EC May/June, 2004

An inherited skin defect in certain family lines of Quarter Horses is cropping up with increasing frequency, leading to heartbreak for horse owners.  This genetic flaw is characterized by abnormal skin that tears easily. Any trauma or pressure may literally pull the skin apart.  The problem is often not discovered until the young horse goes into training–when the simple act of wearing a saddle creates massive injury to the skin–and the horseman realizes that the promising youngster can never be ridden.

This devastating skin abnormality is called hyperelastosis cutis and often called HERDA (hereditary equine regional dermal asthenia, a term that means dermal weakness in certain areas of the body).

We still don’t know exactly what it is, and researchers are still looking at the biochemistry of the skin.  The name for it may eventually change once scientists find out more about it. In humans there are about 12 types of hyperelastosis cutis and this disorder is known as Ehlers-Danlos syndrome, but only one of those types is very much like the disease in the horse.  The skin problem is well-known in humans (and each one of those 12 types might be caused by one or more genetic defects in different human families), and also occurs in mink, dogs, cats and cattle, but we’re just now learning about it in the horse.  In veterinary literature there are only a few brief descriptions of it.

The problem was first documented in the early 1970’s when occasional cases were brought to veterinary clinics for treatment– horses with torn skin, open and oozing wounds, or hematomas on their backs or necks.  At first no one realized there was a common thread linking these horses.  Owners and veterinarians who tried to treat them were baffled and frustrated.  Then a professor at UC- Davis (the late Tony Stannard DVM, PhD) began keeping track of the similarities in these lesions, and looking at the pedigrees of affected horses–the first clue that they were all related.

RESEARCH –

Research on this genetic flaw is being done at Cornell University in New York (led by Dr. Nena Winand, Department of Molecular Medicine), UC-Davis in California (led by Dr. Stephen White, a veterinary dermatologist) and at Mississippi State University, where Ann Rashmir, DVM (Associate Professor of Equine Surgery and Medicine) oversees the study program (which began in 1999) and keeps a group of affected horses for observation.  Dr. Rashmir usually has between 12 and 15 horses in the group.  The horses are part of an ongoing breeding trial, and researchers are determining that this is a recessive (hidden) trait that must be inherited from both parents in order to show up in the offspring.

This trait has been associated with some of the most popular bloodlines in cutting and reining horses–bloodlines found in many Quarter Horse pedigrees (and some Paints and Appaloosas, since a lot of Quarter Horse genetics have been used in these breeds).  “If you have a multi-million dollar stallion, or want to figure out what stallions you can safely breed a mare to, you’d be interested in our breeding trial,” says Rashmir.

“The original purpose for having this herd was the breeding trial, and we will have that completed this year.  We have enough of those mares in foal now to finish this.  Another thing we are doing with these horses is looking at the skin biochemistry–what exactly is wrong with the skin.”  She is doing this study in collaboration with the researchers at Cornell University.

Dr. Stephen White at UC-Davis, who oversees the research program there, has been looking at skin biopsies.  White and his colleagues have gathered skin biopsies from more than 50 affected horses.  White is also participating in the breeding trial.  He has one HERDA foal and Rashmir has 6 or 7 more coming.  With 8 foals on the ground, they can confirm whether this trait is recessive, since statistically this is the number they need to see.

SKIN BIOPSIES

“We are also looking at skin biochemistry–at the difference between normal horses and HERDA horses.  We’ve found skin biopsies to be a very good way to determine whether or not the horse has this problem.  Horses that have hyperelastosis cutis have skin that always splits in the same area,” says Rashmir.

Skin is made up of layers.  The outer layer is the epidermis, which covers the thick middle layer (dermis).  The deepest layer is the subcutis.  These three layers are bound together by connective tissue called collagen.  “These horses’ skin always splits in the middle of the dermis (the middle layer of the skin).  That’s one of the hallmarks of similar problems in other species.  There are several diseases in which the skin splits there, but those are either elastin or collagen diseases, and this one is a collagen disease–which limits the other possible choices in the horse.  So the biopsy is diagnostic,” she says.

Veterinarians have to be very careful how they take the skin sample, however, for it to be properly evaluated.  “We do most of the biopsies ourselves, though when veterinarians around the country are trying to get help on a diagnosis I spend quite a bit of time on the phone explaining how it should be done.  The biopsy, if not done correctly, can be quite frustrating in trying to evaluate,” she says.

