All Categories

BLOG POSTS

1/1/2030

Genetic diversity of a million dogs

1/28/2026

By Carol Beuchat PhD

One measure of genetic diversity is the fraction of loci with two alleles that are different. There are two expressions of heterozygosity: expected heterozygosity (He) is what we would expect to see if the population is breeding randomly, and observed heterozygosity (Ho) is the actual fraction of loci that are heterozygous.

Because heterozygosity depends on actual allele frequencies, two populations with the same COI can have different levels of observed heterozygosity. I won’t go into the math involved, but suffice it to say that you can’t assume that Ho is necessarily 1-COI; that is, you can’t predict one from the other, especially in small, bottle-necked populations (think purebred dogs).

One tricky thing to warn you about is that inbreeding can vary from 0 to (theoretically) 100 percent. But heterozygosity is measured using SNPs, which are “biallelic”, meaning that for a given locus, there are only two possible states. Say you have two alleles, A and B; some dogs will be AA, some will be BB, and some will be AB. Because AB and BA are the same, at most only half of the dogs can be heterozygous. As a consequence, graphs of heterozygosity scale from 0 to 0.5, not 0 to 1.0.

I have made use of published data for heterozygosity of various breeds of dogs (from Bannasch et al. 2021, and the massive study by Donner et al. 2018; ) to produce histograms that make it easy to compare genetic diversity within and across breeds. Within breeds, the range of values reveals the amount of variation in the sampled population. The Donner study supplied data for individual dogs, so I could display them as a histogram. In the Bannasch et al. study, the information provided was the range (blue line) and median (closed circle). (You can browse through the graphs here - https://www.instituteofcaninebiology.org/heterozygosity_donner.html )

For comparison, the distribution of Ho for a mixed breed population of dogs shows that most mixed breed dogs have Ho > 0.4, and in many Ho is > 0.45. As you scan through the graphs for breeds, you can see that there is much variation in Ho, with some showing many dogs with Ho > 0.4, while in other breeds the most dogs are < 0.3 (Basenji). (Note that for some breeds where the sample size is very small, you might see just a few bars that don’t say much about to expect for the breed.)

These data are very interesting to browse, and can reveal a lot about the genetic health of a breed. Breeds with less genetic diversity in the population are shifted to the left. This tells you that if a breed is trying to breed away from an undesirable gene (or towards a favorable one), the low heterozygosity (read “diversity) could make this difficult. For breeders faced with developing a cross-breeding program to introduce new genetic diversity into the gene pool, the best candidates for those crosses will be the ones with high heterozygosity and low COI; the worst choices will be breeds with low diversity, and you want to avoid high levels of inbreeding because all puppies will inherit the same allele from a parent for homozygous loci.

www.instituteofcaninebiology.org/hi_low_heterozygosity.html

I made two quick graphs to show this. One graph displays the heterozygosity and inbreeding data for the top breeds for genetic diversity, and the other is the breeds with the highest inbreeding and lowest heterozygosity. If you’re looking for genetic diversity for a genetic rescue program, you might steer away from the breeds on the low diversity (although they might be useful for other reasons). I am also working on some analyses that show how diversity in a breed varies among populations in different countries (coming soon…).

Information about heterozygosity can help us make better breeding choices, and Ho is one of the statistics that will be available for all breeds when the updating of the DogsArk Breeding Tool is finished (soon...).

(Access the graphs for each breed here - )
https://www.instituteofcaninebiology.org/heterozygosity_donner.html

REFERENCES

Bannasch, D, and others. 2021. The effect of inbreeding, body size and morphology on health in dog breeds. Canine Medicine and Genetics 8:12. https://doi.org/10.1186/s40575-021-00111-4

Donner, J and others. 2018. Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLoS Genetics 19:31010651. https://doi. org/10.1371/journal.pgen.1010651

You can learn more about the genetics of dogs in ICB's Online Courses.

*** Population Genetics for Dog Breeders ***

Visit our Facebook Groups

ICB Institute of Canine Biology
...the latest canine news and research

ICB Breeding for the Future
...the science of animal breeding

Revealing the genes for polygenic disorders

1/18/2026

By Carol Beuchat PhD

When a genetic disorder or trait is caused by a single gene, the usual protocol is to identify it and create a test to detect it. We can now test for hundreds of single mutations, which allows us to prevent producing any affected animals by screening potential parents before mating.

But for the many disorders thought to be polygenic, we have no simple solution. Identifying multiple or even dozens of genes or loci (a region on the chromosome where a gene is located) that seem to be associated with a particular disorder is of little use to the breeder. Should dogs carrying risk alleles be removed from the gene pool? Do you breed dogs together that have some of the risk alleles? How many overlaps is safe? There are no guidelines and no way to estimate the risk. Unfortunately, many serious and common problems appear to be polygenic, and we have been able to do little to control them. So things like cancer, epilepsy, cardiac and kidney disease, immune system disorders, and more sit like subterranian explosive devices scattered across the genomic landscape of your breed undetected.

DNA tests are not useful for these complex disorders, but we do have techniques that can provide more information about risk for polygenic disorders using just a pedigree database. The analysis uses information about the genetic relationships among the dogs in a population and the identity of animals that are affected with the disorder to determine the genetic risk of a disorder based on the genetic contributions from affected ancestors. This strategy uses a statistical technique called cluster analysis, and requires no information about the genes that might be involved or mode of inheritance.

What does cluster analysis do?

Cluster analysis using pedigree data does not test marker-trait associations. Instead, it tests whether family structure based on ancestry correlates with the distribution of affected animals.

In plain terms, it asks:

“Do dogs with this trait disproportionately descend from the same ancestors?”

The analysis does this regardless of the complexity of the pedigree, so it can identify risk that would be undetectable by studying individual pedigrees. It uses information about the affected animals, but also their relatives, to estimate the accumulation of genetic risk in lines and individuals.

This analysis has obvious advantages over trying to identify the specific genes involved. Polygenic disorders or traits might involve dozens or even hundreds or genes, each with a small effect, but which collectively affect the expression of a trait or disease. Teasing apart the effects and interactions of many genes is difficult, and even if you could, you would still not know how to use this information to make breeding decisions. Great knowledge, but not useful to the breeder.

With a pedigree database, however, we can determine risk of producing affected dogs, putting a valuable tool in the hands of breeders that can use this information to take some of the uncertainty out of mate selection. With the right analysis pipeline, breeders can use basic information they already have about pedigree relationships and health records to, for the first time, put these data to good use in mate selection.

What cluster analysis can detect well:

Lineage-associated disease risk (cancer, epilepsy, cardiac)
Performance traits concentrated in working lines
Fertility, longevity, and survival patterns
Popular-sire amplification effects

These analysis are particularly useful for:

Polygenic traits
Founder effects
Rare risk alleles
Line-specific risk accumulation

The analysis does not require:

Knowing the causal variants
Assuming additivity
Detecting large effect sizes

What this technique cannot resolve alone:

The specific causal gene
Within-family segregation
Environment vs genetics without controls

What you do and don't need:

You do need a pedigree database that includes affected animals
You need to know the Identity of affected animals
You need to Identify a population of dogs for analysis that includes the current breeding stock
You do not need to know the "unaffected" status of a dog (e.g., for problems that show up later in life)
You do not need large numbers of affected dogs

The beauty of this technique is that you don't need DNA data, your pedigree database doesn't have to be perfect or complete, and it will produce information that is actionable for beeders immediately. It produces a map of risk superimposed on the pedigree that identifies where breeders need to avoid selecting parents that are both from within the risk population. They can, however, breed dogs with risk to dogs outside the risk population to retain genetic diversity in the breed.

I recently analyzed a pedigree database for Yorkshire Terriers to identify dogs at risk of producing offspring with liver shunts. The database was relatively small, only about 30,000 dogs (only a fracion of the complete breed database), which included about affected 40 animals. From this, the dogs with geneticc risk in the current population were clearly identified, giving breeders the opportunity to produce litters with low risk of liver shunt while protecting the genetic diversity of the current breeding population.

If your breed is struggling to manage complex health problems for which we have no suitable tests, this analysis might provide the information you need to avoid risk and the incidence of some of the most serious health problems in dogs.

Finding the genes for a genetic disorder without DNA

1/7/2026

By Carol Beuchat PhD

Commercial DNA analysis has changed the way we breed dogs, giving us the ability to prevent disorders caused by recessive mutations with just a cheek swab. It has been less successful at addressing polygenic disorders. Identifying 12 genes "associated" with a health issue, with none identified as directly causal, poses a selection nightmare for breeders. What if your bitch has 4 of them and a potential mate has numerous others? What is the risk of producing puppies with problems? Can you discard all dogs with any of the genes, or even some of them, from the breeding program?

This is becoming a huge problems. Many breeds are wrestling with disorders that seem to be genetic because they run in breeds or families, but breeders can only guess at levels or risk involved in breeding a pair of dogs. Without some way to shed light on the underlying genetics of a probem, breeders have to weigh personal responsibility for health outcomes without useful information about risk.

Several years ago, I wrote a blog post that described a way for breeders to deal with genetic disorders when nothing was known about the genes involved or mode or inheritance (Cool tricks with Kinship Coefficients, part 3: "How can I manage a disease without a DNA test?" ). In the past, the technique has been used to address several othewise intractable genetic problems in dogs, but it seems to be forgotton now that we look to DNA analysis to address genetic problems.

Recently, I was asked by some breeders of Yorkshire Terriers in Norway to see if I could help with the problem of liver shunts in this breed, and I decided to see if I could shed some light on the genetic basis of the problem using this technique.

The analysis uses a statistic computed from population genetics called the kinship coefficient, which quantifies the degree of relatedness between two dogs, assessed either from pedigree data or DNA. For a male and female, you determine the kinship coefficient for the pair, and that value is equal to the expected average coefficient of inbreeding in their puppies. This works because the kinship coefficient compares the genetic makeup of the sire and dam, then uses their genetic similarity (i.e., their relatedness) to estimate the degree of inbreeding if their genes were combined to produce puppies. In fact, this is how predicted litter COI is estimated in software that does test matings.

So we have a statistic, the kinship coefficient, that allows us to assess the genetic similarity of two dogs. If you have a dog with a health issue (or any trait for that matter) that is suspected to be genetic, you would expect the dogs that are genetically similar to your dog would be more likely to carry the genes for the trait than dogs that were less similar. If you wanted to choose a mate that is less likely to carry the genes responsible for the health problem in your dog, you would look for individuals that are less similar genetically.

This seems logical enough, but how does this actually identify the dogs you could breed with that would have a lower risk of producing the disease? First, we need to identify as many dogs as we can that have been identified with the disorder, and we need the pedigree ancestry of these individuals. For a dog that has been diagnosed with the disorder, we know that it carries the risk genes that were inherited from its parents. This allows us to identify carriers of the risk genes, even though they are not affected and we don't know which specific genes are involved.

Armed with the pedigree information for affected dogs in Norway, I performed a "cluster analysis" that identifies groups of closely related dogs using a "family tree" called a dendrogram, which is a visualization of the genetic reationships among groups of dogs. When I superimposed the information about affected Yorkies on the dendrogram, they all clustered in one group of relatives and there were none anywhere else among less related dogs.

What we have done is identify the dogs that carry the genes that produce liver shunt in Yorkies without knowing what those genes are. Breeding together two dogs from that same cluster of related dogs would increase the risk of producing puppies with liver shunt; breeders can reduce risk by simply avoiding those pairings. In fact, here is where the kinship coefficient between your bitch and a sire would tell you how similar they are genetically. You than reduce risk by finding a pairing with a lower kinship coefficient.

This almost seems magical, but it's a very powerful technique. We have no easy way to breed for or against polygenic disorders or traits using DNA data, and staring at a pile of pedigrees doesn't tell a breeder much about risks in a quantitative way. But we know that the degree of genetic similarity of a pair of dogs will depend on how closely related they are. Just as we can use kinship coefficients to predict the average inbreeding of a litter of puppies, we can use them to evaluate risk of a genetic disorder.

The clever thing about this type of analysis is that it can be used for any trait with a genetic basis. It will work better when the heritability of the trait or disorder is high; that is, when most of the variation in the trait is due to genetics, and relatively less is a consequence of environmental (non-genetic) factors. In either case, it is a way of addressing genetic issues that are complex, involving both genes and environment. Most breeds have some issue that they are trying to deal with by selective breeding, but without any useful genetic information except knowing individuals that are actually affected. This is a way to address those problems.

We don't need DNA data to solve every genetic problem. Back before DNA analysis was available, breeders worked out ways to provide information about genetic risks knowing only about affected dogs and their relatives. Today, many breeds are struggling to manage health issues. Breeders should be aware that tools are available to help map a genetic landscape that seems to have no useful landmarks.

On evaluating breeding stock

9/5/2025

By Carol Beuchat PhD

We evaluate the traits of a dog to assess its value as breeding stock. Indeed, this is the stated (historical) purpose of dog shows. But to evaluate a dog as breeding stock, we have to assume that our assessment based on of phenotype (what you and a judge see in the ring) is a reasonable reflection of the "genetic value" of that dog. In fact, many traits are polygenic, and many genes interact with other genes in producing genotype, so in fact your assessment of physical phenotype might not be the best way to assess the genetic value of a dog.

If breeders care about preserving the genetics of the best dogs in a breed, or in preserving the genetics of their own line, they should welcome the opportunity to evaluate not just the main dog of interest, but also as many of that dog's relatives as possible - siblings, parents, offspring, and even more distantly related animals.

Here's why.

Breeding is about producing dogs that have the genes for the traits we want. Selection of mating pairs assumes that the breeder can select for the genes they want by evaluating phenotype. Of course, we know that many traits are polygenic, and for many there is also a strong envionmental influence on phenotype (which you can evaluate by computing heritability - and you should). In fact, phenotype really isn't that good at evaluating phenotype for most traits breeders care about, because genetics often can explain only 15% of 30% of the variation in a trait among dogs (this is the definition of heritability).

So the clever breeder would want to assess not only the potential sire or dam of interest, but also the relatives of those dogs. You will get a better assessment of genetic value of a dog for a particular trait by evaluating not just a single dog, but it's parents, littermates, and (best of all) its offspring. This allows you to determine an "estimated breeding value" (EBV) for the particular traits of interest. Dogs that inherited the traits you want and pass the genes for those traits on to their offspring have genes of high genetic value for those traits. The more information you have for the relatives of a dog about the traits of interest, the better you can assess whether a dog is likely to produce puppies with the traits that you are looking for in your dogs. Indeed, this is the basis of prepotency.

To evaluate the genetic value of a dog for a particular trait, you must evaluate the relatives of a dog you might want to breed to. Even if those dogs are not the best specimens (because they got a less fortuitious assortment of genes than the pick of the litter), or they will never be bred, or even if they have been neutered or spayed, a dog's relatives are collectively a gold mine of information you can use to guide your breeding decisions.

There is currently a ruckus onine about the AKC considering allowing dogs with limited registration in the ring. Breeders should welcome this for two reasons. First, for the information it can provide about the traits of those dogs that can be used to inform the calculation of estimated breeding values.

There is a second consider, which is an argument against limited registration, which prohibits that dog from being bred. If you cross two "good" dogs each puppy only gets half the genes of each parent. Some puppies will inherit a selection of genes that produces a stunning puppy; others will get less appealing features just by the random assortment of parental genes that they inherit. Breeders will often keep the pick of the litter for breeding and send the rest off to pet homes (some with limited registration).

If you want to "protect" your lines, this is not the way to do it. Your lines are a collection of genes that have been selected for over generations. To preserve your lines, you need to preserve those genes. The best way to do that is to breed at least TWO puppies in a litter (which would preserve about 75% of the genes in both parents), or better yet three (which would preserve about 87% of the genes of your carefully selected parents. The dogs you would put on limited registration nonetheless might have the genes to produce spectacular offspring with the right pairing that results in a more fortuitious blend of genes.

Generations of being highly restrictive in mate choice has resulted in a breathtaking loss of genetic diversity in many breeds. In general, only 15-30% of purebred dogs produce a litter. You can't preserve the genes that produce quality animals, or that define your own lines, by discarding part of the gene pool every generation.

Everyone wants healthier dogs. But no amount of selective breeding, or even DNA testing, will improve dog health while we continue to breed in a way that is genetically destructive. We need to distinguish between what is custom and ideology from the basic genetic principles that much be respected if we wish to produce healthy dogs.

Why you need information about every puppy -
https://www.instituteofcaninebiology.org/blog/if-knowledge-is-power-know-every-puppy

Here is a lesson about estimated breeding values from my online course "Managing Genetics for the Future".

Breeding Values

Breeding for the traits you want is very easy if there's only one gene involved and you know which dogs have it. But most things are influenced by many genes and you have no way to know what they are or which your dog has, so it's like trying to paint a landscape when you can't tell the colors of the paints apart until after the painting is done. You can't predict if you'll get what you want when you can't see the colors of the tubes.

You usually don't know the genes your dog has for a particular trait. But it is those genes that determine the "breeding value" of the dog for that particular trait. Dogs with all the right genes for a trait have high breeding value, and dogs that only have some of the right genes have lower breeding value. For traits that are heritable, you want to be able to select for those particular genes. What we need is a way to predict the breeding value of a dog without actually knowing the genes the dog actually has, or even which genes are involved in the trait.

For this, we can use something called "Estimated Breeding Values" (EBVs) which are just that - estimates of the true (but unknown) breeding value of a dog for a particular trait.

The first thing we need is some way to evaluate the phenotype of the trait of interest in each dog. If we wanted estimated breeding values for hip dysplasia, we would need hips scores from each animal. They could be numerical (e.g., 1, 2, 3, 4, for bad to good; or 5.1 or 2.8 for some measurement like the Norberg angle or amount of subluxation), or qualitative (bad, fair, good, excellent). It doesn't matter - just some way of expressing an evaluation of the particular trait you're interested in. These scores or evaluations for hips are clues to the genotype of the animal, but because we know there is an environmental influence as well, we know they won't be perfect, but just an estimate.

How can we estimate an animal's breeding value for a particular trait? If the trait is heritable, knowing the phenotype of the animal's relatives will tell us something about what genes an animal is likely to pass to its offspring.

Pedigree #1
Let's look at the pedigree below of dogs that have been scored for hips - good, bad, and unknown. We're thinking about breeding to one of the puppies in the litter of 7 at the bottom, and as it would happen the dog we really like (third from the right) has a rating of "bad". Should you use this dog?

The parents of that litter both have good hips. The grandsire (top left) has good hips, the granddam is unknown. The scores of the parents of the dam are unknown, but the rest of the maternal granddam's litter are all good. Just eyeballing this information, it seems likely that the sire and dam of the litter have good genes for hips, and that the bad hips on the dog we like could be the result of a fall off the front porch at 6 weeks, or too much kibble as a pup, or some other non-genetic cause. He might have bad genes for hips, but it's not too likely because we have information for a good number of relatives and there is no evidence that there are genes for bad hips hiding anywhere. So you might decide that your pick dog is a good bet to produce your next litter.

Pedigree #2
Let's change some of the information about these dogs and evaluate again what you think about your pick out of that litter of seven.

We have two dogs with bad and two with good in the litter, and two with no information. There is no info on the dam or her granddam, but the granddam's littermates had good hips. The sire has good hips as does his sire.

This one is a bit trickier. There are a few worrisome hips in there, and some missing data. What would you do?

Pedigree #3
Here's one more pedigree, and this one is downright complicated. You want to know whether your pick in that litter of 7 has a good breeding values for hips. But looking at this pedigree, it's tough to decide.

Making decisions based on pedigrees can be a real guessing game. But you know that there is a genetic component to hip dysplasia, and you know how these dogs are related, so it seems like there should be some way to come up with a number that would tell us something about the genotype of a particular dog.

This is what EBVs do.

EBVs take into consideration the available hip information for the relatives of a dog as well as their relationships to each other. Littermates and ancestors give us added information that we can build into our estimate of breeding value for the dog we're interested in. And if the dog were to produce a litter, the scores for those puppies could substantially increase our confidence in our estimate of the breeding value of that dog.

In the next section, we'll work through producing EBVs for a very simple pedigree.

Estimated Breed Values Example

BASICS OF EBVs
EBVs use information about the phenotypes of a dog and its relatives to predict genotype of a dog, its "breeding value" for a particular trait. As you looked at the pedigrees above, you were trying to deduce the genetic value of a particular dog for hips based on information about its littermates and other relatives, but as more information is added to the pedigree - which should allow you to make a better guess - it gets harder and harder to mash it all up in your mind to come up with some evaluation of the dog you're interested in. Plus, you might have some biases that interfere with making a completely objective evaluation, like how well you get along with another breeder, or what you know about temperaments of some of these dogs (which would be better to evaluate separately), and even your ability for abstract thinking.

We can eliminate bias and isolate the information about hips from potential environmental effects and anything else that could confound our ability to predict the genetics of a particular dog using EBVs. The EBV of a dog is the RELATIVE genetic value of a member of a breeding population, so if you add data to pedigrees the EBVs of the dogs will change, and hopefully become more accurate predictors of genotype. So EVBs calculated from one group of dogs will not necessarily be comparable to those from another group of dogs unless you have some way of comparing those populations with each other in a standard way (and there are ways to do that). But this is really no different from the evaluations you do in your head, which can only be based on information you have about the dogs.

