Dominant White


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The blog here continues to be somewhat silent while I work on the next book, “Equine Tapestry – An Introduction to Colors and Patterns“. What began as a reissue of the front portion of Volume I, Draft and Coaching Breedsface in color has (predictably) taken on a life of its own. The original text touched on the as-yet-unidentified pinto patterns, with an attempt to classify the different categories of sabino-like patterns visually. Since that time, quite a few more pieces of the puzzle have fallen into place, and that has lead me to do a major overhaul on that material.

One of the things that became clear to me with this new information was that the way I personally organize my files was leading to blind spots in my understanding. I have mentioned before that a huge part of my research involves massive notebooks with images and pedigrees. Because I am a visual learner, sorting things this way helps me make connections that I might otherwise miss.

Notebooks

I have organized information in notebook pages like these for more than 20 years. Soon after I began, I started sorting the information by breed. Because so much of my interest centered around which colors were present in which breeding population, this made sense. What I began to suspect, working on the new book, was that I needed to rearrange some of my notes by color groups, rather than by breed. The previous structure was great for seeing how some of the louder sabino patterning arose in the Arabian breed. Seeing how that worked convinced me that the louder horses were some kind of new mutation, and not just a more extensive expression of the existing “flashy white” in some lines. Laid out in a breed-centered notebook, it was clear how these louder horses – horses like Rhocky Rhoad – might come from flashy families (like Khemosabi), but their (numerous) relatives did not generally look unusual, while their own descendants most certainly did.

But this same structure made it harder to make connections about the colors themselves. The sheer volume of information – I have thousands of horses on file, and many times that number waiting to be included – made those connections more dependent on my working memory. Writing more has meant less time for musing, and with it the chance that I would make those mental jumps. When recent papers made it clear that my hunch about horses like Rhocky Rhoad were correct, I decide it was time to set up a parallel set of notebooks for the pinto pattern categories, starting with the W-series (W1-W20). I was hoping this would give me better insight into how the patterns within that group – the group previously called “dominant white” – worked. With luck, I might stumble upon the best way to present this very varied, and not-entirely-helpfully-nameed group in the new book.

I now have all twenty of the known W mutations, along with images of every known or suspected carrier, in a single notebook. The first thing that jumped out at me was something that has been a bit of a hobby horse for me for some time now. That was how many of these lines involved blue eyes. Of the twenty families, six have blue-eyed individuals. In some cases, like the W5 family member Sato (above), just have a blue segment. Others have a full blue eye, or even two blue eyes, thought that last is actually pretty rare.

This is not surprising to anyone who has looked at historical records of white-born horses. Blue eyes are not infrequently mentioned. They are mentioned in connection with some of the old European studs that previously bred white-born horses. Early researchers also comment on their occasional presence. Nowadays, a search on the internet will turn up any number of commenters that will tell you that this “obviously” means the horses carry a splash pattern. You can even find those who will assert that no KIT mutation ever produces blue eyes in a mammal.

That was part of why I included the image of the panda German Shepherd a while back. She has a newly-identified KIT mutation, and she most certainly has blue eyes.

FrankieSM

Interestingly enough, most white patterning in dogs has proven to be caused by mutations to MITF – not KIT. In horses, MITF is the gene associated with splash patterning – and with blue eyes. For those familiar with dog coloring, the “extreme piebald” found in many sporting breeds, the “color-headed white” pattern in Collies and Shelties, and many forms of “Irish Spotting” have all been mapped to MITF. None of these patterns is associated with blue eyes in dogs. There is a MITF mutation in dogs – the one that produces white in Boxers – that produces blue eyes on rare occasions, to this is not an absolute, but generally speaking these MITF mutations are not associated with blue eyes. (For more information on the different MITF mutations in dogs, this a good site.)

The common theory in horses is that these W-series horses must have a splash mutation as well. And they may. Certainly there are far more mutations for white patterning than previous expected. I have long thought that the numbers of blue eyes on the dominant whites, particularly among the founder horses (ie., the horse that carried the initial mutation) were just too high for them all to happen to have a splash mutation as well. I did not have an exact number, though – just a sense that it was high. But the new sort gave me a number – six of twenty. That’s a lot, especially with breeds where there is no evidence of the presence of the one splash pattern (classic splash, SW1) known to remain cryptic in its heterozygous state. The other “new” splashes are dominant mutations, and a good bit more obvious in terms of phenotype.

