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CID An Update by Mary-Jane Parkinson

SCID: An Update by Mary-Jane Parkinson

Funny, this business of breeding Arabian horses. Breed Ibn Bad Legs to Bint Bad Legs, and odds are you'll get Less Than Perfect Legs. Breed Low Back to Ms Low Back, and chances are you'll get Even Lower Back. But breed Prince Nearly Perfect to Bint Gorgeous Gal and you might get Most Beautiful Ever, and you could possibly produce The Great Tragedy, a foal doomed to early death because of its inability to fight off infection.

All a matter of the seen and the unseen.

In the cases of the conformation defects, they are obvious in the parents and probably in the grandparents. In the case of the doomed foal - a SCID-affected foal in lab talk - the outward appearance gives no hint of the genes that could capriciously combine to produce the tragedy of Arabian and Arabian-related breeding. The best-intentioned, most thoughtful, knowledge-based breeding in the world could produce a SCID foal.

Until June 1997, that is. That's when the Arabian horse community first heard the news of the development of a test that would determine the SCID (Severe Combined Immunodeficiency) status of a horse. So the 1998 breeding season is the first in which breeders may utilize this test to ensure they do not unknowingly produce a SCID-affected foal (often referred to as a "skid" foal). A long way from the devastating days of 1973 when the condition was first diagnosed and labeled as CID; a term not understood by the best of the scientific community became a part of the breeder dilemma. Enough to match up legs and backs and type and tail carriage and athletic ability, but here was an unknown and unseen element that must be dealt with. And of course the greater frustration was that no one knew how to deal with it.

Lance Perryman, D.V.M., represents the continuity of the research from 1973 on. He recounts: "The disease in Arabian horses was first described by Travis McGuire in January 1973. At that time, I was a graduate student at Washington State University at Pullman, and McGuire was my major professor. Although my thesis had nothing to do with horses, I was in his lab and became familiar with the work he was doing. When I finished my Ph.D. in 1975, I took a faculty position and from then on, I was heavily involved in SCID research."

The lab at WSU became one of the three labs in the country set up to do the diagnostic procedure on SCID foals. Diagnoses came only through postmortem analysis in those days, so blood and tissue samples were sent to one of the labs for work-up. SCID foals typically become ill at about one month of age and inevitably die before the age of five months for the simple reason that their flawed immune systems leave them vulnerable to infection.

"One of the important early questions asked was this: Is SCID a genetic disorder and, if so, how is it inherited?" Dr. Perryman remembers. "Investigators in Australia published the first paper saying that SCID was a genetic disease inherited as an autosomal recessive trait. Travis McGuire and Marinel Poppie published a paper in 1977 wherein they reported that their research suggested the same conclusion. And in 1980, Richard Torbeck and I published a paper in which we confirmed those findings. Now, we knew two important factors of the research: that SCID is a genetic disorder and that it was inherited by an autosomal recessive trait. So it was absolutely obvious that what the Arabian horse community needed was a reliable way to detect heterozygotes."

In those early years of research, concerned breeders learned a few genetic terms, or attached new meaning to familiar labels. For instance: Autosomal, meaning that SCID is not sex-linked, and therefore it could be carried and transmitted by either sire or dam. Recessive trait, meaning that to produce a SCID foal, both parents must carry, and give to the foal, the defective gene. Heterozygote, meaning an individual with both the recessive and dominant gene for a specific trait.

Early studies led researchers to believe that two to three percent of Arabian foals were SCID foals which suggested that about 25 percent of the Arabian horse population carried the recessive gene. Scary business for breeders dealing with an unknown. Breeders stayed with matings that had not proven disastrous and made new choices with great trepidation, standing at the side of their mares and reciting daily incantations to the gods of the autosomal recessive and monitoring newborn foals with an unusual intensity. Prospective horse owners took a look at the scene and many decided to invest their time, money, and emotions in other breeds.

Breeders constantly dealt with the lack of knowledge of SCID. A California stallion had sired more than 100 foals - and his owners felt comfortable that he was not a carrier - before a mating to a carrier mare and the matching up of genes produced a SCID foal. The stallion was gelded and sold as a performance horse. In the 1980s, Bazy Tankersley of Al-Marah Arabians imported a stallion from England for use in her large herd. He came with the rumor that a grandsire had sired a SCID foal. Bazy tested the stallion in the only way then available, by offering free breedings to owners of 16 known carrier mares. The results were exactly what we had learned by that time were the odds: One-fourth of the foals were SCID-affected and died. That stallion was gelded and sold.

Unfortunately, the rumor mill found great grist in the SCID issue, and the old Arabian grapevine hummed day and night.

