Introduction 0:03
For the love of goats! We are talking about everything goat. Whether you’re a goat owner, a breeder, or just a fan of these wonderful creatures, we’ve got you covered. And now, here is Deborah Niemann.
Deborah Niemann 0:18
Hello everyone, and welcome to today's episode. This is going to be especially interesting for those of you with Nigerian Dwarf goats. We are going to be talking about carpal hyperextension in that breed, and the possibility of a genetic connection to the disease. And we are joined today by Erica McKenzie, Professor of Large Animal Medicine at Oregon State University, and Leah Streb, a third-year laboratory animal medicine resident at the University of California in Davis. Welcome to the show today doctors.
Leah Helene Streb 0:56
Thank you.
Erica McKenzie 0:57
Thank you for having us.
Deborah Niemann 0:58
It's so great to have you here. When people ask me about this, I don't have a whole lot of insight. I've been raising Nigerian dwarfs for 22 years, but I've never seen it. So when I heard that there was possibly a genetic connection, then it all made perfect sense to me because I have not bought a doe since 2005, and I've brought in a very small number of bucks. So the possibility of bringing in some kind of new genes like that would be pretty slim. Where did you get the idea to do this research?
Erica McKenzie 1:29
It was actually driven by a client who has her own Nigerian dwarf goats. And so it was a really interesting situation, but she brought this to me as a problem probably about three years ago and said, listen, a lot of owners are concerned about this. A lot of owners are experiencing this within their herds, you know, limited numbers of animals, but she felt that there was a wide range of owners that were seeing this. And so she was quite concerned and felt that the university basically had an obligation or a duty to investigate this disease and to try to determine why was it happening and was it potentially heritable? I'll admit that orthopedics are not really an area that I'm interested in. I'm a medicine specialist, so I don't like to look at legs and they're not really an area that I'm interested in. But, you know, her enthusiasm and her persistence were quite remarkable, and she presented us with, you know, a list of animals that were potentially affected that she knew of. Had permission to do so, she also had pedigrees, etc. So she started off with a database, which was an appealing place for us to start. She was quite medically knowledgeable herself, and that really helped us.
Erica McKenzie 2:43
And then, really, it was just fortuitous. I had considered the project, but as a solo effort, and certainly with many other projects I was working on, it wasn't really something I felt I could take on at that time, and then Dr. Streb came to me looking for a potential project out of the blue. And when I asked her, do you like goats? She said, I love goats. And so I thought, well, you know, here's a potential project. Does it interest you? And if you want to do it, then we'll do it together as a team. And so that's how it all kicked off. And on top of that, having the two of us involved, which was- We couldn't have done it without each other, was the fact that clients and people affiliated with the goat industry were wholeheartedly willing to fund it. So we opened a donation platform. It was an atypical way to get research funding, but we opened a donation platform through the university, and, you know, the industry really stepped up. I think it's a sign of how concerned many people are about this disease, but they stepped up and they funded the work. So it was a really interesting collaboration between the veterinarians and the clients and the goat owners out there.
Deborah Niemann 3:50
Wow, that is really exciting. I am always enthusiastic when I hear about new research projects, because there's just so much that we don't know yet. Can we take just a quick step back and tell us what exactly is carpal hyperextension?
Erica McKenzie 4:06
Well, I think the owners beat us to it, again, you know, there was already a Facebook page specifically for carpal hyperextension syndrome with 400 members at the time that we started this. So they'd already given it a name. I honestly don't know where that name came from. Dr. Streb is much more familiar with the Facebook page than I am, since I'm not on social media, but I don't know if you saw any origins for that name, Dr. Streb.
Leah Helene Streb 4:32
No, you know, I think there was kind of the initial blog that started this whole thing, like several years ago, that was like- I forget the name of it now, but I think that's maybe initially where the name started or it kind of just, you know, took off from there. But it's a very descriptive name and describes what the condition is doing. So, you know, it definitely makes sense. You know, there's hyperextension of the carpus and yeah.