IDENTIFYING THE DEFECTIVE GENE –

“UC-Davis, Cornell and several other places are working on a genetic test for this problem, and we are trying to help with that, as well.  We have identified the bloodlines and are hoping to present the carrier stallions that we have discovered so far, at the AAEP (American Association of Equine Practitioners) meeting this year.  We’ve traced it back to Poco Bueno and his immediate ancestors,” says Rashmir.

Eventually the geneticists will track down the defective gene and horses can be tested.  In the meantime, they have been looking at foals from certain stallions being currently used for breeding and determining which of these stallions are carriers.  A list of carriers will soon be available for horse breeders.

All affected horses are related to one another and all have inbreeding links that have doubled up the recessive trait.  The defective gene did not cause a problem in the early horses because they only had half the equation; it has to be doubled up (one copy of the gene from each parent) in order to express itself.  The defect was carried forward in a certain percent of the offspring (without showing up), until some of those descendents were bred to each other.  With inbreeding and linebreeding so prevalant in producing today’s top athletes (doubling up popular bloodlines), we’ve seen the skin problem popping up with more frequency.

“About 95 percent of the horses we see today with the disease trace back to Poco Bueno or King,” says Rashmir.  The problem with the early pedigrees is that some are not entirely accurate.  There are some questions about the actual sires and dams and it may differ depending on which authority you use.  There are carriers in other disciplines besides cutting horses; any horse that traces back to Poco Bueno or King has a chance for being a carrier (Poco Pine, for instance, a horse found in many pleasure horse pedigrees, was a carrier).  King, the sire of Poco Bueno, was a son of Zantanon, the famous Mexican racehorse.  Zantanon was a son of Little Joe, by Traveler, a horse of unknown breeding.  Eventually the researchers will know whether or not the defective gene came from that side of King’s pedigree.

SLEUTHING THE PEDIGREES –

Dr. Nena Winand, at Cornell, says that it’s very important that everyone with horses of Quarter Horse bloodlines become aware of this defect.  It’s not just a cutting horse problem, and it’s not rare.  “Poco Bueno and King are foundation bloodlines that many horses have in their background.  Some people will tell you that they’ve had these bloodlines for years, and linebred them, without any problems.  That may be true in individual cases, but I explain to people that there are some foundation linebreeders who are having this problem.  Some have produced affected foals and are not admitting it.  Others admit it, and we are working very closely with some of these breeders.”

“There are a handful of foundation Quarter Horse breeders who are refusing to acknowledge the fact that Poco Bueno bloodlines can carry this problem.  They don’t want to believe it.  They don’t understand the science behind how we do these tests.  A person has to separate feelings from fact, and this is really hard to do, with a horse as great as Poco Bueno,” says Winand.

This is a devastating problem, emotionally and financially.  People spend a lot of money on a horse or a breeding fee and then find the horse can never be ridden.  “Some folks in other disciplines besides cutting and reining have concentrated on these bloodlines and HERDA-affected animals have cropped up in their breeding programs.  Even if they haven’t spent a lot of money for their horses (as compared with the high priced cutting horses), they are very attached to their animals; if they have one that’s affected, it’s a very emotional and disturbing situation,” she says.

“At this point it is indisputable that Poco Bueno passed it on, and it’s probably also a fact that King passed it on.  Back farther than that, we do not really know much about some of those pedigrees.  And we are also aware that some pedigrees were faked–at least before parentage verification was possible,” says Winand.

“Still, we have more than 100 pedigrees in which we have traced the carriers, and there is not one exception, in the pedigrees that are complete.  Even if there is a little bit of slop around the edges in pedigrees of the early ancestors (and we can’t go back and test them–it all has to be done by pedigree inference) what we know about the animals that are being bred right now and producing these affected foals, is very clear,” says Winand.

“A horseman can’t afford to lose $70,000 to $100,000 on a horse and this is literally what is happening to people when they get an affected horse,” she says.  So these researchers (many of them are horsemen themselves) are trying to do all they can to study this and help breeders make informed decisions.

“We don’t know everything about this disease yet.  We do know this is the bloodline that’s affected, and that it is an autosomal recessive disorder.  So we can predict what you will produce if you mate a carrier with another carrier.  The defective gene has not yet been identified but everyone is working on that.  Here at Cornell we are working on that, UC-Davis is working on it, Texas is about to start working on it and there are people in Canada and Europe working on this.  We’re hoping we can come up with the gene quickly–it’s imperative that we develop a test soon, for this disorder–but it’s not an easy thing,” says Winand.