Because absolute proof of SCID status was not available other than through necropsy, many breeding stallions and numerous bloodlines and countries of origin were maligned, often by association or innuendo. The lift of an eyebrow in a significant tackroom conversation could almost end a stallion's breeding career. Dead foals were not always posted and because the symptoms of a SCID foal's last illness are similar to foal pneumonia, foal deaths were often attributed to pneumonia and probably pneumonia deaths to SCID. More material for the rumor mill.

As more horses were identified as carriers in those years, some non-scientific observations came to light. In reviewing known and suspected carriers, breeders in the United States and overseas noticed a correlation between carrier status and certain traits associated with Arabian type (the large eyes, the short dished head, the beautifully shaped ears, the tail carriage, and others) and a dramatic flair or unusual presence. The conjecture (and it's only that) is that Arabian breeders over the centuries have selected for these features and have inadvertently brought SCID along with them.

But back to those trying to solve the SCID issue. As a part of the research at Washington State University, Dr. Perryman and his cohorts assembled a small herd of known SCID carriers - two stallions and about 35 Arabian and part-Arabian mares. "That herd was absolutely vital to our research," Dr. Perryman notes. "We would know much less about SCID had it not been for the generosity of breeders and owners who donated these carrier animals. With the herd, we had a defined population of horses we could sample."

The Arabian horse community rallied to the need for continuing research, donating to the Morris Animal Foundation which funneled grants to researchers nationwide. The National Institutes of Health provided grants (in part for maintaining the Pullman herd) as the research paralleled investigation of combined immunodeficiency in humans. Grants totaled over a half million dollars.

"We looked for enzyme deficiencies, all sorts of possibilities, and then in the very early 1990s, we made the observation that SCID foals had a problem with DNA repair. And that led us on the right track," Dr. Perryman continues.

"When one is looking for a genetic defect and the only fact you have is that it is a genetic defect, if that's all you know, then looking for the precise gene defect is an awful lot like looking for a needle in a haystack. Until the DNA repair observation, we weren't even in the correct haystack, but we didn't even know that.

"When I entered into collaboration with Katheryn Meek, D.V.M., an immunologist at the University of Texas Southwestern Medical Center Lab in Dallas, a human research facility, we observed that SCID foals did not have DNA-dependent protein kinase activity. Once we knew that, not only were we in the correct haystack, but now we had a powerful magnet that we could use to grab that needle. Once we made the identification, the next step was to clone the gene that encodes that enzyme (from both carriers and normal horses) - actually one particular part of the enzyme - and then sequence that gene. When the cloning and sequence work was completed through the work of Dr. Euy Kyun Shin, Dr. Meek's colleague, we determined that SCIDs are missing five base pairs in the gene that encodes the so-called catalytic subunit of DNA-dependent protein kinase, the component that is defective and thereby precludes proper function of the immune system. And isn't that a mouthful?

"Did we all cheer at this finding? The word euphoria applies well. This was such an important problem because we'd known for so long that the Arabian horse people needed this information in order to make informed decisions. The essence of research is that you pick important problems and you persist in your efforts until you resolve those problems. We persisted long (for nearly 25 years) and hard on this one."

By June 1997, a test for determining SCID status - carrier, clear, or SCID-affected - was announced, offered through VetGen LLC in Ann Arbor, Michigan. Although VetGen does not disclose figures on numbers of tests processed, one clue to the extent breeders have availed themselves of the test comes through the tag "SCID tested clear" on ads for breeding stallions for the 1998 season. Tested horses are categorized as "Clear," "Carrier," or "SCID-affected" (the foal with the lethal inheritance), in confidential reports mailed to owners. (See our talking point SCID page for more details.)

"The test is all about making informed decisions," says Dr. Perryman, "and I see it proving valuable in at least three ways:

"First, it will help individuals make informed decisions when they're purchasing horses and it will help them establish fair market values."

"Second, it helps individuals make informed decisions in structuring breeding programs. Let me expand on that a bit. No breeder would ever choose to knowingly breed a carrier mare to a carrier stallion anymore, would they? Now, for the first time, there's a way to make sure that doesn't happen. If owners are willing to test their stallions and their mares, they can ensure that such matings will never occur. And if that's done, then never again would a SCID foal be produced to die of that unfortunate disease. Breeders now have a tool they can use to gather all the information they need to structure a good solid breeding program."

"Third, it allows breeders to replicate the otherwise highly desirable traits of horses that are known carriers. For the record, I don't own any horses, but let me speak as if I do. Assume that I own a stallion, a highly desirable stallion, good conformation, doing well in the showring, siring fine-looking foals. Desirable, but unfortunately a carrier of the SCID trait, so my goal is to retain his many desirable characteristics in a replacement stallion that is not a carrier."