What is interesting is that the one horse that is often asserted by online commenters to “surely be a splash” is the well-known Arabian stallion Khemosabi. This is based on the fact that he has multiple blue-eyed descendants. What became clear as I resorted these records was that yes, he does have a number of blue-eyed descendants. However, all those in my files are also members of the two W-series mutations that occurred in his line. One would expect, if Khemosabi carried a splash mutation (at least, as we currently understand the pattern), it would appear in more than two lines. He did, after all, sire over 1,250 foals. Finding it in two lines, which also just happen to be those that have formally identified white spotting mutations, seems to suggest that the blue eyes are part of the pattern and not some additional inherited trait.

There are caveats to this, of course. Blue eyes are notoriously underreported. When I began to suspect that the louder sabino expressions in Arabians were new mutations, I printed out the markings files for the families where they occurred. So in my files are the marking diagrams for all the first generation Khemosabi descendants. It is quite possible that there are horses in that group with blue eyes that were not part of the registration records. Blue eyes in Arabians are still considered a serious fault, so there is some incentive to overlook it when filing a description, especially for an eye that is not completely blue. (I am always looking for images and records of blue eyes in Arabians, if anyone has them, by the way!)  I cannot also be sure that some of the other lines – the fourteen that are not included as having blue eyes – might not also have blue. In many cases, eye color is not mentioned at all,  and there I have defaulted to the assumption that the eyes were dark. That is not the same as knowing the eyes are dark, though.

My next task is to assemble the even larger group of suspected dominant white horses into one notebook. When that task is complete, I should be able to do another post about the status of the blue eyes in that group as well.  Well, that and get a little closer to a finished book!

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I think I need to work on final book edits every spring, because it seems to guarantee that a paper will come out within that time period. Animal Genetics has a short communication out with three new KIT mutations and one new PAX3 in horses. There are also two papers out on KIT patterns in dogs, which is new. Before this, the piebald patterns in dogs had been mapped to MITF, which in horses is the other site for splash white. The picture above is the German Shepherd that carried the de novo mutation. (I must give a special thank you to her owner for allowing me to include it here.) I had intended to put together a longer post on this pattern, known as panda, because it touches on the subject of blue eyes in KIT mutations. She obviously has blue eyes, and her owner confirmed for me that some of her descendants have had a blue eye or blue segments in their eyes. This follows the pattern that I have seen in the historical records of some suspected Dominant White horses (also presumed to be KIT mutations). Blue eyes do seem more common in the originators, and then appear to occur sporadically – often in a less pronounced degree – in the descendants. Interestingly enough, the MITF mutations are not associated with blue eyes. In fact, this family of Shepherds was the first instance I noted where blue eyes in dogs were linked with a form of white spotting so I was particularly happy to see the mutation formally identified.

What is interesting about the new equine discoveries is that they really do not fit neatly into existing naming categories. The KIT mutations have been assigned numbers in the “W” series, but at least one appears to be subtle white-booster rather than a true dominant white. I had been urged by a couple of researchers, as I got close to my publication date, to avoid the use of the term “sabino” and just use “white spotting”, and I see now why. I suspect this will become more complicated as time goes on and more mutations are identified. One thing does seem clear, and that is that several of these sites mutate often – apparently in ways both large and small!

Just as I did with the book last year, I’ll be updating the text to reflect this new information for the new full-color supplemental book. I had feared there might not be much new information, but this coupled with some of the things I have been researching in the last few months should make for a lot more content as well as more abundant (and colorful) images!

This horse has one copy of the frame mutation. Horses with two copies of the mutation are not viable.

In the previous post I talked about how the physical location of a mutation can limit the possible pattern combination. There is another potential limitation, which is viability of the organism.

Those of us that like horse colors, particularly the white patterns, are accustomed to thinking of colors as something that is added to what would otherwise be a horse of ordinary coloring. So the horse above has white markings on his body in addition to his chestnut coloring. That is certainly how a lot of artists would approach painting such a horse.

