Dog Breeding and the new science of genetics:
12 years ago, in December of 2005, Dr. Kerstin Lindblad-Toh of the Broad Institute in Massachusetts, produced the very first complete genome sequence of a dog. It was from a boxer call Tasha, and her genome was officially designated as Canfam 1.0. The amount of data contained in just one individual dog’s genetic sequence would still today completely fill 25 DVD discs. This year, in the UK alone, the Leonberger has become one of 77 breeds undergoing complete genome sequencing as part of the Animal Health Trust’s Give a Dog a Genome project. Huge amounts of data are being generated through this and other similar efforts, and it will take years to decipher and put it all to use.
But it will happen.
The point here is to underline just how young the science of genetics actually is. We are all pioneers in this new era, and It is no surprise that breeders are on a steep learning curve as we try to understand it all. But it is imperative that we all get involved and start to expand our knowledge about how these things work. We are only going to see more - not less - DNA testing in our dog breeding future, because the more we decipher the genetics of our various breeds, the more their actual genetic diversity is declining. And there is potentially no greater threat to that diversity than a misunderstanding of how inheritance works.
Of course breeders have always grappled with the complexities of inheritance; that is how the breeds themselves were created. But the tools available to the breeders of the past were limited. To begin with, they had pedigree analysis, which actually required a deep and broad knowledge of the actual individuals whose names appeared on those pedigrees, and what issues they may or may not have carried. Secondly, pedigree dogs arose during the era of big kennels, with large numbers of breeding dogs, which provided the ability to breed frequently and to roll through generations rather quickly. If problems emerged within an individual dog or bitch’s line, they could be removed from the breeding programme without threatening to bring the whole kennel down. Now, small hobby breeders with perhaps just one or two breeding bitches can face ruin if an issue emerges. Because of this, it is understandable that they have so much more invested in each individual animal. And finally, good breeders have always had (and still do have), what we might call their gut instinct; a knack for knowing a promising match when they saw it, which probably also relied more than a little bit on luck.
But fundamentally, one could accurately say that all that those breeders of the past really had to work with was phenotype – what the dog looked like – and that the hidden mysteries of genotype – the genetics behind that look - remained hidden to them. This of course could lead to unexpected consequences. Most breeders by now have heard of the dangers lurking behind the merle gene, which is the classic cautionary tale in dog breeding. Not only does it produce interesting variations to coat colour, but a double merle can also lead to deafness and blindness- which are completely non-intuitive consequences.
In the past, the social expectations were also quite different from what they are today, and the culling of breeding “mistakes” was much more acceptable than it would be today. Thankfully, things have changed considerably in modern times, and animal cruelty laws are now common in most western societies. Indeed, we are entering into an era where ethical breeding is the only publicly accepted approach, backed up by threats from pet insurance companies to exclude puppies from un-tested parents, and the threat of lawsuits brought by puppy buyers against their breeders. Animal welfare laws are evolving, and some are now suggesting that these should also be used to penalise breeding that is not considered to be “genetically ethical”. These changing expectations are becoming a fact of life for pedigree dog breeding going forward into the 21st century, like it or not.
Adapting to the future:
So, how do true breeders adapt?, and here I exclude those whose sole motivation is financial gain. Perhaps it is helpful to go back to first principles? What are the breeder’s primary goals? Some may believe it is to win at shows, and that this is the only meaningful marker of success. If a flashy dog is a consistent winner, then it must therefore, be a good example of the breed. Others hold to a deeper ideal, believing that their role is fundamentally to preserve (or indeed enhance) the uniquely defining qualities of the breed itself, with show success only a secondary concern. For them, life span, or temperament, or breadth of pedigree may be the highest goal.
Neither point of view is more correct than the other. They both have merit. And wherever an individual breeder falls on the spectrum between these two poles, there are a few widely accepted starting principles for us all to remember:
First, we are looking to breed an entire dog, not simply a good pair of hips, a flashy mover or a dark eye. You need the full tool-kit of genetic diversity to give you a broad range of options. Without choices you cannot make changes.
Narrow genetic diversity within the breed limits a breeders’ choices and reduces options. Paint yourself into a corner and you have no way back out again.
