By Carol Beuchat PhD

You probably lie awake at night wondering about this. How do dogs get water into their mouth without putting their face in it. And how do they manage to get so much of it on the floor?

Science now knows.

As I'm sure you are aware, dogs can't suck. It has to do with the fact that they have "incomplete cheeks" (yours are "complete"), so they can't pucker up and generate negative pressure to pull water into their mouth. What they do is actually more interesting - they essentially "pull" water into their mouth. They dip their tongue into the water and curl it back on itself forming a cup that contains water, then they draw it quickly into the mouth. This creates a column of water behind the accelerating tongue that also draws the water into the mouth. And they don't do this especially carefully. Cats don't make such a mess because they dip their tongue in the water more delicately. It's finesse, really. (The link above also has a cat video.)

Easier to watch than explain -

More here...

By Carol Beuchat PhD

Those with a fascination for the genetics of coat color in dogs will no doubt be familiar with the excellent website Genetics of Coat Color and Type in Dogs created by Dr Sheila Schmutz, a geneticist at the University of Saskatchewan in Canada.

A new paper by Schmutz and D.L. Dreger ( 2014) adds a few new wrinkles to our understanding of the complexity of canine coat color, focusing on three genes in the pigmentation pathway: the Agouti signal protein (ASIP), Melanocortin receptor 1 (MC1R), and Beta-defensin 103 (DEFB103). They argue that the usual characterization of non-additive genetic interactions of coat color genes as either dominance deviation or epistasis is too simplistic. They suggest that some additional types of non-additive genetic interactions should be considered, including "multiple modification" and "specific modification", and they provide some examples of each.

You can download a copy of this interesting paper from the link below.

By Carol Beuchat PhD

A new study just published (Heske et al 2014) documents the incidence of epilepsy (both idiopathic and symptomatic) and mortality rate in 35 breeds of dogs in Sweden, and the Boxer is (unfortunately) the clear winner by far in terms of both.

The study was based on insurance data for the years 1995-2006, and the data were expressed as either incidence or mortality per 10,000 dog-years at-risk (DYAR; equivalent to 10,000 dogs followed for 1 year). The study population consisted of 665,249 dogs, for which there were insurance claims for epilepsy from 5013 dogs. Males had both higher incidence and higher mortality than females (1.4:1). They found that breeds likely to be kept only as companions had higher rates of survival than those likely to be dual purpose - companion as well as hunting, herding, and working, perhaps reflecting a willingness to invest more in treatment of companion dogs. Females survived longer than males after diagnosis. In general, dogs lived only 1.5 years after diagnosis.

NOTE: These data are for ONLY the 35 breeds with the most records in the Swedish database. So for example the boxer is not necessarily the breed worst affected by epilepsy; it is the breed with the highest rate and mortality among the breeds used in this analysis. Most dogs in Sweden are insured, so this is a reasonably accurate assessment of incidence and mortality for the breeds they studied.

By Carol Beuchat PhD

Many canine genetic disorders are caused by autosomal recessive mutations. A dog with only one copy is usually unaffected if the other copy of the gene is the normal version.  But if two animals that both have one copy of the mutation are bred, there is one chance in four that an offspring will be affected because it receives two copies of the mutation. This is from the simple Punnett square - 25% of the offspring will get two copies of the normal gene, 50% will be carriers, and 25% will be homozygous for the mutation.

With the availability of DNA tests for many genetic disorders caused by autosomal recessive mutations, breeders can determine the carrier status of a dog and completely eliminate the risk of producing affected animals. Because these DNA tests reduce the potential risk of producing an affected dog from 25% to 0%, they are a very powerful way to manage specific genetic disorders in purebred dogs.

Unfortunately we have DNA tests for only a fraction of the known mutations in dogs, and there are probably hundreds more recessive mutations lurking in the gene pools of our dogs that we know nothing about. It's easy to see how we can manage the risk of problems from recessive mutations that we can test for, but what can we do about all the ones we don't?