Erica McKenzie 5:08
And so for people who may not understand that, basically what we're describing is that the front knees bend backwards. So it's a- they don't bend sideways. The legs don't deviate in or out in what we see to be the classically affected animals. It's just they bend backward at the front knee and it can be one or both legs. So it is quite a bizarre situation and it certainly can lead to lameness and deformity and concerns about whether these animals should be bred or not.
Deborah Niemann 5:37
Yeah. That was my next question is that as a person who has bad knees, it makes me wonder, like, is the goat in pain when they have this and does it shorten their productive life?
Leah Helene Streb 5:48
Yeah. So, I mean, there were kind of varying degrees of lameness that we saw throughout the study. Some animals were extremely lame to the point where they couldn't stand on their front legs for extended periods of time. While there were others that kind of seem to become static in the development of the condition and then kind of just either compensated or didn't really have any lameness associated with that, but it definitely can cause pain and quality of life issues for sure.
Deborah Niemann 6:29
Okay. And what has your research showed you so far?
Erica McKenzie 6:34
Well, it probably makes sense to lay out how we tried to approach the problem because when you're dealing with a potentially heritable disorder, you have to have a very clear description of what animals are affected. What do they look like? You have to be careful about who you choose as representative and then you have to be very careful about how you choose your controls. Otherwise, you just kind of muddy the genetic waters, so to speak, and you won't pull a gene out of that kind of situation. So it was really important that we defined the goal of building a description of the clinical disease that was accurate. So that was our first main goal was to describe what does this look like? How can you basically assess an animal and say that it does or doesn't have this disorder? Our next goal was to determine if there were management factors that might be influencing whether animals got this disorder or not. Was there a mineral deficiency for example? Was it the way they were fed? The way they were housed? And then third of course was our interest in could this be genetic, and if it is genetic do we have evidence that it is inheritable? So we were very careful to only examine pedigreed animals. We made sure that we had for every affected animal, we tried to have two related controls and preferably a first degree relative like a parent or offspring or a direct sibling that was over two years of age because many of these animals are affected by two years of age or before that, so we wanted to try to make sure that any animals we were deeming as probably healthy were old enough to have had the chance to show the disease. So we're very careful about how we selected our population. Owners presented us with animals they felt were affected. And then Dr. Streb can go ahead and describe how did we then kind of confirm that these animals looked like they had the disease, and what samples we took.
Leah Helene Streb 8:26
Yeah. So for each animal, we did an extensive survey to collect lots of information, including what we call signalment. So, you know, sex, age, use of the animal. In addition to their clinical history, did they have any previous traumas that maybe would have contributed, which then would have kind of- we wouldn't have used them in the study. Dietary history, what the owners were currently feeding. And this was given to both the cases and the control animals. And then we also did physicals where we collected their body condition scores, body weight. And then we did what's called goniometry of the carpal joint. And so a goniometer is, it's used in human medicine to basically measure the flexion and extension of a joint. And it's kind of like two rulers attached to this like round circular thing that just measures the degree, and so we did that on both to determine what the normal animals carpi look like while they're standing and weight bearing and compared that to the case animals. We also took brachial muscle circumference to see if there was any muscle atrophy associated with the condition, as well as toe splay measurements. And then we collected blood on all of the animals to run a trace mineral analysis and also for our future DNA work. And then for some of our more severely affected animals to kind of contribute to that clinical description we were talking about, we did x-rays, ultrasound, MRI, and eventually submitted them for necropsy. And these were animals that were very severely affected, their quality of life was affected, and the owners were going to euthanize them anyway. So we, you know, were able to kind of use that to contribute to information about the disease. And then we constructed the pedigree and did the genetic work, which we'll kind of talk about a little bit more. Yeah, it's a pretty extensive project for sure.
Deborah Niemann 10:47
Yeah, that is really extensive. I can't think of anything you left out. You really covered the gamut there in terms of trying to figure out how the animals were affected and what could have caused it. So I know the study is not finished yet, but what have you- are there some conclusions you've come to so far?