A breed is strong overall if it has many clear family lines and regional populations to select between, rather than only a handful of over-used lines world-wide. No one has an absolute monopoly on a line with strong type, elegant movement, correct tails, good eyes and hips. But if the whole world population reduces down to one or two popular lines in an effort to achieve these qualities quickly, then we could well see an explosion of dangerous traits with poor options for breeding away from them.
And finally, we must all strive to safeguard the genetic health of the breed and this includes managing genetic illnesses. The first fundamental goal here is simple: Do not produce affected individuals.In today’s breeding environment, to be considered to be an ethical breeder, we have a duty to do genetic testing where those tests are available. It is no longer acceptable to breed without knowing the status of the parents. So, it is perhaps helpful to do a quick run-through of the types of pre-breeding screening that we find. There are, very broadly, three categories:
1- Tests of the genotype- These are direct DNA tests for confirmed genetic liability genes. These tests are very specific, and are highly reliable - if cross-contamination has been ruled out. For the most part these tests will focus on identifying conditions caused by single gene mutations, which is not very helpful for illnesses derived from complex or polygenic inheritance.
2- Test of the Phenotype- these are physical examinations aimed at identifying clinically affected individuals, such as through hip x-rays for example. Although not as dependable as genetic tests, schemes such as hip screening have proven to be valuable in helping to identify patterns of inheritance of complex conditions, and to therefore reduce the propagation of such debilitating illnesses in future generations.
3- Pedigree analysis- which is making breeding choices that rely solely on an assessment of risk based on having a correct knowledge of probable carrier and affected status of the ancestors and relatives behind your breeding pair. Of course this can be very useful, especially when trying to assess the risks associated with complex inheritance, (polygenic illnesses for example), but this is completely reliant on obtaining full and accurate information on these related ancestral dogs. And, let’s face it, people are often not so free to share such information.
When it comes to known genetic illnesses, surely our goal must be to decrease the carrier frequency within the population as a whole. But remember, an individual carrying one malfunctioning recessive gene still also contains many thousands of valuable genes. Carriers are vital to diversity of the population overall, especially when a test for a recessive illness means that they can fully contribute to the next generation, whilst ensuring that their genetic risk never does any harm. Testing is a gift to breeders, because it allows us to save the lines, while at the same time Isolating the defective recessive genes so that they can eventually be eliminated.
Managing genetic disease:
So, perhaps it would be helpful to look more closely into how we can manage these inherited illnesses. In the case of dominant mutations, your number one goal is to not produce more illness. You know that, even if bred to a clear mate, statistically 50% of the offspring will also be affected, and it is simply immoral to proceed knowing this. But one goal we should all remain mindful of is to not throw away the whole line. Therefore, one needs to consider replacing affected dogs with normal siblings, parents, or prior-born offspring, thus preserving the basis of the line and the breadth of the breeding programme. This may not be as good an individual phynotypically as the affected individual being replaced, but it is very similar genotypically, other than being clear for the dangerous mutation. Therefore, one can progress the overall breeding programme with much of the quality still intact.
In the case of recessive illnesses, if you have a test available, then, as mentioned earlier, you can safely manage the condition secure in the knowledge that you can prevent the breeding of any puppies that will become ill. It is also critical to remember that you can (and should) eventually select clear progeny to carry on the line without the defective mutation being perpetuated. This is characterised as the “Breed and Replace” strategy. This may take more than a single generation, which is not a problem, but the emphasis here should be to retain any quality individual in your breeding programme, whether they are a carrier or not, with the aim of perpetuating those attributes into your future lines, and ultimately selecting an equally good off-spring who is themselves clear of the mutation to carry on with in the future.
If instead, breeders rush to exclude carriers for each recessive test that emerges, they will very swiftly risk decimating the genetic diversity of their lines and the breed overall. That is a clear misuse of genetic testing.