This is a really important question, and one we don't often consider. The question we should ask first is whether we really need to worry about those unknowns. We don't know what they are or what problems they might cause (and of course, a mutation might be "neutral" and not cause a problem at all), so how big of a problem could they be? Consider that the mutations that we now have tests for only showed up on the radar because people starting seeing dogs affected by a genetic disorder. Before this, the mutation could have been passed from parent to offspring without harm for dozens or even hundreds of generations. As a general rule of thumb, we can expect every animal to carry a few mutations that would be lethal in a homozygous offspring, and many more will have some significant impact on health. So there are no doubt many, many more recessive mutations in the genomes of our dogs that will surface and cause problems if puppies get two copies.

If we can agree that we should assume that the genome of every dog will carry some mutations we don't know about that have the potential of causing trouble, then it is important for us to consider the risk not just from known mutations, but from those unknown mutations as well. We know that we can reduce the risk of affected offspring to zero with a simple DNA test, and that is certainly worth doing. But what can we do about the mutations we can't test for? Can we do better than just cross our fingers and hope?

Fortunately, we can. We understand how recessive mutations work. Puppies that get two copies will be affected, so our goal should be to find a way to reduce the risk of breeding two carriers. (There is no risk from breeding a carrier with a dog that is clear of the mutation.) But since we can't know who carriers are, or how many there might be in the population, how can we approach this problem?

If a mutation is recessive, a puppy that gets two copies will be affected, so the risk of producing affected puppies is equal to the probability of inheriting two copies of the allele, which is the same as the coefficient of inbreeding. As in this graph, the risk is therefore directly proportional to COI.

We know that if we breed two carriers, the risk of affected offspring is 25%. If we can do the DNA test for that mutation, we don't need to use COI to estimate risk; whatever the COI, we can know the specific risk from that mutation from our test. We can breed a litter with a COI of 10%, or 25%, or 50%, or whatever - and know absolutely that the risk of producing affected puppies is zero as long as only one parent carries the mutation.  So in this case, our graph looks like this:

So this is great. If we have a DNA test, we can reduce the risk of affected puppies from 25% to zero.

Now, how do we deal with all of the mutations we don't have tests for? These will behave as we described above - the COI of the puppy (the probability of homozygosity) will be the same as the risk of being affected. The higher the COI, the greater the risk of producing puppies affected by some genetic disorder caused by one of the recessive mutations that we know nothing about.

If you are DNA testing your dogs (and you should be!), you are reducing the risk of a known genetic disorder from 25% to zero. But that doesn't affect the risk from unknown mutations. Presumably, if a new mutation is discovered and a DNA test is available, you would see the value in testing for that as well if there is any question that it might be in your lines.

A responsible breeder can't know the risk of producing affected puppies from an unknown mutation, but they CAN manage that risk, and the rule is simple:

Risk goes down when COI goes down, for both the known and the unknown mutations.


This means that you can reduce the risk of problems from any and ALL recessive mutations by reducing the COI of the litters you produce. Instead of adding each new DNA test to the expense of health testing your dogs, you could effectively manage the risk of genetic disease by managing the risk of homozygosity, using COI as the yardstick.

By Carol Beuchat PhD


Try this little quiz testing your knowledge of the genetics of breeding:

1) What would you do if you wanted to increase the number of genetic diseases caused by recessive mutations in your breed?

2) What would you do if you wanted to reduce the size of the current gene pool?

3) What would you do to make a particular mutation "go viral" in your breed?

4) What would you do to reduce the effectiveness of the immune system?

5) What would you do if you wanted to increase the risk that a line of dogs or even a breed would go extinct just by chance because of the accidental loss of some critical gene?


ANSWERS
1)  Breed related dogs because they are most likely to have the same mutations.

2)  Restrict the number of dogs that are bred so their genes don't get passed to the next generation.

3)  Breed a dog that has that mutation as many times as possible, to get many copies of that gene into the offspring of the next generation.

4)  Because the immune system requires high genetic heterogeneity to function properly, breed for homozygosity and lower genetic diversity by breeding related dogs generation after generation.

5)  Keep the breeding population small by restricting breeding to just a fraction of the population and breeding as few dogs per litter as possible.


Well, how did you do?

