Data from -

• Bellumori TP, TR Famula, DL Bannasch, JM Belanger, & AM Oberbauer  2013 Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010).  J Am Vet Med Assoc 242: 1549-1555. (pdf)

NOTE: The data from which the information presented here was derived is appended at the bottom.

Much ink has been spilled arguing about the health of mixed breed and purebred dogs. I haven't traced the history of this debate, but I imagine it has been fueled by two issues: first, the high burden of genetic disorders in purebred dogs, and second by the sentiment of some that people should adopt shelter dogs instead of purchasing a purebred. The argument from one side is that mixed breed dogs are healthier than purebreds, and this is rebutted by purebred breeders as a fallacy.

What makes this complicated is that there are many purebred dogs that live long, happy lives, and others that do suffer from an inherited disorder, and of course the same can be said of the mutt of mixed heritage. To get beyond the anecdotes, what we need are data, and a recent study provides them.

The study by Bellumori et al (2013) used medical records from the veterinary clinic at UC Davis for more than 27,000 dogs and compared the incidence of 24 genetic disorders in mixed versus purebred dogs. The abstract of the paper is included at the bottom of this page.

Here is what they found: 

1) The incidence of 10 genetic disorders (42%) was significantly greater in purebred dogs.

2) The incidence of 1 disorder (ruptured cranial cruciate ligament; 4%) was greater in mixed breed dogs.

3) For the rest of the disorders examined, they found no difference in incidence between mixed and purebred dogs.

(Note that they indicate subclassifications of epilepsy but counted it as a single disorder in the list of 24.)

The data in the study are presented as a mean odds ratio (OR) comparing purebred to mixed breed dogs. An equal risk for a disorder in purebred and mixed breed dogs would have an OR = 1.  To make the data easier to visualize, I have computed (OR* = 1-OR), for which equal risk in purebred and mixed breeds dogs would have a value of 0, and higher odds for purebreds would have OR* > 0, and higher odds for mixed breeds would have OR* < 0.  Therefore, in the graph below, positive values (above the horizontal line) indicate that the odds risk is greater for purebreds, and negative values indicate greater risk for mixed breeds. Asterisks (*) on bars indicate that in 50 comparisons of affected dogs with matched control sampling sets, there was a significant probability (p < 0.05; i.e., less than 5%) that pure and mixed breed dogs differed in expression of the condition.  (See Methods and Materials: Statistical Analysis in Bellumori et al 2013 for details.)  

Again, for 10 of the genetic disorders, risk was significantly higher in purebreds, and for one (cruciate ligament rupture) it was greater in mixed breed dogs. 

An interesting thing to note is that with the exception of one disorder, patent ductus arterioles, the odds ratios are higher for purebreds, but these failed to meet the criterion for statistical significance (hence no asterisk). This does not mean that the incidence in purebreds and mixed breeds was the same, only that they failed to find a statically significant difference in this study. This might be because they had inadequate data to detect a difference, or that in fact purebred and mixed breed dogs are the same and the differences in these data can simply be an artifact of sampling. (They incidentally found a significantly higher risk of being hit by a car in mixed breed dogs, which of course is not a health disorder and presumably not genetic.)

For the 10 genetic disorders which were significantly more prevalent in purebred dogs, I have created graphs that include the 5 breeds with the highest rates of affected dogs plus the value for mixed breeds.

This study concluded that purebred dogs have a higher risk of at least 10 of the 24 genetic disorders examined.

Nevertheless, the findings of this study in the lay press and among purebred fanciers were not so clearly expressed. Some examples:

• "It has been publicly discussed for years that hereditary disorders would be a direct consequence of the strict selective breeding of pedigree dogs and that for this reason the purebreds would have a much greater risk of developing hereditary disorders than mixed breed dogs. According to the latest research by Bellumori and his group, this assumption does not seem to hold. Indeed many diseases seem to be as common in mixed breed as in pedigree dogs" (Moller, on the MyDogDNA website; pdf)

• "A new study on the prevalence of inherited disorders among American mixed breed and purebred dogs has negated the common assumption that a mixed breed dog is always healthier than a purebred dog" (Quickfall 2013).

