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Making better decisions about hip and elbow dysplasia: the era of genomics is here

8/2/2017

 
By Carol Beuchat PhD
Should you breed a dog that doesn't have excellent hips or elbows? How much less than excellent is still "good enough"? Most dogs, especially of larger breeds, can't boast about having excellent hip scores. So how does a breeder decide what to do? You might see a a hip x-ray posted in a Facebook group with a plea for advice from other breeders. "Are these hips really that bad? Are they bad enough to remove a dog from the breeding pool completely?  
If all you have is the evaluation or x-rays for a single dog, you really don't have enough information to make a good decision. The reason is something called "heritability".
Many traits are affected by both genetics and environment. Heritability tells us about the relative contributions of genes and environment to the variation in a trait in a population. The key word here is variation. Some of the variation in a trait among individuals is because they have different genes, and some will be due to non-genetic (i.e., environmental) factors. The fraction of the variation accounted for by genes is the heritability of the trait in that population.

The heritability of a trait is specific to a particular population measured at a particular time. A different population could have a different heritability for a particular trait, and even the same population measured at different times can have different heritability. A trait can have a high heritability in a population of animals raised and measured under the same identical conditions (i.e., genes account for most of the variation in the trait), while the same trait can have low heritability in animals raised under different conditions (i.e., differences in environment account for a lot of the variation in the trait).
If you're trying to select for or against a trait that is influenced by both genes and environment, this presents a problem. If heritability of the trait you're interested in is relatively low, this will mean that phenotype - what you can see or measure about the trait - is not necessarily a good reflection of the animal's genotype, and of course it's genes you're trying to select for. 
So when you're trying to make breeding decisions based on traits affected by both genes and environment, you must remember that what you see is not necessarily what you get. A dog with moderate hip dysplasia might have been very overweight as a puppy, or loved jumping off the side of the front porch every afternoon to greet the mailman. Those hips might reflect the adverse influence of non-genetic factors - the "environment".
What do we do about this dog with the less than perfect hips? Was it environment? Or was it genes?

We don't know what genes affect the risk of hip dysplasia. But a dog will share some of its genes with relatives - parents, siblings, and offspring. We can learn more about the genes in a dog by knowing about the hip evaluations of closely related dogs. Let's look at some examples.
Here's a simple pedigree with information about the relatives of a dog you are thinking about breeding that has a less-than-stellar hip score (he's the fellow with the red dot on his head in the third row). You find out that the dog's siblings have acceptable hip scores, the sire and dam are also good, and in fact even back another generation the dogs either have good hips or no information. You would probably be making a good bet to assume that your dog has inherited favorable genes for normal hips.
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If the pedigree looked like the one below, it would be a bit harder to decide. There is a sibling with bad hips, and there are litter mates with no information. (Maybe bad scores weren't submitted???) There's no info for the dam, and missing information in earlier relatives. Did two pups in this litter get genes that predisposed them to hip dysplasia, or did these two pups love to push each other off the front porch when they were little? Should you breed this dog? What would you do?
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​Unfortunately, this next pedigree is probably more like what the average breeder will have to deal with. Bad hips, missing data, no patterns, and it's anybody's guess if all you have is this pedigree information to work with. What would you do with this one???
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What you need for this problem is a statistical technique called "estimated breeding values" (EBV). This is a way of mathematically predicting the "quality" of the genes in a dog for a particular trait. You can determine the EBV for a particular trait from pedigree information, and some kennel clubs are now providing EBVs for hips and elbows to breeders.

However, with high resolution genotyping we can now determine genomic EBVs directly from DNA (gEBVs). Using DNA is especially powerful because we don't even need to know the relationships among the dogs we have data for. The software evaluates the DNA for each dog, accounts for whether they are affected or normal for the trait, and spits out a number that reflects the breeding value for a particular dog. 
The singular beauty of gEBVs is that they can be used for any trait, and you don't need to know anything about the genes involved or mode of inheritance. In a nutshell, you can manage a genetic disorder without first launching a research project to hunt for the genes. You simply need the trait information for as many dogs as possible, and their high-resolution DNA genotypes. 
Why aren't we doing this? Until now, we didn't have the DNA data or the computing tools, but the ICB Breeder Tool will have this capability. The same DNA test you would do for health testing in your breed can also produce a research-quality genotype that can be used to determine genomic estimated breeding values. This information can be provided for breeders who can then choose the breeding pair that has the lowest risk of producing problems in the offspring - or the highest probability of producing some desirable trait. Furthermore, we can assess in young puppies the genetic risk of disorders that only appear late in life. 

Because all the math is done behind the scenes, there are no privacy issues with data. A dog simply has a gEBV based on the information available for related dogs, without the breeders needing to know the specifics of that information. There is no need for secrecy, no fears of getting hung out to dry on Facebook. 
Genomic breeding values should revolutionize dog breeding. Even better, they should eliminate the need to invest thousands of dollars, and months or years of waiting, in research studies that might never produce information that is useful to breeders. We have invested millions of dollars in cancer, epilepsy, allergy, heart, and kidney research, and for all this we have just a handful of genes that breeders can test for. There is a better way.
We will be rolling out genomic breeding values in the ICB Breeding Tool as soon as we have enough data for a breed to do it. Talk to your fellow breeders about it. For this to work well, the more data available the better, even for dogs that are not intended to be bred, because their DNA and trait status will improve the power of the estimate of breeding value.

If you think you can get enough participation to set this up for your breed, please let us know and we will work with you to get it set up.

You can read more about genomic selection here -
Boichard et al 2016. Genomic selection in domestic animals: principles, applications and perspectives. (Open access)

BTW, if you want to learn more about estimated breeding values and how they can be used to improve selection in your breeding program, consider enrolling in our course, Understanding Hip and Elbow Dysplasia. We'll show you how to evaluate that very tricky pedigree above, and discuss how much easier it will be to toss the pedigree and work directly with the genotypes! The next class starts 7 September 2017.

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