April 2012

As I posted briefly yesterday, the new paper on splashed white had a lot of surprising information, not the least of which was the horse pictured in yesterday’s post. A number of people wondered about his identity, and most particularly about his breed. His name is Apache du Peupe, and he is a four year-old Freiberger. The Freiberger is also called the Franches-Montagne, which sometimes leads to confusion. The horses in the picture above (courtesy of Wikimedia Commons) are quite typical examples. Freibergers are among the last of the European light draft breeds, though in more recent years many breeders have focused on a slightly lighter riding type, which is why I choose to shift them – and a few others, like the Frederiksborg – to a later volume rather than include it in the draft and coaching breeds.

Because they were originally included in the upcoming volume, I had looked into the range of colors in the breed. Apache came to my attention during that time. Freibergers were already interesting because they had a well-documented family of dominant whites. Those trace back to a white mare, Cigale, born in 1957. She was the source of what eventually became the first formally identified dominant white mutation. Hers is the mutation that got the designation W1. That is what I thought Apache was, until I realized that he was not related to Cigale. In fact, his parents did not look all that different in color from the two horses pictured above.

Here he is again, from yesterday’s post:

This is his sire, Noble Coeur. This is his dam, Muscade. Both are clear bays with socks and minimal face markings. Apache and his parents are the kind of horses that sat in my “don’t fit the theory” file when I first wrote about maximum sabinos (sabino whites) in the 1990s. The horses that did fit that theory turned out to be Sabino1, the spotting pattern that results in a white horse when homozygous. All the horses that fit the theory had parents with a high number on my ranking scale for white markings, while most of the horses in the “don’t fit” file had parents that fell short. Typically they did have some white, but it was a stretch to say they were marked like the others. Had Apache and his parents come along at that time, they would have ended up in that same file. Many of the horses there (R Khasper, White Beauty, Puchilingui) were later identified as dominant whites.

So I wondered if Apache was another new dominant white mutation. But there was another aspect to him that made me wonder, and that is why – up until yesterday when he appeared in the splashed white paper – he was in my “mystery” files. If you look closely at his picture, he looks diluted. If he were a Paint horse, or almost any other American stock or gaited breed, I would assume he was buckskin. Here are more pictures that give that impression.

Cantering (with is spin visible to show no dorsal stripe)
Conformation (quite current, shot in 2011)

That was what was so unusual about him. His parents are, as the links show, quite ordinary bays. And even allowing for the fact that he probably has a good portion of white hairs mixed in his coat, the tones give the impression that the actual hair is diluted. His owners called his unusual color “macchiato”, for the coffee drink, which suggested that he was cream-colored in person. Since his parents were not diluted, and since I had no evidence that cream (or any other dilution) was present in the Freiberger, I wondered about the accuracy of his pedigree. Pattern mutations do appear, but a pattern and a dilution all in one horse?

And now with the publication of the splashed white paper, we know that is exactly what he has: a mutation that is both a dilution and a white pattern. Researchers parent tested him using 13 markers, confirming that he really was the offspring of the parents of record. What’s more, they tested blood, hair roots and sperm to rule out mosaicism. Mosaics are animals that have two separate sets of cells with different genetic coding. Horses that are patched with black and chestnut, for example, are mosaics. Apache is, genetically speaking, all one horse with the same genetic makeup throughout his body. They also looked at the genes currently known to produce dilutions, and found nothing out of the ordinary. So he’s not a cream, a silver, champagne, pearl or dun. He is what is called a de novo mutation – something new.

The new thing that he has is a mutation at the same location as splashed white, which is the MITF gene. The color Apache’s breeders named Macchiato is a form of splashed white. Technically that makes four identified splashed white patterns, although researchers declined to name his SW4, perhaps in deference to what his breeders were already calling the color. So far the other MITF mutation for which we have numerous examples to study, SW1, does not seem to have the diluting component. The third, SW3, is said to be rare and none beyond the two horses pictured in the paper have come to light so far. Neither of those two horses appear diluted, but two is not a lot of data, especially when one is too white to really evaluate base color on anyway.