Erica McKenzie 11:06
We have a large amount of data still, and we haven't completed our statistical analysis of it. But in terms of the description of the affected animals, you know, ultimately, I think we evaluated over 100 animals, about a third of which were affected, and then the others were related controls for the most part, and then eight to ten animals actually went through euthanasia and tissue assessment. So massive amount of data from the survey on supplementation and diet and age and housing and sex. We don't really see a clear indication that bucks are more affected than does, for example. And then we don't have a smoking gun lesion yet in terms of tissue assessment. We are waiting for some special stains on the tissues that we collected. There was certainly a clear difference between affected and control animals in the joint angles. So I think we feel pretty good that goniometry can help distinguish when an animal does have carpal hyperextension from when an animal doesn't. The goats that had normal knees and were not felt to be affected by the owners, had joint angles of zero, basically. And then animals that were affected were often minus 15, minus 20, sometimes minus 27. And also on x-rays typically had secondary arthritis. You know, we did retrospectively evaluate for CAE infection, which can cause arthritis as well. So that question did come up as a possible CAE led to this. Pretty much all of the animals that we assessed were either testing negative or from closed herds. So we don't have evidence that disease is involved. And then Dr. Streb can talk to you about her extensive genetic work that she's done so far and the pedigrees that we have evaluated. We are working with Carrie Finno at UC Davis, who's a geneticist and is helping us extensively with this work.
Leah Helene Streb 12:57
Yeah. So we collected registration numbers so that we could construct this five generation pedigree map for each individual that we then threw in this software called Pedigraph that mapped all of the animals included in the study, and then used additional information provided on the ADGA Genetics and some of the other farm websites, and were actually able to trace all the way back to a single buck, which was pretty interesting for sure. It does make sense because the breed does come from a very small pool of individuals, but it was pretty interesting to see that we could trace all of the animals that we included in this study alone back to a single male. And then from there, we isolated DNA from all of these animals and then sent them off for genotyping. And then we're able to basically compare the cases and control animals DNA and see if there were any differences there and really see if there is a specific gene that we can point to. And we're hoping to include more animals in that analysis as well. We need more funding to do that work.
Deborah Niemann 14:16
Wow, that is fascinating. Are you willing to say the name of the buck?
Erica McKenzie 14:24
No, absolutely not.
Leah Helene Streb 14:25
No, yeah. That has been something that's come up a few times. You know, we want to protect the identity of the animals in our study. And then, of course, a lot of the animals that we traced back to are either long dead or we can't confirm that those animals were affected and so it really just isn't the best ethically to just be like "here's, you know, pointing to this". So I think that the best thing that owners can do is trace within their own animal populations any affected individuals that they've had, you know, show up on their farm and tracing back where those animals have come from whether that's from their own farm or other individuals getting together and kind of developing their own little pedigree maps. Yeah.
Erica McKenzie 15:20
And it's not uncommon to see what can be perceived as a founder effect when you have narrow genetic lineage. So, you know, it would certainly be too early for us to say, "Hey, there's this one buck and he caused all of these problems". You know, we really can't say that yet. And we do know that both bucks and does can be affected. And both are pretty prolific in this breed, right? Well, one buck can breed a lot of does, but these does also have multiple babies. And so at this point, we don't see a strong sex difference between who's affected and who's not. And this possible founder effect may just be chance related since it is such a small genetic pool, but all along, the overarching goal of this study has been, one, to try to demonstrate enough evidence that it is genetic. And two, if it is genetic, can we get to the point of isolating a gene so that owners could simply do a hair or blood test? Because obviously it's very complicated to try to do all these advanced forms of imaging. And, you know, we don't have a biopsy, for example, that you can do. And goniometry has its own failings as well.
