. But I
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Kris Hiney: yeah.
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Samantha Brooks: Right? Right? So what you probably saw were signs of a painful, uncomfortable muscle disease. So a lot of horse owners would take what they saw, and they would call it tying up, which is really kind of an umbrella term. But they'll be stiff. Those muscles will be tight. They might have an awkward gait. If it's extremely painful, they'll kind of break out in a sweat and just refuse to do their job.
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Samantha Brooks: And sometimes, if those muscles start to break down. Some horse owners will actually start to see a brown colored urine, and that's their kidneys just trying to help to flush out the byproducts of that
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Samantha Brooks: that muscle, that muscle breakdown. That's that's in a pretty severe case, and and the severity of it, as you mentioned it, interacts with other genetic alleles, including the Mh. Being the the poster child for that, and depends on the number of copies.
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Samantha Brooks: The other thing that we discovered early on, especially once we knew the gene itself is, of course, there's a strong interaction with the environment and with diet.
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Samantha Brooks: So this is another reason I love to tell this story is that once we knew what the allele was, it was we could much more strategically target that dietary management of the condition which
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Samantha Brooks: I have to admit I am not a nutritionist.
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Kris Hiney: I am, we'll be okay.
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Samantha Brooks: We're good, we're covered. We're at least safe.
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Samantha Brooks: But the typical recommendations are right for a low carbohydrate diet that's going to reduce a lot of those really traditional sweet feeds. They've got a lot of sugar in there, right? And you're going to change out those calories for things like fats, because, remember, this particularly, allele changes the storage of sugars. So if you start using fats instead of sugars, you kind of
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Samantha Brooks: avoid the issue by by going around it a little bit. They also benefit from making sure that they get regular exercise, you know, tying up was at 1 point called Monday Morning disease, because you take these hard working carriage and draft horses, and they get the weekend off where they're not burning up those carbohydrates. They'd start stocking them away in the muscles, and then come Monday morning. They were sore and uncomfortable and couldn't work right.
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Samantha Brooks: So
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Samantha Brooks: we got a handle on things in large part due to the knowledge we gained from from genetics. But now we're actually learning quite a bit more about this condition, in part because we've started just testing more broadly.
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Samantha Brooks: So a few years ago. Another group followed up on the initial research, and they documented that the Allele frequency for this condition
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Samantha Brooks: we hear about it a lot in stock horses, right? But it was actually broadly present, especially among our heavy draft horses.
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Samantha Brooks: So in in a paper from
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Samantha Brooks: a number of years ago. Not too long ago they observed that two-thirds of Percheron horses had at least one copy.
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Samantha Brooks: and about almost just shy of 40% of Belgian draft horses had at least one copy.
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Samantha Brooks: but we don't hear very often, at least not these days of our draft horses. Having these
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Samantha Brooks: critical life threatening
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Samantha Brooks: episodes of Pssm.
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Samantha Brooks: right? I mean, we know they tie up, but it doesn't seem to be as much of an issue, probably because a draft horses, we know, are easy keepers. We're usually a little bit better about staying on a forage-based diet and not feeding them a bag of sweet feed.
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Samantha Brooks: They tend to do more low intensity, long period work. If they are working
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Samantha Brooks: it. It may just be coincidental that it's easier to manage, but it raises the question scientifically.
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Samantha Brooks: If this is a terrible disease, why is it so common in draft horses.
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Kris Hiney: Right? Because it should have. If it was a functional issue, it would have taken them out when they were workhorses. Right? You wouldn't have kept breeding the ones that were like. I die.
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Samantha Brooks: Right. Yes, Darwin, Darwin would happen they would die. Survival of the fittest, and the allele frequency should be in theory should be decreasing.
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Samantha Brooks: The hypothesis is, and of course we would love to have the opportunity to test this. But the hypothesis is that actually, when you're in the typical feast and famine cycle of a horse that might be living more out on the open range, or on a say, a farm out on the great plains, 100 150 years ago
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Samantha Brooks: you would have all this rich grass in the spring and summer.
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Samantha Brooks: and then you'd have to survive through winter, and horses used to drop a lot of weight in winter. We manage them carefully now and give them these wonderful, complete, supplemented diets, but it used to be horses would drop a lot of weight. And so one hypothesis is that if these horses
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Samantha Brooks: are prone to protect those carbohydrate stores and their muscles, it's like they have a lock on the pantry, right? So when, when
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Samantha Brooks: calories are scarce.
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Samantha Brooks: their metabolism might be a little bit more conservative, and could potentially be a little bit protective
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Samantha Brooks: from starvation.
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Kris Hiney: Okay. So it had a bit of an advantage back in the day.
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Samantha Brooks: That's our guess. We we don't. We don't have it fully tested, but that's a hypothesis. So.
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Kris Hiney: Does that kind of go with these guys? And one of my favorite papers on on these horses, and I always use these diagrams was the
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Kris Hiney: how
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Kris Hiney: quickly these horses clear, glucose out of the system compared to a normal horse. So I always compare them to a glucose sponge. They're like, suck it right up. You give me anything, and I'm gonna stir.
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Samantha Brooks: Where we are.
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Kris Hiney: For safety, so.
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Samantha Brooks: Yeah, they are. They are those really, really fastidious squirrels that as soon as they find a nut they squirrel it away, and they save it for rainy day. That's a i. This is our hypothesis, right?
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Samantha Brooks: So all right. That's our historical anecdote for for the section. And what about the horse owner for today. Right?
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Samantha Brooks: one thing that we are starting to hear reports of, and that doesn't necessarily have
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Samantha Brooks: the level of scientific research that I wish it did is that we are beginning to suspect that there's also a behavioral component to this condition, right? And
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Samantha Brooks: maybe that makes a lot of sense, because, you know, muscle pain is not fun
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Samantha Brooks: and muscle pain, for many different reasons, is known to cause behavioral issues, especially in the ridden horse, and so I'm starting to hear, especially from some of our extension clients here in Florida.
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Samantha Brooks: that they're like, you know. I got this horse. Everything seemed fine. We started to gear up for the show season, and then all of a sudden they were back sore. And I've done the chiropractic, and I've done the magnetic blankets, and I've done all the weird things that we try as horse people and like we really can't figure it out. My vets talking about a muscle biopsy, but I'm not really sure.
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Samantha Brooks: And they'll say things like, Oh, well, Canada left. You won't. Canada the right, you know. Weird, weird training things. You might think well, they need a better trainer, you know. They need to go try the Magna wave, or Shock wave, or whatever the newest thing is.
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Samantha Brooks: Right. I mean, this is what horse people say is, they start. Say.
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Samantha Brooks: I'm just going to go. Send them down the road for a couple of weeks and spend a few $100 and see if we can't sort it out.
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Samantha Brooks: Well, some of these folks, I've said, you know.
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Samantha Brooks: Why don't you test them? Oh, you know I don't. They're not a bloodline that carries PSM. 1, and I'm never going to breed this horse. Why would I need genetics, and lo and behold.
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Samantha Brooks: they go and test these animals and turns out maybe they only have one copy. Maybe they're a very mild case. But
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Samantha Brooks: that Pssm, one can cause muscle pain that can lead to behavioral issues that, you know can be
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Samantha Brooks: easily confused with a whole lot of other things like back soreness or dental pain or
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Samantha Brooks: lameness of varying degrees. And in some of these situations these horse owners have come back and said, you know, I put them on the Pssm. One diet, and it fixed my horse.
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Samantha Brooks: Right, yeah.
