EQUUS - - Applied Genetics -

While ge­netic tests for dis­eases, col­ors and parentage can pro­vide DNA “proof” of a con­di­tion, those look­ing for genes as­so­ci­ated with per­for­mance-re­lated traits yield less de­fin­i­tive in­for­ma­tion. How or whether these genes are ex­pressed can be in­flu­enced by train­ing, en­vi­ron­ment and other fac­tors.

For in­stance, per­for­mance test­ing, aimed pri­mar­ily at Thor­ough­breds, looks at mul­ti­ple genes to at­tempt to pre­dict a horse’s speed, stamina and over­all po­ten­tial for suc­cess at the race­track. One fac­tor these tests an­a­lyze is the myo­statin gene, which con­trols the amount of mus­cle mass de­vel­oped. Other com­po­nents of the tests may pre­dict a foal’s height at ma­tu­rity as well as whether he will do bet­ter on dirt ver­sus turf tracks.

Gait test­ing iden­ti­fies a mu­ta­tion on the DMRT3 gene that in­flu­ences a horse’s abil­ity to per­form lat­eral gaits. The mu­ta­tion is re­ces­sive—horses with two copies of the gene are com­mon in Ice­landic Horses, Paso Fi­nos, Ten­nessee Walk­ing Horses and other gaited breeds. The ef­fects of car­ry­ing only one copy of the mu­ta­tion varies by breed, but those horses gen­er­ally per­form the lat­eral gaits with less speed and fa­cil­ity.

Hav­ing a par­tic­u­lar “per­for­mance” gene isn’t a guar­an­tee, how­ever. Af­ter all, many a rac­ing phe­nom has had full si­b­lings who washed out at the track, and ev­ery so of­ten a horse with a mod­est pedi­gree takes the show world by storm. DNA is only part of the equa­tion.

An­other test, de­scribed by its man­u­fac­turer as “cu­rios­ity vs. vig­i­lance,” an­a­lyzes a mu­ta­tion that af­fects dopamine0 re­cep­tors in the horse’s brain. Horses with two copies of the re­ces­sive gene are de­fined as more cu­ri­ous—that is, more in­clined to take an in­ter­est in and ap­proach new ob­jects. Horses with only one or no copies of the gene are more vig­i­lant, or less in­clined to ex­plore their sur­round­ings.

“An over­sim­pli­fied ex­am­ple of this might be that horses who test pos­i­tive for ‘cu­rios­ity’ might out­per­form those who do not in, say, a trail com­pe­ti­tion,” says Christa Lafayette, CEO of Etalon Inc. of Menlo Park, Cal­i­for­nia, who adds that the real util­ity of the test will only be known once own­ers be­gin in­ter­pret­ing the re­sults. “It’s go­ing to be in­ter­est­ing to see what own­ers say about it and whether or not they find a cor­re­la­tion be­tween cu­rios­ity/vig­i­lance and cer­tain types of ac­tiv­ity.” sire and dam. If the sire is un­cer­tain, then sam­ples can be sub­mit­ted from all pos­si­ble sires.

By com­par­ing in­her­i­ta­ble traits in the DNA, these tests can con­firm a foal’s parentage with ef­fi­cacy greater than 99 per­cent; an in­cor­rect sire can also be ex­cluded with 100 per­cent cer­tainty. “We com­pare the ge­netic pro­file of the sam­ple of mane or tail hair sub­mit­ted to our data­base pro­files of the sire and dam,” Graves says. “We ver­ify the par­ents and send those re­ports to the reg­istries.” How­ever, these tests do not re­veal the breed of an in­di­vid­ual horse.

Own­ers seek­ing to reg­is­ter their horses are the most com­mon users of equine ge­netic test­ing. “The DNA test for parentage ver­i­fi­ca­tion rep­re­sents the largest num­ber of sam­ples tested,” Penedo says. “Most horse breed reg­istries now re­quire DNA test­ing for reg­is­tra­tion, which trans­lates to hun­dreds of thou­sands of horses be­ing tested yearly around the world.”