It is understandable that many of us will be disappointed to receive a carrier result on a prize specimen, and for us to consequently think less of that individual or even to then exclude them from our breeding programme. But in the words Professor Jerold Bell, the eminent geneticist from Tuft’s University, who is himself a breeder of Gordon Setters;
“That is absolutely the worst possible decision that you can make. … Because it is one gene out of hundreds of thousands that are in your dog. And it is one gene that you can absolutely control…”
Therefore, one must overcome this gut-reaction, and instead look at the whole dog. Seeing it not just for that one faulty gene, but instead seeing all of the other qualities it possesses and that you wish to perpetuate. By mating that individual with a clear partner, you can do just that, and also select a clear descendant to carry forward all of those many other fine points, free of the dangerous mutation. It may be that a puppy with a clear pair of the specific genes appears in the next generation. It may not, and you will have to try again. But we must all place the value of quality and overall diversity above the fear of the identifiable single recessive gene. It is not just our own breeding programmes that we are responsible for, but it is also the overall quality and diversity of the breed itself that each of us shares a collective responsibility for.
Therefore, to summarise in the words of Paula Henthorn, Professor of Medical Genetics at the University of Pennsylvania;
In the case of a recessive disease, a direct genetic test “should NOT alter who gets bred. It should only determine WHO THEY GET BRED TO”.
Please think about this.
There are more and more tools being made available to the pedigree dog breeder every year, and as I said, we are all on a steep learning curve. But we must use our heads and not lose sight of the fact that, although the science of genetics is still relatively new, experienced breeders have been grappling with inheritance since the beginning. Let us not lose the lessons of the past and begin to throw away our valuable breeding lines because of becoming overwhelmed by the modern tools of the future.
As I wrote earlier, the healthiest state for a breed to be in is to have several strong – and individual – lines, each producing quality examples of the breed. Lines that are distinct from one another, rather than all deriving from the same handful of foundation stock. Lines that honour the breed by conforming to the standard- those points that contribute to making this breed what it is. And that after all is what creates the Leonberger that we have all come to love so dearly today.
To conclude, I once again quote the words of professor Bell:
“Breeders are the custodians of their breeds and of their gene pool…Above all, they must do no harm. It is the ethical responsibility and obligation of all breeders to perform the available required pre-breeding genetic health tests on prospective breeding stock prior to any breeding. All genetic disease cannot be prevented. However, we do now have the knowledge and the tools to improve the genetic health of puppies. “
We can, and we should.
Sharon Springel
November, 2017
12 years ago, in December of 2005, Dr. Kerstin Lindblad-Toh of the Broad Institute in Massachusetts, produced the very first complete genome sequence of a dog. It was from a boxer call Tasha, and her genome was officially designated as Canfam 1.0. The amount of data contained in just one individual dog’s genetic sequence would still today completely fill 25 DVD discs. This year, in the UK alone, the Leonberger has become one of 77 breeds undergoing complete genome sequencing as part of the Animal Health Trust’s Give a Dog a Genome project. Huge amounts of data are being generated through this and other similar efforts, and it will take years to decipher and put it all to use.
But it will happen.
The point here is to underline just how young the science of genetics actually is. We are all pioneers in this new era, and It is no surprise that breeders are on a steep learning curve as we try to understand it all. But it is imperative that we all get involved and start to expand our knowledge about how these things work. We are only going to see more - not less - DNA testing in our dog breeding future, because the more we decipher the genetics of our various breeds, the more their actual genetic diversity is declining. And there is potentially no greater threat to that diversity than a misunderstanding of how inheritance works.
Of course breeders have always grappled with the complexities of inheritance; that is how the breeds themselves were created. But the tools available to the breeders of the past were limited. To begin with, they had pedigree analysis, which actually required a deep and broad knowledge of the actual individuals whose names appeared on those pedigrees, and what issues they may or may not have carried. Secondly, pedigree dogs arose during the era of big kennels, with large numbers of breeding dogs, which provided the ability to breed frequently and to roll through generations rather quickly. If problems emerged within an individual dog or bitch’s line, they could be removed from the breeding programme without threatening to bring the whole kennel down. Now, small hobby breeders with perhaps just one or two breeding bitches can face ruin if an issue emerges. Because of this, it is understandable that they have so much more invested in each individual animal. And finally, good breeders have always had (and still do have), what we might call their gut instinct; a knack for knowing a promising match when they saw it, which probably also relied more than a little bit on luck.