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Kris Hiney: Yeah, I had so interestingly. That little horse that I had. She had a lot of behavioral quirks that you know when you say that make me think maybe she was tying some of these exercise spouts with some of the subclinical pain, and then I was around another young horse that knew the sire was a carrier. I don't know if he was a 1 or a 2, but that
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Kris Hiney: horse, starting on her saddle like you just never got to where saddles were comfortable, and she was always what you'd say hard back.
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Kris Hiney: and I was a hundred percent like is not her fault right? So there's nothing in the the training behavior like, there's something wrong with her. Because it.
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Kris Hiney: Yeah. You just knew there was something physiologically going on with them.
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Samantha Brooks: Right. And how many like thousands of dollars do a lot of people spend trying to figure this out when 100 for the genetic testing could have pointed them in the right direction. As soon as that full hit the ground right? So
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Samantha Brooks: I, my, my, take home message there is that even if you have a non-stock horse, because these alleles are very common in breeds like the Percheron, which is contributed to even some continental warm bloods. This one should stay on the radar for anyone who has a working horse, and it's nice to know about.
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Samantha Brooks: And here's my last little, you know, I, personally, as a scientist, I really hate anecdotes, but
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Samantha Brooks: like horse people love them right? Right? Like, I want to know what's the p-value. What's the statistic? And it never communicates science very well to normal humans. So my favorite anecdote was, is that many years ago I, when I, not long after I started teaching here at Florida. Actually, when we finished the genetics
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Samantha Brooks: section in class, one of my students came up to me and said, Hey, you know I had a horse that had this had this Pssm. One allele. I was like no way. Tell me about it. Tell me your story. So she came from a ranching family, and they raised a few young horses every year, and they had, you know, their favorite broodmare. They had
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Samantha Brooks: had gotten her into this really nice stallion and this young filly out of that match they were so proud of. That was probably the best filly they had had out of their program, and so they thought, well, we're really gonna invest in getting her a solid education. And so
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Samantha Brooks: yep.
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Samantha Brooks: it's better to the center, to the expensive, well-renowned trainer, because they were just so excited about this prospect. They just thought, you know, she's going to be fantastic.
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Samantha Brooks: lo and behold! A few weeks later the trainer finds her laying down on her stall, completely recumbent.
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Samantha Brooks: unable to rise.
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Samantha Brooks: And you know they go through a battery tests. Go through, you know. Call the vet all these things all over everything. And eventually she ended up being euthanized for kidney failure.
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Samantha Brooks: After. Then they, the fillies, died. Then they go back to try to put the pieces together. It turns out
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Samantha Brooks: she had PSMM 1,
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Samantha Brooks: and she went from being essentially out on the range here in Florida, which is some pretty, lean grazing
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Samantha Brooks: to a high
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Samantha Brooks: pressure training program, and he immediately put her on a very expensive performance. Horse diet
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Samantha Brooks: packed full of sugar, packed full of sugar
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Samantha Brooks: worked, or, you know, started on around. Penning started doing all the training things.
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Samantha Brooks: and she had an episode so bad that it was lethal.
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Kris Hiney: Wow!
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Samantha Brooks: Right? So so when people say, Oh, you know, this genetic testing stuff is expensive, I say, well.
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Samantha Brooks: you know, compared to having a dead horse. Sometimes it's just good insurance, just good to be prudent. So.
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Kris Hiney: Yeah.
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Kris Hiney: Now, before we leave this one and go to my middle bullet on confirmation, I do have to ask you about 2, because people ask about it, and I just report what I know as far as validation. But I want the geneticists to weigh in on
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Kris Hiney: because they're out there. The tests on Pssm type 2.
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Samantha Brooks: Right? So this is. This is a challenge I have to mind my language. This is a case of buyer. Beware! Cause there are some very slick looking websites that
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Samantha Brooks: will advertise that they have a PSMM Type 2 test.
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Samantha Brooks: But they are lacking. Some
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Samantha Brooks: absolutely required key.
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Samantha Brooks: Scientific.
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Samantha Brooks: Yeah, sort of check boxes to make sure that these things aren't complete junk, right? Because genetic testing in animals is
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Samantha Brooks: essentially unregulated.
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Samantha Brooks: So anybody can start accepting hair samples from animals and can tell you that they're testing for almost anything. It's not considered false advertising. It's not like genetic testing in humans which is carefully regulated.
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Samantha Brooks: so as of right. Now, the PSMM 2 tests that are advertised have 0 scientific evidence, evidence of efficacy. And
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Samantha Brooks: there are now publications documenting that, in fact, they do not work at all. They do not. Yep. So there's a paper Stephanie Valberg and her and colleagues
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Samantha Brooks: have a paper out, showing that in a large library of horses who were
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Samantha Brooks: Pssm. One negative but positive on a muscle biopsy. So they have the clinical signs and the diagnostic
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Samantha Brooks: that this test that was being advertised commercially was
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Samantha Brooks: completely unrelated. No correlation
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Samantha Brooks: whatsoever.
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Samantha Brooks: which is tough. So I mean, you can, because we know a little bit about the biology of the condition that means you. If you have a horse who say you pull a swatch of hair, and he's pssm, one negative, but your vet still has a hunch that there's something going on you you need to go on and do the muscle biopsy.
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Samantha Brooks: or
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Samantha Brooks: you can switch them to that PSM. 1 prescribed diet, and see if it works.
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Kris Hiney: Yeah, that's what I usually recommend, like, you know, if you don't want to do all that, just see what happens. But be clinical about it right? So adhere to the diet document. Really be objective about. Do you see a difference in the horse?
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Samantha Brooks: Yeah, E, exactly. Exactly. So I in general, I tell folks to look for a couple of things. So if you're and there are a number of genetic testing companies out there now, particularly
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Samantha Brooks: looking at race horses and groups like that that make some very
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Samantha Brooks: expansive claims about what their tests can can do so. I always suggest you need to ask for the scientific publication. Say, Okay, what are the citations for the tests that you're offering? And if the company says, well, we don't publish our results because we're afraid it will get stolen, and we don't want another company to start running our tests. Then run away as fast as you can.
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Samantha Brooks: Right? That is the most pathetic excuse I have ever heard, because genetic tests are not protectable by patents anymore here in the Us. And they're just making excuses for something that they have not fully done due diligence on to make sure that it actually works. So they're hiding. That's smoke and mirrors.
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Samantha Brooks: You can tell him Dr. Brooks said so.
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Kris Hiney: I Will.
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Samantha Brooks: Only look for tests that have been published in the scientific literature.
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Samantha Brooks: And then, beyond that, it's nice to look for groups that participate with the International Society of Animal Genetics and their parentage testing.
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Samantha Brooks: it doesn't necessarily. It's it's I'm not really concerned with what their individual scores or ranking will be, but it says that they participate in this international organization, and that they are a part of the conversation. When these more reputable companies get together to discuss
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Samantha Brooks: how to to start to to manage some some sort of standards, particularly for parentage testing. So those are my 2 litmus tests. And if the company that you're looking at doesn't conform to those 2 things. Then
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Samantha Brooks: walk away.
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Kris Hiney: 'kay.
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Samantha Brooks: Run away!
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Kris Hiney: All right. We are on to number 2. Confirmation in thoroughbreds
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Samantha Brooks: Right? So this is the complex story. It's 1 of my favorite loci, because it just keeps popping up in so many different unexpected places. But it, you know, we often hear well, thoroughbreds just don't have any genetic diseases. And well, that's not necessarily true, or that other than these really crazy claims of the speed, gene and performance testing for thoroughbreds, which is not necessarily in the realm of reality. Right now
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Samantha Brooks: there, there is one particular locus. That is very important for health in the racehorse, and of course our thoroughbred has contributed to a lot of our other breeds stock horses, namely, as well as our sport horses.