But from a genetic standpoint, that’s not what has happened. Generally speaking, white patterns result when one of the genes involved in pigmentation is impaired. Something prevents the normal function of the gene, and as a result pigment is not distributed in the normal fashion.  That is what we see most clearly, because changes to coloration are really obvious. But those same genes do not just regulate color, and those other functions may be effected as well. Hampering coloration is largely cosmetic, but altering the function of the gene can have more serious implications.

That’s why horses with two copies of the frame mutation are not viable. With just one impaired gene, the horse is not completely pigmented (ie., it has white patches) but is still functional. The horse still has one non-mutated copy of EDNRB, the gene involved with the frame pattern. It can “pick up the slack” for the necessary functions that gene performs. When the horse inherits two copies of the mutation, there is no backup and the gene cannot perform its function in the development of the embryo. In this particular case, no pigmentation occurs, which is why the resulting foals are white, but more importantly the colon is incomplete which means the foal cannot survive.

Lethal White Syndrome is probably one of the best known problems with color because it involves the heartbreak of a live birth of a foal that must be humanely euthanized. Other colors, most notably the various forms of Dominant White, are also thought to be lethal when homozygous. Like the frame mutation, two copies impair the function of the gene to the point that the embryo is no longer viable. The difference between Dominant White and Frame Overo is that the embryo is lost early enough that no foal is born. This may explain why programs centered around breeding white-born horses in the seventeenth and eighteenth century were often plagued by infertility issues.

At one time, roan was also thought to be a homozygous lethal. (Photo from Wikimedia Commons.)

 

In the past, before tests were available, lethal conditions like this were determined by analyzing production numbers. If the ratio of mutated to non-mutated offspring was off, and if true-breeding individuals could not be found, the trait was suspected of being lethal when homozygous. That was why roan was assumed to be a homozygous lethal for so long. Initial studies of production records showed that the ratios of mutated offspring were like those of a homozygous lethal, rather than a simple dominant. Proven homozygous roan stallions have since been identified, so it is clear that two roan genes are not always lethal, at the very least.

So what does this have to do with the KIT mutations? In the comments section, there was speculation of the last post about whether or not mutations could crossover, resulting in a single gene with two separate mutations, rather than two separate genes with one mutation on each. Not asked, but an equally valid question, is whether or not a gene that already contained a known mutation could mutate again. If either were to happen, the next question would be could the situation result in a viable embryo? Would the added layer of impairment change the coloring, or would it damage or even destroy the organism? Have we not yet seen a horse with three KIT mutations (one on one gene, two on the other) because the statistical chances are infinitesimally small, or because the function of some gene is too compromised to result in a viable embryo?

I have wanted to bring up a more technical aspect of horse color for a while, but have struggled with the best way to present the information. Part of the problem is that the way we talk about horse color is misleading. For this to make any sense, I will have to clarify some terms.

We often talk about horse colors as if they are genes. We say, then, that a horse like the one pictured above has one copy of the “sabino gene” and one copy of the “tobiano gene”. It is true that the “torn tissue” look to his pattern is very typical of what a horse looks like when it has both Sabino1 and Tobiano. He is a Spotted Saddler, so he would likely test positive for each color. Saying he has the Sabino1 gene and the Tobiano gene is a simple way to get that idea across.

The trouble is that there is not a specific Sabino1 gene. There isn’t a Tobiano gene. Sabino1 and Tobiano are mutations of an existing gene. When we say that a horse has the “tobiano gene” or the “not-tobiano gene”, what we really mean is that the gene that was there from the start is either mutated (tobiano) or not mutated (non-tobiano). This makes sense when you think about it. Why would an organism carry around a gene that is essentially the absence of a trait?

This might seem like semantics, except that some of what we think of as separate colors occur on the same actual gene. They are different mutations, but they share a location. In the case of Sabino1, the mutation occurred on a gene known as KIT. Other mutations found on or very close to KIT are tobiano, true roan and dominant white. This might not seem important until you remember that an animal has two copies of any given gene, one from each parent. It can only give one to any individual offspring. If a horse only has two KIT genes, then it can only carry two mutations – one on each copy of the gene. That means you only have two slots to fill with KIT mutations. A horse could be homozygous for tobiano, but then he could not also carry Sabino1. His two KIT slots are already filled.