"Now that the test exists, I would go out and find myself a number of mares that I believe my stallion would nick well with. I would test those mares and make sure they do not carry the trait, breed the mares, and test all the foals at birth. We know from the genetics of the disease that with carrier-to-clear matings, there's a 50/50 chance that the foals will be clear, a 50/50 chance that they will be carriers. I would identify the colts that are clear, sort them out for desirable qualities I want to perpetuate, and invest my resources and energy into bringing them along."

SCID 0: Ideal Breeding Scenario SCID 2: Safe Breeding Scenario SCID 3: High-Risk Breeding

Here are the expected statistical outcomes of clear-to-clear matings, clear-to-carrier matings, and carrier-to-carrier matings. Breeding clears to clears (Figure 1) will produce 100 percent clears. Breeding clears to carriers (Figure 2) will result in foals with a 50/50 chance of being clear, a 50/50 chance of being carriers. Foals produced by clear-to-carrier matings should be SCID tested. Breeding carriers to carriers (Figure 3) gives each foal a 25 percent chance of being clear, a 50 percent chance of being a carrier, and a 25 percent chance of being a SCID foal - a foal that will die before five months of age.

Successive foals from repeated matings don't necessarily march along in the chart order. Each foal - no matter the order in which it was foaled or how many foals the mating has produced - has the same percentage chances of being carrier, clear, or SCID (as above). For example, producing two clear foals from a clear-to-carrier mating doesn't mean the next one will be a carrier. Within each type of mating, the chances are the same for each foal. Much like a Las Vegas roulette wheel. The wisdom of breeding selection in the next generation will determine how quickly the breed can rid itself of the SCID gene.

"It's important for breeders to understand how heterozygotes (carriers) are produced, and that's why testing of all breeding stock has real value," says Dr. Lance Perryman. "It's also important for breeders to understand that, with the test as a breeding tool, they can ensure that no more foals will die of SCID. That can cease, if people want it to cease. And no one will have to take that emotional and economic hit again."

"The most significant factor in all this is that Arabian people now have a tool - a tool that allows them to obtain the information they need to make informed decisions. To ignore the 'warnings' implicit in test outcomes would be irresponsible, failing to utilize a useful tool, making poor use of knowledge.

"Informed decisions again come into play when owners test only part of their herd or only breeding stallions. The bottom line is that the only way to know whether a horse is free of the trait is to test that individual horse. Try this scenario: Assume a breeder has two stallions that have tested clear and assume that some of the untested mares are carriers, but most aren't. It's a fact that no SCID foals will result from the breeding of non-carrier stallions to carrier mares. But anytime you breed a non-carrier to a carrier, you have a 50/50 chance of producing a carrier. So although that breeder will have no dead foals, he/she will unknowingly perpetuate SCID gene transmission."

As with any innovation, the test spawns more questions: To what extent will Arabian breeders take advantage of the test? To what extent will they disclose test results? To what extent will judges of halter (breeding) classes be able to disregard whatever knowledge they may have of an entry's SCID status?

The Arabian Horse Registry of America and International Arabian Horse Association responded to the announcement of the test by creating a joint committee charged with determining how best to maximize it. Last August, the committee - comprised of Ann Bowling, geneticist at the University of California at Davis; Georgene Holasek, D.V.M.; Jim Rooker, D.V.M.; and Ray Cerniga, D.V.M. - made its recommendations. Briefly, they are:

  1. Testing should not be mandatory.
  2. Any two carriers should not be mated; non-breeding horses do not need to be tested.
  3. Testing of breeding stallions is encouraged because management of the disease is easier through stallion selection schemes.
  4. A foal of untested parents that exhibits pathological symptoms should by tested for SCID.
  5. The most effective sampling technique should be utilized for collection by an owner or veterinarian.
  6. Alternative testing laboratories should be designated to give owners options for independent confirmation of results if considered necessary.
  7. Legal language should be developed which can be offered to stallion owners for inclusion in breeding contracts.

At the IAHA annual convention in November, in a cooperative effort with VetGen, convention delegates purchased 120 test kits that were offered at a group discount rate. This effort represented IAHA's longtime concern with SCID. In the 1980s, its FOAL commission (Fight Off Arabian Lethals) advocated restricting the spread of SCID by not selling, leasing, transferring, or breeding any known carriers or their offspring without disclosing this information to those involved. Later, FOAL attempted to maintain a confidential repository of carriers identified through laboratory postmortems of foals.