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Samantha Brooks: So anything that's a high frequency in thoroughbreds is is going to be relevant to many different groups. Of course. So
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Samantha Brooks: this particular locus. It's on equine chromosome. 3, and you might see it under a couple of different names. My favorite name
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Samantha Brooks: is Lcorl LCOR. L. That's the name of the the gene that we think is the the functional impact for that for that area.
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Samantha Brooks: I 1st came to know this allele when we did a big, comprehensive study of body size, not just withers height, but overall scale and shape
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Samantha Brooks: in diverse horse breeds. This L corl region was the the single spot in the genome that had the largest effect of anything that we studied there.
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Samantha Brooks: But then, a few years later, some friends of mine at the Cornell Vet school gave me a call. They're like, Hey, you know, we were working on this disease called recurrent laryngeal neuropathy or rln, and something weird came up, and we're wondering if you could come by and take a look. So, sure enough.
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Samantha Brooks: I I walked over there and started to look at their stats, and lo and behold! It was my good friend L. CORL had just popped up again
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Samantha Brooks: out of the middle of nowhere.
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Samantha Brooks: So
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Samantha Brooks: what is this recurrent laryngeal neuropathy. Right? Well, horse owners know this as roaring.
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Samantha Brooks: or it might be called a bad airway. It's a little different, you know. Racehorse people are real worried sometimes about soft palate
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Samantha Brooks: issues and tongue issues. Roaring is specific to the larynx. So you'll get partial paralysis
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Samantha Brooks: of of the larynx itself. Now as a
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Samantha Brooks: day to day horse, you may not notice, but when they need to gallop, or they need to move a lot of air to exercise that paralyzed larynx partially closes over their windpipe, and they can't move enough air. So some of these loud
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Samantha Brooks: breathing racehorses, they'll really be a problem on the track, because they'll show a lot of promise, and then they just don't have the speed, because, frankly, they're suffocating. They can't breathe.
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Samantha Brooks: It's also an issue, because the larynx is important for closing when a horse swallows to make sure that bits of grain and hay
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Samantha Brooks: don't end up in the lungs. And that's a problem, because if you start to get feed stuff in the lungs, you're going to be prone to lung infection.
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Samantha Brooks: So day to day it can be. It can be an issue issue as well.
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Samantha Brooks: We have no effective veterinary treatment for RLN. Or roaring. There is a tie back surgery which can eliminate some of the performance problems, because it just holds that larynx open all the time. But then, when that same horse goes to try to eat.
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Samantha Brooks: that larynx is completely open all the time, so they're that much more likely to accidentally inhale some of their some of their feed.
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Samantha Brooks: So you would think all right. This sounds like a bad thing again. Right? The story. The story is not sounding good. We're on a debbie downer moment, right?
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Samantha Brooks: As it turns out, this is another allele that sounds like a terrible disease that is
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Samantha Brooks: at a fairly high frequency in a lot of populations, and not just, you know. I told you initially that we were looking at body size and scale.
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Samantha Brooks: So it's not just at a high frequency, and horses who are often big like the draft horses. We see it in a lot of other groups, too. And you think.
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Samantha Brooks: why on earth would that be?
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Samantha Brooks: Well?
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Samantha Brooks: If we look at some studies in in race horses, there are some strong correlations between body size
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Samantha Brooks: and earnings on the track, right? So a really neat piece by Burt Stanier and Rebecca Splan and I apologize. I'm forgetting the 3rd author. They showed a strong correlation between the length, particularly in the forelimbs, and think of the shoulder and humerus and dollars earned on the track
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Samantha Brooks: right? So this particular allele.
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Samantha Brooks: when we look at height in the thoroughbreds, and we did a follow-up study on those thoroughbreds that had. RLN.
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Samantha Brooks: If you have 2 copies of it.
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Samantha Brooks: They're almost 3 inches taller at the withers.
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Samantha Brooks: That's that's a
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Samantha Brooks: pretty big effect. Size. It's going to convert all all things being equal, that horse is going to have an advantage on the racetrack
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Samantha Brooks: on the downside. They're 12 times more likely to have roaring as an airway disease.
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Samantha Brooks: Not always gonna have it, but but far, far more
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Samantha Brooks: likely right? So it seems that as we have selected racehorses to be taller.
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Samantha Brooks: we have as a sidecar probably brought on a whole lot more bad airways, because the fastest, easiest way to make them taller at the moment appears to be to have this Lcorl allele.
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Samantha Brooks: Hmm!
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Kris Hiney: So when did that work come out? Because I was just thinking my notes that I used for class on
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Kris Hiney: on that one laryngeal hemiplagia a from a number of years ago, had in there that it was taller horses, but I had never heard the Lcorl.
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Samantha Brooks: Right like like we've we've had this horseman's wisdom that the taller horses are more likely to happen right, and and for many years I would hear folks tell me. Well, it's because their necks are longer.
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Samantha Brooks: So that recurrent laryngeal nerve is this amazing? You know, weirdo of physiology, and that that nerve has to go all the way from the spine around the aorta, and in this long path
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Samantha Brooks: back up to your voice box. And it does this in all sorts of weird creatures, like a giraffe. A giraffe has a recurrent laryngeal nerve that takes this U-turn down around the aorta and back up to the to the larynx. And if you think of things like bronchosaurs, the really long ones, brontosaurus. Yeah.
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Kris Hiney: I think dinosaurs, yeah, brontos.
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Samantha Brooks: Yeah, right? They probably had the same thing. So the recurrent laryngeal nerve is a bit of an Achilles heel for a lot of species, and the thought was, well, their necks are just longer, so they're just more likely to damage it somehow. And
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Samantha Brooks: I I mean there may be something to that. But there's a lot of tall horses who never have that issue. And so we're beginning to wonder. Now.
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Samantha Brooks: does the L. Corl
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Samantha Brooks: have
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Samantha Brooks: multiple jobs in the body, like a lot of our genes, have multiple jobs in in the body like, I think we might have mentioned last time that frame. Overo is important for white spotting on the coat, but also for nerves in the gut.
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Samantha Brooks: It's just more efficient to make each gene work like a Swiss army knife. It means that Mother Nature doesn't have to have enormous genomes. She can just make use of the same tool a little bit differently in different places in the body. So it's possible that L. Corl at certain stages of growth is important for regulating that skeletal growth in a young horse, and we're going to come back to that point.
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Samantha Brooks: But then it might also be important for protecting
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Samantha Brooks: nerves against
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Samantha Brooks: damage
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Samantha Brooks: due to all sorts of environmental onslaughts, and as a result, that longest nerve there the recurrent laryngeal is, is accumulating damage
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Samantha Brooks: faster and developing this degenerative disease and paralysis
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Samantha Brooks: by coincidence in the taller horses right, just because the tallness comes from the same gene that the nerve disease might come from.
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Samantha Brooks: It's a hypothesis.
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Kris Hiney: So. But do they talk about this in any other species, or is it only in horses? I know dogs have laryngeal paralysis, because I have one like, if you name a disease I'm like, oh, this is my personal experience with that thing.
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Samantha Brooks: Yeah. Well, lots of critters, I mean, any kind of damage to that recurrent laryngeal nerve can definitely result in laryngeal paralysis. Right? So this. This is obvious. We don't have any excellent genetic models that really mimic what happens in the horse in terms of their susceptibility to the disease. But it's a good question, especially you think about a dog much smaller bodied animal, right?
