Episode 18: Dr. Casey Carl DVM - Coat Color Genetics

Be sure to check out the resources below for more information and context for this episode!

About Dr. Casey Carl DVM: Dr. Carl is the Associate Medical Director at Paw Print Genetics. He is a veterinarian and is a strong proponent of using preventative medicine to limit animal suffering. He has experience working with the AVMA in addition to his 4 years in clinical practice.

Laura and Dr. Carl talk about the primary colors in dogs, and what the different loci mean (you may have heard of things like e-locus or k-locus). Dr. Carl gives an overview of how genetics works in influencing what colors dogs are.

They then discuss what affects nose color and foot pad color (it isn’t always the same as what affects coat color!).

Get a brief overview of how genetics works, what genetic mutations entail, what loci are, and what we’ve learned from the dog genome over the past decade.

Dr. Carl explains what merle is from a genetic standpoint, as well as what harlequin and merlequin are in Great Danes. He also describes the health challenges associated with breeding merle dogs.

Resources:

Canine Base Coat Color Genetic Flowchart

Your Guide to Canine Color and Trait Genetic Testing

Transcript

INTRO Laura Reeves Welcome to the Good Dog Pod! I’m your host, Laura Reeves. Here at the Good Dog Pod, we are all about supporting dog breeders and responsible dog ownership. Join our mission and help change the conversation—because we are all stronger together! Good Dog is on a mission to build a better world for our dogs and the people who love them, through education and advocacy. The Good Dog Pod provides dog lovers with the latest updates in canine health and veterinary care, animal legislation and legal advocacy, canine training and behavior science, and dog breeding practices. Subscribe, and join our mission to help give our dogs the world they deserve.

Laura Reeves [0:52] Welcome to the Good Dog Pod! I am your host, Laura Reeves, and I’m very excited to be joined today by Dr. Casey Carl, who is the Associate Medical Director for Paw Print Genetics. We are going to talk about (as I was just saying to Dr. Carl) a very hot-button topic, and that is coat color. We’re going to do a coat color genetics 101 primer course with Dr. Carl, so welcome. I sure appreciate your time, sir.

Dr. Casey Carl [1:21] Absolutely! I’m really excited to be here. It’s great to be with you. 

Laura Reeves [1:24] Excellent. So, our listeners love to know all kinds of things about their dogs, and the burgeoning dog genetic testing is really amazing and it gives us the ability to better predict what we’re going to see from our litters. So, with that, I’m very excited for you to talk about some of the primary colors, if you will, in dogs. Am I saying that right? 

Dr. Casey Carl [1:50] Yeah, yeah. There’s a few different loci or locations that we talk about. They’re kind of the foundational coat colors. They’re kind of the base coat colors. To get an understanding of those is really helpful because then you can apply some of the other mutations that are more modifying to those, and they will actually modify these here. So it gives us kind of a framework to start with, to get an understanding.

Laura Reeves [2:10] Okay. So you suggested we start with (and I think this is great) E-Locus, A-Locus, and K-Locus. E-Locus, which is actually the one I know about in my breed, and M-Locus. 

Dr. Casey Carl [2:22] Yeah, yeah. I think those are great—especially starting with the E-Locus is good because it kind of derails the pathway. They kind of go different ways, depending on what’s going on, because dogs that have two copies of the mutation of the E-Locus can’t produce black or brown, so it kind of changes the direction.

Laura Reeves [2:38] So you’re saying E-Locus, from what you’re telling me, is shades of cream, apricot, and red? Solid white, but not necessarily albino. Correct? 

Dr. Casey Carl [2:47] Yeah. Right. It’s not albino. There are some mutations that have been discovered that have caused albino in some breeds, but many white dogs actually—the E-Locus does play a role in that. For instance, white Poodles, also white Shepherds—they are what we refer to as “little e, little e” (e/e) at the E-Locus, meaning they’ve got two copies of the mutation there, but they also have two copies of a different mutation that is currently going by the I-Locus or Intensity Locus. Dogs that have two copies of that mutation along with their two copies of the E-Locus mutation will tend to be more towards the white spectrum, a very, very light color, like Poodles and those white Shepherds. There are many other breeds that seem to carry that as well. But in terms of a lot of the overall shades of color that you can get from a dog that’s e/e, we haven’t quite worked all of that out yet. So it’s not always easy to predict what shade they may be. Dogs more on the red end of the spectrum—many times people will try to breed red dog to red dog or at least dogs that they know produce red, because it tends to retain that red color a lot better, that fox-red that we see in some Labradors or the red in Poodles. They tend to retain it a little better when you’re breeding two red dogs together than if you, say, bred a red dog to a cream or a red dog to an apricot.