A GENETIC TEST –

“The genetic test that scientists are working toward is a bit tricky.  Several labs are working on developing it and it may still be two years away.  The genetic test for a similar disease in humans has already been worked out.  When it came to finding a genetic test for the disease in cattle, we found it was at basically the same spot on the same gene as it is in humans, which made it easier.  But it’s not the same in the horse!  We have to look a lot farther.  It was easier to find the gene for HYPP because it, too, is similar to the disease in humans.  The marker was already there and it only took one summer to find it in horses and create a genetic test.  But this is more difficult.”

There are three different ways to approach it, she says, and each lab is probably doing its own method.  Hopefully someone will come up with it soon.  “In the meantime, we need to identify these horses early on before people become attached to them and put a lot of time and money into them.  It’s so heartbreaking.  If we can identify them without having to biopsy all these horses as foals,  it would be better.  We are working on a way that can hopefully identify them early and do it non-invasively,” she says.

Once the genetic test is figured out, horsemen can easily test their animals by sending in hair samples for DNA testing like they do now for HYPP.  “It might have to be blood samples at first because that’s the easiest to test with less processing–like it was at first with HYPP.  Ideally, eventually the hair will work and people could just pull a few mane hairs to send in,” she says.

This disease is very different from HYPP, however, and she hopes people don’t think of them the same way.  The skin defect is not dominant like HYPP and does not express itself (in affected animals) as readily–but when it does, it is more likely to be fatal.  “This disease is not a horse problem, it is a problem in the way we breed horses.  All animals have undesirable recessive traits.  Some of the horses that are carriers are spectacular animals and very athletic.  And if you don’t breed them to a related horse, you’ll never see a problem.  It is not the carrier that’s the problem; it’s the way we breed them.”  If people can make informed decisions on how they breed these horses, they can continue using them for breeding.

COMING TO GRIPS WITH REALITY –

Some people still refuse to believe there’s a problem with Poco Bueno bloodlines because they have been raising these horses for years and have not seen any affected animals.  Winand says, “What many people do not understand is that right now, in 2004, the bulk of the Quarter Horse population as a whole is not inbred to Poco Bueno, so we are not seeing a lot of HERDA affected horses across the board.  Not all Quarter Horses have been linebred and inbred like the performance horses (cutters, reiners).  But when you look at the pedigrees of HERDA affected horses, 100 percent of these horses are double bred Poco Buenos, and you understand the difference.”

You might go many years breeding horses that have Poco Bueno in their pedigree and never have a HERDA affected horse if you don’t double up that bloodline very much.  “The reason that some foundation horse breeders are refusing to believe that Poco Bueno is the problem is that many of them have selected descendants that were NOT carriers–because not all of them are,” says Winand.

“Another reason some are refusing to believe it is that some of the people they are talking to are lying about whether a certain horse has ever produced a HERDA-affected foal.  We know that, and have told them, but they still don’t want to believe it.  The facts are that HERDA-affected horses have shown up in a foundation registry and they are linebred Poco Buenos.  This is unfortunate because people need to know the risks.  Some people say there are only a few cases of affected horses, but statistically speaking, it’s a huge number.  The statistical significance is off the charts,” says Winand.

Most horsemen have been supportive of the research and very concerned and interested in having the facts spelled out so horse owners can learn about the problem.  “Most of the prominent cutting horse trainers have called us or been in contact with us and have been very supportive and positive about our work.  Many of them have had experience with HERDA and many have not and do not want to.  The cutting horse industry on the whole has not given us a negative, unwilling-to-believe reaction.  They want to get this figured out and find ways to prevent it.  I think the tide has recently changed.  People who were earlier reluctant to talk about it are now saying, ‘Yes, this is out there; we’ve known about it but now we are prepared to deal with it.’  People are starting to come to grips with this,” says Winand.

Carol Zipper, a horse breeder at Santa Ynez, California has been tracking down information about HERDA and trying to spread the word about it ever since a friend’s filly was diagnosed with the problem.  Carol has written a number of letters trying to persuade various organizations to tell their members about HERDA.  “I keep pushing at this, not because I’m a researcher, but just because I am a concerned horseman and want the associations to recognize this problem and deal with it and help educate horse owners,” she says.