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Samantha Brooks: Like the length of the nerve compared to a horse. It's not even in the same same ballpark. So
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Samantha Brooks: yeah, I'm a little skeptical that it's just taller. It's getting stretched out more. It doesn't, doesn't, doesn't really
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Samantha Brooks: float with me.
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Kris Hiney: Jive, right? Interesting.
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Samantha Brooks: So
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Samantha Brooks: one more caveat to the story
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Samantha Brooks: I just mentioned that this L. Corl
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Samantha Brooks: has been now documented in many, many studies to contribute to body size, withers, height, leg, length, lots of different conformational measures. There's a huge study in.
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Samantha Brooks: and some warm blood horses in Germany, where they looked at 5,000 animals, and they correlated the LCORL, locus to things like relative hoof size, and
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Samantha Brooks: many different traits that they study, and in the inspections for warm blood registration.
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Samantha Brooks: so so you're a nutritionist, right? So I'm going to tell you this is a gene that seems to make them grow faster.
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Samantha Brooks: Are there any red flags for you, and thoroughbreds and sport horses growing fast.
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Kris Hiney: Yeah, typically, if you don't balance their diet very well.
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Samantha Brooks: Alright. So what's that red flag? Number one on your list? What's it? Gonna be.
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Kris Hiney: I mean OCDs and joint disorders.
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Samantha Brooks: Yep.
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Samantha Brooks: yep, you get a gold star for the day. So, sure enough, there's a couple of studies that show that across the whole genome, particularly in warm blood horses, because that's where most of the work's been done to date
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Samantha Brooks: that this allele confers risk for OCD. Particularly L. Corl specifically, in warm bloods. It was statistically more likely in hock and Tarsus, maybe Fetlock as well, but they looked at different locations.
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Samantha Brooks: different locations. So
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Samantha Brooks: when I win the the powerball lottery. And for some reason I decide I'm gonna go buy a racehorse. Here's what I'm gonna do.
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Samantha Brooks: If I'm buying a young horse.
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Samantha Brooks: I'm going to immediately, genetically test them for this locus, and if they carry it, I'm going to very carefully balance their diet. I'm talking like a weanling.
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Samantha Brooks: Make sure that we monitor that growth
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Samantha Brooks: to protect those joints, because we know that you can nutritionally influence growth rate, and that that has a strong influence on the frequency of Osteochondrosis. So that came from a study in France actually was very well done.
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Samantha Brooks: Then. The other thing I'm going to do is say, I want to buy an adult horse. And yeah, you know, nobody reports any airway noise, but nobody's done. Nobody's scoped them at a full gallop yet, you know. So I'm going to go out, and I'm going to buy a horse who, all things considered, as promising, and is tall because we know tall, longer legs seems to convert to dollars on the racetrack.
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Samantha Brooks: and I'm going to make for darn sure that they do not have this particular locus, so that I reduce my chances of having a horse that'll show promise, and then turn up with a bad airway. Later.
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Kris Hiney: Okay.
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Samantha Brooks: So I'm going to try to avoid lameness and airway problems by looking for the tall horse that doesn't have this locus.
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Kris Hiney: Okay.
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Samantha Brooks: We'll see. That's my retirement plan, anyhow.
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Kris Hiney: That's awesome.
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Kris Hiney: So can I ask you another racehorse, one so you'll have to confirm. I don't remember the name of this one I just remember like Pcr, but that can't be it.
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Kris Hiney: So it was the one that was the same gene linked to the love of wheel running in hamsters.
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Kris Hiney: Does that one ring a bell.
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Samantha Brooks: Is it? Is it? DRD. 4.
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Kris Hiney: That does not sound right.
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Samantha Brooks: No, no, no, it was a it was an athlete. So it's not a behavioral trait. It's an athletic trait.
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Kris Hiney: Yeah, it was supposed to be linked to performance and thoroughbreds, but they had found the gene
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Kris Hiney: and linked it to behavior in gerbils or hamsters, or something in the ones that were more likely to be like. I'm on the wheel, and I'm running run and run. So it was linked more with like
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Kris Hiney: a little bit more that desire to run, and they had.
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Kris Hiney: So maybe that had only come around in one paper and isn't super common. But I had read that one I was like that was really interesting.
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Samantha Brooks: You know it's not ringing any. It's not ringing any any bells per se. But this was so I
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Samantha Brooks: and here's prior to the issue right was this, was this marketed as a motivation gene.
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Kris Hiney: Maybe that was it the motivator. But I had read like the maybe a scientific abstract or something. I didn't read it, and just like popular press. But maybe that's what it was called the motivator gene.
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Samantha Brooks: Right? Right? Right? Right? Well, I will definitely. I will definitely look for that scientific publication again. See if we can go see if we can go back and find that. But it makes a lot of sense right? And before we get sucked into the behavior rabbit hole.
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Kris Hiney: Me all
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Kris Hiney: I'm doing it again.
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Samantha Brooks: I know we're doing it again right. But you know, you wonder you gotta wonder like, why do these race horses continue to run despite in many cases having athletic injuries, just like human athletes. Anytime you go out and run hard and play hard.
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Samantha Brooks: It's gonna take a toll on your body, and and they, you know, seem to really, really thrive on it. And so it makes a lot of sense that.
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Samantha Brooks: all things being equal.
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Samantha Brooks: the the the component that will make the difference is what worst people call heart right. And if they're not talking about cardiovascular fitness.
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Samantha Brooks: they're talking about that desire to perform, and that desire to run, and that desire to please right? So I you know I will look up the details on that and see if we can find a scientific publication. And maybe we just have to come back and do a 3rd podcast.
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Kris Hiney: Yeah, I like it.
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Kris Hiney: I'll have to try to dig that up myself. So because I definitely remember it mostly in in rodents, and then they were trying to make a a jump there.
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Kris Hiney: So
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Kris Hiney: alright, but we're gonna PIN that one
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Kris Hiney: So because we wanna not make stuff up and get people excited about stuff we don't know.
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Samantha Brooks: Yeah.
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Kris Hiney: All right. So now we're on to warm. Blood's fragile, foal syndrome. That doesn't sound like a good thing for owners.
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Samantha Brooks: No, it doesn't sound like a good thing. So so this one in the literature.
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Samantha Brooks: It, you know, this test has actually been around for a long time. Gosh!
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Samantha Brooks: Think 2,009 ish at least, but about 4, 5, 6 years ago it kind of all of a sudden hit the popular press and became a big controversy in a lot of our sport horse communities.
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Samantha Brooks: so fragile, full syndrome, and you'll sometimes hear it called the warm blood, fragile, full syndrome, that that's an unfortunate misnomer, that that was caused by some
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Samantha Brooks: coincidentally narrow research done early on. We now know that the fragile, full allele is present in many different breeds all the way from halflingers to race horses to you know you name it. It's been around, I think the difference is, it's in a very high frequency in our sport horses in particular. But there are known cases, and even in thoroughbred race horses. There's some case studies.
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Samantha Brooks: This particular variant is in a gene that's important for connective tissue.
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Samantha Brooks: So you know, connective tissue does many things. It's important for skin. It's important for tendons. It's important for joints, right?