Determining EBVs for a trait
Let's walk through a very simple pedigree and analysis to see how this works. Here is the pedigree for a group of 9 dogs (there are also a few unknown parents).

We can redraw this as a standard pedigree to make the relationships clearer.

We have information for four dogs about a trait we're interested in that was scored from 1 to 5, with higher scores being better; these numbers are in red.

We want to know which of the dogs, 6, 7, 8, or 9, has the highest breeding value (i.e, the best genotype) for our trait. We don't have trait information about any of the other dogs in the pedigree.

You might look at this and that the only information you have to work with are the scores for those 4 dogs. But there is more than that. Those dogs are all related to each other - some are full sibs and all share a grandsire, dog 1. So you know they share genes from dog 1 that affect their status for the trait we're interested in. We just need to figure out a way to to use the relationship information to make a prediction about genotype for each of our 4 dogs.

We're about to do some simple math. Don't let your eyes glaze over. These calculations are VERY simple and you'll never have to do them yourself. But it's useful to know where numbers come from, so don't sweat it; just follow along. Remember, these are actually the steps you might try to go through in your head when you evaluate a pedigree, but instead of making a wild guestimate we're going to see how we can do a tiny bit of simple math that will let us hang numbers on a tree that will allow you to compare dogs in a quantitative way.

Determining relatedness
The first thing we need to figure out is the level of relatedness of each of these related dogs to each other. We know that progeny share half the genes of each parent. So the genetic relatedness of 6 and 7 to their parents 2 and 3 is 0.5. We are going to continue to figure out the pairwise relationships for all of the dogs and collect that information in a table with 9 columns and 9 rows. We can color in these first comparisons in orange. Notice that we have to do this for both places where those pairs of animals appear in this matrix.

The other set of numbers we can fill in is the relationship of a dog to itself, so comparing 1 to 1 the relationship is 1.0, and 2 to 2 is 1.0, and 3 to 3 is 1.0, so you can fill in all those numbers, which will fall on the diagonal in the table.

Next, what is the genetic relatedness of 6 to his grandsire 1? Because a dog gets half the genes of its parent, with each generation the influence of an ancestor goes down by half. So 6 has half (o.5) the genes of 3, and 3 has half (0.5) the genes of 1. Therefore, 3 should have [(0.5)(0.5)], or one quarter, 25% of the genes of its grandsire 1. So in our table, we can put this number in for the relationship of 6 to 1, and it's the same for the sibling 7 (in yellow).

Before we go further, we need to remind ourselves that although we know that a dog has exactly 50% of the genes of a parent, it doesn't necessarily have 25% of the genes of a grandparent. That's because the sample of genes it gets from a parent is random and might include more genes that came from one grandparent than the other. In fact, it is highly unlikely that a dog will get exactly 25% of its genes from a grandparent. So when we calculate relatedness of dogs related more distantly than parent and offspring, the number we get is just an estimate. Just like flipping a coin 20 times and getting 13 heads instead of 10, the sample of genes a dog gets from its parent won't necessarily be exactly half of the genes from a grandparent.

We see in this pedigree that we have two sets of siblings that share a common grandsire. We can figure out the relatedness of dog 8 with dog 3 by accounting for each step between them. If you've taken the (free!) ICB course about coefficient of inbreeding (COI Bootcamp), you will remember this is exactly what we did when we traced paths to come up with a prediction of shared alleles. If you haven't taken the COI course, what we're going to do next might not immediately make sense to you, but we're not going to do a separate lesson on this step. It's enough if you understand the general principles, which are that each step in a pedigree represents a sampling of 50% of the alleles of the immediately related dog, and by counting up how many steps there are connecting one dog with another we can estimate their genetic relatedness.

We're going to trace a path like this:

8 ---> 4 --> 1 --> 3

At each of 3 steps, we have a factor of 0.5 to account for, so we estimate the relatedness of dog 8 to dog 3 as

(0.5)(0.5)(0.5) = 0.125

This will be the same for all of the pairs of dogs that are 3 steps from each other, so we can fill in those values in our table (green).

We have one more set of relationships to figure out, this time between dogs 6 and 7 with dogs 8 and 9. This is just like the one we just did but with an additional step, as here:

8 ---> 4 --> 1 --> 3 --> 7

Just like before, we count the steps between the first dog and the last dog in the path (4), and multiply 0.5 by itself that many times. So

(0.5)(0.5)(0.5)(0.5) = 0.0625

We can fill in those values in our matrix (pink).

So now we have a matrix with estimates of the degree of relatedness of each of the related dogs in our pedigree. And remember, you'll NEVER have to do these calculations yourself (!!!). You input your pedigree into the computer and it spits this matrix out in an instant.

Heritability
There's one more thing we have to consider when we evaluate the breeding value of a dog for a particular trait, and that's its heritability. If the heritability of the trait is zero, then we're done here; if it's 1, then we know that any dog that got the gene(s) will have the trait. But the heritability of most traits is somewhere between 0 and 1, and we need to take that into consideration when we try to estimate the breeding value for that trait.

You learned how heritability is calculated from your BugsVille simulation. Let's say that the heritability of the trait we're interested in here is 0.2, or 20%.

Computing the EBVs
Okay, here is where we give all of this information to the computer, the black box does some mystery math (called "matrix algebra") that is no fun to do by hand, and something else called BLUP (Best Linear Unbiased Prediction, also no fun to do yourself), and it spits out some numbers that tell us something about the breeding values of our 4 dogs. Remember, these are estimates - we can never know the true breeding value unless we know the actual genes involved, but this is a quantitative prediction, which will be far more accurate than what you would come up with by squinting at the pedigree, testing the wind, and making your best guess.

So, the computer grinds away on these data and comes out with some numbers (males in blue, females in red).

The first thing you'll notice is that we got estimates of the genetic value of every animal in the pedigree except for the unknowns and dog #1, because he has no known ancestors. Then, notice that some of these numbers are positive and some are negative. This is because the EBV for a dog is relative to the population average. Our rating scale was positive numbers from 1 to 5, so a dog with a positive value is better than the average (numbers in green) and if negative is worse than average (numbers in red).

These numbers tell us some interesting things. From the traits scores we recorded, we would have thought that dog 9 (score = 5) and dog 7 (score = 4) had the best potential to produce offspring with good scores. In fact, dogs 8 and 9 have the same breeding values (0.13), and dog 7 in fact has a negative score, as does her littermate dog 6. The actual test scores for these dogs would have led you astray in evaluating these dogs - you probably would have decided that dog 7 was more valuable to you genetically than dog 8, but in fact the genotype for 7 is worse than the population average for the trait you scored.

Remember - these EBV scores were based on three kinds of information: your scores for each of 4 dogs, how all of the dogs are related to each other, and the heritability of the trait in this population. The estimated breeding values you get might not be at all what you thought they were, but this technique has been used for decades in the breeding of domestic animals and plants and has been shown to be superior to any other method of improving the selection for particular traits.

Managing multiple traits
You can also use EBVs for multiple traits at a time. Say you are interested in selecting for 3 traits at the same time. One trait is of foremost importance (e.g., a potentially lethal disease), and the other two less so (e.g., litter size and temperament). You can weight the evaluations for each trait and compute an EBV that takes into consideration those weights. You want good litter sizes and great temperaments, but your foremost concern is minimizing the risk of producing puppies with a potentially lethal disease. Guide dog breeding programs might use 7 different traits in their calculations, including ones for health, size, temperament, coat, or whatever else that is important to them.

How can EBVs be used?
EBVs can be used for ANY trait that is heritable. They have been widely used for decades in the breeding of livestock for production, and although they are not widely used by the show dog breeder, they are starting to be used in dogs.

Health, conformation, and behavior traits in guide dogs
Hip dysplasia in dogs (e.g., in the UK, Finland, and US)
Syringomyelia and Chiari Formation in Cavalier King Charles Spaniels
Breeding programs to improve behavior
Improvement of working abilty

EBVs in horses
You can get a better idea of their potential from the types of traits they are being used for in horses. Notice also that EBVs can be based on DNA information if the association between a trait and DNA is known.

Do estimated breed values work?

You will remember that phenotype (P) depends upon both genetics (G) and environment (E):

P = G + E

When you're looking at hip scores, or at one descended testicle, or an x-ray of dysplastic elbows, or the MRI of a Cavalier King Charles Spaniel suspected to have syringomyelia, you are assessing phenotype only. You have no idea how much of the variation you see from animal to animal for your trait of interest is attributable to genetics and how much to environment. Because selection can only operate on genetics, knowing the true genetic value for a trait in a particular dog is extremely EBVs they have been proven to be of great value in the artificial selection of particular traits in livestock and other domestic animals.

"But", you say, "dogs aren't livestock". Can EBVs be used successfully in dogs?

Here are a couple of examples. You will see that in both, the efforts of breeders to control a genetic problem had little success before the adoption of EBVs.

Historically, Boxers have had a high incidence of cryptorchidism (one or both testicles fail to descend). If neither testicle descends the dog will be sterile (the heat of the body interferes with sperm production), but a dog with one testicle is fertile although prone to testicular tumors. Apparently, most living Boxers can trace their pedigrees to four German stud dogs - Sigurd von Dom and his three grandsons, Utz von Dom, Dorian von Marienhof, and Lustig von Dom. All four of these dogs produced cryptorchid offspring.

First efforts to reduce the frequency of cryptorchidism in Boxer began in 1942, with a total ban on breeding cryptorchids. Nevertheless, the incidence of cryptorchidism increased over the next 40 years from about 6% in 1941 to 10% in 1981in East German dogs. In West Germany, it increased from 7% in 1959 to 14% in 1985. In 1985, concerns about genetic diversity in the breed prompted encouragement to breeders to breed to lesser known males, but this did not improve the incidence of cryptorchidism. The unification of Germany in 1984 improved access to a broader gene pool, but cryptorchidism increases unabated for the next 10 years. In 1996, once again strict regulations on breeding were imposed, excluding a bitch from breeding if she produced cryptorchid offspring in 2 litters, and eliminating sires with more than 15% cryptorchids in at least 20 offspring. These measures reduced the frequency of cryptorchids, but it also removed 84% of the reproductive dogs from the breeding pool and improvement tailed off after a few years.

Finally in 2000, Germany removed all restrictions related to cryptorchidism and instituted the use of estimated breeding values (EBVs) to improve selection against cryptorchidism. Within only 3 years they saw marked improvement. This information is from a report published in 2003; more recent information is not available, but it would be very interesting to see if there was continued improvement or if cryptorchidism was at least reduced to a tolerable level.

EBVs have been use for some time to reduce the frequency of canine hip dysplasia (CHD) in many breeds. These are data from a breeding program against CHD in the Hovawart. Again, because selection against phenotype failed to produce consistent improvement for several decades, severe breeding restrictions were instituted in 1984 that banned all affected dogs from breeding. This actually made things worse, reducing the number of unaffected dogs and increasing the number of dogs classed as borderline.

In 1989, selection based on EBVs was instituted, and this produced immediate, significant improvement in hip scores, and in only 5 years more than 80% of all dogs had normal hips and severely afflicted animals were nearly eliminated.

These are dramatic examples of the improvements that can be achieved in just a few years by using EBVs to guide selection instead of phenotype. EBVs also breeders to distinguish between, for example, dogs with bad hips and dogs with the genes for bad hips - essentially separating the potential influence of environment from the underlying genotype that the breeder is really interested in. This means that fewer animals will get removed from the gene pool, because dogs with a bad phenotype but good genotype for the trait of interest can be kept in the breeding stock for potential use.

Using EBVs for selection can produce one problem that is common to phenotypic selection as well. If everybody rushes to the dog with the best EBV score, this will increase inbreeding if care is not taken to balance the reproduction of animals across the breadth of the gene pool. This should be a basic part of sound genetic management of a breeding population of animals anyway, regardless of the scheme breeders are using to make breeding decisions.

EBVs will be new to many dog breeders, but in fact they have been used for decades to guide breeding decisions of service dogs. Using EBVs, a well-run organization can manage genetic disorders, limit inbreeding, and produce dogs with the traits that are important in a service dog, even in a closed gene pool. This improves the efficiency the breeding program because more of the dogs produced are suitable for service.

Dog breeders can used EBVs to dramatically improve their ability to improve the traits they want and reduce or even eliminate the ones they don't. EBVs can be used on any trait that can be evaluated by the breeder - temperament, size, herding ability, coat quality, heart disease, "showiness", hip dysplasia - anything you can judge to be better or worse, desirable or not desirable. EBVs are becoming available in more and more countries, and they are the most powerful tool now available for improving the health and well being of dogs.

Did you learn anything useful about estimated breeding values? Consider taking the online course from which these units were shared, "Managing Genetics for the Future". Learn more here -

https://www.instituteofcaninebiology.org/openreg-managinggenetics.html

You can learn more about the genetics of dogs in ICB's Online Courses.

*** Population Genetics for Dog Breeders ***
Next class starts 30 March

Visit our Facebook Groups

ICB Institute of Canine Biology
...the latest canine news and research

ICB Breeding for the Future
...the science of animal breeding

Inbreeding does not preserve type

8/24/2025

By Carol Beuchat PhD

This has been bothering me for a while, and I won't write a long discourse about it now, but we really do need to think about this.

Breeding programs usually focus on producing dogs that conform to the breed standard. The usual strategy is to use inbreeding to "fix" the traits for type so they are reliably produced every generation. The problem with this is that it assumes there are separate genes for each of these traits, and reproducing the trait is accomplished by producing homozygosity in the relevant genes.

The Newfoundland before brachycreep.

I am reminded of this problem every time I see one of the breeds that demonstrates what I am calling "brachycreep" - shortening of the muzzle, doming of the head, spacing of the eyes farther apart - physical changes on a trajectory towards a brachycephaic head. I have talked about this before, moaning about the loss of a decent muzzle and skull on the Newfoundland, but you can see the same thing in other breeds. Many purebred dog breeds are becoming versions of the Pug. (This is no doubt how the Pug originally came by its breed-defining appearance.) This is an unintended consequence of the way we breed, altering by inbreeding the very traits we want to preserve.

The problem, however, is that traits can be the result of many genes, these might interact with yet more genes (epistasis). Most importantly, however, it might be the heterozygous state (two different alleles) of a gene that produces the desired phenotype. So inbreeding that produces homozygosity can in fact prevent the expression of a desired trait. This would not be unusual in animal genetics. In fact, homozygosity could be the reason many traits are being pushed to extremes, even though breeders are not selecting for extreme phenotypes. Crossing two dogs with moderate traits and heterozygous for the relevant genes, could produce offspring with homozygosity and extreme traits. Inbreeding generation after generation does cannot preserve type, because the composition of the gene pool is continuously changing. The notion that inbreeding is preserving type is easily falsified on first principles.

Does your breed have brachycreep?

To learn more about the genetics of dogs, check out
ICB's online courses

***************************************

Visit our Facebook Groups

ICB Institute of Canine Biology
...the latest canine news and research

ICB Breeding for the Future
...the science of animal breeding

Genetic status of the Cavalier King Charles Spaniel

8/17/2025

By Carol Beuchat PhD

The Cavalier King Charles Spaniel suffers from a number of serious health conditions. Syringomyelia and Chiari malformation are common in the breed and cause painful neurological issues. A disorder of the heart valve disease is also widespread in the breed, causing heart murmurs and, ultimately, congestive heart failure.

The gene pool of the breed has been reduced over the years by bottlenecks and popular sires. As a result, the breed suffers from extremely high inbreeding (35-40%) and loss of genetic diversity, so mitigating the health issues by selective breeding within the breed is unlikely to be successful.

The health and welfare issues have drawn enough attention that a lawsuit in Norway banned breeding, and several European countries are also placing restrictions on breeding. However, several kennel clubs have initiated cross-breeding programs with the hopes of introducing new genetic diversity and eliminating the health issues. It will be several years before the outcomes of these efforts are apparent, but the steps are being taken and there is reason to hope that this wonderful breed can be restored to good health.

I have added the Cavalier King Charles Spaniel to the DogsArk Breeder Tool using Embark DNA data so that breeders can take advantage of the advanced analyses that are possible with these data, and I summarize the some of this information below. The DNA data are for anonymous dogs and do not contain information about health and trait markers. However, Embark data submitted by breeders can be incorporated into the analyses (see how here). For an example of what those analyses would look like, check out the Labrador Retriever on the menu of Breeds.

Below I summarize the information about genetic status of the breed from the DogsArk breeder tool. Note that analyses that require data for specific genes or mutations are currently absent, but they can be added with the submission of Embark DNA analysis to DogsArk.

SYNOPSIS
These analyses were prepared using the DogsArk Breeder Tool.

Inbreeding in the Cavalier King Charles Spaniel is very high, with most dogs greater than 25% (equivalent to a cross of full siblings from unrelated parents). There is very little genetic diversity in this sample of 51 dogs, so apart from a handful of dogs that might be useful, there is little breeders can do to bring down levels of inbreeding by breeding within this population. It would be worth sampling dogs from several different populations worldwide to evaluate how much genetic variation there might be geographically. It is definitely worth also sampling dogs from puppy mills and casual breeders not breeding for show; both might have lower levels of inbreeding and might represent different lines than the dogs produced from show lines by Cavalier breeders. However, restoring genetic and physical health to this breed will require crossing to dogs that can reduce homozygosity and restore genetic diversity of the breed. The breed-specific traits can be restored in backcrosses in a breeding program designed to protect the introduced diversity.

Breeders can use the DogsArk Breeder Tool for analysis of genomic data of individuals as well as an overview of the genetic status of the breed or population. Kinship coefficients can identify the dogs that are genetically most valuable and also prevent over-representation of genetically restored dogs in subsequent generations. Updating these data on a regular basis will provide breeders with the information they need to guide the breed back to genetic and physical health. Finland, Norway, and Sweden have begun cross breeding programs, and it would be ideal if US breeders can create a population of Cavaliers that can provide dogs with good type for outcrossing, and vice versa. Submitting Embark files to DogsArk for as diverse a sample of dogs as possible will be valuable for tracking the outcome of a crossbreeding program.

SUMMARY
The Dogs and Data
The information summarized here is extracted from the pages for this breed on DogsArk and is based on data obtained from Embark Vet for 51 Cavalier King Charles Spaniels (CKCS). The dogs are anonymous and nothing is known about their origin, but most were probably from the US. There is no health or trait information for these dogs.

I processed the data using standard protocols for SNP data from the Illumina HD Canine Bead Chip (high density, >200,000 SNPs). The analyses were performed using Golden Helix SNP and Variation Suite software. The algorithms the software uses are sourced to published studies validating their output. All information is from the DogsArk website (https://dogsark.org/breedertoolpages-2/cavalier-king-charles-spaniel/)

Inbreeding (F)
Data for inbreeding, kinship, and heterozygosity are summarized in the table and displayed in the set of four graphs below. I will summarize each briefly below.

Genomic inbreeding in CKCS is among the highest of any breed (42.1%, Dreger et al 2018; 41.1%, Bannasch et al 2021 ), averaging 36.5% in this sample of dogs. Even the lowest level of inbreeding in this sample of dogs was 26.9%, greater even than the average expected in a litter produced by full siblings with unrelated parents.

Fixation Index (Fis)
In a randomly breeding population, the average Fis (fixation index) would be zero. Fis of individual dogs is determined as their F minus the average F of the population. Therefore, a value of Fis greater than zero indicates that the parents of the dog are more closely related than the average in the population, suggesting purposeful pairing of closely related dogs.

The average Fis in this population is close to zero (0.025), but there are some really high values (up to 0.279), that reflect choice of mating pairs more closely related than average in this population.

Kinship (K)
The level of inbreeding in a litter of puppies is predicted by the degree of relatedness or genetic similarity of the parents. This is quantified by the kinship coefficient (K); that is, the kinship coefficient of a bitch and sire (the parents) is equal to the predicted (average) inbreeding in their hypothetical litter.

The mean kinship (mK) for a dog is the average of all of the potential pair-wise kinship coefficients in the population of interest. Dogs that are closely related to many others in the population (e.g., offspring of a popular sire) will have a high mK; dogs carrying alleles that are uncommon in the population will be genetically less similar on average to the rest of the population and, for them, mK will be relatively low.

In a randomly breeding population, we would expect the histograms for inbreeding and mean kinship to be similar. The histogram of mean kinship for the animals in this population of Cavaliers is similar to that for inbreeding. The average mean kinship is 0.299, which is less than the average level of inbreeding (36.5%). This means that levels of inbreeding could be reduced somewhat by taking advantage of parental pairings that were less related. Note that the average includes three very low values, so the median mK is somewhat higher than the mean but still less than the average inbreeding.

Observed Heterozygosity (Ho)
Heterozygosity is a measure of the amount of genetic variation in a population. Inbreeding, selection, and genetic drift can result in the loss of alleles from the gene pool, which will be reflected in lower heterozygosity. If every locus is heterozygous, the observed heterozygosity (Ho) will be 0.5.

The data for observed heterozygosity (Ho) in this population of Cavaliers indicate substantial loss of genetic diversity (mean = 0.268). This is consistent with high inbreeding and also probably reflects low diversity in the foundation dogs and historical bottlenecks.

Identifying Dogs of High Genetic Value
The individuals in a population that are genetically most valuable have the lowest mean kinship. In Cavaliers, there is a single individual with very low mK (approx. 0.05; CKCS-1005), and for all but a few dogs, mK exceeds 0.25.

