Location matters


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 original gene 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 of those genes 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, because each occupies one – but not both – of the two genes. The genetic material would have to crossover in order to get the two mutations on one gene, and thereby have a true-breeding pattern combination (ie., a sabino1-tobiano that produced sabino1-tobianos when bred to solid mates). That is not actually impossible, but it is very unlikely.

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. 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.

Updated: Recent studies of KIT mutations in pigs suggest that the situation with this particular gene, and the number of mutations found there, is quite complex. Meanwhile continuing research on white patterning in horses would suggest that the gene has a high tendency to mutate. So while some KIT patterns, like roan and tobiano, or sabino1 and tobiano, appear to behave much like they have an allelic relationship, it is too soon to say that from the menu of all possible KIT mutations, a horse might only ever have two of them.

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14 Responses to Location matters

  1. Mel Miller November 2, 2011 at 10:58 pm #

    Your posts are always so informative and interesting Lesli. Thank you!

  2. J Ferre November 3, 2011 at 12:17 am #

    really great posts….is splash suspected to be on or near kit?

    • The Equine Tapestry November 3, 2011 at 5:11 am #

      The current thinking is that splash is not located on KIT.

  3. Danielle November 3, 2011 at 12:21 am #

    As a student of genetics from a while back (at least 15 years ago), from what I remember during sexual reproduction it is VERY likely that genes will ‘swap’ or recombine with each other during the production of gametes. At least this is how multiple mutations can be explained. This would lead me to believe that if KIT is a chromosome that has 2 distinct mutations (Tobiano & Sabino) and they are not extremely close in location on the same gene/chromosome, that it is entirely possible for a gene ‘sometime and somewhere’ to be produced that has BOTH of these mutations on it ;0) Please correct me if I am mistaken here. Of course the parent horse would have to be heterozygous for those traits but it IS possible in my understanding to eventually have a KIT chromosome with both mutations located on it. That is, unless the specific mutations have to do with exactly the same region on KIT (like a swap for one chemical base producing Sabino or a deletion of that same chemical base producing Tobiano). Forgive me, I have just been scanning the emails about white face markings in tobianos but I think this may apply to that situation as well.

    • The Equine Tapestry November 3, 2011 at 5:34 am #

      What you are talking about it called crossover. That is where the contents of one chromosome swaps material with another – essentially reshuffling the deck. But what chromosomes swap is genes, since a series of genes make up a chromosome. To reshuffle the two KIT mutations, you’d need the genes themselves to reshuffle their contents, rather than the chromosome to reshuffle its genes. (KIT is a gene on the ECA3 chromosome.)

      What could make the situation you describe possible is when the mutations are not actually on the same gene, but are merely near it. Scientists talk about “genetic distance”, which is a way to describe how close two traits are on a chromosome. Technically if something is on a separate gene, it can crossover, but the likelihood is greatly reduced if the genetic distance between the two is small. Closely spaced genes tend to travel together, so it isn’t a purely random shuffle.

      • Danielle November 3, 2011 at 8:53 am #

        OK – so the mutations are in the same gene in a series of genes on the same chromatid. I am not familiar with the specific cellular mechanism that controls recombination at this time. Although it looks like a recombinase (RecA) is involved. So the genetic ‘distance’ of these two mutations is relatively close. Strictly speaking, I don’t know of another reason other than chance where mutations like recombination only occur with different genes since theoretically an occurrence can happen anywhere along the sequence of individual bases.

        In a quick wikipedia search, I discovered a process called gene conversion where I think it would indeed be possible for both of the mutations in the same gene (KIT) to occur on the same chromatid.

        Of course all of this is very far-fetched statistically in nature as we know it now ;0) BUT with the introduction of genetic engineering, I don’t see any boundaries. Speaking to horse artists, I think ‘license’ would apply when combining these traits in the same horse.

  4. Danielle November 3, 2011 at 12:46 am #

    OK – this is from a quick search on the KIT gene (and it is a late hour where I am located). An inversion of the sequence in KIT causes the Tobiano pattern and an exon skipping causes the Sabino pattern. If this is correct, then I think it would theoretically be possible that a single KIT gene ‘could’ inherit both mutations. The chances may be statistically very slim, but again depending on the locations in the actual sequence of the gene itself, due to recombination mutations, an inversion AND whatever codes for/determines the exon skipping mechanism could appear in the same gene. Maybe it hasn’t happened yet in nature, but it may just become a reality someday!

    • The Equine Tapestry November 3, 2011 at 5:43 am #

      I should have put the previous reply here, since it’s at the bottom of the page. Sorry about that!

      There is another issue involved, which is viability. That will be the topic of the next post which will hopefully go up later today.

      • Danielle November 3, 2011 at 8:57 am #

        I can’t wait to hear about viability ;0) I love this blog – thank you. I just knew there would be a market for equine color genetics – even though my graduate advisors told me no-one would fund studies. Stepping out of the field to raise a family, I see many strides have been taken in just such a direction as I imagined! I EAGERLY wait for the publication of your book ;0)

  5. Pauline H November 4, 2011 at 7:10 pm #

    I was under the impression that Frame was on the KIT gene as well – but then again, I don’t really know that much about it. Where is Frame located?

    I’d also like to thank you so much for such interesting articles!

    • The Equine Tapestry November 4, 2011 at 10:21 pm #

      Thank you for the comment, Pauline. I am glad you are finding the articles interesting. 🙂

      Frame is one of the non-KIT patterns. It’s on EDNRB.


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