• "A new study by researchers at the University of California, Davis, indicates that mixed breeds don’t necessarily have an advantage when it comes to inherited canine disorders."  UC Davis press release

Unless you examine the study, these statements would all leave you to believe that the study demonstrates that purebred dogs are "just as healthy" as mixed breed dogs. But there is some careful parsing of language in each of them - "A new study...has negated the common assumption that a mixed breed dog is ALWAYS healthier" (emphasis mine). Okay, fair enough. Mixed breed dogs have more ruptured cruciate ligaments. 

And another hedge: "mixed breeds don't necessarily (emphasis mine) have an advantage when it comes to inherited canine disorders." This would seem to be saying that the default argument is that mixed breeds are healthier, usually but not necessarily, whatever that means. So indeed, "this assumption does not seem to hold", but for nearly half the disorders examined here the mixed breeds came out on top.

This study found that purebred dogs have a significantly greater risk of developing many of the hereditary disorders examined in this study. No, mixed breed dogs are not ALWAYS healthier than purebreds; and also, purebreds are not "as healthy" as mixed breed dogs. The results of this study will surprise nobody who understands the basics of Mendelian inheritance. Breeding related animals increases the expression of genetic disorders caused by recessive mutations, and it also increases the probability of producing offspring that will inherit the assortment of genes responsible for a polygenic disorder. 

The authors of this study tackled a very important question that is difficult to address because collecting the "perfect" data set is impossible. Using data on clinical occurrence of disease is fraught with difficulty because of many sources of potential complication - perhaps purebred dogs are more likely to receive veterinary treatment than mixed breeds, and comparisons among groups (e.g., afflicted vs not, purebred vs mixed) are confounded by unequal sample sizes or differences among groups in the age, sex, etc of animals. It's a statistician's nightmare. (In fact, a highly regarded statistician, Thomas Famula, was involved in the study.) In fact, the "perfect" comparison will never be done.  But this study presents a large compilation of data and a thorough analysis that is the first (and might be the only) attempt to explore differences in predisposition to disease in purebred and mixed breed dogs.

By Carol Beuchat PhD

The pedigree is the genetic history of a dog. The pedigree database of a breed is the genetic history of the breed. For breeds that began with a group of founder dogs and since have maintained a closed stud book, knowing the relationships among dogs in a breed can allow you to extract information about how the gene pool has changed over the generations, and it can also reveal the current "genetic structure" of the breed.

If you think of all of the animals in your breed as spread out across a landscape, but organized in clusters of genetically similar animals, you can envision of the genetic structure of your breed as the arrangement of these genetic clusters and their distances from each other. For instance, we might imagine all of the living Golden Retrievers on a landscape with two clusters, one that will be mostly bench-bred dogs, and another with dogs from field lines. We could zoom in on the bench line cluster and see that it is divided perhaps into groups of dogs in different countries, with the American dogs as a big cluster, and the UK dogs as a cluster that might also include a lot of dogs from other countries with strong British influence. Zooming in again, we might be able to distinguish clusters of genetically similar dogs that reflect particular kennels that have been especially influential and productive. As you zoom in and scan around, you can also see smaller and smaller clusters, and if you go far enough you could see the clusters of all offspring produced by a particular sire and dam.

These clusters of genetically similar dogs are the consequence of how we breed dogs, and in fact they are typical of all domestic animals. In purebred dogs, breeding is not random; if it was, existing clusters would become less and less distinct over time until eventually all of the dogs would be in one big clump. Instead, we tend to breed dogs that are related because they share particular traits that we want to produce in the offspring. Over generations of breeding within a group of related dogs and selecting for the desired traits, the dogs in the group become more and more similar genetically, and their similarity to dogs in other groups decreases. When breeders talk about "outcrossing", they are referring to breedings between dogs that are in different clusters. The more dissimilar the clusters are genetically, the greater the degree of outcrossing.