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Samantha Brooks: So when you have a defect, and this is a defect that disrupts the ability of that enzyme to function. These horses have fragile connective tissue. That's how it got the name. And so if you have 2 copies of this allele, it's considered lethal, and if that foal survives to birth. The case studies show that they have
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Samantha Brooks: terrible things like torn skin all over their limbs, extremely lax joints. Sometimes they have open abdomens, and they have, deformation of their skeletal spine, and really very sad and and
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Samantha Brooks: extremely unpleasant. And so, when it was initially discovered, it was just assumed. This is a recessive lethal disease, and it's only in warm blood horses.
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Samantha Brooks: Alright. Well, you know what happens when you assume things right. What does Mother nature like to do?
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Samantha Brooks: So, sure enough.
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Samantha Brooks: as we studied this condition more, we learned a couple of very interesting things. 1st of all, that it's not a warm blood disease, not in any way, shape or form. It's in a lot of different breeds.
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Samantha Brooks: And then, second, we did start to see that in some subgroups of sport horses. It was at a remarkably high frequency.
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Samantha Brooks: and
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Samantha Brooks: that was a bit of puzzling, because this one pretty clearly. You know, the these fulls are not compatible with life. We really thought, you know, natural selection should be
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Samantha Brooks: really
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Samantha Brooks: driving this one
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Samantha Brooks: out of the gene pool, not bringing it in. But of course, we as humans, we like to to throw a wrench in the works. And so we start. Some foot groups have started looking at
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Samantha Brooks: what are some other things that might happen
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Samantha Brooks: if you have a single copy of this particular variant.
393
00:50:59.020 --> 00:51:02.959
Samantha Brooks: Now, humans have variants at this locus.
394
00:51:03.399 --> 00:51:14.190
Samantha Brooks: There's actually many different. There's a whole family of syndromes that are similar. But there's just a couple case studies of humans that have a variant at this locus, and we could tell that they had
395
00:51:14.190 --> 00:51:33.139
Samantha Brooks: lower enzyme levels and a few interesting physical characteristics like slightly better than average flexibility, and in some members of the family of syndromes that even have sort of a slightly more narrow rib cage and slightly longer limbs and overall average increased height.
396
00:51:33.950 --> 00:51:57.249
Samantha Brooks: Humans with this condition also have a couple other bad things, so they're at a higher risk for things like an aortic dissection where that huge blood vessel in your aorta might spontaneously rupture, and they're at a slightly higher risk for stroke. They sometimes have eye problems, spine problems. And of course, you know, blood vessels need strong connective tissue to hold them together, so they sometimes have issues there.
Samantha Brooks: So so based on what we know in humans. Some research groups started to look at what might be going on in these carriers. And there was a lovely study done. And I think about 3,000 Swedish warm blood horses where they documented that they could. They could see strong correlations between presence of just one copy of the allele. So these horses, you know. You just look at them across the field. You really can't tell
405
00:52:45.730 --> 00:52:55.790
Samantha Brooks: one copy of Allele, and these they scored significantly better in some of the inspection metrics for things like canter quality.
406
00:52:56.000 --> 00:53:00.929
Samantha Brooks: And they have another thing. I think it's called dressage suitability.
407
00:53:01.060 --> 00:53:04.560
Samantha Brooks: So they were scoring significantly better
408
00:53:04.740 --> 00:53:16.680
Samantha Brooks: in those those categories. So of course, you know, this is an area that we're quite interested in. So my graduate student presented some of her research at the last Ess meeting.
409
00:53:16.900 --> 00:53:21.490
Samantha Brooks: and if her PI would ever get around to finishing the revisions on the paper and getting it resubmitted.
410
00:53:21.870 --> 00:53:36.659
Samantha Brooks: it should come out in publication very soon, but she could see that there was a disproportionately large number of thoroughbred horses competing at the international level. In eventing that carried
411
00:53:36.710 --> 00:53:42.420
Samantha Brooks: one copy of this particular allele. So if you're a thoroughbred and you're getting retrained as an eventer.
412
00:53:42.570 --> 00:53:46.600
Samantha Brooks: it looked like there was a statistically significant effect
413
00:53:47.150 --> 00:53:52.129
Samantha Brooks: on your likelihood of success from carrying one copy
414
00:53:52.280 --> 00:53:53.789
Samantha Brooks: of this particular
415
00:53:53.840 --> 00:53:54.900
Samantha Brooks: disease.
416
00:53:55.090 --> 00:53:55.970
Samantha Brooks: Gene.
417
00:53:56.870 --> 00:54:04.059
Kris Hiney: So is that not similar to the story on Herda as well like it sounds like the exact.
418
00:54:04.060 --> 00:54:04.450
Samantha Brooks: Taxi.
419
00:54:04.450 --> 00:54:05.070
Kris Hiney: Thing.
420
00:54:05.070 --> 00:54:11.299
Samantha Brooks: It? Yeah, doesn't it ring some bells? And actually, Herda is among that same family of condition.
421
00:54:11.300 --> 00:54:14.800
Kris Hiney: This really sounds like the same thing.
422
00:54:15.300 --> 00:54:28.529
Samantha Brooks: I think I think the big difference at this point is that the funding never really emerged to fully tell the Herda story. So we had some great work on tendon biopsies and ex vivo that showed that
423
00:54:28.550 --> 00:54:37.020
Samantha Brooks: herda a single herda allele would change the elastic properties of those tissues when measured in the lab postmortem
424
00:54:38.191 --> 00:54:48.799
Samantha Brooks: but I don't think anyone has ever had enough scientific funding to go through and really document that the Herda Allele was changing
425
00:54:49.030 --> 00:54:57.360
Samantha Brooks: the, you know, scores for for things like reining or cutting the disciplines where it's commonly
426
00:54:57.530 --> 00:55:04.820
Samantha Brooks: commonly found. But that is the hypothesis that that these horses are just a little bit more elastic.
427
00:55:04.850 --> 00:55:08.239
Samantha Brooks: and maybe just a Scotch taller, a little bit longer limbed.
428
00:55:08.280 --> 00:55:16.590
Samantha Brooks: So so they are a bit more glamorous as movers, certainly for the dressage horses.
429
00:55:17.146 --> 00:55:20.060
Samantha Brooks: and and therefore they're under positive selection.
430
00:55:20.670 --> 00:55:21.600
Samantha Brooks: And
431
00:55:21.840 --> 00:55:26.189
Samantha Brooks: that creates a challenge right? Because that means, you know, some of our very top
432
00:55:26.240 --> 00:55:28.170
Samantha Brooks: best performing horses
433
00:55:28.370 --> 00:55:33.420
Samantha Brooks: when it comes to herda and fragile foal. That means right among stock horses and our sport. Horses
434
00:55:33.490 --> 00:55:35.829
Samantha Brooks: probably are carriers for this disease.
435
00:55:37.220 --> 00:56:01.790
Samantha Brooks: and we have to be very careful who we're going to cross them to when it comes to mares. It scares me just a little bit like I really wish we could get additional funding for this work because of some of the similarities we see in humans with the condition right? Humans are with one allele are more likely to suffer things like a joint dislocation or a catastrophic aortic rupture. Right?
436
00:56:01.800 --> 00:56:08.799
Samantha Brooks: And so I worry a little bit about the durability of our sport horses and our cutting horses.
437
00:56:09.616 --> 00:56:25.273
Samantha Brooks: That will be brilliant performers, because they have one copy of this allele, but they may also be more prone to injury. So somebody wants to fund that study. I'm ready and waiting. We've got some great locomotion tools and all the genotyping stuff we need to. Do. You know.
