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PAINT HORSE
History
| Characteristics | The
APHA | Lethal Whites
Lethal Whites:
The Pedigree Perspective
Dr. Debbie Duffield, Portland State University
Q: What did you learn from the surveys submitted by the
association?
A: When we looked at the surveys, we felt that the biases that were built
in on people reporting lethal whites overwhelmed the interpretation. We
tried to get rid of that bias by sending a random poll to breeders asking
only for the first foal born that year, and its sire and dam. The question
we were asking ourselves was, if we look at all overo-to-overo breedings,
do we get one- quarter solid foals, one-half overos, and one-quarter lethal
whites?
Q: What were the results of that poll?
A: The numbers were right on. We feel that the poll strongly supported
that the overo Paint gene is acting predominantly as a lethal dominant
as Dr. Bowling predicted. By that, I mean that a horse that is overo is
a heterozygous horse. It has one overo gene and one non-overo gene. A
solid Paint is one that has two non-overo genes, and a lethal white is
one that has two overo genes. That doesn't rule out modifiers that impact
how much color, or how high or low color extends. It just says that most
of the time it is going to operate that way, and people can pretty safely
base their breeding programs on that.
Q: If the overo gene is dominant, how would you explain
cropouts (when two Quarter Horses, two Thoroughbreds, or a Quarter Horse
and a Thoroughbred, produce an overo foal)?
A: There are two things that could be going on. There could be modifiers
that do indeed hide an overo periodically. However, we think it is more
likely that the actual overo pattern isn't fully described yet--that sometimes
horses that are considered, say, Quarter Horses, are actually overos.
They are just not identified as such. What we did was go back to every
example we had in our files where there was a cropout. And there was always
an instance where we would suspect that at least one of the horses in
their background had been an overo, by looking at its picture.
Q: Does this mean that a lot of Quarter Horses are actually
overos?
A: Actually, we thought the problem would be bigger than it is. We have
heard stories for years that often Quarter Horse people hid those little
bits of white when they registered the animals. So, we thought that the
problem was going to be extensive among Quarter Horses. But when we did
the poll there were very few real cropouts.
Q: How do you explain lethal whites that have occurred
from overo-to-solid or overo-to-tobiano crosses?
A: If you asked me, could I get a lethal white from an overo and a tobiano,
I would say no. However, we do occasionally see that. The reason that
we see it is because there is actually overo there, it just isn't called
that. In fact, the true cross is probably overo-to-tovero. A lethal white
should not occur from an overo-to-solid cross, either. However, some of
the "solids" may actually be overos that are not classified as overos.
The only true combinations that should produce lethal whites are overo-to-overo
and overo-to-tovero.
Q: Do tobiano breeders need to worry about lethal whites?
A: We want to alert tobiano and overo breeders to some conditions that
we see coming up a lot. More and more, people are mixing the two lines.
We're seeing a lot of it in our tobiano testing. What is going to happen
is that after awhile, horses which kind of look tobiano, but have overo
in them, are going to start throwing lethal whites. If someone stepped
into that picture down the line when those horses were doing that, they
might think lethal white syndrome was linked to the tobiano gene.
Q: Did you find that lethal white foals occurred more
frequently among certain families of horses?
A: We never really saw that certain lines of overo horses produced lethal
whites more than any others. What we did was to go back through all the
polls and pull out lineages and check to see if there were any that tended
to come up again and again. We did have certain horses whose names came
up more, but it was because people were breeding to them more often. If
you took into account the total number of breedings to that horse, the
proportion of lethal whites still fell into the normal ratio. More likely
than not, although we don't feel that we've proven it, it was not that
certain lines had a higher possibility of lethal whites, it was merely
a reflection of breeding preference.
Q: Is the likelihood of a lethal white foal related to
the amount of white on the parents?
A: We saw no indication that the amount of color on the parents gave any
statistical leaning to the probability of getting a lethal white foal.
Like with the lineages, what we did see was that although a lot of lethal
whites seemed to be coming out of O3- and O4-type horses (color types
shown on the registration form), when we looked at how many breedings
occurred between horses of different color types, most of the breedings
were between O3s and O4s. So, again, the trend was probably related to
what people were choosing to breed.
Q: Do all overos carry the lethal gene?
A: According to this theory, all overos would carry the lethal white gene,
meaning it's the overo gene itself, and if you get two copies of it, you
get lethal white syndrome. We haven't seen any evidence that there is
an overo gene that doesn't carry it. However, there may be other types
of spotting, like sabino, that might not carry it because they might be
different from overo. However, we didn't have a good way to separate,
say, sabinos, from frame overos in our study, so we can't really address
this point.