“A lot of people are scared unnecessarily because they do not understand the disease.  They don’t understand that not every Poco Bueno descendent is a carrier.  The stallion they may want to breed their mare to may not have it.  The son of a known carrier (an unproven young stallion, for instance) may not be a carrier.  There is a 1 in 4 chance that he could be normal.  This is what needs to be empasized–the probabilities and percentages,” she says.

A sad thing is that some of the best cutting bloodlines have a high share of carriers.  “The only 2 foals that Poco Lena had– and she was one of the best cutting mares ever–were Dry Doc and Doc O’Lena (both by Doc Bar) and they were both carriers.  The chance of that happening were pretty low but it did.  At first Dr. Winand thought the flaw came through Doc Bar, but it came through the other side of the family, from Poco Bueno through Poco Lena.”

The chances of mating a carrier with a carrier are growing  because there are so many carriers being produced.  “What bothers me most in the performance disciplines (cutting, reining) is that some of the breeders and trainers don’t care if they get a few foals they’ll have to dispose of,” says Carol.  They are willing to double up carriers and gamble to get the traits they want even though mating carrier to carrier gives only a 25 percent chance of producing a “normal” horse (and a 50 percent chance of producing another carrier, and 25 percent chance of having an afflicted foal).

“Breeders should be gelding more of these carrier stallions.  It’s not necessary to have this many stallions.  For some reason, most trainers in performance horse careers think they have to ride a stallion but that’s nonsense.  Several National Reining Horse Association champions have been mares and geldings,” she says.

She feels that a grass-roots effort is the only way to educate horsemen.  Since it will be at least two years before they find the marker and develop a DNA test, horse owners have to figure out how to slow this down in the meantime.  “AQHA was slow to recognize the problem with HYPP, but at least this time they are admitting there is a problem and that it does trace back to Poco Bueno,” she says.

Carol has been disappointed in the lack of interest or action taken by many of the organizations she’s contacted.  Some of the associations she’s written to have responded by saying there are differences of opinion about the defect and that the bloodline research is not convincing.

“I’ve responded by suggesting they go to Mississippi and look at that research herd.  If you can come away from looking at those horses and listening to Ann Rashmir tell you what the bloodline research is and you still think there needs to be more research before you can talk about this, then you’ve been snowed!  I have no patience with the people who are trying to protect themselves and denying that there’s a problem.  It’s too bad that one of the Foundation Quarter Horse groups feels threatened.  They think that Poco Bueno is being insulted.  But that’s not true,” she says.  He was a great horse with some great descendents; you just don’t want to double up those that are carriers.

“The key word with many associations, however, is sponsors. Various groups feel their sponsors are not going to be happy and that some will drop out if they think there’s a problem.  If all the associations come clean and say they have a big problem and are going to solve it (‘here’s what it is and here’s what we need to do, and we need help’) then the sponsors will feel they are honest and straightforward and will stay with them,” she says.  If it’s a positive thing, there will be trust and support.

“But if it’s hushed up and denied and becomes a scandal, some sponsors won’t want anything to do with it.  It’s best to be honest and to think about the fact that the real victims are the horses not the people.  Accurate information needs to be spread.”

Carol feels strongly that breeders should be responsible and ethical.  “I own a stallion and if I found out that one of his babies was flawed, I would have him gelded so fast!  Any of the foals by my stud that I go see, the owners probably think I’m nuts, but I walk up and pull on the skin to check it to see how loose it is.  This flaw is not something you want to perpetuate.  The only way to prevent having a fatally flawed foal (until they come up with a DNA test) is to outcross, rather than inbreed or linebreed. I’ve been looking for a Thoroughbred stallion of Quarter Horse type, for an outcross, but they are hard to find,” she says.

Winand says, “All too often when a problem crops out in a breed (of horses or cattle) it isn’t acknowledged for awhile, like it isn’t real.  But mutations happen all the time–in plants, animals, every living thing.”  We have to make sure the undesirable mutations do not become prevalant and perpetuated in the breed.

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  Some folks in other disciplines besides cutting and reining have concentrated on these bloodlines and HERDA-affected animals have cropped up in their breeding programs.
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  Another reason some are refusing to believe it is that some people are lying about whether a certain horse has ever produced a HERDA-affected foal.