This probably makes more sense when it is understood that most color mutations are one-time events that happened a very long time ago. Sabino1 has been documented in Siberia in the early Bronze Age, so it is at least that old. Horses like the one pictured here descend in an unbroken line from whatever early ancestor carried that first Sabino1 mutation. One of his KIT genes is that same gene with that same mutation. His other KIT gene comes from the whatever horse carried the first tobiano mutation. That pattern has been found in Eastern Europe later in the  Bronze Age, so like Sabino1 it is really old. Were he not a gelding, he could in turn pass on one of those – either tobiano or sabino1 – to his offspring. One, but not both.

This has implications for artists like myself because we tend to mix-and-match the details of different patterns to get certain visual effects. What we have to be careful about is whether or not the limitations of gene locations make something impossible. If a horse can only carry two KIT mutations, and true roan and tobiano prove to be on KIT or linked to KIT, then is a homozygous tobiano roan possible? Is a roan tobiano with cat track markings – a trait closely associated with homozygosity in tobianos – accurate? And what about the other colors and patterns that have not been mapped to a specific location? What conflicts will become apparent when more mutations have known locations? We know, for instance, that the leopard complex gene (varnish roan) is not located on KIT, but what about the patterning genes that work with leopard complex to make the more vivid appaloosa patterns? It is often assumed that all combinations are possible, though they might be so rare that actual living animals cannot be found with them. That is probably a mistaken assumption, with some combinations not possible because of location conflicts.

This also has implications for people who study horse color. Homozygous tobianos are an interesting example because they obviously have two KIT-related mutations. Still a high percentage of homozygous tobianos have face markings. The commonly accepted wisdom is that tobiano by itself will not place white on the face, yet KIT is often assumed to be involved in ordinary face markings as well as the sabino patterns. Does the fact that many homozygous tobianos have broad blazes suggest that some sabino patterns are not, in fact, located on KIT? Or does it suggest that in its homozygous state, tobiano does start to place white on the face?

It is also important to breeders, who may find that attractive combinations do not necessarily breed true. Many Paint Horse breeders have already noted this situation with roan tobianos. Roan has not yet been definitively mapped, and it is thought to be close to KIT rather than on KIT. Still genes that sit close to one another tend to travel as a package, and that is definitely the case with roan and KIT. Roan tobianos typically have a roan parent and a tobiano parent, and they usually pass along either roan or tobiano to their foals, but not both.

Gene location is pretty technical stuff, but the information has a lot of practical uses.

Recently a discussion of Dominant White came up on another forum, and as often happens the question of the naming of the pattern was raised. When the first study was published, many felt that the pattern was part of the sabino series and should have been named Sabino2. (Sabino1 had been identified a short time prior.)

In that discussion, someone suggested that Dominant White was disproven in an article I wrote many years ago. Because I have encountered that comment before, and because I hate to contribute indirectly to the confusion around the two patterns, I’m going to condense my response to that statement here. I had intended to do a revision to the article shortly after the first Dominant White paper was published, but I never found the time, so this will have to do for the moment.

The article was originally written sometime around 1992 and updated again in 1997. It was intended to question the current thinking (that is, early to mid-1990s thinking) about Dominant White. Back then I wasn’t sure that I was right, because there were so many gaps in the information. From the article:

This is not to say that dominant white horses do not exist, but I am personally skeptical, having never found one I could prove wasn’t more likely a sabino white.

Also:

Given the breeding records of the aforementioned white horses, I have come to wonder if Dominant White really does exist. But it is clear that even if it does, the majority of white-born horses are probably sabino whites.