Q: Could this explain why the incidence of lethal white
foals from overo-to-overo crosses isn't as high as 25 percent? Or is there
another explanation?
A: I suspect some of them are aborted. There were some cases in our studies
where mares had aborted, so it's possible. That might also be one reason
why the lethal white number isn't right at 25 percent in some studies.
Q: If the researchers at the University of Minnesota are
able to identify the markers for the overo gene, how will that affect
breeders?
A: You've still got a problem on your hands. It's important to find a
marker, but until you can do amniocentesis (analysis of the mare's amniotic
fluid) on horses, you still won't know before the baby is born whether
it is lethal. So the technology of being able to test a fetus has to be
developed, too, for the marker to be useful. Right now the question is,
did my foal get two copies of the gene, or not? When the markers are identified,
you still have to find a way to get in and get a blood sample from the
baby. (They can't use the blood of the mare.) From what I understand of
horse reproduction, that's a problem. You can't easily do an amniocentesis
on a horse. As the technology changes, and as they start to do in-vitro
fertilization with horses, then breeders can capitalize on using the markers
when they are developed. With in-vitro fertilization, embryos that are
going to be lethal whites can be weeded out, and those that are normal,
or overo, can be implanted. Cattle breeders are using this technology
right now with in-vitro fertilization. They can test embryo cells after
they have begun to divide to see whether the embryo is carrying a particular
marker. Then they save the embryos that aren't, and get rid of the embryos
that are. Therefore, use of a marker for lethal white also requires the
acceptability of in-vitro fertilization. But I think that's all coming.
Everything is changing so fast.
Q: What can breeders do now to avoid getting a lethal
white foal?
A: For the individual breeder, if they breed overo to truly solid, then
they will not get lethal whites. They can also breed to a true tobiano.
With any overo-to-overo cross, they have a 25 percent chance of getting
a lethal white. The way I look at it for the industry is that it's just
the cost of breeding overos. Certainly, individual breeders may have difficulty
with that because they only have one mare and if they get a lethal white
foal, that takes them out for the whole season. But at this point, with
just the current technology, they are not going to be able to get away
from this problem.
The Genetic Perspective
Dr. Elizabeth Santschi, University of Minnesota
Q: From what point does your study begin? You say you
have a candidate gene for lethal white syndrome?
A: There are a couple of genes that have been identified in people and
in mice that have been found to cause conditions that are very similar
to lethal white syndrome. What we're doing is looking at these candidate
genes and sequencing them--determining what their base pairs actually
code for in normal horses and in lethal whites--to see if there is a difference.
The copy of the gene that is in the lethal whites will hopefully be very
different from those in normal horses. What that will mean is that there
is a high likelihood that that gene is responsible for the condition.
It could be that it's not these two genes and we have to go somewhere
else. But if we're successful, and find that a mutation in one of these
genes is responsible for this condition, then we go on and start looking
for that gene in various horses that had some lethal whites in their pedigree
and make sure it is not present in those that did not. Then we can say
more conclusively that this gene is responsible for lethal white. What
we have to do is test a bunch of mares--those who have produced lethal
whites, and, for instance, Arabian mares, who never produce lethal whites.
We have to make sure the mutation is never found in horses that never
produce lethal whites, is found in a certain percentage of mares that
have produced lethal whites, and is always found in foals that are lethal
whites.
Q: What kind of time-frame are we looking at?
A: Within about six months we should know whether or not the genes we
are most interested in are the culprits. But even if this particular gene
is not responsible for lethal whites, it is the first time these genes
have been sequenced in horses, and that is valuable in itself.
Q: The current theory based on pedigree research strongly
shows that overo-to-overo crosses will produce solids, overos, and lethal
whites in a 1:2:1 ratio, meaning lethal whites will occur in 25 percent
of all matings. Does this theory contradict your study?
A: It could turn out to be something that is simple Mendelian genetics,
which is where the homozygous state of the gene is lethal. Then, if you
have a heterozygous mare, you certainly don't want to breed her to a heterozygous
stallion, because 25 percent of the time you are going to get a lethal
white foal. If you were to assume that every overo was a heterozygote--if
it was simple one-gene inheritance--then all overo stallions should sire
the same percentage of lethal whites. But we know that's not true, right?
Nobody talks about any one horse siring 25 percent lethal whites. People
talk about it being around the 8 to 10 percent level.