But what is interesting is that Apache’s mutation has a human equivalent. The human Tietz Syndrome is caused by a similar mutation. The Office of Rare Diseases Research describes Tietz Syndrome this way:

Tietz syndrome is a genetic condition characterized by profound hearing loss from birth, fair skin, and light-colored hair. This condition is caused by mutations in the MITF gene.

A second human MITF mutation causes Waardenburg Syndrome. Again from the Office of Rare Diseases Research:

Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes.

So a similar mutation in human beings causes pale hair, piebald patches (in the Waardenburg Syndrome) and pale eyes. It also causes deafness, which was also true for Apache, who tested to be deaf.

That raises the question of whether or not other as-yet-unidentified splashed white patterns might not have a dilution component like that seen in Apache. Certainly several of the horses from the Bald Eagle line have a very similar base color to Apache du Peupe. I had assumed that, being stock horses, the were getting their diluted color from the other parent. It would certainly be worth looking at the members of that family to confirm that those with diluted base colors actually had a diluted parent. That isn’t something that ever would have occurred to me to look for, because “dilution” and “white pattern” were completely separate categories of colors up until yesterday. As I said, it is an exciting time to study horse color, because there really is something new to learn all the time!

So that’s three of the four mutations. Someone probably noticed that one got skipped. That is SW2, and if Macchiato complicates how we categorize mutations, that one complicates how we are naming them. I’ll open that can of worms in the next post!


The long-awaited splashed white paper has now been published in PLoS Genetics. The full article can be read here.

As a number of people predicted, the MITF gene is involved, but there are also some surprises. One of them is that the authors looked into the odd case of the Freiberger stallion, Apache. Above is his picture from the paper, and the link from his name will take you to a site with more pictures. His owners called his odd color and pattern “macchiato.” He’s been in my “mystery” files since I first stumbled across him a year or so ago, so I was tickled to see that he was included in the paper.

It will take me a day or so, but I will try to put up a plain English summary of the paper. It is an exciting time for those of us interested in animal coloration!

Just a quick note that the previous post on dogs was composed during our family’s annual trip to Pawleys Island. I am still shaking the sand off my feet and realizing just how much was left undone while I enjoyed the live oaks and the azaleas. If you are waiting for a reply from me, or if your message was caught in my (over-vigilant) spam filter, don’t give up yet! I should be caught up in the next day or so. (Or at least as caught up as I ever actually manage to be!)

These two Dogue de Bordeaux have the extremely narrow, upright nostrils that are common in the breed. This and other anatomical exaggerations are why the Dogue is included in the Kennel Club list of high profile breeds subject to separate vet checks at shows. (Photos from Wikipedia.)

As I mentioned in the previous post, I want to do a series of posts on the subject of genetic diversity. Obviously the primary focus of this blog is horses, but for this particular topic I will be jumping back and forth a bit between the world of dogs and the world of horses. The situation in many purebred dog breeds is quite dire. With few exceptions, horse breeds do not face nearly such difficult circumstances, and because of that, most breeders of horses do not face the same difficult choices. Still, the factors that allowed purebred dogs to reach this point are not entirely absent in horses. It is also true that because dogs are so pervasive in our culture, many people have had their views, particularly those about what constitutes a ‘proper breed’, influenced by the world of pedigree dogs. For that reason, I will present the situation with dog breeding as a cautionary tale for those interested in horses.

So what has happened to dogs? Three independent inquiries were made in the aftermath of the British documentary Pedigree Dogs Exposed. These produced three separate reports: the Bateson Report, the APGAW Report and the RSPCA Report. All three groups found that the health and welfare of purebred dogs were compromised, and highlighted two contributing factors. The first of these was selection for exaggerated anatomical features. The second was the dramatic increase of inherited disorders brought about by inbreeding.