438
00:56:25.580 --> 00:56:47.622
Kris Hiney: This is like that double edged sword that that if this confers advantage, then you could use those markers to select for that, but then you increase its frequency in the population. Where where then? And I've literally had this conversation. In class, where I was like, okay, if you cross, you know, heterozygous heterozygous, you have the
439
00:56:48.360 --> 00:56:51.085
Kris Hiney: the pretty good chance right of
440
00:56:51.690 --> 00:56:53.870
Kris Hiney: homozygous.
441
00:56:53.870 --> 00:56:55.269
Samantha Brooks: One in 4, 1.
442
00:56:55.270 --> 00:57:01.229
Kris Hiney: Right, and they were like, well, that sounds like good odds to me. And I was. I was like horrified. I was like.
443
00:57:03.250 --> 00:57:24.590
Samantha Brooks: You know, I hear that I hear that same. I hear that same justification from a lot of horse breeders, and from the large operations that might be breeding 20 or 30 mares. I kinda believe it like they they're just gonna take that loss and write it off. But I also hear things like I heard a few years ago about a paint horse breeder who had 4 mares.
444
00:57:24.810 --> 00:57:33.450
Samantha Brooks: and in one year she had multiple lethal white Overo affected foals because she was trying to make the popular cross.
445
00:57:33.450 --> 00:57:33.870
Kris Hiney: Yeah.
446
00:57:33.870 --> 00:57:42.003
Samantha Brooks: And in that one year, losing half or more of a full crop did her in. She's like I'm done, you know. Aside from the financial costs. There was the emotional costs, right.
447
00:57:42.250 --> 00:57:42.890
Kris Hiney: Yeah.
448
00:57:43.330 --> 00:57:47.909
Samantha Brooks: And then you start thinking about. Well, you know, if these horses are more prone to blow a tendon.
449
00:57:48.440 --> 00:58:13.140
Samantha Brooks: am I really gonna want to invest 6 or 8 years into training this horse only to have them start to go lame when they're at the peak of their their performance. Age for sport horses right? So big, it's a big investment. So so if you ask me if I'm going to go to a claiming race and spend, you know a few $1,000 on 3 or 4 thoroughbreds to try to flip and retrain as eventing prospects.
450
00:58:13.180 --> 00:58:35.849
Samantha Brooks: I'm gonna see if one of them isn't a fragile full carrier. And I, that's gonna be the one I'm gonna take home, because they're gonna have a better than average chance to go into the upper levels. But you know, if I'm a warm blood Mare breeder, I'm probably gonna avoid this thing like the plague, because I don't want to have any risk of having an affected foal when I cross to some of the most popular stallions, and if I'm looking to buy a horse.
451
00:58:36.030 --> 00:58:39.099
Samantha Brooks: I'd love to find the fancy mover that didn't have this allele.
452
00:58:39.640 --> 00:58:42.429
Samantha Brooks: because I'm I'm gonna be looking pretty
453
00:58:42.930 --> 00:58:44.320
Samantha Brooks: pretty critically
454
00:58:44.430 --> 00:58:47.270
Samantha Brooks: at their tendons and and joints.
455
00:58:48.197 --> 00:58:57.040
Samantha Brooks: If they are, if they are a carrier. Now, one of the things in our research that we've really found pretty interesting is now that we've started to look at videos of hundreds
456
00:58:57.170 --> 00:59:03.809
Samantha Brooks: sport horses in motion as we we had to kind of reinvent the wheel and make a new tool. So we're in a tool building phase at the moment.
457
00:59:04.050 --> 00:59:14.480
Samantha Brooks: And when we look at these videos and we start to cluster them, we can see the fragile carriers in the data, in the way that they move right? So the Swedish group focused on judging scores.
458
00:59:14.880 --> 00:59:18.030
Samantha Brooks: we can see it quantitatively now in the flight path.
459
00:59:19.116 --> 00:59:20.230
Samantha Brooks: But we
460
00:59:20.320 --> 00:59:32.159
Samantha Brooks: we can. It statistically makes a difference, right? But when we look at those same characteristics across the whole population, I can see horses, who are fragile, negative, but move like a fragile full carrier.
461
00:59:33.490 --> 00:59:42.439
Samantha Brooks: So I either. They magically got a different gene that helped out their elasticity of their gait. But hopefully, isn't Recessive lethal, or
462
00:59:42.500 --> 00:59:47.990
Samantha Brooks: we have other potentially Recessive lethal alleles circulating in the population that we just haven't
463
00:59:48.430 --> 00:59:50.339
Samantha Brooks: investigated or discovered yet.
464
00:59:53.020 --> 00:59:54.370
Kris Hiney: fun. Times.
465
00:59:54.370 --> 00:59:58.219
Samantha Brooks: Right. There's your your segue into
466
00:59:58.510 --> 01:00:01.260
Samantha Brooks: need, more need, more research. So go ahead.
502
01:03:22.110 --> 01:03:30.939
Samantha Brooks: You know. Yeah, I hear about this a lot, right? Everybody says, Oh, you darn geneticists! Every time I turn around you're giving me bad news like.
503
01:03:31.350 --> 01:03:33.560
Kris Hiney: It's all bad news these days.
504
01:03:33.560 --> 01:03:34.020
Samantha Brooks: Right.
505
01:03:34.616 --> 01:03:35.270
Kris Hiney: You know.
506
01:03:35.270 --> 01:03:43.165
Samantha Brooks: It is. Well, this is true, this is not. This is not just horse genetics, you know. It's gosh! Let's not even look at politics or anything like that. Right now.
507
01:03:43.480 --> 01:03:54.320
Samantha Brooks: I mean, here's the thing right. Those diseases are there, whether geneticists study them or not like taking the ostrich strategy of sticking your head in the sand.
508
01:03:54.720 --> 01:04:00.020
Samantha Brooks: Not a good plan, because then these things will sneak up on you. You lose your best foal out of your barn.
509
01:04:00.700 --> 01:04:04.670
Samantha Brooks: And and you've taken a huge economic loss. And
510
01:04:04.930 --> 01:04:10.830
Samantha Brooks: technology is improving so that the cost of genetic testing is continuously coming down
511
01:04:10.890 --> 01:04:14.299
Samantha Brooks: continuously coming down right? So you know.
512
01:04:14.970 --> 01:04:24.829
Samantha Brooks: a few decades ago Carfax was a new thing, and you're like, Geez, do I really need to pay that extra 20 bucks to get a title search report on this car. I'm thinking of buying, and
513
01:04:24.870 --> 01:04:33.950
Samantha Brooks: you know he's like, I don't know. But these days it's almost a given that if you're looking at a used car, you're gonna get a title, search report or a car fax, you know. So
514
01:04:34.140 --> 01:04:53.950
Samantha Brooks: is because they just made sense. It was such a. It was an investment that was so effective at preventing that occasional disaster that the numbers just made sense, and it eventually trickled through into our modern culture. And I think genetics will get there, too, right?
515
01:04:54.040 --> 01:05:05.560
Samantha Brooks: A $100 here or there. That will. Yeah. It'll give you a long list of tests these days, like, I am just so tired of this. Oh, I want to pay $25 for this one, and for this one you've got
516
01:05:05.860 --> 01:05:16.589
Samantha Brooks: dozens, if not now, hundreds of alleles that could be relevant to you like I don't have time to cherry, pick them. I'm just gonna throw the kitchen, sink at them, spend my 100 bucks.
517
01:05:16.600 --> 01:05:34.410
Samantha Brooks: Sometimes I come up with those random, unusual things like my little bay Mayor that has frame overo. Right? So you know it. Just I know it's exhausting. I know it's tiring, and we, as scientists, are working hard to improve how we communicate the value of these things to the industry.