My assertions then were based on the picture I had, but I knew I wasn’t looking at a complete picture.  And like almost all researchers who look at a partial picture, my analysis was skewed by the specifics of the group I had to study. When I began assembling information on white-born foals, the most common horse used to illustrate Dominant White was the Tennessee Walking Horse. They were mentioned, and their photos almost always
appeared in anything about Dominant White. I had access to not only the stud books, with all their elaborate detail, from when the breed had a high proportion of whites, but I also lived just a short ride from the registry headquarters where I had been given free use of their archive materials. I could get as complete a picture as might be possible fifty or sixty years after the fact, and that picture said that each and every white Walking Horse had two sabino parents.

In fact, it said that each had a highly marked sabino, because I had an elaborate numbering system for weighing how much white the sabinos had. Some of the assumptions behind those numbers were wrong, but it happened to give me accurate results for the wrong reasons! (Lesson learned there about the limitations of stud book records.)

That specific conclusion was accurate. What I was looking at in the Walking Horse records was not dominant white. It was an incompletely dominant form of sabino. Sabino1 is a really old mutation, as the study done on colors in ancient remains showed a few years ago. It’s spread out through a variety of breeds, but there probably isn’t another one that has such a concentrated population of them as the Walking Horse, particularly as the breed was at its founding.

I moved from the Walking Horses out to other know cases of whites, but if you read the paper that information is much more sketchy. I didn’t have access to the kind of pedigree and production records I had with the Walking Horses.  What I had was a lot of anecdotal evidence that white-born horses in other breeds produced what looked like sabino.

But even so, there were weak spots in the theory that *all* these horses were sabinos. There were horses that only fit the pattern if you allowed for a really liberal classification of sabino. That didn’t fit what I saw with Walking Horses, where the parents of whites were scoring high on my “how white is the horse” scale. At the time, I wondered if linkage to chestnut was hiding sabino, which I mention in the article. I intended to explore that idea more thoroughly in a future paper, which never got written – and probably just as well, since I fundamentally misunderstood linkage! (Lesson learned about the limitations of studying phenotype without a background in the molecular end of genetics.)

Those exceptions did bug me. In fact, I had them all tagged in my own research files as oddities. I have often said that as a researcher, where you are wrong is where you learn. Because the weak spots in a theory are usually where new information is going to come, I tend to flag them in my files. The horses that were flagged as not fitting the theory of sabino white where: R Khasper, Cigale, Mont Blanc, Patchen Beauty and Sneuwwijte.

Three of those are, of course, among the families later identified as Dominant White. Mont Blanc was not part of that study but he certainly fits the same profile.

The last one isn’t as well-known. Sneuwwitje (Snow White) was a Groninger that appeared in the Wiersema book in the 1970s. I had a copy when the article was written, but I could not translate it. The pedigree and color information was there, and I could see that she didn’t fit the profile. If I had access to the sort of automated translators we have now, I would have found at least part of the puzzle that I was missing. That’s because Wiersema outlined in detail the exact theory I proposed; that is, that sabino x sabino crosses produced white foals. (I go into detail in the upcoming book about the different Sabino1 families in the Groninger, and the breeders who were using them to produce white horses.)

Then he discusses the white-born Sneuwwitje, who did not fit his pattern. She was from solid parents, and then when she was bred to different test mates, she produced 50% white or colored foals. That is, of course, exactly what would be expected from a Dominant White. Solid parents (ie., she came out of nowhere) and a 50% production rate of white or pied foals. (Where she a sabino white, you’d have sabino parents and a production rate of 100% pied foals.) He then states that there must be two different types of white-born foals, which of course is exactly what the dominant white study proved almost forty years later.

Since that time I’ve been able to translate not just his book, but a number of papers from other early twentieth century German researchers that were making similar observations. They also studied the “white-born” (weissgeboren) horses and were finding horses like Sneuwwitje. In fact, knowing the behavior of the two different genes, it’s pretty easy to tell which group (W or Sb1) a given researcher might have been studying.

In closing I do think that calling the two different genes separate names is a good idea. Yes, they do look indistinguishable from one another in many cases. I certainly wouldn’t blame anyone for advertising a more patched variety of dominant white as sabino, since that is what most horsemen are going to call the horse based on the appearance. But when talking about the actual genetics, the two different names help clarify the fact that these horses that look alike don’t actually breed alike. The ways that they are different – like whether they can appear out of nowhere or not, are able to produce all pintos or not, are lethal or not – have important implications for breeding decisions, so anything that highlights that is probably helpful.