Late in 1997, Jay McClure, D.V.M., of the Department of Medical Sciences, University of Wisconsin, who has been involved in study of the SCID trait for a number of years, presented details of the research and the test to the annual meeting of The American Association of Equine Practitioners. "To my surprise, a lot of veterinarians were not aware of the test. Some had heard of it but had no idea on procedure, so they found the material helpful. Generally, I feel the test was well received, and it is valuable because of its accuracy and the wholly confidential reporting of test results."

Unfortunately, with this new knowledge has come a revival of the witch-hunt atmosphere of the 1970s and 1980s. Guilt by association: "Ibn Soandso is a carrier, so I won't breed to any stallion in that sire line." An unreasonable response. The fact that a horse tests carrier means only that one of its parents is a carrier. Perhaps both. The same thinking that applies to the grey coat color in Arabians works here. We know that a grey Arabian must have one grey parent. But both parents may be grey. All ancestors of carrier-tested horses should not be "condemned."

Or, "We're not going to test because we don't have SCID in this area." Or, "We just don't have SCID in the lines we're breeding." Or, "We've bred so many foals, we'd surely have a SCID foal by this time if it were in the herd." Researchers have long been aware that SCID is no respecter of geography, bloodlines, countries of origin, breeder longevity, number of foals sired/produced, breeder intuition, breeder optimism, horse husbandry practices, or other animals (wild and domestic) at studs. One breeder questions the validity of the test; another questions the existence of the SCID condition itself. Others object to the cost of the test ($180, herd discounts available). The charges for a veterinary call and treatment at the first signs of a foal's vulnerability to infection will likely exceed the cost of the test.

Some breeders developed plans for testing over a period of time. Ralph Sessa, Jr. and Cory Soltau at Blackhawk Valley Arabians began by checking their foundation mare TW Forteyna and "a two-year-old colt we'll breed to a few mares this year." Both tested clear. "We're in the process of checking another mare. If she tests carrier, we're not going to panic. We'll just breed her selectively," Ralph relates. "I've been appalled at the less-than-positive responses I've gotten when I ask stallion owners whether the stallions they're advertising have tested clear. The test is the biggest breakthrough within the last 20 years and breeders really need to know stallions' SCID status before they send mares or have semen shipped. If stallion owners are not willing to test their stallions, I don't want to breed to them." All of which supports Dr. Perryman's contention that when test results are not disclosed the marketplace will sort this out fairly quickly.

At Cal Poly Pomona, Cal Kobluk, D.V.M., director of the Kellogg Arabian Horse Center, plans to test all stallions and mares used in breeding there. "We feel testing is important to planning future breeding," says Dr. Kobluk. "As soon as funding is available, and it should be soon, not only are we going to test the 30 or 40 breeding animals at the center, but we will also test the horses that have recently been introduced in our Heritage Program to reestablish some of the original Kellogg bloodlines. With the test we can intelligently breed any carriers and take advantage of their superior genetics. And at the same time contribute to the elimination of SCID in the breed."

Don Severa of Varian Arabians recently made a clear result of SCID testing a contingency of a mare purchase. "Four of our breeding stallions - Desperado V, Bravado Bey V, Hucks Premier V, and Sundance Kid V - have tested clear," says Don. "At this time, we have no plans to check mares. How many foals have been produced by Varian Arabians in the last 48 years? Thousands probably. And never has there been a known SCID foal from all those matings. Yet we were certainly one of the first farms to test every one of our stallions. I realize this doesn't mean we have no carrier mares. We plan to use the clear status in our advertising of the Varian stallions, and we believe it will become custom and practice in the breed to do so. Whatever we do as breeders, now that we have the test, we must avoid stigmatizing owners of carriers. Also, now that we have the test, breeders have some serious choices to make on the ways we use it to lower the incidence of SCID carriers in the population. Not producing SCID foals is just the first step."

Bazy Tankersley has been breeding Arabians for almost 60 years and has produced nearly 2,500 foals. "Probably one of the most inbred herds in the country, and we've never produced a SCID foal," says Bazy's farm manager Dennis Eikenberry. "Mrs. Tankersley is very knowledgeable about SCID and a stickler on avoiding it; for the present we feel comfortable testing the breeding stallions only, rather than 200 horses. AM Seagfreed, SSA Csea Dream, AM Gypsy Vision, Opalo, AM Clem Dreamon, AM Love Lightly, and AM Power Raid have all tested clear."

The Arabian Breeders Association (ABA) advocates the testing of all stallions and all possible suspect breeding stock. Mare owners are encouraged to ascertain the SCID status of any stallion they are considering, and owners of otherwise highly desirable carriers are encouraged to consider the positive effects of maintaining those animals' genetic characteristics through thoughtful breeding and selection.