Erica McKenzie 16:23
So, you know, a blood or hair test would be great, but it would also be wishing for this disease to be genetic, which is not something that we would really want to do to our clients either. So we're kind of in this gray area right now of trying to evaluate and understand our data. It hasn't been peer reviewed because it's not published yet. So there may be confounding variables we have not recognized in our own data. So I think it's important that it goes through intensive scrutiny before we come up with a blanket statement that people should not breed these animals. We have also seen some people who have CH animals that breed them and say, you know, I've never seen it again, and maybe some of these animals did traumatize a leg and developed a backward bend, so we don't really know yet. Certainly, we have a great preliminary data set here. And I think we've got very adequate opportunity to get some additional funding as a result of having strong preliminary data, but definitely a lot more work to be done on the genetic front.
Deborah Niemann 17:21
Yeah, one of the reasons I asked the question if you were willing to reveal the name of the buck is because with social media, lots of rumors go around. And so if somebody hears that it was buck XYZ that caused this, then they should just disregard that as a rumor that has zero backing, because you're not going to tell people who it is.
Leah Helene Streb 17:46
That does not come from us. So, yeah.
Erica McKenzie 17:48
You might also find that buck is in the lineage of all the normals too, right? So it's very easy to jump on something that looks interesting and be incorrect, which is why we're not announcing it. Yeah, because we really can't say yet. We don't know.
Deborah Niemann 18:02
And it sounds like it's definitely a recessive gene that could hide for a while. And then-
Erica McKenzie 18:08
I don't think we know that either. I mean, it's a fairly prolific disorder. You know, when you look at the Facebook page, it's got 1100 members now. I don't know if that's because every one of those people has seen it or has an animal. But I feel like we went to a relatively small number of properties to gather a fairly large number of affected animals. So to me, that's not typical for a recessive trait. But obviously, the geneticists are able to trace patterns and be much more sure. Yes, this is behaving like a sex link disorder or an autosomal dominant disorder or a recessive disorder. And so I think we're still waiting for more genetic assessment before we can say that for sure either.
Leah Helene Streb 18:48
Yeah, it's possible that it is recessive, and that just because the breed is so, just in general inbred, because it's from a small population and that's why we're seeing it so much more regularly, because maybe you have more just heterozygous animals that are then breeding and you're seeing a higher ratio of animals that are being affected. But we really can't say that yet.
Deborah Niemann 19:12
So is it possible for people still to donate to the research? And if so, how would they do that?
Erica McKenzie 19:20
That's a great question. Yeah, we are certainly interested in pursuing additional genetic work. I think it's been estimated that it's going to be about $50,000 or $60,000 for us to do that. We have exhausted preliminary funds that were generously provided by our goat owners in basically assessing and performing genotyping- initial genotyping on over 100 animals. So the money they gave, gave us a lot of data. And we're very, very grateful for that. But the reality is when you start doing whole genome sequencing, it becomes expensive quickly. So right now, there's still two ways that we can accept money at Oregon State University. And the first is that people can make a check that is payable to the OSU Foundation, and that can be sent to 4238 Research Way in Corvallis, Oregon, 97333. And if they write in the check memo section, that it's large animal medicine/wonky leg. When we were trying to raise money for this project, I just gave it what I thought was a catchy name that described these animals, which was as having wonky legs. The second way is that you can go to the OSU College giving page. I don't know that I have an actual link for that one, or you can reach out to Anna Justice, at Oregon State University. As long as you attach wonky leg to that, any donation, that will get to us.
Deborah Niemann 21:07
Okay, and we'll be sure to put that in the show notes also so that if somebody's driving when they're listening to this, they can go to the website and get the information to make the donation. So what is your next step once you get the funding?
Leah Helene Streb 21:22
So next steps are to obviously further genotype the region of interest that we wanted, including more animals to provide more robust evidence for a gene within that region. And we definitely want to make sure that we publish what we currently have to get that peer reviewed. And that will probably be our first next steps because we're going to need that probably to get the amount of funding that we need for our next steps after that.
Deborah Niemann 21:55
How much more work do you feel like you have to do before you'll have the answers that you are looking for?