Runs of Homozygosity (Inbreeding)
The location of inbreeding on the chromosomes of each dog is visualized in this chart, in which blocks of inbreeding (“runs of homozygosity”) are indicated in blue. There are regions that are homozygous in most individuals (seen as vertical stripes, e.g., on chromosome 6 and 11). This might reflect selection across all individuals for a trait of interest located near those blocks of homozygosity. Runs of homozygosity are more likely to harbor deleterious mutations. So breeders should consider selecting mating pairs strategically to minimize homozygosity in offspring by avoiding potential parents with shared regions of homozygosity.

Population Genetic Structure
Based on the data for kinship coefficients, there is some apparent genetic structure in the breed, shown here as about five subgroups. Even though the animals in the population are all closely related, this chart identifies subgroups that can indicate where to find pairs of least-related dogs.

This chart can also be used to identify least-related dogs based on kinship coefficients. All 51 dogs are listed across the top of the table and down the left axis, and the number in each cell indicates the kinship coefficient for that pair. For easier viewing, the cells are coded as: K < 0.0625 (6.25%; green, equivalent to a cross of first cousins), K = 0.125 (12.5%; yellow, half-sib cross), and K > 0.25 (25%; red, full sib cross). The red diagonal represents each dog compared with itself. The chart shows that there are just a few dogs that could produce litters with average COI less than 5%; otherwise, all other pairings would produce average levels of inbreeding between 6 and 12% (inbreeding levels produced by mating first cousins and half siblings, respectively).

As described elsewhere (see www.DogsArk.org), this dendrogram can be used to identify dogs at genetic risk of particular disorders or traits without knowing the genes involved. This can be especially useful when a polygenic genetic influence is expected. It requires only that the individuals with the trait of interest be identified. (See my post about how to read dendrograms.)

For more information about using kinship coefficients in dendrograms to evaluate the potential expression of heritable traits see Cool tricks with Kinship Coefficients, part 1: "Is this dog really an outcross?".

For more information about using cluster analysis and dendrograms to explore genetic patterns in disease and traits in a breed, see “Cool tricks with kinship coefficients, part 3: “How can I manage a disease without a DNA test?”

Finding Genetic Diversity in a Breed
The limited number of animals in this dataset might not be representative of the larger population of the breed worldwide, which would include dogs outside the US, as well as dogs from pet and high volume breeders. Breeders might be able to find dogs among these with relatively low relatedness to this population.

Potential Impacts of Breeding Strategy on Health
If the population examined here is representative of the larger breed population, it indicates that there is little useful genetic variation in this breed that can be exploited to reduce levels of inbreeding. Of course, it would be worth doing a survey of other populations, but knowing the history of this breed, breeders are unlikely to find populations of dogs that could be exploited to make a significant genetic improvement in the breed.

Under the circumstances, breeders should initiate a crossbreeding program that is strategically designed to restore both genetic diversity and the structure of the skull that is predisposing for development of syringomyelia of Chiari syndrome. To do this, the dogs to be used in cross breeding should be selected after considering the specific issues to be remedied in the program .

You can learn more about the DogsArk Breeder Tool here -

DogsArk narrated tour -
https://dogsark.org/dogsark-breeder-tool-tour/

DogsArk interactive kinship tool tutorial -
https://dogsark.org/kinship-matrix-tool/

Managing the genetic health of the Basenji population

7/29/2025

(Reprinted from The Basenji, May/June 2012)

By Robert C Lacy PhD & Carol A Beuchat PhD

In response to the paper by Thompson (2012), we wish to provide some information about issues relevant to managing the genetic health of the pedigree Basenji population. Thompson provides a valuable introduction to the principles underlying genetic management of breeding programs for rare and valuable populations. One of us (RCL) has been involved in the development and application of these concepts and methods for the preservation of endangered species for the past 30 years, and we agree with Thompson that many of the principles that have been developed for optimal management of threatened species have value also for the management of breeds of domesticated animals. However, there are also differences in the goals and feasible methods that should be considered when adapting the lessons from endangered species management to breed management. Below, we address some of the issues raised by Thompson that might need clarification or further explanation.

1) When numbers such as 5-15 founders, or no fewer than 6, have been provided by conservation geneticists as the minimum number necessary to build a viable population, the context has been emergency efforts to sustain a wildlife population or species, and the emphasis is very much on a “minimum” number. Even when the possible loss of an entire species is at risk, it is debatable (and it is vigorously debated!) if it is worth putting resources into trying to build a breeding population from fewer than 6 founders. As Thompson notes, a recommendation of 20 effective founders is typical as the starting point to rescue a population at risk of extinction (Lacy 1989). Beyond the recommended minimum of 20 effective founders, zoos must carefully consider the incremental benefit of starting with larger numbers of founders, because of the considerable cost – sometimes including even the potential to seriously damage the remaining wild population by overharvesting – of importing an additional 10 to 20 individuals of a large wildlife species that is likely difficult to capture, handle, and transport.

2) General statements about minimum number of founding individuals necessary to build a viable closed population are based on models of population genetics that assume an "ideal" population where breeding is either random or will be managed to preserve genetic diversity using a breeding strategy designed for this purpose. An example of this would be a captive zoo population of a species where reproduction is carefully managed to minimize loss of genetic diversity and changes from the original, wild traits over generations. The strategy pursued in such a management plan would be to maintain equal genetic contributions of all founders to subsequent generations, as this would maintain the maximum amount of the original genetic diversity.

In populations of animals (whether species or breeds) where management of reproduction is not focused purely on the preservation of the full range of characteristics (good and bad) of the founders, the assumptions underlying the "ideal" estimate (as above) are not met. Some of the variation brought into the population via the founders will likely be lost in the first few generations, and the number of founding individuals will need to be greater in order to provide an adequate genetic base for future breeding. Indeed, even in breeding programs for endangered species in zoos, we know that in spite of our best efforts some initial “potential founders” will not contribute to future generations, so that we need to start with more sometimes many more – wild-collected animals to achieve 20 effective founders.

This would likely even more so be the case in a population of purebred dogs for several reasons. A breeding plan designed to maintain as much of the founding genetic diversity as possible would require the collective cooperation of all breeders as it must use all existing reproductive dogs in an optimally designed and rigorously managed breeding scheme. But dog breeders have specific breeding priorities of their own, such as selection for particular traits in their dogs (e.g., color, leg length, behavioral traits), or preferences to use particular individuals in their breeding program. Their breeding options might also be constrained by geography, or by available space and other resources. The presence of known genetically based health issues will also influence breeding decisions, and selection against genes that can cause health problems (while sometimes necessary) further reduces the variation across the rest of the genes as well, because the selection by definition reduces the number of breeders contributing to the next generation. Thus, it seems highly unlikely that all custodians of breeding individuals could fully cooperate with a breeding strategy designed to ensure equal contributions of all founders to subsequent generations. With selective breeding, the genetic diversity in the founding population can be substantially reduced in just a few generations (Oliehoek, Bijma, & van der Meijden 2009; Maki 2010).

3) If a large number of founders cannot be obtained initially, or if some of those lineages are lost or under-represented in subsequent generations, or if breeder goals will necessarily include selection for desired traits and against genetic problems, then low and declining diversity of the population can later be increased or restored through the addition of new founders – if available – to the breeding stock. This can bring back genetic variants that once represented the species or breed but were lost by chance, reverse incidental fixation of deleterious genes and accumulated inbreeding, and provide the diversity necessary for continued modification and improvement through selection.

4) Full analysis of the population genetics of the (worldwide) pedigree of Basenjis has not been done, so there is no information about how well the genetic diversity of founders has been maintained, or about the degree of inbreeding in the existing population. A genetic analysis using pedigree information for all dogs back to founders could provide substantial insights as to the value of any additional founders. This information would also allow breeders to make the best possible decisions about the use of their breeding stock by identifying populations of dogs that are most critical to maintain in the breeding population, and the degree of imbalance in the contributions of founders to the current generation (Lacy 1989; Ballou & Lacy 1995).

5) Basenjis are one of the (very) few breeds where a large population of animals from which the founders were originally drawn still exists in Africa, and these animals have not been subject to an organized breeding program, so mating has likely been more or less random. Consequently, we can expect that in such a population, a diversity of genetic alleles will still be present. Selecting animals randomly from this well-mixed gene pool is most likely to yield a genetic subsample that reflects the actual genetic diversity in the native African dogs. If the selection of animals is not random (for example, certain traits are desired, or some traits simply do not result in dogs that will be successful breeders if brought out of Africa), or if the dogs cannot be collected across the geographic range (possibly resulting in some lineages in Africa being sampled several times), then a larger number of new founders is required to obtain a good representation of the diversity of the breed.

6) We assume that the desire to increase the genetic heterogeneity of the pedigree Basenji population is motivated at least in part by concern about the possibility of unacceptable levels of genetic diseases in the future as a consequence of the small size of the founder population and subsequent inbreeding. Such problems have arisen in many breeds (canine and otherwise) that descend from small numbers of founders or have small breeding populations, and can be difficult to counter once the problems become prevalent enough to be to make it clear that restoration of genetic variation is needed. However, one issue breeders might be concerned about is that the addition of new animals can introduce again to the breeding stock potentially deleterious genes. We do not believe that this problem will be significant enough to override the benefits of restored genetic variation. The problem is not that deleterious alleles exist – as it is the case that all animals carry some deleterious recessive alleles and a few new ones arise by mutation every generation – but rather that in a small population or one with few founders some of the deleterious alleles can be expressed in homozygous condition in a number of animals. It should be noted that natural selection continues to work on wild populations, and with much greater force and efficiency that in populations under our care, so that deleterious alleles will have been held to very low frequencies. In a large, genetically diverse population, therefore, the probability of producing offspring that are homozygous for the disease allele is very low.

Especially for Basenjis, which in Africa are subject to strong natural selection when they fend for themselves, it is reasonable to expect that in the absence of evidence to the contrary, the animals should be genetically healthy, and a checkup from a veterinarian should satisfy to catch anything that might become a problem. Again, the key to managing health issues is maintaining the genetic diversity of the breeding dogs. If a deleterious allele does become common enough to be a problem for the breed, selection against that allele might be practiced, but we need to recognize that such selection will also reduce the genetic diversity across the rest of the genes, and any beneficial traits carried by the dogs that are removed from breeding will be lost (Lacy 2000). Thus, having high diversity within the breeding stock is essential both to minimize expression of deleterious traits and to allow selection to be practiced when desired without inadvertently jeopardizing the genetic health of the breed.

7) Thompson (2012) discusses the often-cited number of 50 and correctly notes that this refers to a recommendation for a minimum effective population size, not the minimum number of founders. For the reasons discussed above, achieving the recommended 20 effective founders, might require fewer or more than 50 initial imported animals. The recommendation of 50 as a minimum effective population size derives from a desire to minimize the accumulation of inbreeding subsequent to the founder generation.

The definition that Thompson gives for effective population size is correct only under very specific and idealized circumstances. Effective population size is not, in general nor in most populations, "the current number of breeding individuals in a population that contribute genes to succeeding generations." Effective population size is the number of breeding animals in a theoretical random breeding population that would experience the same rate of change in allele frequencies, or the same degree of inbreeding, as seen in the actual population (Lacy 1995). The number of breeding animals will be close to the effective population size only if breeding is truly random. Of course, in any real breeding program, breeding is far from random and some lineages contribute more to the population as a whole than others, because breeders select for specific traits or are limited in their choice of sire. In pedigreed dog breeds, the effective population size will likely be substantially smaller than the actual number of breeding animals, and this leads to more rapid loss of the genetic diversity that was brought in via the original founders.

The recommendation of a minimum effective population size of 50 is equivalent, mathematically, to a recommendation to keep the rate of increase in the coefficient of inbreeding below 1% per generation. This recommendation arises from the centuries of experience of animal breeders regarding what level of inbreeding can be accepted for a moderate number of generations without incurring risk of genetic damage in the form of higher frequency of genetic defects and lower overall average fitness of individuals. High levels of inbreeding have well documented deleterious effects including reduced fertility, decreased litter size, lower birth weight, lower survival, decreased resistance to disease, and decreased tolerance of environmental stress (Charlesworth & Willis 2009; Keller & Waller 2002; Lacy 1997; Ryan et al. 2002). Not every inbred animal will be affected, but the probability of problems increases and the average level of performance declines. Moreover, it is not predictable which lineages will suffer from inbreeding problems, and selection programs aimed at reversing inbreeding problems usually have only limited effectiveness (Lacy 2007).

8) Whenever possible, within breeding programs for rare wildlife species we start to seek out new animals to boost genetic diversity again whenever the cumulative mean inbreeding level increases to about 5% or more. When cumulative inbreeding levels reach 10% or higher, we consider the need for new animals to be urgent. For example, the Association of Zoos and Aquariums recently decided to open up breeding of even endangered species to exchange with private breeders who are not accredited members nor bound by association policies that require registry of animals in studbooks, when the breeding population mean inbreeding rises above 10% -- unless a plan is in place to quickly bring in new founders to restore the lost variation to the more tightly controlled population.

Thompson (2012) mistakenly describes the goal of 90% of the diversity of the source population (equivalent to cumulative inbreeding no greater than 10%) as the goal for starting a population, whereas the 90% criteria is actually widely applied as the limit for acceptable genetic decay over the long-term (e.g., 100 years) for a viable population designed to sustain and represent the source population. I.e., 10% loss of diversity is not the benchmark for an acceptable starting point, but rather is often defined as an end point below which a population should not be allowed to descend, or as the point at which quick action should be taken to obtain new founders to restore variation.

While conservation biologists do aim to start breeding programs of wildlife with at least 20 effectively contributing breeders (i.e., 97.5% of source diversity), we recognize that after a number of generations of propagating a small breeding stock, we often cannot avoid losing some or even much of the diversity that had been present in the founders. The goal of never dropping below 90% of the source population diversity drives both the recommendation to start with much more diversity than this, and the recommendation to maintain an effective population size greater than 50 so that further losses are no more than 1% per generation. A simple calculation shows that if the starting diversity is about 97.5% and 1% is lost in each subsequent generation, then the population can be sustained above the 90% goal for only 7-8 generations. Although this short-term strategy often is acceptable for endangered species breeding programs that are designed to be a temporary reserve for a species until they can be returned to a better protected wild habitat (e.g., as has been done with condors, black-footed ferrets, Mexican wolves, and red wolves), presumably people who sustain special breeds of dogs are interested in longer term preservation. Therefore, good genetic management will require more initial founders, a much larger breeding population allowing slower inbreeding, more rigorous control over breeding based on pedigree rather than expressed traits, and/or periodic replenishment of diversity with new founders.

9) Inbreeding levels in some dog breeds are already substantially higher than 10% (Leroy et al 2009; Leroy 2011). Although we are not aware of the value for Basenjis, we would expect that it is probably higher than 10% as well. For perspective, a mean inbreeding level of 10% is the equivalent of having the genetic diversity that would be provided by only 5 founders – which would not seem to be a very good representation of the breed. So for the pedigree Basenji, which is an unmanaged population (i.e., there is no single authority responsible for making breeding decisions), and which has limited opportunities for introducing new breeding stock on a regular and continuing basis, we would recommend that breeders should not forego the opportunity to add new animals whenever dogs representing the breed can be added to the breeding programs. This will help to maintain the genetic diversity in the population as a whole in the face of the conflicting demands on breeders.

For all purebred dogs (and wildlife species, for that matter), the goal is healthy animals that represent the breed well and can continue to respond to selection. Selecting only for breedspecific traits without also actively working to sustain the underlying genetic diversity needed to produce a healthy dog would ultimately result in failure. Two well established and even fundamental principles of genetic management are that (1) accumulated inbreeding almost inevitably causes reduced fitness and performance in a sexually reproducing species, and (2) variation is necessary to allow successful selection for desired traits or against deleterious traits. With adequate knowledge of the ancestry and current genetic structure of the breed, and some prudent breeding strategies, breeders can achieve their breeding goals while protecting the health of their animals and safe-guarding the future of the breed. Pedigree analysis software is available for assessing the effective population size, the loss of genetic variation to date, the rate of accumulation of inbreeding, and the potential benefits of adding new founders (Lacy, Ballou, & Pollak 2012). Genetics management advisors who are experienced in pedigree analysis for zoos would likely be available to assist by providing analyses and advice to Basenji and other dog breed groups. Regularly updating the genetic analysis of the population as new individuals are added by birth or introduction, and revisiting the breeding plan in light of new information, is the best strategy to assure the health of the breed for the long term.

Robert C. Lacy, Senior Conservation Scientist, Chicago Zoological Society Committee on Evolutionary Biology, University of Chicago Science Advisor, SSC Conservation Breeding Specialist Group, International Union for the Conservation of Nature.

Carol A. Beuchat, Founder and Scientific Director, Institute of Canine Biology.

REFERENCES

Ballou, J.D.. & R.C. Lacy. 1995. Identifying genetically important individuals for management of genetic diversity in pedigreed populations. Pp 76-111 in J.D. Ballou, M. Gilpin, & T. Foose (eds). Population Management for Survival & Recovery: Analytical Methods and Strategies in Small Population

Conservation. Columbia Univ. Press, NY.

Charlesworth, D. & J.H. Willis. 2009. The genetics of inbreeding depression. Nature Reviews 10:783-796.

Keller, L.F. & D.M. Waller. 2010. Inbreeding effects in natural populations. Trends in Ecology & Evolutions 17: 230-241.

Lacy, R.C. 1989. Analysis of founder representation in pedigrees: Founder equivalents and founder genome equivalents. Zoo Biology 8:111-124.

Lacy, R.C. 1995. Clarification of genetic terms and their use in the management of captive populations. Zoo Biology 14:565-578.

Lacy, R.C. 1997. Importance of genetic variation to the viability of mammalian populations. Journal of Mammalogy 78:320¬ 335.

Lacy, R.C. 2000. Should we select genetic alleles in our conservation breeding programs? Zoo Biology 19:279-282.

Lacy, R.C. 2007. Understanding inbreeding depression: 20 years of experiments with Peromyscus mice. Pages 327-329 in F.W. Allendorf and G. Luikart. Conservation and the Genetics of Populations. WileyBlackwell, New York.

Lacy, R.C., J.D. Ballou, & J.P. Pollak. 2012. PMx: software package for demographic and genetic analysis and management of pedigreed populations. Methods in Ecology and Evolution 3:433-437.

Leroy, G. 2011. Genetic diversity, inbreeding and breeding practices in dogs: results from pedigree analyses. Veterinary Journal 189:177-182.

Leroy, G., E. Verrier, J.C. Meriaux, & X. Rognon. 2009. Genetic diversity of dog breeds: within-breed diversity comparing genealogical and molecular data. Animal Genetics 40:333-343.

Maki, K. 2010. Population structure and genetic diversity of worldwide Nova Scotia Duck Tolling Retriever and Lancashire Heeler dog populations. Journal of Animal Breeding and Genetics 127:318-326.

Oliehoek, P.A., P. Bijma, & A. van der Meijden. 2009. History and structure of the closed pedigreed population of Icelandic Sheepdogs. Genetics Selection Evolution 41:39.

Ryan, K.K., R.C. Lacy, and S.W. Margulis. 2002. Impacts of inbreeding on components of reproductive success. Pages 82-96 in: W. V. Holt, A. R. Pickard, J. C. Rodger, and D. E. Wildt, eds. Reproductive Science and Integrated Conservation. Cambridge University Press, Cambridge, UK.

Thompson, J. 2012. How many founders does it take to make a breed? The Modern Basenji 2: 26-27.

Questions about cross breeding

7/29/2025

By Carol Beuchat PhD

There are lots of questions about cross breeding, and the problem in the dog fancy is that there is precious little data to address them. In the absence of data, discussions consist of opinions and assumptions, along with a fair amount of fear around the thought that a breed could be ruined or even lost due to cross breeding.

First of all, no breed will be lost due to cross breeding. In fact, the major obstacle to restoring genetic diversity to breeds is getting the introduced genetic material distributed through the breed. Genetic diversity can't spread like a virus. It must be deliberately transmitted by breeding. With many thousands of dogs scattered worldwide, and with inbreeding levels in many breeds through the roof, it will take a mighty effort involving many, many breeders and lots of planning by scientists to make a significant difference in the gene pool of a breed. And of course, it's quite easy to "protect" dogs from the introduced genetics; just don't breed to them or their descendants. So, fear or ruining a breed is unfounded and can be crossed off the list of things to worry about.

Next, we need to consider the genetic situation of purebred dogs. It's not the case that contininuing to breed in the existing (closed) gene pool is "protecting" the breed. The fact that this results in a steady deterioriation in health and fitness (reproduction, survival, etc) should be clear enough evidence that something critical to the essence of the breed is being systematically lost over the generations and genetics explains why. Healthy animal populations have very low levels of inbreeding. Inbreeding causes homozygosity, which replaces two different alleles with two copies of the same one. If the lost allele was functional, some genetic information is lost along with it. Every breeding to a related dog produces more homozygosity, and more alleles are lost, so while the downward trajectory might not be readily noticible over the short term, it does become apparent sooner or later. Increasing homozygosity cannot produce better dogs. It simply can't. So continuing to practice inbreeding as we have for decades is making a choice to do something that is harmful both to individuals and the breed.

Inevitably, the liveliest arguments are about what dogs to cross to. Because dog breeders have not historically done much organized cross breeding, they fall back on what they know (or believe) about breeding purebred dogs. But the purpose of purebred dog breeding is very different than that for cross breeding. It would be quite a surprise if the same procedures suited both.