But fundamentally, one could accurately say that all that those breeders of the past really had to work with was phenotype – what the dog looked like – and that the hidden mysteries of genotype – the genetics behind that look - remained hidden to them. This of course could lead to unexpected consequences. Most breeders by now have heard of the dangers lurking behind the merle gene, which is the classic cautionary tale in dog breeding. Not only does it produce interesting variations to coat colour, but a double merle can also lead to deafness and blindness- which are completely non-intuitive consequences.
In the past, the social expectations were also quite different from what they are today, and the culling of breeding “mistakes” was much more acceptable than it would be today. Thankfully, things have changed considerably in modern times, and animal cruelty laws are now common in most western societies. Indeed, we are entering into an era where ethical breeding is the only publicly accepted approach, backed up by threats from pet insurance companies to exclude puppies from un-tested parents, and the threat of lawsuits brought by puppy buyers against their breeders. Animal welfare laws are evolving, and some are now suggesting that these should also be used to penalise breeding that is not considered to be “genetically ethical”. These changing expectations are becoming a fact of life for pedigree dog breeding going forward into the 21st century, like it or not.
Adapting to the future:
So, how do true breeders adapt?, and here I exclude those whose sole motivation is financial gain. Perhaps it is helpful to go back to first principles? What are the breeder’s primary goals? Some may believe it is to win at shows, and that this is the only meaningful marker of success. If a flashy dog is a consistent winner, then it must therefore, be a good example of the breed. Others hold to a deeper ideal, believing that their role is fundamentally to preserve (or indeed enhance) the uniquely defining qualities of the breed itself, with show success only a secondary concern. For them, life span, or temperament, or breadth of pedigree may be the highest goal.
Neither point of view is more correct than the other. They both have merit. And wherever an individual breeder falls on the spectrum between these two poles, there are a few widely accepted starting principles for us all to remember:
First, we are looking to breed an entire dog, not simply a good pair of hips, a flashy mover or a dark eye. You need the full tool-kit of genetic diversity to give you a broad range of options. Without choices you cannot make changes.
Narrow genetic diversity within the breed limits a breeders’ choices and reduces options. Paint yourself into a corner and you have no way back out again.
A breed is strong overall if it has many clear family lines and regional populations to select between, rather than only a handful of over-used lines world-wide. No one has an absolute monopoly on a line with strong type, elegant movement, correct tails, good eyes and hips. But if the whole world population reduces down to one or two popular lines in an effort to achieve these qualities quickly, then we could well see an explosion of dangerous traits with poor options for breeding away from them.
And finally, we must all strive to safeguard the genetic health of the breed and this includes managing genetic illnesses. The first fundamental goal here is simple: Do not produce affected individuals.In today’s breeding environment, to be considered to be an ethical breeder, we have a duty to do genetic testing where those tests are available. It is no longer acceptable to breed without knowing the status of the parents. So, it is perhaps helpful to do a quick run-through of the types of pre-breeding screening that we find. There are, very broadly, three categories:
1- Tests of the genotype- These are direct DNA tests for confirmed genetic liability genes. These tests are very specific, and are highly reliable - if cross-contamination has been ruled out. For the most part these tests will focus on identifying conditions caused by single gene mutations, which is not very helpful for illnesses derived from complex or polygenic inheritance.
2- Test of the Phenotype- these are physical examinations aimed at identifying clinically affected individuals, such as through hip x-rays for example. Although not as dependable as genetic tests, schemes such as hip screening have proven to be valuable in helping to identify patterns of inheritance of complex conditions, and to therefore reduce the propagation of such debilitating illnesses in future generations.
3- Pedigree analysis- which is making breeding choices that rely solely on an assessment of risk based on having a correct knowledge of probable carrier and affected status of the ancestors and relatives behind your breeding pair. Of course this can be very useful, especially when trying to assess the risks associated with complex inheritance, (polygenic illnesses for example), but this is completely reliant on obtaining full and accurate information on these related ancestral dogs. And, let’s face it, people are often not so free to share such information.
When it comes to known genetic illnesses, surely our goal must be to decrease the carrier frequency within the population as a whole. But remember, an individual carrying one malfunctioning recessive gene still also contains many thousands of valuable genes. Carriers are vital to diversity of the population overall, especially when a test for a recessive illness means that they can fully contribute to the next generation, whilst ensuring that their genetic risk never does any harm. Testing is a gift to breeders, because it allows us to save the lines, while at the same time Isolating the defective recessive genes so that they can eventually be eliminated.