If we know there is genetic structure in a population of animals such as a dog breed, we can use that information in a very clever way. Let's say you have a colony of Labrador Retrievers that are being bred to produce service dogs. There has been an increasing problem of elbow dysplasia in the dogs, which of course is very undesirable in a dog headed for a career where its ability to perform particular duties is essential. Elbow dysplasia appears to be genetic, but despite decades of genetic research, the genes that cause it remain a mystery. So now you have a serious genetic issue in your breeding stock and no DNA test to screen for it. It would seem that you have little choice but to remove the affected dogs from the breeding program, and possibly also their parents, siblings, and offspring, aunts and uncles - and how far should you go? Clearly, this is going to adversely affect the size and diversity of your gene pool. Is there a better way?

If you have the pedigree records for your dogs, you can use that information to reconstruct the genetic landscape for your breeding colony. With genetically similar dogs grouped together, maybe you can identify clusters that have more than their fair share of dogs affected by elbow dysplasia.

In fact, this is exactly what happened to the Royal Dutch Guide Dog for the Blind Association (Ubbink et al 1998). They found that 17% of the 250+ dogs in their colony had elbow dysplasia. To develop a breeding plan that would reduce the incidence of elbow dysplasia in their dogs while minimizing damage to their gene pool, they used their pedigree information to reconstruct the genetic landscape of their breeding dogs, clustering together dogs based on genetic similarity. After they established the clusters, they superimposed on this landscape the locations of all of the dogs that had been diagnosed with elbow dysplasia.

This is a "dendrogram" of the genetic relationships of the dogs in the Dutch breeding colony. A dendrogram is a tree-like diagram that clusters dogs by degree of relatedness, then connects the clusters with branches that reflect the relationships among them. (If you're not familiar with dendrograms, you can learn how to read them HERE.)

This dendrogram instantly told them is that all of the cases of elbow dysplasia in their colony were occurring in a group of related dogs indicated by the partially shaded bars at the bottom of the tree. They could assume that all of the dogs in the groups with affected animals are a risk for elbow dysplasia because they have a high degree of genetic similarity. Removing just the dogs in those groups from the breeding program should be effective in reducing the incidence of elbow dysplasia in their colony.

Think about how useful this would be in the management of a genetic issue in your breed. Instead of shuffling through hundreds of pedigrees looking for patterns, instead of trying to figure out the mode of inheritance of a complicated trait, instead of spending a fortune on research to locate the genes causing the problems, you can home in on the likely genetic source using a diagram of the genetic structure of your breed. You don't need to know the genes involved. You don't need to know mode of inheritance. You don't need to spend thousands and wait years in the hope that geneticists will get lucky and find a single gene that you can test for.

Furthermore, you can do this with ANY trait that has a genetic basis. It can be a disease, a behavioral trait, a point of conformation, pretty much anything. And in fact, the more heritable the trait is, the more clearly it should be revealed in specific clusters on the genetic landscape.

And think about this. If you had a dendrogram of all of the currently reproductive dogs in your breed, and if people reported information about health issues in their dogs when they were diagnosed, the clusters containing affected dogs would become apparent as the reports came in. You would be able to identify emerging problems or developing patterns long before they became significant enough for breeders to realize there was an issue. Furthermore, reporting doesn't even need to be complete. More data would definitely be better, but missing data won't prevent you from figuring out where in the breed a problem is coming from. And if it should be necessary to do any DNA analyses, you would know where to find the dogs that are most and least likely to carry the genes of interest, which would make it much easier and less expensive to nail down the problem.

Think about how useful this would be. With an up-to-date pedigree database, you could produce a diagram of the genetic landscape of your breed that would help you nip genetic problems in the bud, and it would also be useful to identify where to find dogs to breed to that are unlikely to carry the genes you want to avoid. It could also help you identify groups of dogs that would be appropriate for outcrossing because the diagram will reveal the clusters that are less similar genetically to the one your dog is in. In fact, breeders of Icelandic Sheepdogs were able to identify the dogs in their small breed that were most valuable genetically because they carried genes that were rare in the breed, and from this they could develop breeding strategies that would minimize the loss of valuable genetic diversity and make the best use of the diversity remaining in the breed.