Q: Is it possible that the percentage of lethal whites
appears less than 25 percent because of early embryonic death?
A: Some people talk about early embryonic death, which is what they think
happens with a lot of homozygous HYPP horses. However, talking to Paint
breeders, they don't seem to think that they have any higher incidence
of mares resorbing or being in foal and coming up empty than anybody else.
But of course that hasn't withstood scientific scrutiny.
Q: How else can you explain the observation that lethal
whites occur significantly less than 25 percent of the time in all overo-to-overo
matings?
A: It is hard to know for sure, but I do talk to Paint breeders a lot.
Many say, "You know, I just don't have that many lethal whites," whereas
other breeders either admit it, or people who have bred to their horse
say it sires lethal whites all the time. I think we may find out that
there are genetic differences between splashed whites, sabinos and frames,
just like there is more than one gene that controls spotting in mice.
With this, it is possible that not all combinations will produce a lethal
white foal in the homozygous state. How that all sorts out is going to
be very interesting. It would seem that frame horses tend to be the ones
that are most likely to produce a lethal white. But we have seen lethal
whites out of sabino stallions. And splashed whites are so uncommon that
I'm not really sure how they fit in. We are going to try and stick with
the frames in our study for now, because that will make it simple. But
then we'll branch out into the other types of overo. Something else that
I think is a bit of a problem is, what is an overo? Dr. Phillip Sponenburg
says that overo has come to mean anything that is not tobiano. I think
we have to be very specific about what we are calling an overo. That's
why the registration papers that have the pictures on them are so valuable
to us.
Q: Is there any factor besides genetics that may contribute
to lethal whites?
A: There has been some research done in England with twin horses. Some
guy took an embryo, split it in half, and put the halves into two different
mares. The foals that were born were very similar, but they didn't have
the same white markings. According to the old nature vs. nurture argument,
any trait is a combination of genetics and environment. What is the intrauterine
environment that can affect the melanocytes--the cells that contain color?
They migrate from the neural crest, which is where the nervous system
develops, out to the body to give it color. What they do is stop at a
certain point of the body or leg, and no color develops past that point.
We don't know what message these cells get in order to move. In lethal
white foals, we know they don't get the message at all, because neither
the melanocytes nor the nerves that innervate the gut move. Some gene
doesn't get turned on to make the protein that tells these cells to move.
Q: How would you genetically explain a cropout?
A: Even if overo is dominant, if there are genes that regulate its expression,
it can be hidden. For instance, if there is a second gene that is modifying
the expression of white, and the horse does not get white over its knees
or hocks, a horse that is genetically an overo could be classified as
a Quarter Horse. I can look at some of my lethal white pedigrees, and
a stallion that I know has sired a lethal white will sometimes be seven-eighths
Quarter Horse. That confuses me, because Quarter Horses are supposedly
not overos. But maybe what they are is minimally-marked overos. If we
can find this gene, then perhaps we can go back and look within different
phenotypes, and determine whether those horses carry this gene.
Q: What is the long-term goal of this study, as far as
helping breeders avoid producing lethal white foals?
A: What we're hoping to do is develop a genetic (blood) test that may
be somewhat crude, but which may provide breeders with some information
about a better way to avoid lethal whites. Will we stumble upon something
that will help them breed for color? Maybe so, although I sure wouldn't
guarantee it. Lethal whites may be the price we pay for breeding for color,
but it may be that it is only carried in some horses with overo color.
What I'm hoping to be able to find are some overo horses who still produce
color, yet don't carry the lethal white trait. That's kind of way out
in the future, but that's what we'd really like--to get rid of lethal
whites but still be able to have color. In their studies, researchers
at Portland State University found that many lethal white foals came from
crosses of O3 and O4 horses, the two overo color types shown above. However,
Duffield attributed this trend to the fact that these were the most common
color types people were choosing to breed to. This is the classic coat
pattern of a frame overo, which is what the researchers at the University
of Minnesota are focusing on in their study. Dr. Elizabeth Santschi said
it seems that this type of overo tends to produce more lethal white foals
than, say, sabinos (calicos) or splashed white overos. There are three
issues that may account for the fact that we do not see 25 percent of
all overo-to-overo crosses producing lethal whites: 1. Not all lethal
white foals survive to birth. Some are resorbed or aborted by the mare.
2. Not all lethal white foals that are born are reported. 3. Not all patterns
that are currently classified as overo, such as sabino or splashed white,
are lethal when homozygous
Find out more:
*Myths about Lethal Whites
*Question and Answer Discussion
on Lethal Whites
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