Like many other tech­nolo­gies, ge­netic test­ing is be­com­ing faster, more af­ford­able and thus more ac­ces­si­ble. “The cost of se­quenc­ing a horse’s en­tire genome is com­ing down,” Graves says. “To­day, this can be done for about $8,000 to $10,000. Soon, per­haps within 10 years, it will cost only about $1,000. At that point, the av­er­age horse owner will be able to se­quence her horse’s en­tire genome.”

The chal­lenge, says Graves, will be de­ter­min­ing how best to use this in­for­ma­tion. “We still have a lot of work to do be­fore we will know that,” she says. “We need to cre­ate maps of each breed of horse. This will en­able us to look for de­sir­able per­for­mance traits or for ge­netic anom­alies in a horse

that has chronic health prob­lems.”

Could ge­net­i­cally en­gi­neered “su­per horses” ap­pear in the fu­ture? Pos­si­bly, with a new tech­nol­ogy called “gene edit­ing,” which Penedo de­scribes as us­ing “molec­u­lar scis­sors” to in­sert, re­move or re­place DNA se­quences in the lab­o­ra­tory. “I can en­vis­age that it will be tried in horses, but given the costs it is un­likely to be­come com­mon prac­tice,” she says. One ap­pli­ca­tion of this tech­nol­ogy that she does fore­see, how­ever, “would be to cor­rect the DNA se­quence in an early em­bryo from highly valu­able par­ents that is af­fected with a ge­netic de­fect, as de­ter­mined from pre-im­plan­ta­tion em­bryo ge­netic test­ing. The ex­pec­ta­tion is that the de­fec­tive gene could be re­placed by a nor­mal gene, and the ‘edited’ em­bryo could then be im­planted.”

In the mean­time, the num­ber of spe­cific tests avail­able---both for dis­eases as well as other as­pects of a horse’s health and phys­i­ol­ogy---will likely con­tinue to grow as re­searchers learn more about equine ge­net­ics. “It is a con­stantly evolv­ing field,” de Kloet says. “Just as with hu­man ge­net­ics, it’s go­ing to change and evolve in the num­ber of tests avail­able and with re­gard to how the test­ing is be­ing done. We have soft­ware pro­grams and the com­puter abil­ity to go through and look at a bil­lion nu­cleo­tides in only a cou­ple of days.”

To help with fur­ther re­search, Etalon Di­ag­nos­tics of­fers sev­eral tests to the pub­lic, for con­di­tions such as lor­do­sis (“sway­back”), that are in the “dis­cov­ery stage”---that is, although there is some ev­i­dence of ge­netic fac­tors for these con­di­tions, the re­sults of these spe­cific

tests have not been fully val­i­dated by re­search stud­ies. Etalon’s goal is to gain feed­back from own­ers to help sup­port the re­search.

“Our plat­form is col­lab­o­ra­tive, mean­ing that it re­lies in part on feed­back from horse own­ers,” Lafayette says. “We look for as­so­ci­a­tions be­tween cer­tain ge­netic mu­ta­tions and per­for­mance or other health traits based on emerg­ing re­search data. When we see a pat­tern that sug­gests a ge­netic link, we fol­low up with horse own­ers and track the in­put we re­ceive from them. This leads to the dis­cov­ery or con­fir­ma­tion of con­nec­tions be­tween ge­netic mu­ta­tions and re­sult­ing traits faster than would be pos­si­ble if we were to go the con­ven­tional re­search grant route.”

Lafayette ad­mits, how­ever, that this ap­proach is still a work in progress: “Since this kind of horse­owner-driven re­search plat­form has never been at­tempted be­fore, the learn­ing curve is steep,” she says. “We have to con­tin­u­ally ad­just our meth­ods, stud­ies, and the way we ap­proach and present the in­for­ma­tion.”

The de­mand for ge­netic test­ing is al­ready large and is likely to con­tinue to grow in the com­ing years as the tech­nol­ogy de­vel­ops and new tests be­come avail­able. Al­ready, says Lafayette, labs like hers are re­ceiv­ing all kinds of re­quests from peo­ple who want more in­for­ma­tion about their horses: “Big ones, lit­tle ones, wild ones and pocket ponies, all col­ors, all dis­ci­plines. Peo­ple want to know ev­ery­thing from color and health to speed and gait. Folks are ex­cited to talk and learn more about their horses, as are we.”

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