Managing genetic disease:
So, perhaps it would be helpful to look more closely into how we can manage these inherited illnesses. In the case of dominant mutations, your number one goal is to not produce more illness. You know that, even if bred to a clear mate, statistically 50% of the offspring will also be affected, and it is simply immoral to proceed knowing this. But one goal we should all remain mindful of is to not throw away the whole line. Therefore, one needs to consider replacing affected dogs with normal siblings, parents, or prior-born offspring, thus preserving the basis of the line and the breadth of the breeding programme. This may not be as good an individual phynotypically as the affected individual being replaced, but it is very similar genotypically, other than being clear for the dangerous mutation. Therefore, one can progress the overall breeding programme with much of the quality still intact.
In the case of recessive illnesses, if you have a test available, then, as mentioned earlier, you can safely manage the condition secure in the knowledge that you can prevent the breeding of any puppies that will become ill. It is also critical to remember that you can (and should) eventually select clear progeny to carry on the line without the defective mutation being perpetuated. This is characterised as the “Breed and Replace” strategy. This may take more than a single generation, which is not a problem, but the emphasis here should be to retain any quality individual in your breeding programme, whether they are a carrier or not, with the aim of perpetuating those attributes into your future lines, and ultimately selecting an equally good off-spring who is themselves clear of the mutation to carry on with in the future.
If instead, breeders rush to exclude carriers for each recessive test that emerges, they will very swiftly risk decimating the genetic diversity of their lines and the breed overall. That is a clear misuse of genetic testing.
It is understandable that many of us will be disappointed to receive a carrier result on a prize specimen, and for us to consequently think less of that individual or even to then exclude them from our breeding programme. But in the words Professor Jerold Bell, the eminent geneticist from Tuft’s University, who is himself a breeder of Gordon Setters;
“That is absolutely the worst possible decision that you can make. … Because it is one gene out of hundreds of thousands that are in your dog. And it is one gene that you can absolutely control…”
Therefore, one must overcome this gut-reaction, and instead look at the whole dog. Seeing it not just for that one faulty gene, but instead seeing all of the other qualities it possesses and that you wish to perpetuate. By mating that individual with a clear partner, you can do just that, and also select a clear descendant to carry forward all of those many other fine points, free of the dangerous mutation. It may be that a puppy with a clear pair of the specific genes appears in the next generation. It may not, and you will have to try again. But we must all place the value of quality and overall diversity above the fear of the identifiable single recessive gene. It is not just our own breeding programmes that we are responsible for, but it is also the overall quality and diversity of the breed itself that each of us shares a collective responsibility for.
Therefore, to summarise in the words of Paula Henthorn, Professor of Medical Genetics at the University of Pennsylvania;
In the case of a recessive disease, a direct genetic test “should NOT alter who gets bred. It should only determine WHO THEY GET BRED TO”.
Please think about this.
There are more and more tools being made available to the pedigree dog breeder every year, and as I said, we are all on a steep learning curve. But we must use our heads and not lose sight of the fact that, although the science of genetics is still relatively new, experienced breeders have been grappling with inheritance since the beginning. Let us not lose the lessons of the past and begin to throw away our valuable breeding lines because of becoming overwhelmed by the modern tools of the future.
As I wrote earlier, the healthiest state for a breed to be in is to have several strong – and individual – lines, each producing quality examples of the breed. Lines that are distinct from one another, rather than all deriving from the same handful of foundation stock. Lines that honour the breed by conforming to the standard- those points that contribute to making this breed what it is. And that after all is what creates the Leonberger that we have all come to love so dearly today.
To conclude, I once again quote the words of professor Bell:
“Breeders are the custodians of their breeds and of their gene pool…Above all, they must do no harm. It is the ethical responsibility and obligation of all breeders to perform the available required pre-breeding genetic health tests on prospective breeding stock prior to any breeding. All genetic disease cannot be prevented. However, we do now have the knowledge and the tools to improve the genetic health of puppies. “
We can, and we should.
Sharon Springel
November, 2017