518
01:05:34.440 --> 01:05:41.070
Samantha Brooks: But at the end of the day, you know, it makes a lot of sense just like having insurance on your home and having insurance on your car.
519
01:05:41.750 --> 01:05:45.470
Samantha Brooks: It just makes sense economically to get ahead of this stuff.
520
01:05:45.470 --> 01:05:53.249
Kris Hiney: Sure. Yeah. So my, why, one last request and this has actually come from some some stakeholders that I've helped
521
01:05:53.800 --> 01:06:05.460
Kris Hiney: They really want you guys to get the get them some genetic information on PPID horses so that they can head it off at the pass.
522
01:06:05.460 --> 01:06:06.330
Samantha Brooks: Oh!
523
01:06:06.330 --> 01:06:09.199
Kris Hiney: By the ones that are gonna end up with it.
524
01:06:09.200 --> 01:06:26.329
Samantha Brooks: Me, too. Me, too, so I'll tell you. Right after I I moved here to Florida. So this public publication came out. Probably I can't even remember my own citations now, but out of our lab, I think, around 2,016, we published some genetic studies on metabolic syndrome
525
01:06:26.540 --> 01:06:34.489
Samantha Brooks: and the hidden half to that story which is written in like one line. And one of those papers. Is that so? We we focused on Arabian horses
526
01:06:34.730 --> 01:06:49.850
Samantha Brooks: partially because I had another project in Arabians. And so I was leveraging data to cover gaps in scientific funding that frankly, the industry and our scientific agencies were just simply not supporting. So I was trying to to
527
01:06:51.250 --> 01:06:52.439
Samantha Brooks: try to do
528
01:06:52.560 --> 01:07:11.940
Samantha Brooks: double job. A couple of couple of data sets there, and partially because Arabians were a good model for these metabolic diseases, because they have it frequently, but not always, like ponies, are the worst model ever for metabolic syndrome, because, you know practically all of them.
529
01:07:12.060 --> 01:07:13.149
Samantha Brooks: They're gonna have it right.
530
01:07:13.150 --> 01:07:14.165
Kris Hiney: Don't buy a pony.
531
01:07:14.420 --> 01:07:27.340
Samantha Brooks: Yeah, I love my pony. I keep him thin, but you know, so, ponies they're awful like. And even Morgan's super high frequency, right? So I don't have that contrast as a scientist that makes them.
532
01:07:27.740 --> 01:07:28.850
Samantha Brooks: A good.
533
01:07:29.390 --> 01:07:36.670
Samantha Brooks: a good system to identify the important changes in the genome. Arabians were kind of a happy medium.
534
01:07:36.830 --> 01:07:43.965
Samantha Brooks: They didn't get it quite frequently, but they were not anything like Morgan horses, or Connemaras, or or the small ponies right?
535
01:07:44.320 --> 01:07:57.580
Samantha Brooks: that made our jobs a little harder. Right? It's easy when you can just like spit on a pony herd and land on an animal that has Metabolic syndrome makes it easy to find cases. We had to work pretty hard to find cases in our Arabian, so we visited
536
01:07:57.820 --> 01:08:10.609
Samantha Brooks: dozens of sites here in Central Florida. Many gracious Arabian horse owners welcomed us to their farm and showed us all their animals, and we did comprehensive diagnostics, including both physical exam
537
01:08:10.860 --> 01:08:14.379
Samantha Brooks: and endocrinology, from blood samples. Right?
538
01:08:14.830 --> 01:08:29.580
Samantha Brooks: And the 1st thing that we ran up on. That was a real challenge, for our study is that we came up with so many subclinical ppid horses that per typical diagnostic criteria
539
01:08:29.609 --> 01:08:30.990
Samantha Brooks: had the disease.
540
01:08:31.069 --> 01:08:54.099
Samantha Brooks: and you know the owners would say, well, he's an easy keeper. He's a little cresty, but he's also old, you know. We came up with so many of them that it really ate into our sample size, because we are the little bit of funding that we had was focused on metabolic syndrome and insulin regulation. So we were actually testing largely to exclude those ppid horses. And
541
01:08:54.359 --> 01:08:58.089
Samantha Brooks: oh, it was! It was such a huge challenge, such a huge challenge.
542
01:08:58.470 --> 01:09:00.730
Samantha Brooks: so that that really raises a question of.
543
01:09:01.140 --> 01:09:07.739
Samantha Brooks: I believe them a hundred percent, that we are not paying enough attention to this condition, because I I like
544
01:09:08.080 --> 01:09:14.710
Samantha Brooks: a severe case. Most of us can spot from a mile away, but very mild, subclinical one.
545
01:09:14.729 --> 01:09:17.179
Samantha Brooks: Hmm! That one could be a bit tougher
546
01:09:18.008 --> 01:09:30.960
Samantha Brooks: what we ended up doing is. And this is where it came like one line is that in many cases we couldn't entirely exclude all the horses. That sort of were on the borderline kind of fit that criteria for ppid.
547
01:09:31.149 --> 01:09:47.160
Samantha Brooks: And so I actually one of the activities in our in our paper was, I went ahead and genotyped these horses for markers across their whole genome, and I measured the heritability of metabolic syndrome, and ultimately identified some really nice loci for
548
01:09:47.300 --> 01:09:52.940
Samantha Brooks: susceptibility to Ems in Arabian horses. These are at loci, like Adiponectin.
549
01:09:53.899 --> 01:10:03.059
Samantha Brooks: Nutritionist knows what that is right. And somatostatin like these are great like home run candidates for risk for metabolic syndrome. It's really fun work
550
01:10:03.709 --> 01:10:07.349
Samantha Brooks: couldn't get the follow-up study funded, but it was nice.
551
01:10:07.685 --> 01:10:16.819
Samantha Brooks: And like, there's like one line in that paper, we took those cases of ppid that ultimately we had to keep in the study because there were so darn many of them.
552
01:10:17.239 --> 01:10:20.429
Samantha Brooks: and tried to measure the heritability and
553
01:10:22.479 --> 01:10:23.349
Samantha Brooks: nothing
554
01:10:23.689 --> 01:10:27.809
Samantha Brooks: nothing not heritable in the Arabian horse whatsoever. So.
555
01:10:28.549 --> 01:10:35.405
Samantha Brooks: as a geneticist, it got like one line in the paper, and then we kind of swept it under the rug, and then we tried to go and write our next grant
556
01:10:35.799 --> 01:10:45.469
Samantha Brooks: to me this means a couple of things right? It's possible that just like our fat ponies that in Arabian horses they're simply fixed for a risk, Allele, that confers
557
01:10:45.839 --> 01:11:00.299
Samantha Brooks: that susceptibility to ppid. It's possible I don't know that they're really known to be extraordinarily prone to ppid. I'll have to go back. And there are a couple nice little epidemiology studies looking across breed.
558
01:11:00.869 --> 01:11:04.229
Samantha Brooks: But you know, things happen or
559
01:11:05.079 --> 01:11:20.059
Samantha Brooks: possibility. B, there's not a lot of genetic variation contributing to the rate of the development of that neurodegenerative ppid disease. And I maybe can't help a whole lot. Unfortunately.
560
01:11:20.060 --> 01:11:29.540
Kris Hiney: So am I getting too deep into the the weeds here, if, if like, we're saying like, glp one, right? So everybody has the gene. But is it
561
01:11:30.210 --> 01:11:33.969
Kris Hiney: where you work? What about how much
562
01:11:34.060 --> 01:11:40.409
Kris Hiney: of the protein is created? Right? So that post translational like.
