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Are you improving genetic diversity, or just pushing the peas around?

Discussion in 'General Dog Discussions' started by Institute of Canine Biology, Jun 26, 2018.

  1. By Carol Beuchat PhD
    It's the classic scene. The family sits down at the dinner table and Billy grimaces at the food on his plate. He hates peas. HATES peas. So while acting non-chalant and seeming to really dig into his meal, Billy was actually deftly using his fork to push one pea to the other side of the plate, and another up under the thigh bone from his drumstick. A few disappeared under the pile of mashed potatoes, one leaped from the plate and fell to the floor, and soon it looked like he had done a decent job of getting down most of the despised peas.

    But Mom is no fool. "Billy", she says sternly, "eat your peas instead of just pushing them around on the plate!" Busted.

    We risk doing a similar thing when making decisions about the ideal and sire and dam for the next litter of puppies. Let's say you have a bitch you want to breed and you're considering four or five potential sires. You also have some DNA test information that allows you to compare the genetic similarity of the bitch with each of the sire candidates. Selecting the sire that is least similar to the dam should produce puppies with the lowest inbreeding on average.

    But does this tell you everything you need to know? Are you really improving genetic diversity? Or are you just pushing the peas around on the plate?

    Let's consider 2 things. First, let's look at genetic relatedness.

    By "relatedness", we refer to the genetic similarity of a dog to the other dogs in the population. Closely related dogs will be more similar; distant relatives will be less similar.

    There will always be genetic differences between two dogs, no matter how closely related they are, because no two puppies will inherit exactly the same alleles out of all the zillions of possible combinations. So even among closely related dogs, you should always be able to identify a dog that is "least" related, and if you're shopping for sires this one might look like the best bet.

    The problem here is that you can identify a dog that is least related compared to the others, but it might still be very closely related - much more closely related than you would risk breeding to if you knew the actual genetic level of relatedness (First cousins? Half-siblings? Full siblings???).

    Let's consider an example. We have a population of about 80 dogs in a particular breed, and you are sorting through them to identify which of a few sires you are considering is least similar to your bitch. You make your choice and look over the pedigree information, and they don't share any common ancestors for several generations, so you're happy.

    But the kinship coefficients of the dogs would tell a different story. The kinship coefficient for a pair of dogs is the fraction of their genes that are identical by descent. This sounds like it's related to inbreeding, and it is. In fact, the inbreeding coefficient of a dog (the fraction of the genes in an individual that are identical by descent) is equal to the kinship coefficient of its parents. Since we know that most genetic disorders in dogs are caused by recessive mutations, the inbreeding coefficient also tells us the risk of a genetic disorder produced by a recessive mutation.

    If you determine the kinship coefficients between the bitch and each of the potential sires, you will probably find that your choice for sire also has the lowest kinship coefficient, indicating that it is genetically least similar among the sires being considered. However, the magnitude of the kinship coefficient reveals that this "least related" dog is actually more similar to the bitch genetically than you would expect of a full sibling. The actual data for the coefficients of these potential sires are:
    1) 0.388
    2) 0.693
    3) 0.340
    4) 0.398
    5) 0.288
    Sire number 5 has the lowest kinship coefficient so is least related. But that kinship coefficient indicates that he and the bitch are more similar genetically than you would expect for full siblings, which would have a kinship coefficient of 0.25.

    Wow. You wouldn't do a full sibling mating, and this mating would also be a close inbreeding. From the data for the other animals, it looks like there is very high relatedness among many of the dogs in the population, whose kinship coefficients go as high as 0.693!

    When comparing dogs relative to each other, one dog looked like a good choice. But after looking at the actual kinship coefficient of the potential parents, and the estimated inbreeding in the litter that would be produced, you decide that the marriage is much too close for comfort.
    Above, I noted that there were two things we needed to consider when making mate selections based on information about relatedness from DNA data. The first was the absolute, and not just the relative, genetic relatedness.

    The second issue is related to this. Genetically similar dogs will have similar mutations. The least related pair based on kinship coefficients will nevertheless share many mutations if they are as similar as full siblings. They might be from different lines and not share any kin for many generations, but genetic similarity brings with it high risk of producing a genetic disorder. Mating of full siblings, with a kinship coefficient of 0.25, has a 25% risk of pairing up two recessive mutations.

    Let's look at another example. Below is a "dendrogram", a family tree that is based on kinship coefficients determined using a high-density (> 200,000 markers) SNP panel that has considerable power for resolving relatedness among closely related individuals.

    On the panel on the left, I have indicated the results of genetic testing for the mutation responsible for von Willebrand's in this particular breed. Individuals that tested clear have a little "c" at the end of the branch. Individuals that are carriers of the mutation have two asterisks (**), and dogs that are homozygous (and therefore affected by the disorder) are indicated with four asterisks (****).

    You should be able to scan from the top of the chart to the bottom and easily pick out the clear, carrier, and affected dogs. What you will probably notice is that the VWF mutation is widespread in this breed. If there wasn't a test for this disorder, you might think you're avoiding it by choosing dogs that are not closely related to each other. But, as we saw above, all of these dogs are very similar genetically, regardless of how unrelated they might appear on paper.
    Status of VWF test

    Status of 4 DNA tests
    (as 1/2/3/4)
    So, simply choosing to breed to a dog that is the least related "relatively", and is from a different branch of the family tree, will get you no points for improving genetic diversity. Furthermore, a serious mutation is so widespread in the breed, unbeknownst to you, that you stand about a 1 in 4 chance of producing a puppy with a problem. In the case of this particular breed, there are test data for 4 known mutations, and when all those data are considered together, you see that in the population of about 80 dogs, only 7 tested clear for everything. If you're trying to avoid producing a genetic disorder in the next litter, you don't have many ways to avoid it.

    Considering the more complete information for genetic similarity provided by the kinship coefficients, together with the DNA test results, you can see that you aren't really going to improve the genetic diversity in your litter, no matter what you do. You can make all the comparisons and choose what looks like the best one, but it's really just pushing the peas around on the plate.

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