These observations were not new. In 1988 the British Council for Science and Society produced a report on companion animals. It noted the problems in the following statement:

An in­creasing number of hereditary problems are being recognised in companion animals, especially dogs. Many of these are the consequences of inbreeding or breeding for genetically defective animals. Some are the result of deliberate selection for abnormal or unnaturally accentuated physical characteristics for fad or fancy.

As that quote shows, both exaggeration and inbreeding were concerns twenty-four years ago. The observations made in the three reports were not new, but this time there has been public pressure to address the problems.

It is the efforts undertaken by the Kennel Club (KC) to address the first issue – the harmful anatomical distortions – that are currently the focus of much controversy in the British dog world. That controversy has created ripples over in the American dog fancy as well, with representatives from the American Kennel Club (AKC) insisting that such measures will never be taken in the United States. Meanwhile the second largest American registry, the United Kennel Club (UKC) has stepped forward to claim the high ground in addressing the issue.

This first issue will not be the focus of the posts made here. As important as the issue is to the dog world, it is not a widespread problem facing horse breeds. With a few exceptions – extreme heads in some halter Arabians, for example – breeders are not seeking to exaggerate the equine form. Horses are not anatomically malleable the way dogs have proven to be.

(These graphics come from a Belgian blog devoted to ethics in the breeding of German Shepherds.)

It is the second category of issues – those related to inbreeding – that are the bigger concern for horses. There is no question that within the horse world, there are endangered breeds with very small populations. Many of the draft and coaching breeds have experienced dramatic bottlenecks when the engine made them obsolete. It is also true that closed stud books and inbreeding are found in some horse breeds, and that some breeds have seen a rise in genetic diseases.

So why is inbreeding – in dogs or horses – a concern? Here is what the Bateson Report had to say:

Unquestionably inbreeding can lead to a loss of biological fitness. …. Inbreeding can result in reduced fertility both in litter size and sperm viability, devel­opmental disruption, lower birth rate, higher infant mortality, shorter life span, increased expression of inherited disorders and reduction of immune sys­tem function. The immune system is closely linked to the removal of cancer cells from a healthy body, so reduction of immune system function increases the risk of full-blown tumours.

These same observations are echoed in the other two reports. All three drew upon the expertise of geneticists for those conclusions. However much inbreeding is considered a valid tool by some animal breeders, the above statement is not particularly controversial within the field of genetics. Concerns about the downsides of inbreeding are pretty consistent across a large body of studies. It is the growing awareness outside that field that is new.

A few months ago, National Geographic did a feature story on the genetic variation found in dogs. One section jumped out at me when I was reading it, in part because the implications were terrible, and even worse I suspected many readers did not realize it. Perhaps pairing it with the above quote about inbreeding will make it more obvious. (Bold emphasis is my own.)

In short, while the Victorian breeders were crafting dogs to suit their tastes, they were also creating genetically isolated populations, little knowing how useful they might be to scientists in the future. The possibilities are especially abundant for cancer, certain types of which can show up as often as 60 percent of the time in some dog breeds but only once in every 10,000 humans.

Here is a similar observation from a peer-reviewed journal article:

Selection for phenotypic traits has resulted in the latent selection of genetic diseases and some breeds now have a high incidence of particular diseases, for example, the Samoyed, which has a risk ratio if 17.3 for diabetes and the boxer which has an unusually high incidence of various cancers.

The breed specificity of particular diseases lends dogs to be ideal candidates for comparative genetic association studies.

That is the precarious position of purebred dogs in 2012. Their genetically isolated populations have several hundred known genetic diseases. Because the dogs have been maintained in small subpopulations with decreasing genetic diversity, the incidence of those diseases has risen to the point that researchers have found them to be an invaluable resource. That may be good news for those seeking answers to human disease, but it is far from good news for the dogs themselves. It certainly should give pause to breeders of other animals that are considering taking (or continuing down) the same path.

It also merits thoughtful discussion by all involved with the animals affected – those that breed them, those that exhibit them and those that welcome them into their lives as companions.