The test-and-tell approach has worked well for Gene and Sue Mathews of Stage Coach Ranch. About 60 days after their stallion Eqynox was named unanimous 1997 Canadian National Champion Stallion, he tested carrier for the SCID trait. Their letter in Letters to the Editor, Arabian Horse World December 1997, tells of their decision to "go public" with Eqynox's carrier status. "We've had overwhelming support of this stance," says Gene. "Not one negative reaction. We have nearly 30 letters from all around the country, commending our honesty and our willingness to take the risk of going public. And scores of phone calls, including one at 9:00 p.m. Christmas Eve. Most persons - and some have been through the horrors of trying to save a SCID foal - are so relieved that SCID is now being discussed openly.

"Early last December, Eqynox was presented at an open house at Arabco. Presented with flair - in his championship roses and then at liberty, trotting way over level, like a locomotive. He just plain knocked 'em dead and mare owners went scrambling for their checkbooks. Michael Byatt explained to each prospective breeder that Eqynox had tested carrier and that we would only breed mares who had tested clear. None were discouraged by this news and to date 15 mares have been booked to Eqynox (including several Saddlebreds), and we've had tons of requests for videos. The interest continues. Meantime, Eqynox is in training for English pleasure, will debut at Region 9, and go on to Nationals.

"I have difficulty understanding why some don't want to discuss SCID, even now," Gene continues. "With the test, it's just plain good business to come out and say where we are. It's not a matter of being a knight in shining armor. Now we have a management tool. Let's use it.

"We as a breed must recognize the importance of breeding carrier horses of good quality because that genetic pool should not be lost or the breed will suffer. We need to think in terms of preserving traits, rather than discarding individuals or entire bloodlines. We've all heard the horror stories of other animal breeds where mass elimination of specific lines only led to the production of genetic traits far worse than the one breeders hoped to eliminate.

"Also, the days of trying to be a detective, sleuthing out known and suspected carriers, should be over. We don't need a repeat of the witch-hunt. With the test, it does not matter where the trait came from. What matters is that now we [Arabian breeders] need never produce another SCID foal. We go on from here. I have real trouble understanding why stallion owners won't spend the $180 to have their stallions tested. Again, just good business, not simply a matter of conscience.

"We plan to utilize Eqynox to the fullest in our small breeding program. We've been in the business for 15 years, and he is a long-term factor for us - our horse and we want to perpetuate his special qualities. This year, we're breeding our Polish-bred mare *Eukadra to him. And we'll breed our mare NDL Europa (who tested clear) to our stallion Myrlyn (who tested carrier). Earlier, those two produced a very pretty 1996 gelding and last year a fine filly. So we know they're a good match."

Dr. Michael and Karen Eads of Crescent Moon Arabians find themselves in a SCID-management situation. They have a mare in foal to Myrlyn, a Mathews stallion who tested carrier. "We will eventually have all our mares tested and the mare in foal to Myrlyn will be tested prior to foaling to learn what we might expect in the foal," says Karen. "We're praying, of course, that she is not a carrier. We will also test the foal and if he/she is to be sold in the future, the SCID status will be revealed. We're optimistic; if all the wonderful parts of sire and dam go together as we hope they will, this will be a phenomenal foal."

Dr. Perryman, now at North Carolina State University, looks back on the years of research: "We've made several observations over the years that I'm proud of, but none of them am I as proud of as having this test available for use. The exciting thing is that people now have the tool they need to make those all-important decisions."

Meanwhile, there's a sidebar. Last January at the Plant and Animal Genome VI Conference held in San Diego, California, researchers Domenico Bernocco, Ph.D., D.V.M., of Stormont Laboratories, Inc., at Woodland, California, and Ernest Bailey, Ph.D., of the M. H. Gluck Equine Research Center at the University of Kentucky (where he's researched SCID) presented their findings on the occurrence of the SCID gene. "Based on testing 386 Arabian horse foals registered in 1997, the frequency of the SCID gene carriers was 8.29 percent (32/386)," the abstract states. "Using this phenotypic frequency, we would expect 0.17 (1 out of 582) of Arabian foals to be affected with SCID based on a random breeding population."

One short story helps to put SCID in perspective. Visitors to the United States in the late 1970s from a Middle East Arab-breeding country were told of the devastation of producing a SCID foal. The visitor response: "Oh, we've known about that condition in Arabian horses for centuries. We just call it 'Allah's curse' and get on with breeding."

So we're back to the seen and the unseen. But now, lab findings transfer the unseen to a single-page report that provides volumes of direction for all willing to be guided by it.

Will we someday have like direction on bad legs?