Laura Reeves [4:01] Okay, so let’s use, for example, this does or does not address nose pigment, eyerim pigment, things like that? 

Dr. Casey Carl [4:09] It does not address the eyerim or nose pigment or footpad pigment. That is actually dictated more by the B-Locus. If a dog is e/e at the E-Locus, they’ll be that cream, apricot, or red. But the nose will still be dictated by the B-Locus.

Laura Reeves [4:24] Okay, so a big-B (for our listeners who don’t know) is black, little-b is brown. Correct?

Dr. Casey Carl [4:30] Yeah. So the B-Locus—there’s what we call two alleles (or two versions of the gene). One of them is going to be for black, and the other would be for chocolate. Chocolate or brown is a recessive trait, so just like with the E-Locus to be cream, apricot, or red, you have to have two copies of that mutation—one from each parent—in order to actually have that. Brown is the same way. That’s the definition of the recessive mutation, that both parents have to contribute one copy of that version of the gene to have a brown color. But dogs that are b/b, if they are also cream, apricot, or red in their hair coat, then the only part that you’ll notice the brown in them would actually be on their nose and footpads and such. They’ll modify those colors but would not have any impact on the hair coat because that’s already been modified by the E-Locus. 

Laura Reeves [5:17] Okay, so I’m going to have us step all the way back for people—back to even before we get to loci and alleles—and talk about the canine genome. I know everybody knows that we know it, we tracked it down 15-20 years ago. Nailed it, so that we know what’s going on. Right? 

Dr. Casey Carl [5:38] Mhm. Absolutely.

Laura Reeves [5:40] Each gene or pair of genes (that you inherit, one from each parent) affects everything in the dog, just like it does in the people. And so we’re talking about just a small—what do we call it? Is it called a snip? Am I saying that right?

Dr. Casey Carl [5:53] In some cases, yes. So a snip is a type of a genetic mutation which occurs, and that is a very common one that we’ll look for. But there can be other types of mutation as well. But we’re just looking at different versions of the gene, essentially. So these versions are dictated by these particular mutations that we know end up playing a role in changing a color or trait or, in some cases, producing a disease. A lot of times, those different versions of the gene are just referred to as alleles. That’s kind of the terminology that’s commonly used for that.

Laura Reeves [6:24] And loci refers to where on the DNA strand this gene falls. Am I understanding that correctly? I’m not a geneticist! I’m trying to keep it really basic for people.

Dr. Casey Carl [6:32] Yeah! That’s great. I think it’s important for people to understand. Loci is just basically the plural of locus. Locus is just referring to a very specific area of the genome. All of these color loci are named with these letter names. B-Locus, A-Locus, etc. It’s just indicating a very particular location in the genome that we’re looking for.

Laura Reeves [6:54] We have all seen those little curlicue things that represent the DNA. I’m trying to help people visualize what we’re talking about. For listeners, we will have some graphics and some elements that we’ll put up in the show notes that you’ll be able to see, visually, as well as what we’re describing on the podcast. So the E-Locus, we’re talking about cream, apricot, red, white, all that sort of thing. A-Locus and K-Locus—I know very little about these particular areas, so talk to us about that.

Dr. Casey Carl [7:25] They both work together. The way that I think about it that seems to make the most sense is that the K-Locus is essentially the on/off switch for the A-Locus. And the A-Locus itself is what codes for a variety of different patterns, so we could get sable or fawn, we could get something known as wild sable or wild boar, which we see in Dachshunds sometimes (in the Wirehaired Dachshunds). Or we could see tan points or phantom, which we would see in, say, Poodles. Rottweilers or Dobermanns are kind of the classic dog with that appearance. 

Laura Reeves [7:56] Manchesters. 

Dr. Casey Carl [7:58] Yeah, yeah. But in some breeds, they will refer to it as other things, like in some Poodles, you’ll hear it referred to as phantom. But they work together to create these patterns, so dogs that are what we refer to as Ky/Ky (at the K-Locus) have inherited that version of the gene from each parent—that essentially turns on the A-Locus. That’s the signal in that particular dog to express the A-Locus in that dog. And then there are many possibilities that we could have at the A-Locus that would give us these particular colors. There are four different actual alleles or variations on the gene that we look at at the A-Locus. They go by different letter names. One is AY, one is AW, one is AT, and one is a little a. And they all have a hierarchy of dominance, with the AY being the most dominant, which means that if Ay is inherited along with any of the other types, the AY is really the one that would be seen in that dog. That would code for sable or fawn, in that particular dog. Since it’s the most dominant, it tends to be one of the more easy colors or patterns to get, because if a dog has it and is also (as I mentioned) Ky/Ky at the K-Locus, then they should show that pattern. 

