Genetics Studies Have Far-Reaching Benefits

We spoke with E. Gus Cothran, Ph.D., at Texas A&M to learn the real-life benefits of genetic typing, research and testing labs.

You run the genotyping laboratory in the College of Veterinary Medicine and Biomedical Science here at Texas A&M. What genetic services does your lab provide’

We provide DNA typing, for identification and parentage verification. Occasionally we’re asked to give some indication of ancestry (for example, if you want to know whether your Mustang horse has Spanish blood, we might say yes, though we couldn’t give a percentage or say which breed). We can’t yet test for genetic differences that are strictly associated with a specific horse breed, though that technology is available for dogs (and may be possible in the future for horses). We do genotyping related to coat color. We can also test for genetic diseases.

Give us some examples of coat color analysis.

Geneticists know the molecular basis of six coat-color genes in horses, and there are tests for these genes. We can tell you if your horse is carrying a recessive gene. For example, if he’s black but carries the mutation for chestnut, which could come out if he’s bred to a mare that also carries chestnut. We can tell you if your tobiano paint foal is homozygous dominant (will always produce colored foals) or heterozygous (won’t), even before he’s chosen as a breeding stallion.

You have urine samples to run today; tell us about those.

We have samples from a winning race horse with a positive drug test post-race; the owner contested the urine test. When provided with a known sample from that horse, or even an archived record for, say, paternity, we can use DNA testing to determine if the drug-test sample came from that horse or not. Because of the high variability of the DNA systems we test, the probability of two horses — even full siblings — having identical types is on the order of one in one hundred million.

You also type rare breeds where there may be only a hundred or fewer individuals, who could be closely related — can you still differentiate between those’

The variability within the breeds will differ, but even in those closely-related populations we aren’t going to see very many, if any, who have identical DNA types across all the systems.

Do you work with heritable diseases’

Yes, my lab is working directly or in collaboration with other labs to find the genes responsible for five genetic diseases that occur in horses. All these studies are currently employing older technologies, but the whole genome sequence information is already in use and newer technologies will soon be employed as well.

With new technological advances we can build expression arrays that allow us to test which genes are expressed. (Think of expressed genes as being turned on, versus not expressed, which are not turned on.)

If we had a disease that we thought was genetic, we could find out what gene was involved by using typical association methods. But just having the gene does not necessarily mean the individual will have the disease. Using expression arrays, we could then test individuals that had the disease against those that did not and see the differences in gene expression between the two. This would show us what gene (likely with a mutation that knocked out its function) caused the disease.

Breeders selecting for desirable traits might accidentally be selecting for undesirable ones. Is there anything new on this front’

We’re working now with the eye defect Anterior Segment Dysgenesis that occurs in Rocky Mountain Horses. It is very closely linked to — possibly even on the same gene as — the gene for the highly desirable silver dapple color.

You know that chromosomes are basically packets of DNA that are inherited as a unit. Some exchanges of genetic material are made between homolog chromosome pairs during egg and sperm development. During these exchanges, relatively small sections of DNA are likely to stay together and so they are inherited as a unit. The size of this unit is larger in close-bred than in largely out-crossed populations. So in populations where the members are closely related, you have a higher probability of selecting for an unsuspected gene that is next to the gene that you are actively selecting for. If there is a deleterious mutation in the gene it could result in the expression of a genetic disease like ASD.

While you test samples from many breeds, do you handle all the genetic work for certain breed associations’

Almost all the breed testing in the U.S. is done by university labs. We handle all the testing for about 18 associations, most with small populations, like the American Suffolks and the Caspian Horses. When I was at the University of Kentucky we worked with over 50 associations at one time. The Jockey Club uses the University of California-Davis, which is the largest lab of its kind in the U.S.

We also work with associations outside the U.S., for example the Venezuelan Stud Book and the Mexican Sport Horse Registry. There are over 40 labs like ours in the world and they test the breeds in their regions.

Genetics testing labs seem well settled in university settings. Why is that such an ideal relationship’

Well, we are like a business in that we have to be totally self-supporting. However, being associated with a university allows us to put our profits back into research. We’re in the forefront of exploration. We also educate students, both graduate and undergraduate, in genetic research.

Hair and blood are your preferred DNA sources’

We can deal with most any tissue that has DNA. We prefer–due to the economy of scale–to deal with hair and blood because we cycle through those routines all the time. We also need sufficient sample. While we could extract DNA from just one hair, there are enough steps along the way and enough places where something can go not-quite-right that we prefer 25 or 30 hairs so that we have enough for retests.

What part do you play in rare breed conservation’

My role is mainly in strategies for genetic management. By doing DNA typing, I can give an assessment of the level of variability of a breed. With this information we can put into perspective whether that breed is in trouble, potential trouble, or not, genetically.

It’s a comparative analysis. By having genetic variability data from a large number of breeds (for which we know the size and demographics of each breed) we can compare the variation of the rare breed to the others and tell if the breed in question has low, average or high variability. Low variability means that the breed lacks the flexibility to adapt to any changing environments.

We also look at the rate of loss of variability. A closed population (like most breeds) will always be losing variability. But the rate of loss is what’s important, and rare-breed managers want to minimize it. We can look at the breeding practices and advise studbook keepers how to keep the variability high.

One of my studies was with Standardbreds. It’s a large population by horse breed standards, but the trotting segment had been losing variability at an unsustainable r ate. Over 20 years, they lost 17% of their variability. The reason for this was that they were breeding for trotting speed and almost exclusively using particular stallions who produced fast offspring. While it makes sense to breed for speed, the danger is that you can lose the ability to select for other facets of racing performance like stamina, ability to withstand heat, and even fertility. Fertility loss is one of the main problems associated with inbreeding.

So you believe in hybrid vigor’

Absolutely. We see it in horses and in many other species. When you’re looking for a performance horse, there’s no reason not to — and lots of reasons to — choose a crossbred horse. Assuming, of course, that it can do what you’re asking it to. In general, hybrids have better potential to adapt — on an enzyme level — and this can even be related to characteristics like better defense against infection.

Where do we go from here’

At some point, utilizing the new tools that have become available, we can start asking questions about what genes influence the specific traits that are important to horse breeders. These aren’t necessarily single-gene simple traits. We’ll be able to look at quantitative traits and traits that have a number of genes influencing them. It might not be possible to select for all of the genes that influence a trait, but we can take the ones of major effect and select for them while trying to maintain the others.

Article by contributing editor Dr. Sue Stuska. Dr. Stuska earned Ed.D. in Community College Education (Equine Technology) at Virginia Tech. She has worked in positions from groom to guest-ranch head wrangler to professor, teaching equine technology at many different colleges and universities. Her current responsibility involves a herd of wild horses in North Carolina.

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