When it comes to how the different patterns interact, tobiano could be called the top dog. Pretty much no matter what else it gets paired with, the end result still looks pretty much like a tobiano. Sometimes the other patterns add new areas of white, like this tovero here with the bald face and white ear, but visually it is still pretty easy to identify the horse as carrying tobiano.

Here is an pony with both the appaloosa and tobiano patterns. Notice how the white areas from the tobiano just overlay the leopard pattern.

The lighting for that picture was just right to show the tobiano markings. In bright light, it would be possible to miss it. The outline is also lost as the pattern travels up his hindquarter, when it meets what would likely be the pink-skinned area on a leopard.

Here is tobiano overlapping dark-headed frosty roan.

Tobiano even stays intact when inherited by zebra hybrids. (Photo from Wikipedia Commons.)

It is tamped down and made more minimal in donkey crosses, but it is still quite obviously tobiano. (Photo by Amanda Slater.)

Which brings me back to the discussion about white Miniatures from a few days ago. I truly did not think the colt in question was a Dominant White, but rather a tobiano that was rapidly greying out. As a young foal, he looked like a chestnut tobiano. It did lead to the question, though, about what Dominant White might look like paired with tobiano. Would it overlap the pigmented areas (few though they might be in many cases), much like it did with the leopard above? Or would the instructions to make the horse white override the tobiano patterning altogether?

I suspect that the answer lies in the way the two patterns function at the molecular level. I enjoy reading papers about that aspect of genetics, but in many ways that is above my pay grade. As an artist, I am at heart someone who understands the nuances of phenotype (that is, how the horse looks) far more thoroughly than I understand the underlying mechanics. I will need to wait until someone crosses a Dominant White (particularly one of the families that tends towards the “leaky” variety rather than the all-white) with a tobiano to find out.

 

A short time after the posts about Dominant White went out, I was contacted by someone about a family of seemingly white Miniatures. The stallion was advertised as a maximum white sabino, which is often how Dominant White horses are described. The writer wanted to know if I thought the horse was a White or a Sabino. She thought they might be Whites because of this quote from the Wikipedia entry about the color.

Horses with the W3 allele often retain interspersed flecks or regions of pigmented skin and hair, which may fade with time.

That quote was in reference to the third identified family of Dominant Whites, which began with the mutation in the Arabian stallion R Khasper. A few of the other Dominant White families – but not all – have this same tendency. Photos of the Freiberger horses in the original white study (W1, the Cigale family) show this phenomenon really well.

Here is a Cigale descendant as a foal.

Here he is as a mature horse.

(Both photos are from the original journal article by Haas and Brooks.)

The writer wondered if the same thing was happening with the Miniatures. Looking at the pictures, it was clear that whatever else was going on with the stallion, he was a tobiano because he was throwing a lot of tobiano foals from unmarked mares. The fact that some of those tobiano foals turned white really quickly was why Dominant White was suspected. Because the dark areas of their tobiano patterns looked to have uniformly dark skin, my own suspicion was that the foals at least were not White, but early greys.

Andrea Caudill sent the picture at the top of this post, and it is perhaps helpful in this case. The colt is two years old, and almost entirely white grey. His legs are muddy in the photos, but Andrea says they were also white. As a thin-coated race horse in what is probably a wet environment, it’s easy to see his dark skin. In my experience, it can be much harder to tell white greys with extensive markings or facial depigmentation from truly white horses when they are dry and have denser coats.

Some horses, like this colt, do grey really early. Famous white grey breeds like the Lipizzans and Kladrubers have been bred specifically for early and thorough greying. Conversely, breeds like the Percheron have been bred for later greying, so it would appear that greying speed can be manipulated by selective breeding. Perhaps even more interesting, and relevant to the situation with the Miniatures, is that early studies on the silver gene mentioned that pairing silver (Z) with grey (G) produced really rapid greying. I do not believe this was studied in-depth, but it is true that a number of Shetland breeders in the mid-twentieth century were attempting to breed “white” ponies that were in fact early greys. That might be what was happening with the Miniatures in question.

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