Leah Helene Streb 22:03
That's a good question. I mean, it really depends on how quickly we could get the funding for the further genotyping. And that's, I think, really hard to say on how long that will take us to get the funding there. But, you know, it's going to take several months for us to get the manuscript in and accepted. There's probably going to be multiple rounds of edits. And then if there's anything like Dr. McKenzie mentioned earlier- if there's anything that maybe we- a confounding factor that we missed or something that we need to then go do some more data collection to address or anything else that we might need to change. That kind of pushes out further on when that official publication date would be. So it's kind of hard to provide a definitive answer for when we would have the official whether it's genetic or not.
Erica McKenzie 23:04
Definitely the goal to get the manuscript published this year. So I hope that we'll be able to submit that within the next three months. And I think that's a strong place to start from, when you've outlined, this is the clinical description of the disease, this is a preliminary genetic information that we have and based on the pedigrees as well. I think that's a very strong place to start from to say that we have evidence of heritability and what the next steps in genetic fishing will be. Dr. Finno is a very important investigator for us because she is a geneticist with extensive experience at looking at heritable diseases in large animals, so she's definitely going to be integral to ongoing efforts on this disease.
Deborah Niemann 23:49
And if somebody is listening to this and thinking, oh, wow, I have a goat like that. Is it too late for people to submit their goat to the study?
Erica McKenzie 23:58
The preliminary studies concluded. Yeah. We need to publish what we have, but, definitely I see carpal hyperextension part two being where we regroup, we determine now what samples do we need and how we define this population in light of the peer review that we've had, and then go ahead and sample another large number of affected and related controls to do the more advanced genotyping portion.
Deborah Niemann 24:25
Awesome. This is so interesting. Is there anything else that you think people should know about this?
Erica McKenzie 24:31
I think it's a challenging condition because it doesn't exist in literature. Goat owners are clearly very aware of it. But so far right now, the only way we have to objectively identify it is to measure the angles of the knees. Which is an accepted method in animal species and humans as well. But I think people need to recognize we're the first group to try to bring this disorder into the scientific literature. And it will be vetted. It will be vetted strongly by the reviewers, the journal administrators are going to look at this and it's going to be interesting to see what they say because if this does go through and become published, and I believe it will be, I don't have strong reservations about it, it will be basically the first report of this disorder in the scientific literature and it's important for our vets as well as our clients to become familiar with it. Clearly our clients are well ahead of us in this game. They really are. They've driven this whole project from the beginning and it's impressive and it's a nice collaboration that I'm grateful for but we need to get our vets educated on it now.
Deborah Niemann 25:46
Yeah exactly and it's not showing up in any other breeds, just the Nigerian Dwarf?
Erica McKenzie 25:41
Very rarely, I've had one question about a mini Nubian I believe. I found the fact that it was another small stature to be of interest, but we've virtually heard nothing about other breeds and that's another reason why I think we believe this might be genetic.
Deborah Niemann 25:56
Yeah and mini Nubians all go back to a Nigerian Dwarf buck so.
Erica McKenzie 26:00
Oh interesting okay. See there you go educating us again.
Deborah Niemann 26:04
So it would be great to just look at that pedigree and see where it goes back eventually. Well thank you so much for joining us today this is truly fascinating I know one of my Nigerians that I got in 2002, she was one of the first Nigerians registered, and on her pedigree there are goats that say committee registered, so I'm very aware of what a small gene pool they started with back in the 90's. Thank you so much for joining us today this has been so interesting.
Erica McKenzie & Leah Helene Streb 26:37
Thank you for having us.
Deborah Niemann 26:38
And definitely keep in touch. Let us know uh when you get more work done on this.
Erica McKenzie 26:43
Will do.
Deborah Niemann
And that’s it for today’s show. If you haven’t already done so, be sure to hit the “subscribe” button so that you don’t miss any episodes. To see show notes, you can always visit ForTheLoveOfGoats.com, and you can follow us on Facebook at Facebook.com/LoveGoatsPodcast. See you again next time. Bye for now!