563
01:11:40.570 --> 01:11:42.230
Kris Hiney: where do you guys?
564
01:11:43.120 --> 01:11:48.060
Kris Hiney: Because if everybody has the gene, but somehow it gets up regulated.
565
01:11:48.870 --> 01:11:56.550
Kris Hiney: Or would that be linked to another gene, or would that, or am I gonna get this conversation real complicated.
566
01:11:56.550 --> 01:12:18.700
Samantha Brooks: Oh, well, you know, to put it in a nutshell. This is why my job is hard, right? Because most of the time when we go to map a trait. We do not identify that smoking gun, that the change within the protein coding sequence that destroys the function of the gene. Right. We love it when that happens, because it's like in a
567
01:12:19.140 --> 01:12:23.769
Samantha Brooks: a open and shut case for the genetic detectives.
568
01:12:23.780 --> 01:12:35.229
Samantha Brooks: because we know that if you destroy that gene based on what happens in other species, that it's going to be a problem. Yeah. But most of the time biology is made of shades of gray.
569
01:12:35.650 --> 01:12:55.049
Samantha Brooks: and it's going to be a subtle change in the way that Gene is utilized that will result in the traits that we're interested in, and sometimes a subtle change in many genes, and unfortunately, as biologists, we can only right now well and easily understand about 3% of the genome. That's the part that codes for proteins.
570
01:12:55.060 --> 01:13:23.850
Samantha Brooks: The other 97% used to get labeled as junk. And now we know that in that 97% are some important instructions for things like gene, regulation, or post-translational modification, and that our genes work in concert. They are a symphony of co-regulation, so it could be a whole number of genes modifying the function of other genes. And you kind of have to like trace it back through things like binding sites and
571
01:13:23.920 --> 01:13:29.259
Samantha Brooks: networks. And yeah, all the really hard, brainy, brainy kind of stuff. So
572
01:13:29.350 --> 01:13:53.330
Samantha Brooks: it's coming down the pipeline because we started to work. There were some big efforts in functional annotation in the genome. So this is where we look at pieces of the genome that are important for that fine-tuning, how a gene is used, and regulatory sequences for a gene can be right in front of the gene. They can be many tens of thousands of bases away from the gene, but on the same strand
573
01:13:54.020 --> 01:14:15.950
Samantha Brooks: or chromosome, and sometimes they can even be on another on another chromosome, another piece. So mapping those relationships between regulatory regions and their their target genes, it is. It is a huge challenge. It's it's 1 of the top challenges in genetics today, not just for us horse geneticists, but also for human geneticists.
574
01:14:16.957 --> 01:14:21.219
Samantha Brooks: So it's a hard problem. It's important. It's hugely important, right?
575
01:14:21.220 --> 01:14:21.800
Kris Hiney: Yeah.
576
01:14:22.250 --> 01:14:27.999
Samantha Brooks: We're working on it so often when we we can detect a significant statistical effect.
577
01:14:28.150 --> 01:14:39.160
Samantha Brooks: But we may have no way to explain the why that effect is in that spot in the genome whatsoever. But it's still worthwhile to go and try to measure the genetic effect. And then we can.
578
01:14:39.270 --> 01:14:43.480
Samantha Brooks: We can start to to learn more and build some tools.
579
01:14:44.160 --> 01:14:46.009
Samantha Brooks: To try to detect that
580
01:14:46.060 --> 01:14:48.420
Samantha Brooks: and use it for practical purposes.
581
01:14:49.150 --> 01:14:51.639
Samantha Brooks: And while we start to better understand the why.
582
01:14:51.850 --> 01:14:53.530
Samantha Brooks: in the long term.
583
01:14:53.530 --> 01:15:04.249
Kris Hiney: So. And that's why science takes a long time right? I always want to give a plug, for like these are not easy answers like. Oh, I took a hair. And now I know that the answer right? Because it's so much more
584
01:15:04.360 --> 01:15:12.750
Kris Hiney: complex than that. And probably the average person, you know they kind of maybe understand DNA, but not really
585
01:15:12.900 --> 01:15:32.480
Kris Hiney: how the whole thing works. And like that, 97%. That doesn't code. Well, that's where the alien DNA right is for. But yeah, it takes a long time, and it's it's not something that's
586
01:15:32.680 --> 01:15:36.529
Kris Hiney: just a yes or no. Unfortunately, it'd be nice if it, if it was but.
587
01:15:36.530 --> 01:15:45.780
Samantha Brooks: No, no good. Science always raises more questions right? But it brings with those questions a better understanding, you know, like you gotta you gotta know what you don't know.
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Samantha Brooks: and you got to know how to ask the right questions because the wrong questions don't help you at all. Yeah, it's a long-term game. I love it because I participate a lot of the studies that I do encourage the participation of horse owners out in industry. Right? Like I can't maintain herds of hundreds of horses. We just do not have the resources for that. And so I'm often talking to horse owners because
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Samantha Brooks: they've got a horse that they're going to submit to one of our studies. And and I love it because a lot of them, you know, they are so excited they'll email me like every week and every month. And they want to know, how's the study going? How's the study going? And I'm like, it's going, you know, like, I just don't think people realize that sometimes these things take a very long time. So like fragile or lavender foal syndrome we did. It was in our condition, primarily in Arabian horses
590
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Samantha Brooks: a couple of decades ago that study was started by my colleague Doug Anzac at Cornell, and he banked samples and maintained records on that disease for 10 years 10 years
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Samantha Brooks: before we finally had the tools available. So I got lucky in that case. And then I just sort of walked on the scene and used the fancy tools, and and we very quickly had an obvious smoking gun answer and identified the causative variant, but that ignored the hard work that had gone into a decade of saving and maintaining all those records and samples, and talking to horse owners and talking to veterinarians to get them to refer cases to us and things like that. So
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Samantha Brooks: yeah, I think
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Samantha Brooks: sometimes people believe we walk into the lab, and we like pour one test tube into the other, and it turns purple and foams up. And we're like Eureka.
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Samantha Brooks: We have the answer, but it doesn't work that way. And I think that's 1 reason it's really hard to get scientific funding these days, because our culture is so much one of instant gratification. Right, like
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Samantha Brooks: our most popular media format these days, is what the 30 second reel.
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Kris Hiney: Yeah, yeah.
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Samantha Brooks: So our our attention span is
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Samantha Brooks: probably decreasing catastrophically at this point, and this is a long-term game long term investment, investment for the greater good, and some people have a hard time putting aside short-term
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Samantha Brooks: challenges to focus on the long-term gain.
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Kris Hiney: 100%. Well, Dr. Brooks, I really appreciate your time. We did a lot today. So we did the the Big 3 and then went off on some rabbit trails, because I just can't help myself. But it's all really fascinating to me, and you can link up so many things like you said anecdotally, and like, Oh, that totally makes sense and like here's the horseman's lore, and how it all fits together. I think that's pretty cool.
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Kris Hiney: Actually put some of that scientific information, together with the lore that has existed for a while. So good stuff.
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Samantha Brooks: Right, absolutely well, these are great questions, and you know, farmers are really naturally excellent observers. And so sometimes that horseman's Lore definitely points us on the right direction.
01:18:54.150 --> 01:19:14.589
Kris Hiney: Well again. Thank you so much for your time. If you want more information on some of the management practices for some of these different genetic disorders. You can visit us at extensionhorses.com dot. And again, this has been another episode of our tech box talk course stories with a purpose.