Laura Reeves [9:08] Like a sable Collie or a Shetland Sheepdog or something like that. 

Dr. Casey Carl [9:12] Yes, any of that type of sable color. And sable typically would be defined as hairs that have a very light base on them and, as it progresses towards the tip of the hair, it’s going to become black. Interestingly, if dogs are actually b/b at the B-Locus (so they would technically be brown), rather than having a traditional sable with the black tip, the tip would actually be brown or chocolate. They’re going to be a “chocolate sable,” where it would progress to a chocolate tip, rather than the black. Because with that b/b, they can’t produce that black in their hair coat. 

Laura Reeves [9:43] Right. Fascinating. Okay. I work with Wirehaired Pointers, so I’m very familiar. In Europe, there are dogs that are black Wirehaired Pointers. In the US, we have them, but they’re not shown in the AKC show ring. They’re registerable, they do everything else, but you don’t show them in the show ring. So there’s lots of conversation in my breed and in my club. I’ve had to learn way more than I ever wanted to know about big B/little b. Talk to us again, then, about the M. This one can take us completely sideways. We may wind up having a longer conversation about this down the road. The M-Locus is about merle coloration.

Dr. Casey Carl [10:25] Yeah, and merle is a beautiful coat color. It’s become very popular in many breeds. Essentially, it’s a coat color that is very common. You’ll see it very commonly in breeds like the Australian Shepherd and many other breeds. But it’s essentially defined as areas of fully pigmented regions, separated by either a dilute gray color (so a dilution of that color in between those areas) or, in some cases, white in between those areas, which would give us more of an appearance referred to as harlequin in Australian Shepherds. There is a harlequin as well that can be seen in the Great Dane, but there’s actually a different genetic underpinning for that, so that’s a little bit different.

Laura Reeves [11:00] Okay, that was actually my question! 

Dr. Casey Carl [11:05] Interestingly, on that note, Great Danes actually do have this merle mutation, which plays a role in their harlequin, but they actually have a separate mutation as well, that they inherit along with that in order to give them their appearance.

Laura Reeves [11:17] There’s something they call merlequin. 

Dr. Casey Carl [11:20] Yeah, so the merlequin that they refer to—that’s usually situations where they have a variety of different terms that they use when they’re both merle and these other appearances. 

Laura Reeves [11:31] Patched, right. 

Dr. Casey Carl [11:31] Yeah, but harlequin is a very common pattern that we see in Great Danes. It’s just produced in a slightly different way in them, and they can still be merle as well. If they don’t have the harlequin mutation along with it. 

Laura Reeves [11:42] Right. Merle, to me, is one of the most fascinating things, just because there’s so much direction that it could sprawl. 

Dr. Casey Carl [11:49] Yeah, it’s incredibly diverse because of the very nature of the specific genetic mutation that’s happened in it. There’s a piece of DNA that’s referred to as a sign element that has been inserted into a gene (known as the PMEL gene), and that piece of DNA is very unstable from generation to generation, or even from cell to cell. So when the embryo is forming in a female dog after conception, we’re going to have a lot of cellular replication there, to try to be able to form that animal. And every time those cells divide, they have to make a complete copy of the DNA in that cell to give it to the new cell, to produce this new cell. Well, this particular mutation that occurs in merle is very unstable, and the body’s not very good at replicating that particular region, and so it ends up resulting in the size of that piece of DNA changing. Most commonly, it gets smaller in size in dogs. But it can actually get larger as well. If those changes happen in the sperm or in the egg (so, at the location where they could actually be passed on to the offspring), then those changes could actually be passed on to the offspring. Where we get concerned is in situations where perhaps the mutation size gets so small in a dog that it’s technically there, but the dog doesn’t produce any obvious merle pattern. That can happen in very small size mutations. The concern with that is if you happen to take that dog and happen to breed it to a dog that was merle unknowingly, there are some rare circumstances where you might see that the dog that was originally non-merle in appearance actually had that mutation enlarged in size to some degree, so it technically becomes more like a functional merle mutation again. And if that’s passed along with merle from the other parent, and if any puppy gets two copies of merle, you could potentially run into an issue. It’s often referred to as double merle. Dogs that inherit two copies of that mutation quite often will have an excessive amount of white—sometimes nearly all white—and, in many circumstances, they will have hearing or vision deficits associated with that that can be very significant. The general recommendation when we talk about merle is if you’re ever going to breed an obviously merle dog, it’s not a bad idea to test the other dog for merle first, to verify that they don’t happen to carry a version of the mutation. 