This isn't the place for a long discussion about selecting breeds for crossing. But I will make a few comments that will encourage you to think differently about selecting breed crosses.

We have an exestential crisis in purebred dogs. Levels of inbreeding are - in a biological sense - stratospheric. They are highly detrimental to health. They are driving breeds to extinction. We risk losing breeds entirely if we don't fix this. In this situation, there should be only one consideration when selecting a breed to cross to - what animals will introduce the highest possible amount of diversity? For this, you want the lowest possible level of inbreeding in the animals used for crossing. This is because homozygous loci, with two copies of the same allele, will pass on the same allele to all offspring, when our goal is to increase alleleic diversity. So crossing to another purebred (inbred) dog breed is usually not the best option unless there are individuals with exceptionally low levels of inbreeding.

As for crossing with closely related breeds- We know that related breeds usually share some genetics, so this has the same problem as crossing to any relative - it might result in unintended homozygosity. Finally, because cross breeding is a project with a very specific purpose, it is critical that the dogs selected for the project will in fact address the problem you are trying to solve. Compromising on improving genetic diversity because you're worried about temperament or coat color is definitely not what you want to do if the future of a breed hangs in the balance. These are issues that can be address with selective breeding. For this reason, the dogs to cross to should be determined by carefully identifying the problems to be addressed and examining the genetics of the potential crossing breed to make certain those issues will be solved. For this reason, the selection of dogs to cross to will be one of the last decisions you make.

It's great that breeders are thinking more and more about the need for cross breeding and how to go about it. But recognize that to get this right, you will need to base decision-making on facts and expertise that dog breeders don't have. Certainly, opinions and assumptions have no value at all, because they are more likely to be detrimental than helpful given the different goals of purebred and crossbred breeding.

I have been thinking about these issues for a long time, and we seem finally to be at a tipping point where ideas are developing into action. It's a critical time for breeders to have access to expertise and guidance, and for the most part the kennel clubs lack both for the same reasons the breeders do. A couple of kennel clubs have professional population geneticists on board now that do have relevant expertise. But the seriousness of the inbreeding problem and the hundreds of breeds that need immediate attention dwarf the amount of attention and effort a single individual can invest in planning and executing effective projects to restore genetic health to dog breeds. I personally think we need to create a "center of expertise" of some sort that will provide the resources we will need to tackle the huge project of restoring dog breeds to health. I've been thinking about how to do this for a long time (years), and the essential needs are money and a significant number of breeders that will be committed to initiating and participating in restoration projects that will be complex and take years.

Finally, there is a huge need for education. I said at the top that absence of facts results in decision-making based on opinions and fear, which is more likely to result in failure than not. Breeders are not well-versed in the biology and genetics of animal breeding (cross-breeding or otherwise), and there needs to be a big push to remedy this. The immediate advantage will be having discussions about topics like the one for this post that can be based on facts and actual information, instead of speculation couched in fear. Everybody wants to breed better dogs. Will education help? Absolutely.

Keep talking about cross breeding. But replace fear and opinions with facts and data. And stifle the urge to just do something yourself. Crossbreeding projects will necessarily be team efforts. Seek out the professional expertise that can guide crossing programs to success.

Can the King save the Cavalier?

7/29/2025

His Majesty King Charles received a remarkable letter last week.

It was from the organization Qualzucht-Evidenz Netzwerk, a German organization concerned with health and welfare issues of animals that result from extreme breeding.

The letter raised the issue of the serious health problems in many purebred dogs and acknowledged the recent initiatives of several European kennel clubs to improve breeding practices.

It stressed, however, that these initiatives largely relied on voluntary participation by breeders, and in any case the magnitide and scope of the efforts falls far short of what is necessary to make a significant impact on the health issues while inbreeding continues to occur.

The letter highlighted the situation of the Cavalier King Charles Spaniel, with health issues so severe that breeding has been banned in Norway. The breed will also be affected by legislation in a growing number of countries that prohibit breeding of animals that will suffer from health problems.

Their message to His Majesty:

"We are, of course, aware that the Cavalier King Charles Spaniel is named after King Charles II. Yet it is precisely this symbolic connection that has compelled us to address our respectful appeal to Your Majesty. Today, the name “Charles“ - the name of the royal house - is inextricably linked not only with a charming companion dog but also with a scientifically documented and man-made legacy of suffering."

They went on to make a request:

"In this spirit, we reverently hope that Your Majesty might consider granting this cause further, decisive support. We would be most deeply honoured if your patronage could help to usher in a new era of reform by encouraging the Royal Kennel Club to take bolder and more fundamental measures:

• Supporting a fundamental revision of breed standards and breeding guidelines that prioritises functional health, vitality, and quality of life over extreme aesthetic traits.

• Encouraging the formation of an international consortium that brings together experts to counteract extreme breeding practices through concrete, measurable, and science-based breeding standards, thereby restoring the United Kingdom's historic leadership role in animal welfare.

• Initiating a public dialogue on the ethical question of whether a breed so closely associated with the royal name should continue to represent such profound, man-made suffering."

QUEN Fact Sheet for the Cavalier King Charles Spaniel
https://qualzucht-datenbank.eu/fact-sheet-dog-breed-cavalier-king-charles-spaniel/

You can read the letter here -
https://qualzucht-datenbank.eu/wp-content/uploads/2025/07/QUEN_Brief-EN.pdf

We need to rethink the genetics of cancer in dogs

6/18/2025

By Carol A Beuchat PhD

Cancer in Dogs
Cancer affects approximately one in three dogs during their lifetime, making it the leading cause of death (Wu et al 2023). The types of cancer encountered are varied, with sarcomas and carcinomas being most common (Rodrigues et al. 2023).

Types of cancer in dogs and commonly affected breeds

Rodrigues L, J Watson, Y Feng, B Lewis, and others. 2023. Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision thereapeutics. Scientific Reports 13:10935

Rates of cancer in dogs vary widely by breed in purebreds, from about 10% in the Shih Tzu, to as high as 55% Irish Water Spaniel. (Why do dogs get cancer?) The variety in cancer types in dogs and the high rates of incidence across a diversity of breeds make the dog a model animal for translational research.

Cancer mortality in purebred dog breeds

Beuchat CA 2014. Why do dogs get cancer? https://www.instituteofcaninebiology.org/blog/why-do-dogs-get-cancer

Cancer and Body Size
If we look more closely at cancer rates across dog breeds, we find that risk increases with body size. In fact, scientists have argued that this should be expected because larger, longer-lived animals have more cells that undergo many more cell divisions over the lifetime of the animal. If each cell division presents a risk of producing a genetic error that could result in a cancerous cell, larger animals should have more cancer.

Rates of cancer in purebred dog breeds over a range in body weight

Beuchat CA. 2015. Do dogs have more ancer than other mammals? https://www.instituteofcaninebiology.org/blog/do-dogs-have-more-cancer-than-other-mammals

Surprisingly, however, if we look not at dogs but at mammals in general, we see something different. Larger species of mammals do not, in fact, have more cancer than small ones. The risk of being afflicted with cancer is about 20% across a diverse array of mammalian species. Even very large and long-lived mammals like elephants do not have higher incidence of cancer than small ones (Abegglen et al 2015; Vincze et al 2022). The single obvious exception is the Tasmanian Devil, which gets one of the rare contagious cancers that is passed from individual to individual when they bite each other, which they apparently do a lot (Stammnitz et al 2023 ).

Cancer rates in mammal species ranging in size from shrew to elephant

Beuchat CA. 2015. Do dogs have more ancer than other mammals? https://www.instituteofcaninebiology.org/blog/do-dogs-have-more-cancer-than-other-mammals

The absence of the expected effect of body size on rates of cancer in mammals is called “Peto's Paradox”. The explanation for the paradox is a topic of lively debate. One popular hypothesis suggests that evolution has resulted in mechanisms to prevent abnormally high rates of cell division that could produce a tumor. This is supported by the discovery that some very large mammals have multiple copies of tumor suppressor genes like TP53, which suppress the growth of tumors by interferring with cell division (Wu et al 2023). Elephants have 20 copies of the TP53 gene, and these multiple copies could crank out more of the proteins that search out and destroy cancer cells (Abegglen et al 2015; Vincze et al 2022).

Now we can see that the increase in cancer risk in larger dogs is an anomaly. Athough there is lots of variability in the data for medium sized dog breeds, most breeds with the highest rates of cancer are larger. The Rottweiler, Leonberger, Bullmastiff, and Golden Retriever have cancer rates higher than 30%, and in some breeds the incidence of cancer exceeds 45%. Notice that large size itself doesn’t doom a breed to develop cancer; the Deerhound and Newfoundland, for example have cancer risk comparable to much smaller breeds, for reasons that remain to be discovered.

Rates of cancer in various species of mammals and in dogs

Beuchat CA. 2015. Do dogs have more ancer than other mammals? https://www.instituteofcaninebiology.org/blog/do-dogs-have-more-cancer-than-other-mammals

Somatic or Germline Mutation?
For me as a comparative biologist, this is all quite fascinating. But for the dogs, it's tragic. There is clearly a puzzle here that we can't explain with our current understanding of cancer in dogs. Since this is just the sort of challenge I like, I began digging around in studies about cancer in dogs. And I discovered something that completely changes how we should think about canine cancer.

We have assumed that cancer in dogs is genetic and that the risk is primarily inherited. This belief has driven a significant amount of research to identify cancer-causing genes so they can be controlled by selective breeding. But while there is evidence of a polygenic associations with cancer risk in some breeds, there are only few examples of single, causative mutations. Of note are mutations in BRCA1 and BRCA2, which are tumor suppressor genes, which increase the risk of mammary cancer in English Springer Spaniels as they do in humans.

Although the search for inherited, cancer-causing mutations in dogs has not been very rewarding, recent research is revealing that we have been looking for the wrong thing.

In fact, researchers are finding that most cancer-causing mutations in dogs are not inherited, i.e., "germ line" mutations but somatic, meaning that they are created during a dog's lifetime.

In a comprehensive study of 2,119 dogs with various types of cancer, researchers found that somatic mutations in TP53, the cancer suppressor gene we talked about earlier, were present in 22.5% of all tumors, making it the most frequently mutated gene across all canine cancers (Rodrigues et al 2023).

Other breed-specific studies have looked at cancer genes across multiple dog breeds and found that, while cancer rates vary dramatically between breeds, which suggests some inherited susceptibility, specific cancer-causing mutations found in tumors were predominantly somatic rather than germline (Alsaihati et al 2021). For example, in osteosarcoma (bone cancer), which affects certain breeds like Golden Retrievers and Rottweilers at much higher rates, 83% of affected dogs had somatic, non-heritable mutations alterations in the TP53 gene (Sakthikumar et al 2018).

Perhaps most convincingly, a massive analysis of 684 canine cancer cases across more than 35 breeds found that the genetic changes driving cancer development were "tumor type-dependent, but largely breed-independent" somatic mutations (Alsaihati et al 2021). This means that while breeds may have different inherited susceptibilities to developing cancer, the actual mutations that cause tumors to grow are largely the same, random, spontaneous events across all breeds.

And for breeders that have tried with little success to reduce cancer rates in their breeds, this is a paradigm changer. Because somatic mutations are not present in the germ line, the DNA in every cell, but are created during the lifetime of the dog, they cannot be removed by selective breeding. Put another way, we cannot prevent cancer caused by somatic mutations by trying to select against the mutation itself.

A New Paradigm For Canine Cancer
While breeders can't select directly against somatic cancer-causing mutations, they might be able to select against the genetic backgrounds that increase the susceptibility of genes like TP53 to mutation (Rodrigues et al 2023). But without identifying what these are, a more useful strategy might be to restore genetic diversity that has been lost over generations while cancer incidence has increased. Importantly, restoring diversity might address the risk of many types of cancer in multiple breeds, and make a very real difference in the incidence of cancer in dogs.

We're at the beginning of a revolution in our understanding of the genetics of cancer in dogs. New discoveries could provide a tremendous opportunity to develop breeding strategies that will reduce canine cancer to the levels seen in other mammals. With a growing toolbox of sophisticated techniques for genetic analysis and the development of resources to design effective breeding strategies to improve genetic variation, we might be on the brink of something extraordinary: a future where most dogs and the people that love them never face cancer at all.

References

Abegglen LM, AF Caulin, A Chan, and others. 2015 Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA 314:1850-1860. doi:10.1001/jama.2015.13134.

Beuchat, CA 2014. Why do dogs get cancer?

Beuchat, CA 2015. Do dogs have more cancer than other dogs?

Dobson JM 2013 Breed-predispositions to cancer in pedigree dogs. Veterinary Science 2013; doi 10.1155/2013/941275.

Peto R, FJ Roe, PN Lee, L Levy, J Clack. 1975. Cancer and ageing in mice and men. British Journal Cancer 32: 411-426.

Rivera P, M Melin, T Biagi, T Fall, J Haggstrom, K Lindblad-Toh, H von Euler. 2009. Mammary tumor development in dogs is associated with BRCA1 and BRCA2. Cancer Research 69: 8770-8774. doi: 10.1158/0008-5472.CAN-09-1725.

Rodrigues L, J Watson, Y Feng, B Lewis, et al. 2023. Shared hotspot mutations in oncogenes position dogs as an unpaalleled comparative model for precision therapeutics. Scientific Reports 13:10935. doi.org/10.1038/s41598-023-37505-2.

Sakthikumara S, M Warrier, D Whitley, S Facista, J Adkins, et al 2018. Genomic analysis across 53 canine cancer types reveals novel mutataions and high clinical actionability potential. Veterinary Comparative Oncology 22: 30-41. DOI: 10.1111/vco.12944.

Stammnitz et al 2023. The evolution of two transmissible cancers in Tasmanian devils. Science 380: 283-293. DOI: 10.1126/science.abq6453.

Sulak M, L Fong, K Mika, et al. MS. TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife 5:e11994. doi: 10.7554/eLife.11994.

Vincze O et al. 2022 Cancer risk across mammals. Nature 60:263267. doi:10.1038/ s41586-021-04224-5.

Let's put the genetics back into breed history

5/30/2025

By Carol Beuchat PhD

You've probably seen pictures of these amazing statues, the so-called Terracotta Army. These terracotta figures, which were discovered by Chinese farmers that were digging a well in 1974, date to roughly 200 BCE, and were thought to afford protection to the emperor in his afterlife.

They are impressive for a number of reasons. They depict life-sized Chinese warriors, including infantry, cavalrymen, chariot drivers, crossbowmen, generals, and lower ranking officers, as well as muscians, acrobats, and other non-military figures. In addition to roughly 8,000 soldiers, each with unique facial features and wearing the garb appropriate to his rank and duties, there are 150 cavalry horses, and 130 chariots with 520 horses. It is a truly impressive clay army.

Needless to say, the magnitude of the task of creating these sculptures is difficult to imagine. It involved thousands of workers and painstaking work that probably took 30-40 years. The statues were buried in pits 23 feet (7 m) deep, and at least one of these pits was 750 feet (230 m) long and 203 feet (62 m) wide, the length of about about 2.5 soccer fields. Just moving the statues to these pits would have been a massive task.

The point here is that with enough time, determination, and humans to do the work, we can accomplish some truly remarkable things.

But what does this have to do with purebrd dog breeding? Bear with me.

The world of purebred dog breeders is increasingly aware of the need to know more about the genetics of the dogs we breed. Indeed, breeders have been keeping breeding records since even before the first kennel club was established in the late 1800s. These pedigrees recorded the history of a breed, allowing breeders to follow the passage of genes from one generation to the next, and they provided the only information about the potential genetic makeup of a dog. The kennel clubs were formed to create these records and and their mission has been to preserve them in perpetuity.

The registration records of most kennel clubs around the world have survived more or less intact for decades if not a century or more. They represent a priceless compilation of the origins and evolultion of hundreds of extant dog breeds. For those interested in the genetics of a breed, these records can reveal the size of the original gene pool, how diversity was lost, the size and timing of bottlenecks, crossing in of other breeds, and much more about the history and genetics of a breed. (See The Amazing Secrets Hiding in Your Pedigree Database) But for most breeds, complete pedigrees back to the founding dogs are unavailable. Kennel clubs do not make these records available online or as a downloadable file. Breeders might be able to purchase a 5 generation pedigree of a dog, but if you want deeper generations you have to pony up for the connecting pedigrees in the fifth generation of dogs or run down that information yourself. It doesn't make much sense to record and preserve pedigrees if they are not accessible to the people that need to use them. If we believe in genetics (and we do, don't we?), it seems essential that we have the information we need to use genetics to inform breeding strategy.

So, what's the problem here? Kennel clubs could certainly make the more recent digital pedigree records from the last few decades available in a convenient and useful fomat, but alas most don't. The reasons given for not providing easy access to pedigree are usually something about maintaining "control" of the information (a topic for another time). Never mind that the data are mostly out there in bits and pieces put together by breeders, some is incorrect, and most are inconvenient to access.

For the "analog" records compiled in rregistration books before the advent of digital files, the problem with access usually given as the "enormous" amount of work it would take to create digital files for dozens of years of stud books.

Ok, that's a point. There are dozens of volumes of information that would need to be digitized, and in each kennel club in countries around the world. But is getting the information into a digital format "too much work"? Surely the kennel clubs aware that there are already dozens and dozens of breeders around the world typing up pedigree records from old hand written scraps of peper, or from show catalogs, or pedigrees posted on breeder websites. Hours and hours are spent just running down the information. Some breeders have been doing this for years - decades, even - to provide a resource for others in the breed, or (unfortunately, occasionally) to keep the records under control that limits access to others. I know of several large hand-kept pedigree databases that disappeared when the breeder passed away and the computer was tossed out by those tasked with clearing out a lifetime of possessions from Nana's old house.

Go back and look at those Terracotta Soldiers. Making those was a massive task, but there they are, created by armies of workers over many years. Making all those statues was indeed an enormous amount of work. Digitizing 100 years of pedigree records is a sniffle by comparison. And if all those breeders that are already typing could be organized so what they produced was joined with the records kept by the kennel clubs, we would finally have the invaluable records needed by breeders to reveal the mysteries hiding in the pedigree history of their breed.

There really is no excuse now to not get the pedigree records of every registered dog on the planet into a database. Remember, this was the original mission of the kennel clubs. It is no longer necessary to sit at a computer typing away for weeks. I can upload a scan of a page from a registry into software that will do optical character recognition on hundreds of pages in a matter of a minutes. Then I can ask AI to extract the information I need in whatever form I want - Name, date of birth, sex, sire, dam, color, country - and save it to an excel file. The hardest part of this would be creating scans or photocopies of each page. Enlist the help of the hundreds of breeders out there that are already typing everything out by hand, and we could have the files for the purebred dogs of the world available for breeders, researchers, historians, and anybody else with interest.

So, kennel clubs of the world, how about it? We can do this with some readily available software and volunteers that are already typing. We will finally be able to work with deep pedigrees and put the genetics back into the history of dog breeding. And it won't take nearly as long as you think.

There are a number of early volumes of records from the American Kennel Club, the United Kingdom Kennel Club, and US Field Dog Stud books on the ICB website that you can download HERE.

UK Kennel Club 1885 (v.12) - Bloodhounds

An update on the pedigree dog populations in the United Kingdom

5/25/2025

By Carol Beuchat PhD

The United Kingdom Kennel Club has just published a substantial study that documents the recent history of the purebred (pedigree) dogs in its registry (Ilska et al. 2015). It is based on 11,159,418 pedigree records for 222 breeds in its digital archives between 1990 and 2021.

The previous analysis of the registered populations in the UK Kennel Club database is from a decade ago (Lewis et al 2015), so this study is a timely update. They use the same data (with the data in the Lewis study including dogs only up to 2015), so these two studies can be taken together to assess many different aspects of the populations of the breeds and how they have changed over time. The earlier study focused more on genetics, including things like inbreeding, popular sires, and estimates of effective population size (Ne). This new study does more with demographics - population size, fraction of dogs that are bred, numbers of imports and their use in breeding, andthe populations of "purpose bred" dogs (field, conformation, and other activities). The summarized data for all of the analyses are provided in Supplemental Tables.

The results of this study should be no surprise for those that have been following the fancy for the last decade. Only a small fraction of the purebred dogs produced are bred, and the resulting loss of genetic diversity is a persistent force driving up inbreeding coefficients. The size of the pedigreed dog population is declining in the UK, for reasons that are not clear, but importation of dogs and their popularity for breeding is beneficial both to support population sizes and mitigate loss of genetic diversity.

While much information is summarized in the Results and you should review that material yourself, I'm always interested gaining a broader vew of things, and especially to see how breeds compare to each other. Which breed uses the most dogs for breeding? Which breeds are currently increasing in size, and which have declining numbers? Which breeds should be careful about overly-popular sires?

These types of questions are cumbersome to answer using tables of data. After much fussing and fiddling with the information in the various supplemental tables, I finally decided to create graphs of the data that would make breed comparisons easy. It was a bit of a task, but I found the graphs to be very useful so I have provided them on the ICB website where they are accessible to everyone (see he link below). A graph with 220 breeds will have labels too small to read, so for each of the charts I have also provided a large copy you can open that should be easily readable. I didn't do plots of everything but focused on the ones that were of most immediate interest to me. I might add a few more at my leisure if it looks like people are benefitting from the ones already done.