In fact, we do all of these things, but for each we are trying to accomplish some "positive" goal (for example, to fix the traits we want by inbreeding or line breeding, get a bit of that popular sire into our own line, etc.). But we fail to consider the negative consequences that will also result. It doesn't matter how good a breeder you are, or how many years of experience you have, you can't gain the positives without also risking the negatives.

The high rate of genetic disorders in dogs is a direct and predictable consequence of the way we are breeding. There is no mystery to this, no difference of opinion among scientists, no bad luck involved. And it's not rocket science - you don't need a degree in genetics to understand why this is happening.

Unfortunately, the best way to get more of what we have is to keep doing what we're doing.



Check out ICB's online courses and our Breeding for the Future Facebook group

By Carol  Beuchat PhD

The nice thing about models is that they allow you to do "what if" experiments on paper to assess how a system will behave under particular conditions. In population genetics, this can be extremely useful, because you can test different breeding strategies without having to actually produce many litters of puppies.

For example, let's say that a new genetic disorder has been discovered in your breed that is caused by a recessive mutation (we'll call it a), so individuals that are homozygous for the mutation (aa) are identified because they are "affected". To keep it simple, we'll say that affected animals can be easily identified at birth. Breeders will understandably want to eliminate the mutation from the breed, so they begin a rigorous program of removing all affected animals from the breeding population. How long will it take to eliminate the mutation from the breed?

We can use the Hardy-Weinberg equation to address this question:

So even if we remove EVERY affected animal from the breeding population, we will NEVER eliminate the offending mutation from the breed. The only way we can do this (unless genetic drift removes it just by chance) is to also remove carriers - which we could do if we had a DNA test. But now we're talking about getting rid of a lot of dogs.

Go back to the table above, and look at the column in green. This is the percentage of the population each generation that would be carriers. Gosh, we would be throwing out more than 30% of the entire breed population for the first two generations, and another 20% or more for several generations after that (remember we're throwing out aa as well).

That's a LOT of dogs - and their genes - to eliminate, just to deal with that one nasty mutation. It's hard to imagine that you could do this without having serious consequences to the gene pool of the breed. Have a look at this chart of the biochemical steps that need to occur for proper energy metabolism. (Here's a tiny bit of it, just to give you an idea. If you've had some biology, you might remember that circular reaction, which is the Krebs cycle. It's too small to read, don't even try; look at the big version at the link above.)

You'll notice that everything is connected to everything else in very complicated ways - if step 4 in a 6 step sequence doesn't happen because the enzyme in step 3 is missing, then the entire pathway gets shut down. While you're selecting away to improve visible phenotype (topline, tail carriage, foot shape, herding instinct, pigmentation), you are also inadvertently running the risk of mucking up some complicated bit of chemistry that will make or break an animal. Already there are many examples of exactly this in dogs, where one broken step has huge consequences for function. Something this complex is extremely easy to break. (You might want to read Genetic disorders in dogs: breaking the machinery of life.)

It seems obvious that just tossing random genes out of the gene pool could get you into some trouble. Unfortunately, many breeds have done exactly this. Time and time again, a genetic disorder popped up suddenly out of nowhere, breeders decided to manage it by eliminating all dogs with the gene, both affected and carriers, and they decimated their gene pool. Then invariably some other, previously unknown mutation starts causing problems, and the purge cycle begins again. This isn't genetic management. This is breed suicide. But it happens over and over. And it might not be an overt policy to eliminate carrier animals, but if people refuse to breed from them, the effect is the same - eventually, it's a genetic catastrophe that breeders will be unable to reverse.

The original point here was to look at how we can use a simple model like the Hardy-Weinberg equation to see what might happen under certain conditions. We could elaborate on a simple model like this, and for instance add into consideration that breeding is not random apart from the mutation we're trying to get rid of, but instead there is some level of deliberate inbreeding. We could see how a specific rate of inbreeding would affect allele and genotype frequencies in the population over time, and what it would mean to our efforts to manage a damaging allele. Population geneticists now have sophisticated software that allows them to model breeding strategies to determine the most effective way to reach a certain goal, or to determine how long it would take a population to reach a certain size, or how the frequency of a genetic disease would change over time. The permutations are infinite. But at the core of all of these population genetic models is the Hardy-Weinberg law that describes how gene frequencies vary in populations.