Laura Reeves [14:14] Even if it’s smaller and not actually visible and expressed. 

Dr. Casey Carl [14:18] Exactly. There is a lot of controversy about this right now, out there in the dog world. 

Laura Reeves [14:21] Right. I’m saying I’ve been following social media on a conversation about this exact thing in Australian Shepherds, so I really would love to noodle at this a little bit. 

Dr. Casey Carl [14:30] Yeah, it’s a very hot topic. Part of it is that there are many people that claim that there’s no real risk of breeding a cryptic merle dog (a dog that doesn’t show this mutation) to a dog that does have the merle pattern. In many circumstances, I believe that could be true. In many circumstances, people could probably get away with that. At Paw Print Genetics, it’s been our stance, though, that we don’t recommend it. We don’t recommend going that route because there have been rare cases. We actually saw cases of this in our laboratory when we were doing some study with merle: that dogs that were obviously non-merle were having merle puppies in some cases. And it was purely just the situation that I discussed, where they happened to have this mutation enlarge and show that. So there is this rare possibility. The level of disease that it causes in these dogs when they actually do inherit two copies that are of the correct size to have this happen can be pretty significant. So trying to avoid that, obviously, is going to be the best practice. 

Laura Reeves [15:26] So when you say it’s a rare situation—again, I want to drill into this—talk to me. Rare like 0.6/10ths of a percent or 20 percent—I mean, how rare is rare in this sort of thing? Do you have a way to document that? 

Dr. Casey Carl [15:43] We really don’t. And part of it is that the size of that mutation can vary significantly. If you have a dog that is way, way, way down on the very small end, just using statistics, it’s going to probably be much less likely that they’re going to enlarge enough to actually have an issue or have this actually show a merle pattern at some point. Dogs can fall out anywhere in a very large range, and it’s not very predictable as to when or if that will expand in the upcoming generation. Really, it’s very hard to pinpoint. But it does seem to be a relatively rare event. It is much more common that dogs would have the size of their mutation decrease in those events.

Laura Reeves [16:23] Fascinating stuff. Again, using my itty-teeny-tiny level of knowledge, for example, in Wirehaired Pointers, if they do not have a big B making them black, even if their sire or dam had a big B but also a little b and it went to the offspring (they’re liver, they’re brown, what have you)—they cannot produce the black because they don’t express it. How does that compare to the M-Locus and what you’re talking about with the cryptic merle? In other words, “if you don’t show it, you don’t produce it” obviously isn’t the case in these rare instances. How far back do you have to track your solid tri dog to see if there was ever any merle? Do you understand what I’m saying? 

Dr. Casey Carl [17:13] Yeah, that’s a great point. When it comes to merle, it is a little bit different than some of our other traits because it is inherited in this dominant fashion. Dominant is kind of the other common inheritance pattern, second to recessive. Dominant only requires one copy of a mutation from only a single parent in order to actually show the trait. So with merle, merle dogs would only need that one copy to actually produce that beautiful merle pattern—opposed to a situation like brown, where you could technically be a black dog that carries brown and you would never know it by simply looking at the dog. That’s kind of the big difference, because brown is that recessive trait, which, again, requires those two parents to actually pass that on. So that is a big difference. The only time that you wouldn’t see a merle mutation or actually see it visible in the dog is a situation where that merle mutation tends to be smaller. That tends to be the case. I will say, though, that at Paw Print Genetics, we kind of group merle dogs into four general groups based upon the size of their merle mutation and the general appearance that they have. There are other schemes out there that people have developed as well to separate these. I don’t know that one is necessarily more right than the other; it’s just different. There are definitely people that will claim that theirs is better than another, or whatever the case may be, but really when it gets right down to it, most of them fall into these very particular groups. But some dogs just don’t read the textbook, so to speak. There are some dogs that we just don’t understand why, but they end up in a different group even though the size of their mutation falls into what we would expect to see, they may appear slightly different or appear like they’re from a different group. That definitely happens. There’s no defined walls between these groups that we’ve created. They’re all kind of artificial constructs. 