ACCESS THE PAPER, SUPPLEMENTAL TABLES, AND MY GRAPHS
You can access the graphs I created, as well as download a copy of the paper and a zip file of the supplemental tables from the ICB website under the "Projects" tab ("Ilska et al 2025 Figures"). (https://www.instituteofcaninebiology.org/ilska_figures-551693.html)

I was swimming in chart chaos putting these together, so if you spot any errors, please let me know. I hope these are useful to you.

REFERENCES

Ilska, J.J., Ryan, P.B. & Tolhurst, D.J. Modern pedigree dogs in the United Kingdom Kennel Club: a journey through shifting population landscapes and demography.Companion Anim. Health Genet. 12, 3 (2025). https://doi.org/10.1186/s40575-025-00142-1.(pdf)
(https://cgejournal.biomedcentral.com/articles/10.1186/s40575-025-00142-1#citeas)

Lewis et al., 2015. Trends in genetic diversity for all Kennel Club registered pedigree dogs breeds. Canine Genetics and Epidemiology 2:13. DOI 10.1186/s40575-015-0027-4
(https://cgejournal.biomedcentral.com/articles/10.1186/s40575-015-0027-4)

The 5 most important things to know about crossbreeding

2/28/2025

By Carol Beuchat PhD

Using Crossbreeding to Address Inbreeding and Genetic Diversity in Dog Breeds
Effective genetic management of animal populations relies on several breeding strategies, including inbreeding, outcrossing (within a breed), breed crossing, backcrossing, grading up, and rotational breeding. Among these, crossbreeding is particularly useful for creating new breeds and solving genetic problems like excessive inbreeding and loss of diversity.

For dog breeders, crossbreeding is an essential tool for improving genetic health. However, it requires a different approach than routine breeding within a breed. To ensure success, breeders should carefully plan their strategy before starting. Here are some key factors to consider:

1) What problem are you trying to solve?
In purebred dogs, two major genetic concerns are inbreeding and loss of genetic diversity. These issues can lead to increased health problems, reduced fertility, and shorter lifespans. While other traits such as behavior, size, disease risk, or longevity are important, many of these are linked to inbreeding and diversity loss. The best way to improve these traits is to first address genetic health at the population level.

2) How do you choose which dogs to cross to?
Many breeders want to start by selecting a breed for crossing, but a purebred dog breed is probably not the best option. The focus should be on reducing inbreeding and increasing genetic diversity, goals that can be difficult to achieve by crossing with another purebred breed.

Why? Because most purebred dog breeds already suffer from inbreeding and reduced diversity. If you cross your breed with another inbred breed, all of the offspring will inherit the same allele from every homozygous locus. This produces a population of F1 dogs that will all have the same allele at every locus that was homozygous in either parent, making inbreeding a potential problem again after the first generation.

Instead, consider landrace dogs or breeds that are not bred to a strict standard in a closed gene pool. There are about 200 recognized breeds in the UK and US, but hundreds more from around the world, some formally recognized,and some not. Check out Desmond Morris' excellent book, Dogs, which describes over 1,000 dog breeds.

To maximize genetic diversity, look for dogs that:

✔ Have low inbreeding and high genetic diversity
✔ Come from populations that have not been selectively bred to conform to a strict standard
✔ Have escaped kennel club recognition, such as landrace or working dogs
✔ Can be DNA-tested to confirm desirable genetic diversity

Choosing diverse, genetically healthy dogs as outcross partners creates a stronger genetic foundation for future breeding.

3) How should you think about traits?
Your focus in a crossbreeding program should be on genetic diversity, not specific traits.

Why? Because trait selection requires genetic diversity. You can’t select for particular traits if the necessary alleles aren’t present. By introducing new diversity, you are building the genetic foundation needed to re-establish breed traits later.

Also, keep in mind that genetic health is more than just managing disease mutations. Many traits, including immune system function and adaptability, rely on complex genetic interactions. Focusing too soon on specific physical traits can limit genetic progress and reduce the overall health benefits of crossbreeding.

Remember that for polygenic traits, F1 puppies will get a random collection of only half the alleles of the parent used in the cross. It’s unlikely that a puppy will inherit all of the variants involved in a complex trait. Again, focus on capturing maximum genetic diversity, then you can use focused selective breeding to shape traits with the most diverse genetic pantry possible.

4) What about genetic disorders?
Every animal carries recessive mutations, but these typically do not cause disease as long as the locus remains heterozygous (i.e., one normal allele is present). Recessive mutations become a problem as a result of inbreeding, which produces homozygosity. The key to good physical health is low inbreeding is supported by high genetic diversity.

Trying to reduce genetic health disorders by eliminating recessive mutations from the gene pool is difficult (you need to find every last recessive mutation) as well as genetically destructive, because selection against mutations will work against your goal of protecting genetic diversity.

A more effective approach is to:

✔ Focus on maximizing genetic diversity and avoiding inbreeding to reduce the risk of harmful mutations becoming homozygous
✔ Recognize that many disorders are complex or polygenic, meaning we don’t always know which genes are involved
✔ Avoid extreme selection pressure that could narrow the gene pool further

The safest way to minimize risk from inherited disorders is to restore a healthy genetic foundation first.

5) How should backcrossing be handled?
Restoring breed type after a crossbreed introduction often involves backcrossing, but this must be done carefully to avoid losing the diversity you worked to gain.

Let’s look at what happens genetically with each backcross:

First-generation (F1) cross: 50% breed A / 50% breed B
First backcross (A x F1): 75% A / 25% B
Second backcross (A x 75/25): 87% A / 13% B
Third backcross (A x 87/13): 93% A / 7% B

As you can see, each backcross reduces the genetic contribution of breed B by half. If you do serial backcrosses, you will eventually lose most of the new diversity, putting the population right back where it started.

Instead, to retain diversity while restoring breed type, use a structured breeding plan that:

✔ Uses multiple unrelated outcross dogs
✔ Balances careful selection with genetic management tools like DNA testing
✔ Prioritizes diversity early on, before selecting too heavily for traits

This is where expert guidance and genetic testing tools can make a critical difference in the long-term success of a crossbreeding program.

Crossbreeding is a Tool, Not a Threat
At some point, every purebred breed will need to take steps to manage inbreeding and restore lost genetic diversity through cross breeding. This is because animal populations in closed gene pools become more and more inbred over time and eventually go extinct due to inbreeding depression that reduces fertility and lifespan and a high burden of health problem.

As shown above, returning to breed type can be fast and easy, taking as few as three generaetions. But the real challenge is restoring type while keeping genetic diversity intact. Livestock breeders have been successfully using structured crossbreeding strategies for decades, often without access to the molecular tools now available to dog breeders.

For those concerned about potential changes to the breed and its gene pool from crossbreeding, note that the gene pool of your breed is not static now. It changs as a result of inbreeding because:

Every generation of inbreeding increases homozygosity, changing the composition of the gene pool
Every generation, alleles are lost through genetic drift, also changing the composition of the gene pool

Crossbreeding does not threaten breed preservation. In fact, crossbreeding is one of the most powerful tools available to protect a breed’s genetic health and long-term viability. Skilled breeders should use crossbreeding strategically with other breeding strategies like outcrossing and inbreeding to maintain breed quality while ensuring genetic health.

Crossbreeding, when done correctly, should be viewed not as a last resort, but as a valuable strategy for breed preservation and health.

Check out ICB's new online course, Genetic Rescue: The Genetics of Crossbreeding, in which we address how breeders can use crossbreeding to reduce inbreeding and enhance genetic diversity.

Pedigrees and DNA: Two Essential Tools for Genetic Management of Small Populations

2/22/2025

By Carol Beuchat PhD

As a breeder, you know the importance of making good pairings to produce healthy offspring. But did you know that two powerful tools - pedigree databases and DNA testing - can take your breeding program to the next level?

Since the advent of commercial DNA testing, there has been a growing but unfounded belief among dog breeders that pedigrees are no longer needed or useful, and that DNA testing is the new "gold standard". This is unfortunate, because nothing could be further from the truth. In fact, pedigree and DNA data used together are the solid foundations on which to build a breeding program designed for sustainable breeding of healthy dogs. Complementing each other, they provide a complete picture to guide your decisions and maintain the quality of your animals for generations to come.

Here, I summarize the key points made in a nice article (Galla et al 2022) that addresses how to use of both pedigrees and DNA data in the genetic management of animals. Although it is written specifically for conservation geneticists, it applies just as well to dogs, and especially to purebred dog breeds that often have limited genetic diversity and relatively small population sizes. You can download a copy of the paper at the bottom.

Pedigrees: Your Breeding Program's Foundation

A pedigree is a family tree showing the ancestry of an individual animal. While pedigrees may seem old-fashioned in the age of DNA testing, they remain incredibly valuable for breeders. There is a wealth of genetic and demographic information hidden in a basic pedigree that can provide invaluable insight into a breed's history and development. For a good example, have a look at this analysis of the genetic history of the Afghan hound that I put together for their World Congress a few years ago. This is wonderful information and should be available for every dog breed!

Why should you use pedigrees for genetic information?

First, pedigrees are cost-effective and accessible. All you need is a system to record parentage and keep track of generations, and there is inexpensive software available to do this. Second, pedigrees give you a long-term view of your breeding stock's history. Pedigrees allow you to chart the changes in population size and breeding practices over the history of the breed, they can reveal how and why inbreeding and genetic diversity has changed over time, identify important bloodlines at risk of extinction, and explore the patterns in genetic traits and disorders across generations.

Perhaps most importantly, pedigrees let you calculate key genetic information like the inbreeding coefficient of a dog or the predicted level of inbreeding for a litter produced by any pair of dogs. This guides smart breeding decisions to avoid inbreeding and maintain genetic diversity. The pedigree data can also establish the original and current size of the gene pool, the contributions of founder dogs and other ancestors to the gene pool, and how the level of inbreeding has been changing over the generations. The pedigree information can also be used to model the consequences of particular breeding strategies (e.g., how would breeding two versus only one puppy from a litter change the genetics of the breed), and how the number of males used in a breeding program would change the rate of inbreeding.

Note that a five generation pedigree can only tell you about inbreeding that occurred over those five generations, and a 10 generation pedigree documents only the inbreeding that occurred over those generations (and the assumption that the first generation animals are unrelated and not inbred). Short pedigrees will underestimate the true level of inbreeding but the information can nevertheless be useful if you are interested specifically in recent inbreeding.

What about missing data or errors in pedigree databases? Most pedigree problems will result in an underestimate of actual COI, so if your calculated COI is 27%, you can assume that it is at least that high, which is usually all you need to know (i.e., yes, the COI is too high). More generations of data (complete, error-free) in the pedigree will produce better the estimates of true COI. Because pedigree errors are relatively common, techniques have been developed that can verify pedigree relationships using data, even for errors deep in the pedigree, and statistical estimates of relationship can be used when parents are missing. Of course, the best option is to keep good pedigree records (and remember, every registered dog has a pedigree filed with the kennel club of registration), but pedigrees can still be extremely useful if not essential even with limitations from less than perfect data.

A caveat: Pedigrees can provide a wealth of information that you cannot get any other way. But you must understand the data to use it properly. The coefficient of inbreeding (COI) is probably the most frequently used statistic computed from pedigree data, but too many breeders do not understand how it is computed or what it means. Most fundamentally, COI estimates the inbreeding that would occur when a particular dog occurs on both sides of the pedigree. Obviously, it cannot do this correctly if your pedigree does not include the generations where that ancestor occurs. Most dogs were founded on a small number of animals. Because inbreeding likely occurred in the early generations, it is critical that the pedigree is deep enough to include those matings. The calculations assume that the dogs in the first generation of the pedigree are unrelated and not inbred, which is probably not true in many cases. Therefore, the calculated COI estimates the amount of inbreeding that occurred from the first documented generation (which has unknown parents) to the present.

You can learn more about COI in ICB's FREE online course, "COI Bootcamp".

PEDIGREES AND DNA:
ADVANTAGES & DISADVANTAGES

Key advantages of pedigrees:

Cost-effective and accessible
Provide historical perspective on population structure and genetic history
Allow calculation of important genetic parameters (e.g. inbreeding coefficients)
Guide breeding decisions to minimize inbreeding and maintain diversity
Track loss of founder alleles over time
Can provide similar estimates of relatedness to thousands of genetic markers when complete and accurate

Key advantages of DNA analysis:

Can provide more precise estimates of relatedness and inbreeding
Reveals information about specific genes or traits of interest
Elucidates fine-scale genetic differences within a population
Can address pedigree pitfalls like founder relatedness and missing data

Benefits of combining pedigrees and DNA data:

DNA can validate and refine pedigree information
Pedigrees allow for more strategic DNA sampling and analysis
Enables more sophisticated genetic studies and breeding plans
Provides a more complete picture of population genetic health

DNA Testing: A Powerful Complement to Pedigrees

While pedigrees are the foundation of a genetic management program, DNA testing offers some unique benefits.

DNA can reveal subtle genetic differences within your population that may not be apparent from pedigrees alone. Genotypes obtained from high density panels of SNPs (single nucleotide polymorphisms) provide very precise estimates of relatedness and inbreeding. DNA data can provide estimates of kinship that identify the dogs in a group that are genetically "most valuable" because they have low relatedness or genetic uniqueness compared to others.

DNA trait and mutation testing can reveal frequencies and distributions of genes in a population, as well as frequencies and distribution of homozygous and heterozygous genotypes. Because DNA can be used to compare individual markers across individuals, it can be used to localize the populations of animals that are at high probability of producing a particular trait or disease, without needing to identify the genes involved. DNA is also useful to identify subpopulations of a breed that have drifted apart genetically using techniques like cluster analysis of kinship coefficients or principal components analysis.

A disadvantage of relying on DNA data for information about relatedness is that you must be able to get a tissue sample for analysis. For dog breeders, this could be a problem if, for example, you might be interested in breeding to a dog that you don't have access to for a tissue sample. Or perhaps there is a sample of frozen semen that you wish to use but you want to estimate the inbreeding of the potential litter produced. Genotyping a semen sample might not be possible, but a pedigree database could provide the information you need. Of course, while DNA genotyping has dropped dramatically in cost over the last decade, it can still be cost-prohibitive in some situations. Maintaining a pedigree database can be done with readily available software and some time for regular data entry.

PEDIGREES & DNA:
MYTHS AND MISINFORMATION

Myths about Pedigrees

Pedigrees are obsolete
Pedigrees cannot provide good estimates of COI

Myths about DNA testing

You don't need pedigrees if you have DNA tests
DNA testing can eliminate genetic disorders in dogs
DNA "health tests" tell you about a dog's health

Why You Need BOTH Pedigree and DNA Data

Using pedigrees and DNA together creates a powerful toolkit for genetic management. DNA can validate and refine your pedigree information, addressing issues like uncertain parentage. In return, good pedigrees allow for smarter, more targeted DNA testing.

Combining both approaches enables more sophisticated genetic analysis and breeding plans, giving you the fullest picture of your animals' genetic background.

Diagram illustrating the mutual benefits between molecular and pedigree data. (Galla et al 2022).

The combination of pedigree and DNA information can be used to determine the genetic status of a breed and whether a breeding program to restore genetic diversity is necessary. This could be through making use of existing diversity in the breed, but in most purebred dogs there is little diversity to work with and the most effective and efficient solution is cross breeding to dogs that carry the needed diversity. Getting the most from the available data requires skill and experience, so breeders should connect with an expert in conservation or population genetics to assist in the development of a breeding strategy that will be effective. The Lundehund genetic rescue project is a good example of a program developed by biologists familiar with the best strategies to achieve the goal of restoring the genetic diversity of the breed while retaining its unique physical and behavioral features (Melis et al. 2022).

There is an important situation when you need both pedigree and DNA information. Let's say a few dogs have appeared in multiple kennels with green noses. Could this be due to diet? Or is it genetic? Breeders are usually quick to suspect genetics and launch a research study to look for the gene. But many things are influenced by both genes and non-genetic (i.e., environmental) factors, and some things might be entirely the result of some non-genetic factor.

Before you launch a research study, you should determine the heritability of the issue in question. Heritability is a statistic that tells you how much of the variation in a trait can be attributed to genetic variation in genetics and how much is due to non-genetic factors. If the heritability of an issue is very low, you need to look carefully for possible non-genetic factors that might be involved. For instance, an undetected nutritional deficiency might be causing a health problem, or hair loss could be a behavioral issue, or raising puppies on newspaper could be increasing the risk of hip dysplasia.

And the critical thing here is that you need a pedigree database in order to calculate heritability, because it accounts for the pedigree relatedness of the animals with and without the trait. With the pedigree data and knowledge of the affected animals, you can determine whether you should be looking for genes or an environmental factor. If the heritability estimate is high and you have DNA genotype data, you can look for a causative or predictive gene that might be useful as a DNA test.

The advantages of maintaining records of both pedigree relationships and DNA are significant, and the value of the information they can provide together when used to estimate heritability should justify the time and expense of maintaining both.

You can learn more about how to use both pedigree and DNA data to assess the genetic status of your breed and plan a breeding program to reduce inbreeding and improve genetic diversity in ICB's new online course, "ICB Genetic Rescue: the Genetics of Cross Breeding".

RECOMMENDATIONS FOR BREEDERS

Prioritize maintaining accurate pedigree records
Supplement with DNA testing when possible
Collaborate with conservation genetics experts for analyses
Use pedigree data to inform long-term breeding strategies
Stay educated on advances in genetic management techniques

Putting It Into Practice

How can you harness these tools in your breeding program?

Here are some key tips:

Prioritize pedigree maintenance. Start by establishing a reliable system to record and maintain pedigrees. This forms the foundation of your genetic management efforts.
Supplement with DNA when possible. While DNA testing can be pricier, it provides valuable additional information. Consider testing key breeding animals or using it to resolve uncertainties in your pedigrees.
Collaborate with experts. Don't hesitate to reach out to conservation geneticists or breed organizations for help interpreting complex data or developing breeding strategies.
Think long-term. Use the historical perspective from pedigrees to inform breeding decisions that will maintain genetic diversity for generations.
Learn how to use the tools properly. Take advantage of courses that provide an in-depth understanding instead of relying on random Facebook posts or advice from individuals with no actual training.
Stay educated. Keep up with advances in genetic management by attending workshops, reading breed publications, networking with other breeders, and following publications in scientific journals.

By leveraging both pedigrees and DNA, you can develop more effective, sustainable breeding strategies. Your efforts play a crucial role in maintaining the genetic heritage and health of your breed for years to come. With these powerful tools at your disposal, you're well-equipped to breed not just for today, but for the future.

REFERENCES

Galla SJ et al. 2021. The relevance of pedigrees in the conservation genomics era. Molecular Ecology 31:41-54.
https://onlinelibrary.wiley.com/doi/epdf/10.1111/mec.16192

Melis et al. 2022 Genetic Rescue of the Highly Inbred Norwegian Lundehund. Genes 13:163. https://doi.org/10.3390/ genes13010163

The coming transformation in dog breeding

1/12/2025

By Carol Beuchat PhD

THINGS ARE CHANGING!

If you’ve been paying attention, you may have noticed a growing trend: genetic rescue projects are being initiated for several breeds. Some are encouraged or guided by kennel clubs, while others are developing independently. But one thing is clear: change is happening. These changes are poised to transform much of what we know - or think we know - about dog breeding.

Here’s the truth: these changes are coming whether you choose to participate or not. In fact, it's likely that some of these new breeding practices will eventually become legally mandated. Ignoring this shift won’t be an option if you want to continue in the fancy. That’s why now, more than ever, your breed needs the experience and dedication of responsible breeders like you.

If you’re someone who cares deeply about your breed and the future of purebred dogs, this is your chance to lead the way. The tools and techniques you’ll need to embrace these changes aren’t difficult, just new. Think of it like learning how to use a microwave: unfamiliar at first, but simple once you’ve got the hang of it.

The results? Transformational.

Larger litters with lower mortality rates
Healthier, higher-quality dogs with fewer inherited diseases
Longer lifespans for the dogs you love
Breeding that is less stressful and more rewarding

You won’t have to become a geneticist or a disease expert. You’ll be able to focus on what you do best: bringing your expertise, passion, and care to breeding. And with these new tools, you’ll achieve results that were previously unimaginable.

Are you ready to step into this exciting future?

WHAT YOU CAN DO NOW

To prepare for these changes, start by learning the basics of population genetics. This foundation will set you up for success as we move into this new era of dog breeding.

The best way to get started is through courses. ICB has online courses designed specifically for breeders like you and are practical, straightforward, and accessible.

By taking this step now, you’ll position yourself as a leader in this transition, helping to guide the modern dog fancy into the future. Instead of struggling to keep up, you’ll be confidently ahead of the curve.

FREE RESOURCES TO GET STARTED

To make it even easier, ICB offers two FREE courses:

“COI Bootcamp”
“Basic Population Genetics for Dog Breeders”

Both courses are available under the “Courses” tab on the ICB website. These are excellent starting points.

From there, you can progress to additional courses that form a structured curriculum designed to build your expertise step by step. By diving in now, you’ll ensure a smooth transition into using the cutting-edge tools and practices that are coming.

In the meantime, I’m working on a new course about Genetic Rescue, that will introduce some of the new changes that are coming.

HOW BREED CLUBS CAN LEAD THE WAY

Breed organizations have a unique opportunity to provide leadership during this transition. Clubs can encourage their members to get started with the free ICB courses, ensuring breeders begin to build a strong foundation in the essential concepts.

