Puppies from a breed cross will have the health problems of both breeds: T or F?

By Carol Beuchat PhD

I keep seeing the statement in the title, usually in the context of a discussion about the need to improve genetic diversity of a breed with a cross-breeding program.

The people that say this reveal their poor understanding some basic principles of genetics that should be elementary level stuff for every dog breeder. But apparently not. This statement is false, and here's why.

Most of the hundreds of genetic disorders identified in dogs are caused by single, recessive mutations. A dog with one copy of the normal allele and one copy of the mutation will usually be unaffected and healthy. A dog that inherits two copies of the mutation will not, of course, have a copy of the normal allele, so whatever that gene is supposed to do in the body isn't going to happen. It will either be apparent as a disorder of some sort, or it will not be evident at all if the effects are subtle or do something like reduce fertility, or slow down some enzymatic reaction, or slow growth rate. But apparent or not, it can be expected that if a dog gets two copies of a mutation, there will be some sort of functional deficit.​
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​Of course, not all mutations are recessive, but problems caused by dominant genes are easily managed by removing the carrier from the breeding population. The action of a gene can also be affected by the mix of genes in the genome of that particular dog (i.e., polygenic). How these genes affect the health of a dog can be complex and unpredictable, but in dogs polygenic disorders are far outnumbered by the problems caused by simple recessives. 

So, let's just consider the case of the simple recessive mutation.

Most breeds do not share mutations (Donner et al 2018). That is, mutations tend to be breed specific either due to founder effect or because they occurred after a breed split away from the ancestral dogs from which it was developed. A dog of breed A might be homozygous and affected by a recessive mutation, but when crossed to breed B will likely produce offspring that are heterozygous. Because of this, the offspring will not be affected by the disease. In fact, the puppies produced by a cross breeding should be expected to be unaffected by any of the disorders of either parent that are caused by recessive mutations. This of course assumes that the two breeds being crossed are not so closely related that they could share some mutations because of a common origin.

A "borgi", offspring of a Corgi x Boxer cross. (Cattanach)

Now, the offspring of Breed A x Breed B will inherit some of the mutations of both parent breeds. Doesn't this make the offspring worse off than the parents if it carries mutations from both parents? Remember that recessive mutations are only expressed if an animal inherits two copies. The way to prevent mutations from becoming a problem, regardless of origin, is to breed in a way that keeps the risk of a puppy inheriting two copies as low as possible. What does that mean? Related dogs will share some mutations, and the closer the relationship, the more mutations could be shared. To avoid the risk of producing affected puppies, just avoid breeding closely related dogs. You might say that we can do DNA tests to avoid this problem, but in fact we can't. We can only test for the mutations that we know about and have a test for. What about all those other mutations lurking in the dogs that we can't detect? The risk of problems from them is also proportional to the relatedness of the parents. If you have DNA tests for both parents and they do not share mutations, you nevertheless embrace a risk of producing a genetic disorder if the sire and dam are related. If you want to avoid problems from recessive mutations, don't breed closely related dogs.

The fact that different breeds rarely share the same mutations is also the reason why mixed breed dogs are, on average, healthier than purebred dogs. While they might carry more mutations, those mutations are much less likely to be homozygous and therefore be expressed as disease (Donner et al 2018).

​The offspring of a cross breeding will produce offspring that will carry some of those mutations. If those dogs do lots of breeding, they will produce many copies of those mutations packaged in puppies that will enter the breeding population. The way to keep those mutations from being a problem, is to not make hundreds of copies and distribute them throughout the population. Keep them few and rare by nixing those popular sires.

The answer to the question in the title is "false". Make sure you understand the explanations, and next time somebody makes this claim, call them out. The statement is usually made to derail a discussion about how breeders should deal with high levels of inbreeding in their breed. Definitely you should have the discussion, but make sure everybody is armed with facts and a decent understanding of the relevant genetics.

For that matter, tackle the folks that claim that mixed breed dogs are not - and should not be - healthier than purebreds. If we get rid of all the problems caused by recessive mutations, then maybe. But in fact, from the simple facts of genetics, mixed breed dogs are less likely to suffer from disorders caused by recessive mutations than purebreds. Believe in genetics; the world will make so much more sense.

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REFERENCES

Donner J and others. 2018. Frequency and distribution of 152 disease variants in over 100,000 mixed breed and purebred dogs. PLoS Genetics  14(4): e1007361.  DOI: 10.1371/journal.pgen.1007361

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