The first paper of the new year is out, and it is about white markings. This was a topic I had intended to talk about on the old blog, back when the paper on Franches-Montagnes was published. I put it off in hopes that there would be a follow-up. That did not happen, but a similar paper on Spanish horses and this new one on Quarter Horses have been published since then.

The Surprising Things

The Franches-Montagnes study used an elaborate scoring system for white markings described in an earlier paper. This paper used a straightforward system that just noted if there was white – any white – in three different locations: head, front legs, hind legs. I found it interesting to think about how this might give some different information. For example, if there is a factor (or factors) that add color back over white markings, like the patch that seems to be “cutting off” the blaze on the Quarter Horse mare in the picture above, just counting white as “present” on the head might correct for that. It would be an interesting exercise to use the two systems on the same sample group and compare the results.

Like the previous studies, this one supported the idea that separate mechanisms could be involved with markings of the head versus markings on the legs. What was surprising was that in this particular group, white on the forelegs was more common than on the hind legs. Earlier studies had shown hind legs to be more likely to be white. If asked, based on personal observation, that’s the answer I would have given.

The most surprising thing, however, was what they did not find. Past studies seeking candidate genes for white markings had consistently found connections with KIT and MITF. Those are the sites for the sabino and splashed white phenotypes, respectively, so this was not surprising. The authors of this study stated that they had expected to obtain similar results, but neither location was implicated with this population. (I’ll talk more about the specifics of the horses they sampled in a bit.)

Looking for the right neighborhood

To explain what was found, it would probably be helpful to say something about this type of study. Although some classical genetic studies were done in the 1990s – I was not the only one to find the Arabian Registry’s marking diagrams fascinating! – the molecular studies of white markings are still in the early stages. One researcher has likened this stage to finding someone’s house, and the first step is to determine the right neighborhood. You hope to end up at the correct address in the end (find the actual mutation causing the trait), but you need to narrow down where to look for it.

For this, scientists use genome-wide association studies (GWAS) to find candidate regions for further research. The idea is to find differences in the genetic code that a significant number of animals with a particular trait share. Within the “windows” of similarity, researchers then look for genes in that area that are known to be involved in pigmentation. Those can then be studied further in hopes of finding mutations directly responsible.

The only candidate gene that appeared in this study that was previously reported was MC1R. That’s commonly known as Extension, which is one of the major genes controlling pigment-type switching in mammals. The mutation there for chestnut (e) has been implicated before in white markings. (The reason why is a topic for another post.) The new candidates were ZEB2, KYNU, SLC36A1, STX12, MAP3K6 and GJB2. That looks like a lot of alphabet soup, but those are all genes that the authors felt might create markings if their normal function was disrupted. That’s not a guarantee that mutations to those genes are involved; it just means that they are promising “neighborhoods” if you are looking for that particular “house.”

The specific population

The population of Quarter Horses used for this study might explain some of these findings. The sample was taken from breeding horses (stallions and mares) from racing lines in Brazil. The researchers avoided full siblings in an effort to get a diverse group, but the study did focus on racing lines. This might explain why some of the regions significant in other subpopulations (think Gunner and his family) might be missing. The authors noted this with the following comment.

This finding [that KIT was not among the sites detected] provides further evidence that modifying the population under study changes its genetic constitution and consequently the importance of genes for expression of the phenotype.

That was one of the big questions I had when the Franches-Montagne study was released. How much of what was found would hold true for other breeds? If KIT and MITF mutated frequently for large-effect mutations (ie., pinto patterns), how many different mutations might be out there that just produced markings? How complicated would it be to find (and develop tests for) a large portion of the mutations that caused white markings? This study seems to say, “Very.”

Sharing new information

Having unlimited access to scientific journals has been one of the best parts of my college adventure. I was always fortunate that I had people who would pass along newly-released papers, but having the unlimited ability to browse and follow related tangents is a new experience. This has also made me realize how difficult it is to follow interesting developments without that access.

I find it useful to review papers; I print them out and cover them with notes. In the past, I have been hesitant to share this sort of thing on the blog. I consider myself to be learning as I go, and I do not want to presume to speak for researchers about their work. But I want readers to be able to learn along with me, so I’ll be sharing new things as they arise. These will appear under the category, Discoveries. My own research will generally go under the relevant topics (like Sabino) or under the general heading of Observations. That latter category will also be where I share unusual or especially useful photos.