As clubs progress through the curriculum, I recommend incorporating some of your own breed-specific information, which will make the material even more relevant. I’m happy to help your organization tailor these resources to meet your breed’s unique needs; just reach out and ask.

This is such an exciting time to be a dog breeder! The coming changes promise to revolutionize how we approach breeding, making it more effective, rewarding, and impactful. Celebrate these developments and enjoy being part of this historic process!

The first step is simple: get started now with your education.

Let’s embrace this change together and ensure the future of purebred dogs is bright, healthy, and sustainable!

The Importance of Genetic Diversity in Purebred Dog Breeding

1/1/2025

By Carol Beuchat PhD

What does "genetic diversity" mean?
Effective genetic management is crucial for maintaining the health and sustainability of purebred dog populations. Central to this effort is the concept of genetic diversity, which represents the variety of alleles present within a breed’s gene pool. Preserving and enhancing genetic diversity reduces the risks of inherited disorders and improves the overall vitality and adaptability of the population. Genetic diversity also reduces the formation of runs of homozygosity (ROH), which are blocks of contiguous, homozygous genes that trap deleterious mutations and prevent breed improvement through selection.

Why Genetic Diversity Matters
Genetic diversity underpins a breed’s resilience against health challenges, both genetic and environmental. Over time, selective breeding, reliance on popular sires, and genetic drift can erode this diversity, leading to higher levels of inbreeding. This, in turn, increases homozygosity (the presence of identical alleles at a locus), which can unmask deleterious recessive traits and compromise health.

www.instituteofcaninebiology.org/blog/genetic-management-of-purebred-dogs-what-you-need-in-your-toolboxMeasuring and Managing Genetic Diversity
Breeders can use tools from population genetics to assess and maintain diversity. Pedigree analysis offers estimates of genetic contributions from ancestors, while genomic tools provide a detailed and precise view by analyzing allele frequencies and heterozygosity.

These methods enable the calculation of key metrics:

Coefficient of Inbreeding (COI): A measure of the probability of inheriting identical alleles at a locus from an ancestor on both sides of th pedidgree. Lower COI values indicate lower levels of homozygosity; i.e., less inbreeding.
Mean Kinship (MK): Evaluates an individual’s genetic value within the population. Dogs with low MK contribute rare alleles, making them vital for maintaining diversity.
Effective Population Size (Ne): Reflects the genetic size of the breeding population, accounting for unequal contributions among individuals. Larger Ne values slow genetic drift and reduce inbreeding risks.
Founder and Ancestor Equivalents (Fe, Fa): Quantify the genetic contributions of founders and influential ancestors. Low ratios of Fe/Fa indicate diversity loss from bottlenecks or selective breeding.

Practical Applications for Breeders
Using these metrics, breeders can develop genetic management plans that:

Reduce Inbreeding: By selecting less related mating pairs and avoiding overuse of popular sires, breeders can reduce the increase in COI and slow the rate of diversity loss.
Balance Breeding Contributions: Increasing the number of males and females used in breeding and distributing genetic contributions more evenly improves Ne and preserves diversity.
Monitor and Adjust: Regularly calculating diversity metrics helps breeders understand trends and make adjustments to sustain genetic health.

The Role of Data
Accurate data is the cornerstone of effective genetic management. Comprehensive pedigree databases provide historical insights, while genomic analysis delivers precise, real-time assessments of genetic diversity and structure. Combining these approaches offers the best strategy for evaluating and managing a breed’s gene pool.

Breeding For Preservation
Maintaining genetic diversity is essential for the long-term health and sustainability of purebred dog populations. By understanding and applying principles of population genetics, breeders can mitigate the risks associated with inbreeding and ensure a robust gene pool. The tools and data for this work are readily available, and their thoughtful application can guide breeding programs toward a healthier future for all breeds.

We need a new standard for estimating COI from pedigree data

12/22/2024

By Carol Beuchat PhD

When computing the coefficient of inbreeding from pedigree data, how many generations of data should you use?

Ask ten breeders and I expect you will get at least five different answers. Many just do as they see others doing, some only have limited pedigree data and they use whatever is available, and often breeders rely on websites that provide COIs based on the data in that site's database, but for a modest number of generation (usually 8 or 10). I suspect lots of breeders don't know that the number of generations used actually matters.

Well, does it?

The coefficient of inbreeding is probably the single most useful statistic for animal breeding. It tells you about the degree of homozygosity due to inheritance of two copies of an allele from an ancestor on both sides of the pedigree. The key thing to know about this is that homozygosity matters in animal breeding. For many genes, the heterozygous state of an allele (e.g., Aa, versus AA or aa) is the most advantageous, a situation called "overdominance". Inbreeding results in loss of heterozygosity, producing homozygous genotypes, either AA or aa. Consequently, the advantages of heterozygosity are lost, and the resulting deleterious consequences for function are known as inbreeding depression.

Animal breeders documented the negative effects of inbreeding depression over a century ago. They also realized that outcrossing improved inbreeding depression by reducing homozygosity, the benefits of which are called "heterosis" or hybrid vigor. Awareness that the level of inbreeding in their animals affected their profit, animal breeders supported the development of the coefficient of inbreeding by Sewell Wright in the 1920s, which could estimate the level of inbreeding of any animal from pedigree data. To this day, COI remains one of the most powerful tools in the design of breeding plans that balance the negative effects of inbreeding with the benefits for consistency and quality.

When COI is computed from pedigree data, the quality of the database is critical. COI cannot predict inbreeding due to an ancestor that is not in the pedigree database you're using. In dogs, much of the most significant inbreeding occurred very early in breed development. Many breeds also suffered population crashes during wars, especially WWII. In small populations, it's difficult to avoid breeding, so these events define the genetic resources of the breed forever into the future as long as the stud book is closed. The dogs we have today carry the genes passed down from the animals before them. Animals lost to breeding because of a bottleneck are genetically irrelevant. If we are interested in the genetics of today's dogs, only the offspring produced that carried on after a bottleneck matter. The gene pool then is as large and diverse as it will ever be, and if the stud book remains closed, some of that diversity will be lost every generation.

Registrations of some some sporting dog breeds wince about 1910. There two obvious population dips. One in the 1940s that probably reflects the effect of wars. The other is in about 1975, and the cause is unknown, but it could be an artifact of data collection or change in the ways dogs were registered. (from https://www.instituteofcaninebiology.org/kc-gundogs.html)

Both history and genetics indicate that the number of generations of pedigree data used to compute COI should matter, and indeed it does. But the number of generations used for COI in dogs is both variable and seemingly arbitrary. If we are interested minimizing the deleterious effects of inbreeding, then we should be working with COI data that tell us about actual levels of homozygosity, not relative to other dogs or by a subjective opinion of what is "good" or "bad". If we want useful information about inbreeding, we need to be producing COI values that inform us about actual levels of homozygosity.

[This is a bit of an aside, but it is crucially relevant here. Ideally, breeders should have pedigree data that are complete back to founders. By some oversight of breed or kennel clubs, most breeds do not have a complete database back to founders. This prevents breeders com computing what would be the most accurate estimate of inbreeding using data for genetic history. This is a problem we could (and should) solve, and it should be a priority for all stakeholders. Certainly, the kennel clubs could do a lot to help out this with, since they maintain the actual stud book. There is no benefit in blocking access to this information, so we have to ask why they do this. I'm sure many would urge the kennel clubs to get with the program and unlock a hugely valuable resource so breeders - and others including researchers and scientists - can get access.]

So, if we consider the nature of pedigree data (a record of ancestry and population history) together with the need for information about consequences of breeding strategies for population and individual genetics, the depth of pedigree data used in COI calculations should be based on things that matter for genetics, not some arbitrary number of generations.

When a complete pedigree database back to founders is not available, I propose that the most useful, non-arbitrary pedigree depth that should be used in estimates of inbreeding should reflect the timing of historical bottlenecks or the lowest historical population size for more recently recognized (or developed) breeds. This pins down a population of dogs (and their genes) as known ancestors from which all subsequent descendants descend. Breeders need to realize that the COI computed from this population assumes that the oldest generation (our bottleneck population) is comprised of dogs that are not inbreed and not related. This means tht the first generation of descendants from those dogs will have computed COIs of zero. For most breeds, we know this isn't true, but this is the same assumption used in any calculation of COI from pedigree data. What this means, however, is that the COI we calculate from these data represents the inbreeding that occurred from that generation to the present. This defines a specific pedigree depth for calculations of COI. Because many breeds went through bottlenecks at the same time, it allows for comparison of historical rates of inbreeding across breeds.

The other problem this specific "bottleneck" generation for calculation of COI solves is that of the "sliding" COI. If you use some arbitrary number of generations in calculation of COI, as would be the case for online databases and for many breeders that maintain their own databases (e.g., 5 or 8 or 10, for example), adding the most recent (new) generation to the database bumps off the oldest generation to keep the number of generations the same. The calculation of COI must include the historical inbreeding, so cutting off the bottlenecks and other generations where there was lots of inbreeding will result in lower COIs in today's dogs. Remember, the COI calculation assumes the oldest generation of dogs are not related and not inbred, which isn't true. Generation after generation, as you lose the early generations of inbreeding, it will look like inbreeding is going down in your breed - which of course it isn't - leading to the erroneous (and oft claimed) conclusion that "breeders are doing a great job at reducing inbreeding". (If you didn't know this about calculating COI, you need to dip into ICBs's FREE online course, COI Bootcamp. You don't know what else you don't know, and you should be able to see how making a simple mistake can result in nonsense when in fact you think you are being careful and responsible. The course is FREE. Just do it!)

Pedigree data for Basenji. *Year of breed recognition by the American Kennel Club (AKC). (from Dreger et al 2016 Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping.)

We should be using historical bottlenecks as a "starting generation" in calculations of COI from pedigree data. It would be more informative to have pedigree data back to founders, but until the Kennel Clubs of the world decide that the very future of the breeds they register depends on breeders making smart decisions that will prevent further deterioration of gene pools. With a fixed starting generation, we really can see if breeders are adopting breeding strategies that are reducing the rate of inbreeding or, in the case of breeds undergoing genetic rescue, breeders can monitor progress without a large expense for DNA analysis.

Again, until Kennel Clubs step up to provide the data, it is up to breeders to work on creating databases complete back to bottlenecks, but they would gain a valuable tool for making breeding decisions that will reduce the risk of inbreeding depression and protect the health of the gene pool.

What experience and science can tell us about dog breeding

12/20/2024

By Carol Beuchat PhD

happened to run into this post of mine in a from years ago that I had long since forgotten about. It was originally posted to a discussion about health problems in some breed (I don't remember which) that breeders were struggling with without success. Note that I just blogged about this same topic a few days ago.
. . . . . . . . . . . . . . . . . . . . .
Here's the problem.

Breeders are assessing the issues they see in a breed and taking actions to address them based on what they know from their experience as breeders.

If you develop a cough, you pull out the remedy you usually use and wait for it to go away. But if that cough is tuberculosis and not a simple cold, your remedy will not solve the problem and the consequences could be serious. You need to see a doctor, and you need to take the proper medication.

Breeders are aware of the issues in their breed. They respond to these using the tools they are familiar with from breeding, which generally involve culling dogs affected with a genetic problem and breeding away from dogs suspected to be carriers of the genes thought to be causing the health problem. This is treating the cough as if it is a simple cold. In fact, the mutations causing the genetic disorders are not the problem. If we focus on the mutations instead of addressing the actual problem, you will never win.

Every dog has mutations, some you know about and many that you won't until they become a problem. Trying to improve health by targeting these one by one is a game of genetic whack-a-mole you will never win.
We are not winning because we are not focused on the source of the problems.

So, what is the source of the problem? Animals in closed populations can only breed to their relatives. All breeding to related dogs is inbreeding. Inbreeding produces homozygosity - two copies of the same allele at a locus. This is a good thing for the genes for type. It's a bad thing for genes that are broken. A genetic disorder is not caused by mutation bombs that you can simply remove to restore health. A genetic disorder is what results when a dog does not inherit a copy of the allele necessary for proper function. So, we have some loci that have two copies of a good allele; but for all the loci that have two copies of a broken allele, something function will be broken.

We are trying to produce healthy dogs by throwing mutations out of the gene pool. But it's a closed, finite gene pool; eventually we will throw all of the genes out. In fact, animals in closed populations go extinct.

Again. Animals in closed populations - aka closed gene pools - go extinct.

There is no "breeder magic" that will prevent this. There is no "science magic" that will prevent this. Animals in closed gene pools go extinct. Some sooner, and some later, but inbreeding will relentlessly increase over time, and diversity will decline, until so much stuff is broken that the animals can no longer reproduce and survive.

All of the other things breeders usually discuss really aren't relevant to addressing this overarching, unavoidable problem. Should we worry about hip scores, or is longevity more important? What about an eye problem that has a late onset? What about mutations with only mild effects? There is lots to talk about, and discussions have continued...for years.

But here's the only problem we need to talk about: inbreeding and loss of genetic diversity.

Fix this problem and you will have healthy dogs. If you start with a population of healthy dogs and randomly remove 40% of the alleles the breed started with, you will most certainly break things. This breed's average inbreeding is more than 40%; if half of that (20%) is homozygosity for good genes, then 20% of it is homozygosity for bad genes. That's a lot of stuff that's broken.

You cannot select your way out of this problem; remember, selection removes alleles, and lost alleles are the problem. It might be possible to restore some lost genetic diversity by strategically using less closely related dogs for breeding. Genetic analyses can reveal if this is possible.

We have much better tools to guide breeding decisions now than simply looking at stacks of pedigrees and comparing health issues. At the very least, you should be using those. You should know the heritability of all of the traits and disorders under selection (0.06? 0.33? 0.89? You should know the size of your gene pool (is it 57, 18, or 6?). You should know the effective population size of the breed (504? 92? 4?). You should know the pairwise kinship of the breeding dogs in the population; the inbreeding data suggest that the dogs are on average as closely related as what you would get from 3 or 4 consecutive full-sib crosses. Would you ever do 3 or 4 full-sib crosses???? In terms of genetics, that's what you have. You need to know which dogs in the breeding population have the highest genetic value so you can be sure to breed those, and which have the lowest value so they can be retired. You should know how much improvement in all of these things is possible if the existing genetic diversity in the breed is used in the most strategic way. If it turns out that this will not be adequate to restore the breed to health, then you need to evaluate strategies that will.

These are things you won't learn about in 20 or 30 years of breeding. You probably don't know anything about effective population size or kinship coefficients or founder genome equivalents. These are not things you will learn by breeding. These come from the science of population genetics that has been developed over the last 100 years by study of thousands and thousands of breeding programs for both domestic and wild animals. These are the tools used by breeders of other domestic animals. They are used in genetically managed programs for service dog breeding; they work for dogs just as they do for any other animal.

To solve the problems in this breed and in purebred dogs, we will have to correctly identify the cause of the problem (inbreeding and loss of genetic diversity), determine the best strategies for addressing the problem, and design a breeding strategy to effectively and efficiently restore the breed to health.

We have the tools and expertise to do this. We could be doing this NOW.

Why your breed needs a genetic management plan

12/19/2024

By Carol Beuchat PhD

The Importance of Genetic Management

The goal for every breeder is to leave their breed healthier and stronger for future generations. But without the right tools, achieving these goals can feel like navigating without a map.

The biggest challenge for breeders of purebred dogs is high levels of inbreeding and the consequences for health. We know that inbreeding has multiple deleterious effects in animals. It increases the risk of recessive genetic disorders being expressed; it causes inbreeding depression, which also affects health; and it results in loss of genetic diversity, which ultimately increases the rate of inbreeding.

Purebred dogs as a group have exceptionally high levels of inbreeding, a consequence of closed stud books that prevent the introduction of fresh genetic diversity to restore that lost over the generations. In addition, it is difficult for breeders to implement the types of genetic management strategies that would control inbreeding and loss of diversity because they simply lack the necessary information. Creating a genetic management plan requires information about the "genetic landscape" of the entire breed - not just individual dogs, or average values for things like inbreeding and kinship, but also data for the variation in these values in the population.

What's the Problem?

Breeders are recognizing that breeding for health requires that they know more about the dogs and the breed than they did in the past. DNA testing and pedigree analysis can now provide data about the genetics of individual dogs that can be used to reduce the risk of genetic disorders in offspring. What breeders lack, however, is information about the genetic landscape of their breed. When breeders identify a potentially genetic problem, they will try to "breed around" it or remove carriers from breeding. These strategies assume that the genetic solutions they need exist in the breed and they can solve the problem by moving the breed in that direction.

Imagine you are a tourist planning a trip in a place you have never been before. Without a map, you can only navigate by guessing, and you could easily end up in the wrong place or, at the very least, waste lots of time and energy taking wrong turns and running into dead ends. If you don't have the right information, breeding decisions work the same way. Without knowledge of your breed's genetic landscape, you can't plan a path forward or determine if it's even possible to get where you want to go.

The problem here is the assumption that a solution exists within the breed. Remember that recessive mutations cause problems when a dog inherits two copies of the mutation. It's not the presence of the mutation that you have to deal with, but the absence of the "wild type" (normal) version of the allele necessary for the gene to do its job. But breeders focus on mutations, and they diligently try to solve the problem through selective breeding. This takes an ongoing toll on the gene pool, ultimately increasing the risk that some other defective allele will become the next problem in the breed. You can see how this turns into a cycle of genetic whack-a-mole, damaging the gene pool with every cycle while making no progress on the actual problem. This is where we are in most breeds after decades of selective breeding, now guided by DNA tests. We have failed to improve the health of purebred dogs because we have not determined the right path to health. Without a map, we don't see a destination and can't choose a path that will get us there. We invest time, energy, and money, all with fingers crossed, hoping at least that things won't get worse.

What's the Solution?

The solution to this problem is obvious. Breeders need more information about the genetics of their breed. Not just about one or a few dogs, but about dogs characterizing the breadth of the breed's genetic landscape. Breeders need to be able to determine - before they hit the road - that the chosen breeding path will take them where they want to go. They need also to adopt breeding strategies that will not work against them along the way. Simply removing from the gene pool any dog that has some issue, or restricting breeding to just a small fraction of the dogs produced, will perpetuate the situation we have now and foil attempts to improve it. We need to be able to identify dogs of greatest genetic value so they can be prioritized for breeding. We need to identify sires before they have litter after litter of puppies that will skew the entire gene pool in one direction and flood the breed with his unique assortment of genetic mutations. (See Pox of the Popular Sires)

Breeders - and breeds - need is a road map of the genetics of the breed across its entire scope, so breeders can design well-planned solutions to problems. We need genetic management plans that identify a path towards a solution, instead of trying to solve problems by trying to run away from them in some random direction.

We have the information we need to create at least a basic plan for most breeds. Pedigree data and individual genotypes can be leveraged to start filling in the blank areas of the genetic landscape with useful information - where to find dogs with useful genetic diversity, where to find outcross candidates for specific dogs, which sires are overproducing at the expense of other genetically valuable dogs, and more. The information breeders need can be extracted from pedigree and DNA data and used to address the questions breeders ask when making breeding decisions. With regular updates, this information resource can display the current genetic status of both the breed and individual. It can also document the progress resulting from breeding strategies designed to reduce inbreeding and protect and improve genetic diversity.

DogsArk: The Genetic Dashboard

The good news is that we CAN get there. We can improve the health of purebred dogs without sacrificing the traits that make each breed unique. And we can do it efficiently and effectively, with tools and expertise that are available to breeders NOW.

ICB has built a breeder tool called DogsArk that provides the information breeders need for sound genetic management. Using either pedigree or DNA data, DogsArk provides a "genetic dashboard" that allows you to -

Visualize genetic diversity: Identify where genetic diversity is strong and where it is at risk;
Track lineages and traits: discover genetic clusters and understand the distribution of traits and mutations;
Plan sustainable breeding programs: Use real-time data to make informed decisions that preserve your breed's genetic health.

For the first time, we now have the DogsArk Breeder Tool, which will provide the information needed by dog breeders to safeguard the genetic future of their breed. With DogsArk, we can start to plan breeding strategies that will improve the health and welfare of dogs. (We are in the process of adding breeds and data, and the site is still under construction - pardon our dust!)

Have a look at DogsArk and check out the tutorial for guidance. If you have any questions or would like to add your breed to the site, just drop me an email: [email protected]

10 Key things to know about the coefficient of inbreeding

12/17/2024

By Carol Beuchat PhD

Facebook is an echo chamber of misinformation, myths, and unfounded opinions about the coefficient of inbreeding, which is unfortunate because there is probably no statistic (other than the kinship coefficient, which is related) that is more useful to breeders who want to minimize the risk of health problems in their puppies.

Here's my list of the 10 really essential things you need to understand about the coefficient of inbreeding.

1) The coefficient of inbreeding (COI) is the probability of an individual inheriting two copies of an allele from an ancestor on both sides of the pedigree.

Every dog has two alleles at each locus—one inherited from its mother and one from its father. At every locus, there is a 50:50 chance (a probability of 0.5) of passing on either of the two alleles to its offspring. This process is random and happens independently at every locus, in each generation.

2) COI quantifies the chance of homozygosity at any locus; therefore, it is also equal to the risk of producing a genetic disorder caused by the inheritance of two copies of a recessive mutation.

