A simple, new tool for genetic disease management

By Carol Beuchat PhD
About 70% of the genetic disorders in dogs are caused by single, recessive mutations. In most cases, a dog with only one copy of the mutation will be unaffected. This means that breeders can avoid these disorders entirely with DNA tests and appropriate genetic management strategies like reducing the level of inbreeding and preventing the spread of mutations by popular sires.
But what about the other 30% of problems for which the genetics are complex or unknown? There are many of these, like heart disease, cancer, epilepsy, hip dysplasia. These disorders are extremely difficult to manage because we don't have good tools to assess risk or predict whether a dog is likely to be affected.
This is a problem we specifically wanted to address in the design of the new ICB Breeder Tool.
For genetic conditions, risk is greater for related dogs. You can get a general idea of the relatedness of dogs using pedigree information, but every puppy in a litter inherits a different mix of parental genes. Pedigree analysis can provide an estimate of risk, but it can't tell you if a particular dog actually inherited the deleterious alleles for a genetic disorder. If we don't know which genes are causing the problem, what can we do?

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The ICB Breeder Tool provides a way to determine the risk of a genetic disorder without knowing which genes are involved. Here's how it works.

The ICB Breeder tool takes the DNA information from a high-resolution analysis and compares each dog with the others in the population at each of thousands of markers. Dogs that are related will tend to share more of the same markers, and the more closely they're related the more similar they will be. This information is then used by the ICB Breeder Tool to construct a diagram that clusters together the dogs that are most genetically similar, and therefore most closely related. This treelike diagram is called a dendrogram. (Learn more about how to interpret a dendrogram.) ​

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This is a dendrogram that shows the genetic relationships among 11 Chinook dogs. Each of the vertical lines across the bottom is an individual dog.

The analysis has revealed two genetic groups: one on the left with three dogs in red and two in green, and on the right there is a group with two blue, two magenta, and two yellow dogs. The dogs that are most closely related are connected by the fewest, shortest lines. So there is one red dog that isn't as closely related to the other two as they are to each other, but it's more related to the other red dogs than the green ones. This diagram tells us about the actual genetic similarity or relatedness of the dogs in this group.

Now, if we are trying to manage a complex genetic disorder, we can use this dendrogram to help identify where the deleterious genes are in the population even though we don't know what they are.
Let's look at an actual example using elbow dysplasia in Labrador Retrievers (Ubbink et al 1998).

This is a dendrogram for the dogs in a guide dog breeding program. The breeding managers wanted to reduce the risk of elbow dysplasia, so they reconstructed the genetic relationships among the dogs as a dendrogram. They then indicated on the diagram which dogs were diagnosed with elbow dysplasia.

The length of each of the open bars below the baseline reflects the number of dogs in that related group, and the length of the black bar indicates the affected dogs.

From this, they could easily identify the cluster of dogs where the disease was occurring by the locations of the blackend bars. They were then able to eliminate the elbow problem by breeding away from the dogs in those clusters.

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They didn't need to know which genes are responsible for elbow dysplasia. They didn't need to do a research study. They were able to use the information they had about genetic relationships to pinpoint the location of the problem in their breeding stock and reduce the risk of problems in the puppies they produce going forward.

This is a great demonstration of how you can use information about genetic information to effectively manage a disorder with complex or unknown genetics.

This kind of analysis can be used for any genetic disorder or trait, without needing to know anything about the mode of inheritance or the genes involved. It can also be used to identify emerging problems that are appearing in certain lines. For problems like hip dysplasia, cardiomyopathy, autoimmune disorders, cancer, and even temperament, this simple analysis can identify the groups of dogs most likely to be at risk. There is no need to do research on the disease or identify the genes involved.

The ICB Breeder Tool uses the data from a high-resolution DNA analysis to construct the dendrogram of genetic relationships among dogs. This can then be used to provide accurate information about the distribution and incidence of a genetic issue in a population of dogs.

The ICB Breeder Tool is available now to breeders. You can read more about the other ways it can help you reduce the risk of genetic disorders and improve the health of your next litter of puppies.
Genomic analysis is going to revolutionize dog breeding!

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The ICB Breeder Tool is available now
with a great discount while we're beta testing!

Check it out here!​

REFERENCE
Ubbink GJ, J van de Broek, HAW Hazewinkel, & J Rothuizen. 1998. Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations. Vet Rec Feb 28, 1998.

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