Laura Reeves [18:54] Okay. I guess—bottom line—the takeaway on this is if you are breeding dogs and you’re working with the merle gene in whatever you’re breeding, that having some kind of genetic testing gives you information that you wouldn’t otherwise have.

Dr. Casey Carl [19:13] Absolutely. Especially to test that other non-merle dog before you breed it to a merle dog—it’s a really, really great idea. And you had mentioned something about going back in generations and things like that. It’s not really as critical. If you just focus on that immediate parent that is there, that’s going to be the most crucial aspect to that.

Laura Reeves [19:32] Beautiful. I want to hop back to the E-Locus and the white dogs. So you’re talking about a white standard Poodle, a white German Shepherd, a Bichon—some of those types of dogs—we didn’t really get a chance to follow up on that I-Locus. 

Dr. Casey Carl [19:54] The I-Locus is a relatively new genetic mutation that’s been discovered that results in these dogs that are e/e being more close to white. Currently, right now at this very moment, we don’t offer it through our Paw Print Genetic service (that particular test) but we do have a canine genetic screening product called the Canine Health Check that we offer at Paw Print Genetics. That test is on the Canine Health Check right now. We will be bringing it to Paw Print Genetics. I don’t have a specific timeline as to when that’s going to happen, but it is on our list, and we will be bringing it over here soon to Paw Print as well, to order as an individual test, as opposed to a large screening. 

Laura Reeves [20:30] When you’re talking about the E-Locus again, you’ve got everything from a Vizsla (with a self-colored nose) to an Irish Setter—both red, but with a black nose. So that’s the part. Just giving people ideas of the B-Locus that’s involved, correct?

Dr. Casey Carl [20:50] Absolutely. So the B-Locus will play a role in that. One common thing that we talk about with, for example, Labrador breeders (yellow Labrador breeders in particular) is that in most cases, they would really prefer to keep that nice black nose, so one of the things that they’re looking at there is: does this dog carry chocolate, and if so, how do I breed around that so I don’t get a chocolate nose in my yellow Labrador? Because that B-Locus plays such an important role in dictating that nose color. It can be very helpful to use that to your advantage, and it’s pretty easy to breed around if you know what your dogs are carrying.

Laura Reeves [21:20] Right. If you know what you have, you can either make a chocolate dog (if you’re looking to make a chocolate Lab) or you can have a black nose pigment. To me, the advantage of genetic testing is it gives us so much more flexibility. My parents bred field trial Labs way back in the day. You look at that black dog: Does it have three white hairs on the underside of its pad? Okay, it carries yellow. Seriously! That’s how we knew or didn’t know if that dog was going to carry yellow. I think back to those days in the mid-70s, thinking wow, it would’ve been so much easier! 

Dr. Casey Carl [21:58] There are many things that breeders discover, being on the front line out there, about color—things that they’ve just observed in their lines—that we would never know as scientists. I learn so much from our clients, just about the little tips and tricks that they’ve learned over the years to identify certain things in dogs. Most of the research that’s out there comes from somebody observing something. These types of things are very important. And I think it’s really important for us as scientists to listen, to listen to the breeders, to listen to what they’ve known for all these years and pay attention.

Laura Reeves [22:27] There you go. There’s your tip of the day. Three white hairs on the pad of my black Lab. I’m serious. 

Dr. Casey Carl [22:33] I’ll keep that in mind. 

Laura Reeves [22:35] I’m totally serious. Listeners, here’s the deal. Dr. Carl has agreed to do this more than once, so whatever questions you have going forward, we’ll have a link for you in the show notes to shoot us some questions, and we can talk about it some more. We have some future episodes, talking about some of the dilution of the various color genes, which I think is going to be fascinating. I’m very excited to have those conversations. 

Dr. Casey Carl [23:03] Absolutely. There’s a little bit of a disease component to that one as well, which is kind of interesting, so we can definitely talk about that as well. That’d be great.

Laura Reeves [23:10] I think that there’s a lot of great conversations to be had going forward, so I sure appreciate it. 

Dr. Casey Carl [23:15] Yeah, thank you so much for having me. Anybody can reach me at Paw Print Genetics as well, if they want to reach out and have any specific questions about things. I’m always available there as well. 

Laura Reeves [23:23] Excellent. Alright, well until next time. Watch this space!

OUTRO

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