The estimated number of recessive deleterious mutations carried by the average dog is thought to be around 50-100. This number represents mutations that are hidden in heterozygous carriers and could result in a genetic disorder if a dog inherits two copies (homozygosity) of the same mutation.

3) The relationship between inbreeding (COI) and genetic disease (risk) due to homozygosity of recessive mutations is linear. So, risk increases with increasing COI.

Remember that most loci are heterozygous in healthy, freely breeding animals. In dogs, homozygosity results from breeding related dogs. Loss of the normal state of heterozygosity results in inbreeding depression, a suite of negative effects referred to as loss of “fitness.” This includes things like litter size, body size, puppy mortality, lifespan, etc. This effect occurs with ANY level of inbreeding. No level of inbreeding is “safe.”

4) The estimated probability of inheriting two copies of the same allele from an ancestor can be calculated from pedigree data that goes back to that ancestor.

Because dogs are in a closed stud book, there is a finite number of “founders,” and all of the alleles the breed will ever have were contributed by those dogs. The COI of a current dog will be the probability of inheriting an allele that was present in one of the founder dogs and passed on from generation to generation. If those dogs are not present in the pedigree used to estimate COI, the true level of inbreeding will be underestimated. If you use a five-generation pedigree, COI will only estimate the probability of inheriting two copies of an allele from an ancestor in the fifth generation. This means that COI based on a 5 generation pedigree tells you about inbreeding only over those five generations. This will not be the true level of inbreeding so it will not reflect actual risk of producing a genetic disorder resulting from homozygosity of a recessive mutation.

Selecting a specific number of generations (e.g., 5 or 10) to use in calculating COI generation after generation will result in a systematic bias in the result. This is because the current generation gets farther and farther away from the inbreeding that has occurred in earlier ancestors, with the result that the calculated COI will start going down. In fact, for animals in a closed gene pool, inbreeding can only increase over generations (although there might be blips up or down in the average). You can not breed your way back to low inbreeding in a closed population of animals beyond making better use of animals with low relatedness (kinship) to the rest of the population. Breeding related animals in a closed gene pool will always result in an increase in inbreeding over time.

5) The fraction of a dog’s DNA that is homozygous due to inbreeding can be estimated from genotype data from the runs of homozygosity (ROH).

Inbreeding calculated from ROH is an estimate based on several assumptions, one of which is the length of homozygous “runs” (i.e., blocks of homozygosity) that reflect actual inbreeding; i.e., there must be a decision about the minimum length of ROH to be included in the estimate, and this must be specified in the analysis. Choosing different block lengths will result in different estimates of inbreeding, so the expertise of the analyst is critical for the quality of the inbreeding estimate. Determining the “exact” amount of inbreeding in an animal would require information about the entire genome and the ability to identify when homozygosity is caused by inheritance of two copies of the same allele inherited from the same ancestor (“inherited by descent”, IBD) versus two copies of the same allele that did not come from a single ancestor (“identical by state”, IBS). So the COI provided with a DNA analysis using SNP data (e.g., the Illumina Canine SNP panel) is an estimate from calculations based on a number of assumptions.

6) The notion that COI is a dusty relic from the good old days a century ago and is obsolete today is false.

The coefficient of inbreeding is just as relevant today as it was when it was first derived by Sewell Wright in the 1920s. This is because it provides a good estimate of homozygosity due to inbreeding, which is proportional to the risk of genetic disorders caused by recessive mutations. Because it remains the best predictor of genetic risk due to inbreeding, it is widely and routinely used today by animal breeders. Those claiming that COI is irrelevant or obsolete have an inadequate understanding of population genetics and especially do not understand this most basic statistic in the science of animal breeding.

COI is the best predictor of the risk of deleterious effects caused by homozygosity of recessive mutations, whether determined from pedigree data or DNA. If your goal is to breed dogs that are as healthy as possible, you definitely want to know this. The risk of adverse effects due to inbreeding is proportional to COI; risk goes up as COI increases.

COI estimated from pedigree data will depend on the depth of the pedigree data. Deep, complete (no missing data) pedigrees provide good estimates of predicted COI that are usually comparable to homozygosity estimated from DNA. For dogs, 20 complete generations of pedigree data will provide a useful estimate of inbreeding. Note, however, that the risk of genetic disease from homozygous recessive mutations accrues from the lowest levels of inbreeding; COI of only 3% is associated with an increased frequency of seizures in humans. Livestock breeders understand that every 1% increase in inbreeding has deleterious effects. Consequently, the time to worry about inbreeding is when it is very low, when every additional percentage of inbreeding reduces fitness. The negative effects of inbreeding usually outweigh the benefits by about COI of 10% (so livestock breeders try to keep COI below about 6%). So,a 10% COI is not “okay” or acceptable; it represents an average of 10% reduction in health and fitness due to loss of heterozygosity. This should be a bright red line for breeders. It is not the case that COI below 10% is "safe." The risk of deleterious effects is lower but still significant at 8%, or 5%, or even 3%.

7) The meaning or relevance of COI is not a matter of personal opinion.

You might have your own level of acceptable risk in your breeding program, but COI is a quantitative estimate of homozygosity for which the deleterious effects are well documented. Accepting a COI of 10% or 15% as “okay” implicitly accepts the same level of risk of negative effects for health. DNA testing can eliminate the 25% risk of producing offspring that are homozygous for a recessive allele from parents who are both carriers. Carriers produce a 25% risk of genetic disorders, which breeders are willing to pay to avoid. A 25% COI reflects the same level of genetic risk from ANY recessive mutation, including the ones we don’t know about. Paying for DNA testing but then producing a litter with COI of 25% (or more!) reflects a failure to understand what DNA testing tells you, as well as an inadequate understanding of the genetics of inbreeding. Your opinion about inbreeding coefficients is not relevant. It is the best statistic we have to quantify the risk of genetic disorders caused by recessive mutations.

8) COI predicts the frequency of homozygosity of alleles that are identical by descent; it is not a measure of genetic (allelic) diversity.

COI is the fraction of loci that are homozygous for an allele inherited from an ancestor on both sides of the pedigree. By itself, it does not tell you about genetic diversity. (Again, it is simply a probability of homozygosity.) However, breeding in a closed gene pool results in the loss of alleles by two means in every generation – from inbreeding and from genetic drift. So, inbreeding results in reduced genetic diversity, but this is not quantified by the inbreeding coefficient. Furthermore, genetic drift can result in reduced genetic diversity with no effect on inbreeding.

There are specific, objective metrics to quantify genetic diversity. It is common to see COI used in the context of discussions of loss of genetic diversity, but understand that this is because inbreeding results in loss of genetic diversity, so they are correlated. But remember that COI is specifically about the risk of homozygosity of alleles, not an estimate of genetic diversity.

9) Linebreeding is inbreeding, with exactly the same risks as ANY breeding of related animals.

Linebreeding is a breeding strategy designed to increase the genetic representation of a specific ancestor in an animal. Done properly, inbreeding from other ancestors should not be affected. That is, homozygosity of genes passed down from that ancestor should increase, without otherwise increasing the overall level of inbreeding. Linebreeding and inbreeding both involve the crossing of related dogs, and the consequences for homozygosity and risk of producing genetic disease follow the same rules.

10) COI is not "just a tool".

The coefficient of inbreeding is a quantitative estimate of the homozygosity of alleles that are identical by descent. This is the best statistic we have for the risk of producing genetic disease or inbreeding depression in the animals we breed. We should be using COI in the planning of every litter. There is simply nothing better, because it tells us the specific thing we want to know. The quality of COI estimates will depend on the quality of the data on which it is based- pedigrees should be deep and complete (no missing data), and DNA genotypes should be based on a very large number of loci (e.g., 100,000+ SNPs) distributed across every chromosome.

If you learned anything useful here, check out ICB's FREE online course, "COI Bootcamp," which is available from the ICB website.

What turkeys and cows can teach us about selective breeding

11/26/2024

By Carol Beuchat PhD

There are some astonishing examples of what you can accomplish with selective breeding of domestic animals. The humble turkey has nearly doubled in size, from about 13 pounds in the 1920s to about 30 pounds 90 years later, and it's still gaining. This bird more than doubled its size through selective breeding over many generations.

This was accomplished simply by selective breeding of animals in the breeding population. No genes for faster growth or bigger size were added to the mix in the gene pool. So how, then, without adding new genes, can you produce such dramatic changes in phenotype?

Scheltens 2015, Turkeys have gotten ridiculously large since the 1940s; https://bit.ly/3ZqbEcn

Dairy farmers have also produced spectacular increases in milk cows. Over the last 50 years, production has doubled through generations of selective breeding.

Again, how can you start with the gene pool contributed by founder animals of unremarkable quality, and through a few generations of selective breeding transform the descendents into super-producers?

Brito et al 2021

Let me tell you first what won't work to produce animals that are better than their ancestors. Grabbing the top one or two outstanding animals of each generation (the so-called "pick of the litter") might produce better animals in the next generation, but not generation after generation. Over the longer term, this strategy will not ultimately produce the kind of spectacular increases in production quality that have been accomplished in animals like poultry and cattle.

The rub is that while production might increase, the health of the animals declines. Here's how it was described in a recent review of genetic selection for milk production in dairy cattle.

"Despite the great betterment in production efﬁciency, strong drawbacks have occurred along the way. First, across-breed genetic diversity reduced dramatically, with the worldwide use of few common dairy breeds, as well as a substantial reduction in within-breed genetic diversity. Intensive selection for milk yield has also resulted in unfavorable genetic responses for traits related to fertility, health, longevity, and environmental sensitivity." (Brito et al 2021)

The livestock breeders were using the latest breeding and genetic technologies to improve breeding success. What went wrong?

They learned the hard way that choosing only the best animals to breed (i.e., best-to-best) comes up against the hard reality of genetics. They didn't pay attention to inbreeding, which was eroding their gene pool generation by generation, until they finally realized the impact when the cows were unable to reproduce. You're not a useful cow if you produce lots of milk but can't get pregnant - one being related to the other, eh? Note that we're not talking here about breathtaking levels of inbreeding. Inbreeding was less than 10% in 2020 in a variety of milk cow breeds (figure), and the industry was facing catastrophe if they didn't solve the problem of viability.

Brito et al 2021

Livestock breeders have now realized that highly trait-specific selective breeding might improve one feature to the detriment of others that are critical to animal health.

Moving forward, the dairy industry needs to continue reﬁning the current selection indexes and breeding goals to put greater emphasis on traits related to animal welfare, health, longevity, environmental efﬁciency (e.g., methane emission and feed efﬁciency), and overall resilience. This needs to be done through the deﬁnition of criteria (traits) that (a) represent well the biological mechanisms underlying the respective phenotypes, (b) are heritable, and (c) can be cost-effectively measured in a large number of animals and as early in life as possible. (Brito et al 2021)

What seemed like a sensible way to breed to dramatically increase production traits, by restricting breeding to only the best animals in a population, resulted in inbreeding depression that would eventually sink the ship. But this is how we breed purebred dogs. Most have inbreeding greater than 10%, and in more than half of breeds tested, inbreeding exceeds 30%, with some exceeding even 40%.

Are dogs less sensitive to inbreeding than cows? No. Dog breeders are just less sensitive to the consequences of inbreeding than livestock breeders, no doubt because a commercial livestock breeder won't stay in business if the quality of the herd declines.

In milk cows,

"Intensive selection for milk yield has also resulted in unfavorable genetic responses for traits related to fertility, health, longevity, and environmental sensitivity" (Brito et al 2021).

But what we want to know is how, despite significant inbreeding depression, breeders were able to achieve such remarkable improvements in production traits?

In fact, commercial breeders do in fact choose the best offspring of each generation to breed to, but not just the top few animals. They select all of the best performing animals, perhaps 10-20% of the best animals. The goal is to capture the genetic variation present in the best animals. They know thatt each animal is a mix of genes from two good quality parents, and from the same parents this mix will be more fortuitous in some animals than others. The result is a collection of offspring that carry the genes of good producers, and when bred together in the next generation the new mixes of genes will once again produce some animals that are better than others. By selecting many of the top animals in each generation, the gene pool of the popualtion is gradually shifted in the direction of higher productivity as each new generation produces animals with a different mix of genes.

This assumes that genes are at least partly responsible for the traits of interest. If not, or if the influence is very small, you will not see imprrovement in performance with seletive breeding. But as in this example of selection for a trait like speed, selection of the 10% fastest animals in each generation will move the average performance of the animals in the population to higher speed.

Of course, not only must the trait have some genetic basis, but for this to work you need enough genetic variation to produce many new combinations of genes in the next generation of offspring, some of which can perform better than their parents. The key here is genetic varaiation. If you only keep the top animal in each generation, you will lose the genetic variation needed to improve anything. The genes associated with the best performance will become fixed in the population, ending your genetic improvement program.

Inbreeding and strong selection eliminates the raw material - genetic variation - that is necessary for improvement of traits in animals. Because of Inbreeding in each generation of dogs, genetic variation is lost and homozygosity increases, which can drive traits to unwanted extremes. Most breeders realize that breeding together two outstanding but closely related dogs doesn't guaranted outstanding puppies. This is because loci that were heterozygous in the parents can be homozygous in the offspring, which then lose the genetic advantage of heterozygosity. This is called "overdominance", where the phenotype of the heterozygous combination is superior to the phenotypes of either allele when homozygous. For traits that depend on overdominance for the best phenotype, inbreeding will destroy the advantage of heterozygosity.

What's the lesson here?

One of the "pearls of wisdom" often offered by long-time breeders is that you should "breed the best to the best". This suggests that the secret to success is the consistent application of this simple rule of thumb. But what we know about genetics makes clear that, while this might produce nice puppies from a pair of parents, selecting the pick of that litter and doing the same in the next generation will leave a trail discarded genetic variation that might include the raw material you need to produce something better than either parents. It's the shuffling of this variation in each generation that provides the opportunity for fortuitious combinations that can create animals that are superior to their ancestors, generation after generation. This is how we got those massive turkeys and the amazing milkers.

Dog breeders, the value of your dogs is in their genes; it's your money in the bank that will pay dividends generation after generation. Don't toss out the lesser dogs that happened to get the perfect mix of the available variation.

Genetic dashboard (current)

11/8/2024

By Carol Beuchat PhD

DogsArk
The ICB Breeder Tool

OUTLINE OF CONTENTS

DogsArk is designed to assist dog breeders in producing genetically sound puppies while preserving breed genetic diversity. It uses essential genetic concepts, including inbreeding, heterozygosity, kinship, and fixation index, to provide insights for informed breeding decisions.

The tool is structured into three modules:

1. Breed Summary (Module A)
Overview: Offers a summary of the breed's genetic diversity, genetic disorders, and traits.

Features:

Dog Inventory: Provides a database of dogs, distinguishing between anonymous and known dogs.
Genetic Diversity: Summarizes inbreeding coefficients, kinship, and heterozygosity with values for each measure.
Genotype Frequencies: Reports health-related gene statuses and frequency of normal, mutated, and heterozygous alleles.
Body Size, Coat Characteristics, and Sex Chromosomes: Details traits related to color, texture, size, and haplotypes for mitochondrial and Y chromosomes.
Other Traits: Lists additional genetic traits specific to certain breeds, such as brachycephaly.

2. Genetics of Individuals (Module B)
Overview: Provides data for individual dogs on genetic diversity, relatedness, genetic “value,” and traits.

Features:

Genetic Diversity: Displays inbreeding, fixation index, mean kinship, and heterozygosity for each dog.
Traits & Disorders: Lists genes associated with traits and health issues, with options to filter and sort by genotypes.
Genetic Ranks: Ranks dogs based on genetic diversity and relatedness.
Genetic Relationships: Includes a dendrogram and heat map for visualizing genetic similarities among dogs.
Kinship Matrix: Shows kinship levels with a color-coded heat map for assessing relatedness.
Runs of Homozygosity (ROH): Highlights blocks of homozygosity to identify recent or historical inbreeding.
Disease Risk Analysis: Uses a dendrogram to identify breed lines prone to specific diseases.
Principal Components Analysis (PCA): Visualizes genetic subpopulations, helping identify genetic differences within a breed.

3. Test Mating (Module C)
Coming Soon: This feature will predict the level of inbreeding for potential litters from specific parent pairs.

Overall, the ICB Breeder Tool is a valuable resource for breeders seeking to make genetically informed decisions, minimizing genetic disorders while fostering breed diversity. It combines scientific rigor with practical tools, enabling breeders to track and analyze genetic health trends

The purpose of the ICB Breeder Tool is to help you breed genetically sound puppies and preserve the genetic diversity of your breed. It is based on four key genetic concepts in population and conservation genetics. You will become familiar with these as you use the Breeder Tool and learn more about the importance of genetics in breeding decisions.

MODULE A
Genetics of Breeds

Glossary of Key Terms

Allele: One of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.
Brachycephaly: A condition characterized by a shortened skull, often resulting in a flat-faced appearance.
Dendrogram: A tree diagram that represents taxonomic or evolutionary relationships.
Fixation Index: A measure of genetic differentiation among populations, often used to assess the level of inbreeding.
Gene: A unit of heredity that is transferred from a parent to offspring and determines some characteristic of the offspring.
Genotype: The genetic makeup of an individual organism.
Haplotype: A set of DNA variations, or polymorphisms, that tend to be inherited together.
Heterozygosity: The presence of two different alleles at a particular gene locus.
Homozygosity: The presence of two identical alleles at a particular gene locus.
Inbreeding: The mating of closely related individuals, leading to an increased chance of offspring inheriting harmful recessive traits.
Kinship: A measure of the degree of genetic relatedness between two individuals.
Mean Kinship: The average kinship coefficient between an individual and all other individuals in a population.
Mitochondrial DNA: DNA located in the mitochondria, which is inherited maternally.
Mutation: A change in the DNA sequence of a gene.
Phenotype: The observable characteristics of an individual organism, resulting from the interaction of its genotype with the environment.
Polymorphism: The presence of genetic variation within a population.
Principal Components Analysis (PCA): A statistical method used to reduce the dimensionality of data by identifying principal components, which are linear combinations of the original variables.
Runs of Homozygosity (ROH): Continuous stretches of homozygous genotypes within an individual's genome, indicating potential inbreeding.
Y Chromosome: The sex chromosome that determines maleness in mammals.

Essential Concepts
These essential concepts are:

1) Inbreeding: probability of inheriting two copies of the same allele from an ancestor, which is called “homozygous”; it is also the fraction of genes that are homozygous. This measure of inbreeding is represented by the symbol F and is expressed either as a number between 0 and 1 (like 0.12), or as a percentage (like 12%).

2) Another way to express inbreeding is relative to the population. This is also called the “ﬁxation index”, which is abbreviated as Fis. In a randomly breeding population, the average Fis is zero. A breeding of two individuals that are more closely related than average is considered inbreeding and will produce a positive Fis. Breeding two individuals that are less related than average is outbreeding, and Fis will be negative.

3) Heterozygosity is the fraction of genes for which the two alleles are diﬀerent, so it is the opposite of homozygosity, in which the alleles are the same. Heterozygosity is represented by Ho.

4) Your relatives are your “kin”. In population genetics, we express the degree of relatedness between two individuals using the “kinship coeﬃcient”, which is represented as the letter K.

Okay, armed with a few key bits of information, we’re ready to have a look at the components of the ICB Breeder Tool.

The Breeder Tool consists of three modules.

1) The ﬁrst module provides information about the genetic status of the breed.

2) The second module provides information about the genetics of individual dogs.

3) The third module provides predictions of the inbreeding of a litter produced by mating two particular individuals.

Breed Summary

The ﬁrst module Indicates that you are in the Breed Summary module in the upper left corner, and the breed is shown on the right.

This module provides a summary of the genetic information about the breed, speciﬁcally the genetic diversity, genetic disorders, and genetic traits. These are organized under a set of tabs.

Dog Inventory

The ﬁrst tab is labeled “Dogs”. It gives a quick inventory of the dogs currently in the database. It reports the total number of dogs in the data, as well as how many of those dogs are anonymous, which means that their identities are unknown, perhaps because they were part of a research study. Often, we only have basic DNA information for these data and data about genes for speciﬁc traits is not available. DNA contributed by the owner of a dog are “known” dogs, and for these we often have more comprehensive DNA information.

In this example, we have a database of 51 English Springer Spaniels. All of these are anonymous dogs and there are no dogs whose identity is known.

Genetic Diversity

The second tab provides a summary of information about genetic diversity in the breed based on the dogs in the database.

The measures of genetic diversity we use are the four we have described earlier: two types of inbreeding coeﬃcient (F and Fis), kinship, and heterozygosity.

For each of these, the table reports the mean (or average), the median, and the maximum and minimum values.

Genotype Frequencies

The next tab provides information about genes associated with health and diseases.

If all of the dogs in the dataset for a breed are anonymous, there might not be data for some of the rest of the tabs in this module, and the pages will be blank (or contain place-holders).

In this particular breed, dogs are tested for the genes for alanine aminotransferase and dilated cardiomyopathy. For both of these, there are two possible alleles. The chart reports the number of dogs in the sample that have two copies of the normal alleles (they are homozygous for the normal allele), and these are labeled “clear”. The chart also reports how many dogs have two copies of the alternative allele or mutation, indicated as homozygous for that allele, and the number of dogs that are heterozygous, with one copies of both the normal and the alternative allele (heterozygous).

Body Size

The next tab provides information about the genes associated with coat characteristics such as color, texture, or length. In this example, the K locus and E locus are genes for color.

Sex chromosomes

The next tab reports the information about the haplotypes for mitochondrial DNA and the Y chromosome that are found in that breed. There might be many of each of these in a breed, or just a few.

Other Traits

In some breeds there are genes for speciﬁc traits that are not found in most breeds, and these are under the “Other” tab. In this case, this breed carries genes associated with a shortened muzzle, a trait called brachycephaly.

For anonymous dogs, there will usually only be information under the ﬁrst two tabs, for the inventory of the dogs and the statistics summarizing genetic diversity.

BREEDER TOOL TOUR
MODULE B
Genetics of Individuals

Module B provides the information for individual dogs about genetic diversity, relatedness to other dogs in the sample, the genetic "value" of a dog, the genes for traits and known mutations, and the genetic structure of the population. As in Module A, this information is organized on tabbed pages for navigation.

About the Tables
Many of the tables in the Breeder Tool have ﬁltering and sorting features. The icon of the funnel in the ICB Code column indicates that you can ﬁlter this column to just the speciﬁc animals you want to see. The other columns can sorted by ascending or descending values by clicking on the little arrow next to the column label.

Genetic Diversity
Under the ﬁrst tab, labeled “Genetic Diversity”, there is a table that summarizes the data for inbreeding, ﬁxation index (Fis), the mean kinship, and heterozygosity of each dog. Each dog is given an ICB Code that corresponds to a key with the identity of each dog. These are the data that were used to create the "Genetic Diversity" graphs for the breed population in Module A.

Traits & Disorders
Under the next tab is a table containing the genetic information for known genes for traits and disorders. Depending on how many genes were tested, this can be a very wide table and you will need to scroll to the side to see all of it.

You will ﬁnd it very useful to ﬁlter or sort by speciﬁc individuals or particular genotypes that you are interested in.

Genetic Ranks
The Genetic Ranks tab presents charts that rank individual dogs by the value of a particular measure of genetic diversity or relatedness. Each bar is labeled with the ID of each dog.

Where there are many individuals in the database, the ID codes of the dogs can be diﬃcult or impossible to read. In some cases they are readable on a tablet where you can zoom in; in other cases, you can look up the value for a speciﬁc dog and use the scale on the y-axis to see where that dog would fall on the chart.

Genetic Relatiionships (heat map)
The next tab displays a colorful map of the genetic relationships among the dogs in the database in two forms: as a family tree called a dendrogram, where the dogs that are most similar genetically are clustered together, and as a matrix called a “heat map” that compares the genetic similarity of every pair of dogs in the database. The degree of relatedness is indicated by branch length in the dendrogram, and by color in the heat map.

Kinship Matrix
Kinship, which is the degree of relatedness of two individuals, can also be displayed in this other type of heat map called a kinship matrix. This is similar to the heat map with the dendrogram, but in this one the dogs are not ordered. The advantage of this heat map is that the colors indicating the degree of kinship can be customized. In this one, a kinship coeﬃcient of

6.25% or less is represented by green (equal to a cross of ﬁrst cousins),

12.5% is yellow (half-sib cross), and 25% and above is red (full-sib cross). This allows you to quickly survey the levels of relatedness among animals in a population and also to identify speciﬁc levels that you might be interested in.

Runs of Homozygosity
The next tab, labeled “ROH”, contains charts that display “runs of homozygosity” on the chromosome. These are blocks of inbreeding that are the result of inbreeding. The genome is represented by arranging the chromosomes end to end from 1 to 38 across the top, and each row is the information for a particular dog. Blue represents blocks of homozygosity of a speciﬁc minimum length. Because older inbreeding tends to get broken up into smaller blocks, we can use the ROH charts to detect recent vs older inbreeding.

Disease Risk
We can use a dendrogram that depicts the genetic relationships among individual dogs to explore the distribution of a particular trait or gene in the population.

For example, a research study was unable to identify a speciﬁc gene associated with mast cell tumors in Labrador retrievers. However, if we identify the dogs aﬀected by mast cell tumors on the dendrogram, we might be able to identify lines that are predisposed to mast cell tumors.

This technique might be useful for health issues as well as speciﬁc traits of interest.

Principal Components Analysis
The last tab is for a graphical depiction of the genetic relationships among the dogs in the dataset using a statistical technique called “principal components analysis”, or PCA. This can be useful for identifying subpopulations of the breed that are genetically diﬀerent such as show versus ﬁeld lines of a breed, or varieties that diﬀer by color.

Test Mating

Coming soon...Under construction

The Test Mating page provides information for “predicted litter COI”, the average level of inbreeding expected in a litter produced by a speciﬁc pair of parents based on their kinship coeﬃcient.

An eye-opening, interactive lesson in population genetics

10/27/2024

By Carol Beuchat PhD

Let's say you're a responsible, preservation breeder (of course!), and you pride yourself in prioritizing health as a breeding goal. You carefully research pedigrees and ancestry before making mating decisions. You do all the relevant health testing (i.e., mutation testing and phenotype evaluation) for your breed. Yep, this sounds like what we want to see in a purebred dog breeder!

I'm now going to rattle your cage a bit.

What if there are things happening right under your nose that are causing significant deterioration of your breed's gene pool? You realize that this would not be a good thing, and I'm sure you would want to know about it. Reducing the quality of your gene pool will affect breeding in every generation to follow. You rightly think this sounds like something breeders should be monitoring and mitigating if the goal is breed preservation.

One last point before you dive into the fun stuff. These mystery effects could be countering all the efforts (and time and money) you are investing in your efforts to breed better dogs. So not only is there possible damage to your gene pool, there is also a chance that your breeding program is circling the drain and you don't even know it.

What follows is one of the lessons (Module 13, unit 1) from of an online course in population genetics that I created specifically for dog breeders (ICB Managing Genetics for the Future). This unit comes rather late in the course (Module 13 of 15), so you will be missing the extensive background concepts and information leading up to this that would make it more meaningful for you. But I think you can get a lot out of it if you take the time to follow the instructions carefully as you work your way through. Think about your own breed as you do this, and I think you will see some fog clearing. Even better, throw in some numbers for your breed and see if your breed population is as healthy as you think it is.

Above, all, have fun!

Genetic Management: Basic Strategy
Managing Genetics for the Future (Module 13, unit 1)

Genetic management: basic strategyThe reason we have domestic animals of particular breeds is because they are useful to us. Dogs have been put to work guarding, herding, hunting, hauling, fighting, controlling vermin, alerting, guiding, and more, and of course they have been companions as well. Breeding them deliberately allows us to produce that animals that best suit our needs through genetic selection for particular trait. Developing a breed with certain traits is essentially the process of creating a gene pool with the genetic material necessary for those traits as well as the variation necessary to improve or modify these traits as needed. Of course, if you can't breed domestic animals sustainably, your investment in their development and benefit from their use will be lost.

The development and sustainable breeding of dogs went along fine for thousands of years. Breeds that were needed were created, and those that were no longer needed went extinct. Genetic management was accomplished by doing what worked, selecting the best dogs for their purpose, culling the unfit, and finding dogs to breed to that would improve or add desired traits. Purpose and function drove selection, and the requirements that working dogs be both fit and inexpensive to keep insured that health was maintained. In the late 1800s, the purpose and means of breeding dogs significantly changed. Events originally intended for the evaluation of breeding stock turned into contests to identify the "best" specimens, then closed studbooks and "purebred" dogs were created.

This fundamentally changed the way dogs could be bred, and most significantly it removed the possibility of introducing new genes into the gene pool of a breed. The consequence has been the steady and dramatic reduction in both the genetic and physical health of these purebred dogs until we get to the situation we have today, in which the major topics of discussion among breeders are not the traits and quality of their dogs, but how to accomplish a successful breeding in the face of reduced fertility, smaller litters, high puppy mortality, and the increasing number of heritable disorders.

The health problems we have today in dogs are a direct and predictable consequence of a failure to properly manage the gene pools of the breeds. The truth of the biology is that closed gene pools lose diversity inexorably over time, and as homozygosity and homogeneity increase, health and reproductive success deteriorate. Eventually, inevitably, closed populations go extinct.

Sooner or later, if purebred dogs as we know them are to survive, the stud books must be opened and biologically appropriate methods of breeding must be allowed. Until then, breeders need to improve and protect the quality of their breed's gene pool, and in fact they will still have to do this after stud books are open.

The science of breeding and managing populations of domestic animals has developed considerably over the last 100 years, and especially in the last few decades. Genetic management strategies have been extensively explored and perfected in many kinds of animals in thousands of breeding experiments, and in fact some groups such as service dog organizations have adopted modern breeding methods that dramatically improve their ability to manage inbreeding while also producing dogs of reliable type and temperament. Breeders of all purebred dogs need to learn to do this too.

Wild animal species are closed populations too
The African elephant, Grey wolf, song sparrow, brook trout, and thousands of other familiar species of animals have been around for thousands of generations without becoming more and more inbred over time. In fact, most healthy wild animal populations have levels of inbreeding of only a few percent. How do they manage this?

Animals in a single population become inbred on each other. If you split a population, the two populations will also become inbred, but not in the same exact way. Different alleles will be lost by genetic drift, selection will be slightly different, and over several generations they will drift apart genetically. If an animal then moves from one population to the other, it can reintroduce some of the alleles that might have been lost. The ability of animals to migrate among isolated populations is how species minimize the level of inbreeding and depletion of the gene pool over time and, for the same reason, isolation of a population of animals so that migration cannot take place leads to increased inbreeding and genetic drift.

This can work the same way in domestic animals as it does in wild ones, and maintaining multiple genetic groups or lines within a breed is a useful management strategy if used properly. What this effectively does is create multiple open populations within a larger closed one.

The tradeoff is that smaller populations accumulate inbreeding more quickly and the rate of genetic drift is higher, so these things need to be taken into account when planning a breeding strategy.

Since breeding dogs aren't kept in herds or separate physical groups, these subpopulations exist on paper, and management is the process of monitoring the inbreeding and outcrossing as appropriate.

Simulating the genetics of multiple populations
We're going to use a computer simulation that will allow you to see how changes in population size, number of subpopulations, and migration rate (which for dogs is equivalent to a cross to another line) affect the genetics of the overall population.

Go to the PopGen Simulator-
http://www.radford.edu/~rsheehy/Gen_flash/popgen/

You will see two graph axes and a set of parameters you can fiddle with across the top.

Use these settings to start:
Pop. size = 50
A1 allele frequency = 0.5
# of Populations = 1
Number of generations = 200
and leave the "Fitness" boxes all at one, migration unchecked, mutation rates both as zero, and nothing for bottleneck.

Click "Go". In the top graph, you will see that you have lines for the frequencies of two alleles, A1 and A2. Since you set A1 to 0.5, A2 will be the same at the start (because A1 + A2 must equal 1).

In the graph below, you will see lines for how the genotypes change over time. Of course, this is from the Hardy-Weinberg equation that we talked about earlier.

Leave the settings and click "Reset" then "Go" several times, and you will see that you get a different outcome every time. This is because the simulation is modeling the random inheritance of A1 vs A2 each generation. You will see that one allele or the other can disappear entirely from the population, which means the other one is "fixed" - i.e., every individual is homozygous for the remaining one.

Now, let's do some experiments and collect some data.

1) Run this simulation 10 times with the same settings and write down which allele becomes fixed and the generation (roughly) when that happens.

Change the population size to 200, and run 10 times recording the data as above.

Change the population size to 25, and run 10 times recording the data as above.

From you data, you can see that a small population is genetically unstable, and the smaller it is the more unstable and less predictable it is.

2) Change population size to 200, and change number of populations to 2. Repeat as above.
You'll see that the display changes when you do this. Now, we don't get the genotype graph, but two graphs for alleles A1 and A2, and with the two populations plotted on each. This means that the lower graph is the mirror image of the upper one, so you really only need to look at one to see what's going on.

Now, leaving those settings, click in the "Migration?" box and for rate put 0.1 (10%). (The rate values go from 0 to 1.0.)

Run your 10 simulations and note the fixed allele for both populations.

One thing you might notice is that without migration, the allele frequencies of the two populations change independently. They might both up for a while, then one goes down while the other still goes up, and so on. The allele frequencies are changing randomly. What is different when you allow migration?

Play around with the migration rate; try several values, such as 0.01, 0.25, and 0.75. As the rate of migration from one population to the other increases, do the allele frequencies in the populations become more stable or less? Are the populations more similar to each other or less?

Write a little description of your results for these experiments so you'll remember what you found as we move on.

3) Set the population size at 200, A1 allele frequency at 0.5, and now change populations to 3. Run your experiments as before.

Write a few sentences describing how the results with 3 subpopulations are different than 2.

4) In these experiments, we kept the size of each population the same (200). Now let's pretend we have 300 animals and divide them into subpopulations but keep the size of the groups equal. So you will have 1 population of 300, 2 populations of 150, 3 populations of 100, and 6 populations of 50.

We know that diving the population and allowing migration reduces the probability of completely losing an allele and the population is genetically more stable. Now, if you divide the population the simulation is more like the real world because the subpopulations will be smaller.

Run some experiments as before, and fiddle around as you wish with the same settings while thinking about your own breed - its size, subpopulations (perhaps in various countries, different kennels, or different types), and migration rate.

5) Create 3 populations of 100 animals. What is the lowest migration rate that you would need to have to keep from losing one of the A alleles from any of the populations in 200 generations when the initial frequency is 0.5?

6) If you had a population of 300 animals, and you planned to breed in a way that would result in the "migration" of 10% of each subpopulation to another one (doing this via outcrossing), how may subpopulations would you create with your 300 animals to get the best genetic stability in all of them?

7) What did you learn from this? How does the size and number of subpopulations affect genetic stability at a fixed migration rate?

8) Can you think of any "breeder myths" that you just busted with your population simulations?

You made it through this lesson. Did you learn something that changes the way you think about breeding and genetic management (or lack thereof) in your breed?

This was a single unit from a course with 15 modules, each with multiple units (averaging 3-5). Would you benefit from knowing more about how population genetics affects your breeding program?

You can sign up to take this course here,
https://www.instituteofcaninebiology.org/openreg-managinggenetics.html

or have a look at the other courses on offer here -
https://www.instituteofcaninebiology.org/openreg-managinggenetics.html

I do recommend that you take Managing Genetics first because it covers foundational topics necessary to understand the material in other courses.

Mutations are not the problem

10/23/2024

Carol Beuchat PhD

Many breeders stress that the key to improving canine health is DNA testing and selective breeding, and many national kennel clubs and breed clubs endorse this view. However, the evidence does not support the claim that this strategy will prevent genetic disorders or even improve the health of dogs. In fact, it is easy to show why this will not work based on simple principles that any breeder can understand.

Let's say we start with a small population of healthy dogs that are not related to each other. Let's put them on an island and allow them to breed freely for many generations. Over time, individuals in the population will become more and more related to each other because of the limited number of individuals to mate with. Just by chance or through selection, some alleles in one generation will not get passed on to offspring in the next generation and will be permanently lost from the gene pool. At the same time, unavoidable inbreeding will increase the level of relatedness among the individuals. The net effect is that some individuals will have two copies of a dysfunctional allele at a locus instead of at least one copy of of the normal, "wild-type" allele.

The replacement of normal alleles with mutations will results in a decline in health and "vigor", including both genetic diseases and measurable traits such as reproductive success, lifespan, and survival. At this point, the population can be considered to be unhealthy, and the problem is the erosion in the quality of the gene pool.

If this was a dog breed displaying some health issues, we would assume the problem is genetics and start looking for a mutation. Sometimes one is identified, but more often the situation appears to be complex and we are unable to identify a clear cause among what we assume is a background of polygenic effects.

We have had only very limited success dealing with problems like this. There is no easy way to select against multiple unknown genes, so usually animals are removed from the gene pool. But this rarely solves the problem. New animals similarly affected continue to appear, sometimes stimulating more research to find the offending mutations. Ultimately, the solution often becomes the removea of animals from the gene pool once again.

After decades of engaging in similar strategies, breeders have not eliminated any of these problems, except where caused by a single recessive or dominant mutation. Why is this?

We identify the problem as "bad" genes we have to get rid of. Rather, it's not the bad genes that are the problem, it is the LOSS of the normal, functional genes that should be found at that locus. They, of course, are lost through genetic drift and selection with each generation of breeding. If every unique allele in a breed's gene pool was passed on to an animal in the next generation, then the composition of the gene pool would be stable over time, and we should be able to produce healthy, quality animals generation after generation. But we don't breed in a way that protects the contents of the gene pool. Thus alleles are lost every generation, either by design or by chance. We do not protect the genes that are necessary to produce healthy animals, so as they disappear from the gene pool, we have to expect that we will see problems.

Interestingly, most wild animal populations can persist for hundreds of years, maintaining health and function because the complement of genes necessary to produce the animals is constant. How do these unmanaged populations of animals do this? It's simple. The alleles that are lost are replaced when new individuals join from other populations. This is also done deliberately in commercial animal breeding, when a single population is subdivided and managed in a rotational breeding program. This practice restores genes lost from one subpopulation through the introduction of animals from another subpopulation. A carefully run program can continue to breed in a closed gene pool for many generations, simply by preventing the loss of alleles from the gene pool. The valued traits of the animals are preserved and the health and quality of the animals are maintained at a high level.

Note that the gene pools of ALL animals contain mutations. Why don't these mutations result in the number and magnitude of problems we wrestle with in purebred dogs? The dominant mutations are removed if they have a sufficiently detrimental effect on the animals. Others will only cause issues if paired with another copy of the mutation, because the locus for this gene will have two copies of a non-functional gene. What is absent is a copy of the normal allele necessary for a particular function.

The problem isn't that the animal has a mutation; it's that it lacks a copy of the normal allele. Simply "getting rid" of the mutation will not solve the problem. The problem is not a malicious genetic bomb in the gene pool. It's the absence of the normal alleles that should be in its place.

What is critical for breeders to understand is that there is only ONE solution to this problem. It is to restore the alleles necessary to perform every function of the body of a dog. DNA testing will spot a few of the "bombs". But throwing those out still leaves a gene pool without the allelic diversity necessary to produce healthy animals. Every breeder knows from experience that trying to remove mutations by removing animals is fruitless; the result will not be a happy, healthy population of dogs.

Can you see that DNA testing to identify the few mutations we know about will not restore health to dog breeds? As long as the gene pool is closed, we cannot restore the gene pool to health and we will not be able to produce healthy dogs sustainably. If we want healthy dogs, we need to produce dogs with the complement of alleles necessary to support all the bits and pieces of function necessary to be a healthy dog. All breeds in a closed gene pool will already be suffering from a loss of alleles, some of which will result in loss of function. So, not only do we need to breed in a way that protects genetic diversity, we must take whatever steps are necessary to restore the diversity of the gene pools.

Our focus on DNA testing and selective breeding is failing to improve the health of dog breeds, and this is why. Advice to breeders that we can produce healthy dogs if we continue to use our current strategies is simply wrong because it suggests that loss of alleles every generation will have no detrimental effects on health and function. This is impossible.

There is lots we don't know about genetics, but there is nothing that would explain how we might continue to breed dogs as we are without the deterioration we are seeing in the health and quality of the dogs. In fact, the health issues that we wrestle with in purebred dogs are caused by the way we breed. To change the trajectory of declining health in dogs, we must change the way we breed.

The solution to our problem is obvious and conceptually simple. It has been practiced by breeders of other animals for many years. There is no magic necessary, and it's not hard. You do need good information and guidance from individuals that understand the details of population genetics in order to accomplish the genetic rehabilitation of a breed effectively and efficiently. The sooner you start, the sooner we can be dog owners and breeders without also being experts in cancer, epilepsy, kidney failure, or sudden cardiac death.

Finally, the average dog lover is growing intolerant of the high incidence of health problems in purebred dogs. They identify the breeders as part of the problem, and they are not wrong. Pressure on breeders to improve health doesn't seem to be resulting in significant improvement, so the impetus now is legislation that will regulate dog breeding and make it illegal to produce animals that can be expected to suffer from health issues.

Breeders have experience in dog breeding. We must pair this with expertise in the proper genetic management of animal populations. To restore dog breeds to health, we must encourage and support this essential partnership.

<<Previous

Types of cancer in dogs and commonly affected breeds

Cancer mortality in purebred dog breeds

​Rates of cancer in purebred dog breeds over a range in body weight

Cancer rates in mammal species ranging in size from shrew to elephant

Rates of cancer in various species of mammals and in dogs

PEDIGREES AND DNA:ADVANTAGES & DISADVANTAGES

​PEDIGREES & DNA:MYTHS AND MISINFORMATION

RECOMMENDATIONS FOR BREEDERS

​DogsArk​The ICB Breeder Tool

OUTLINE OF CONTENTS

​MODULE AGenetics of Breeds

BREEDER TOOL TOUR​MODULE B​Genetics of Individuals

Genetic Management: Basic StrategyManaging Genetics for the Future (Module 13, unit 1)

Archives

Categories

Rates of cancer in purebred dog breeds over a range in body weight

PEDIGREES AND DNA:
ADVANTAGES & DISADVANTAGES

PEDIGREES & DNA:
MYTHS AND MISINFORMATION

DogsArk
The ICB Breeder Tool

MODULE A
Genetics of Breeds

BREEDER TOOL TOUR
MODULE B
Genetics of Individuals

Genetic Management: Basic Strategy
Managing Genetics for the Future (Module 13, unit 1)