Trying to navigate through the gene pool of your breed without a picture of the genetic landscape, avoiding the genetic landlines you know about and keeping fingers crossed that you won't discover the ones you don't, is like trying to find an address in New York City without a map. The information you need to make your journey safer, easier, and less expensive is available to you now, in the pedigrees that record the genetic history of your breed. 

• G. J. Ubbink, J. van de Broek, H. A. W. Hazewinkel, J. Rothuizen. 1998. Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations. Vet Rec 142: 209-213.

By Carol Beuchat PhD

It seems you can never know enough about genetics. On a regular basis science tells us about a new wrinkle that really messes up what we think we know. If you're a biologist, this can be really exciting, but if you're a dog breeder it can create a lot of discomfort. We're just now realizing that as autonomous as you might think you are, your bacteria are really in charge, making you smarter, sicker, healthier, or smellier, and affecting your hormones, behavior, and immune system. (There is a nice review HERE.) And very recently, we've discovered that they affect the inheritance of traits from mother to offspring in really creepy ways.

While we're worrying about keeping up with the pace of new discoveries in genetics, there are some genetic fundamentals that don't get their fair share of attention. One of these is something called "genetic drift". Jeffrey Bragg, who has been breeding Seppala Siberian sled dogs for many years and knows a thing or two about genetics, calls it "the breeder's hidden enemy" - pretty strong words for something most breeders never think about. (You can read some of excellent essays by Jeffrey on his website, or you can download a collection HERE.)

So what is this insidious force that we should be worrying about? It's a simple concept, and it is described well by the name. Genetic drift is the fluctuation in the frequencies of alleles in a population caused by random chance. There are two alleles at each locus, and inheriting one or the other is like flipping a coin; if you flip a coin 1000 times, you should get pretty close to half heads and half tails. But if you flip the coin only 5 times, you could get - just by random chance - all tails, and if you try it again you might get all heads. If the coin is "fair", the frequency of heads (or tails) should get closer and closer to 50% the more tosses you do.

This phenomenon - the random variation in frequency cause by chance selection of one outcome or another - is the basis of genetic drift. As chance might have it, if one of a pair of alleles gets passed to more offspring more frequently than the other, that allele will have a higher frequency in the next generation. In the next generation, the other allele might do better, and the frequency of that one will rise and the other one will fall. It can happen that, just by chance, the very last copy of an allele can be lost due to genetic drift and the entire population is then homozygous for the other allele. Of course, breeders have no control over which allele of a pair is inherited by a puppy, so genetic drift pushes allele frequencies around in a population just out of sight of the breeder, who is likely completely unaware.

To  give you an idea of how genetic drift works, there is a clever little computer simulation that will let you do some experiments of your own. The software is called Populus and is a Java routine that will run on both a Mac and PC. Here's how you get it:

Go to http://www.cbs.umn.edu/research/resources/populus and download the program.

Populus requires the software Java to be on your computer. It probably already is, but if it isn't you can download it from the link at the green arrow (above).

Double click on the downloaded file and it should open to the program, but you might instead get this warning box complaining that Populus is from "an unidentified dveloper".  To get around this, follow the instructions at the green arrow; basically, you right-click on the program, tell it to open, and confirm the open request.

If all is well, you should see the blue screen. In the upper left, click on "Model", and choose the Mendelian genetics module and the option "Genetic Drift". From the window that pops up choose "Monte Carlo Model" at the top.

If everything worked like it should, you should be all set to go!

In the little pop-up panel, find where you can set the number of generations the simulation runs under "Runtime - Generations", and you will also be able to set the Population Size (N) just below that. On the right panel, we are going to leave "Number of loci" at 6 and "Initial frequency" at 0.5"  (Ignore the boxes for "3N Generations" and "Permit selfing?", as well as the options on the right panel.)

Now let's run some simulations with these parameters:

N = 200
Runtime = 100 generations
Number of loci = 6
Initial frequency = 0.5

Click on the green arrows with the word "View" (upper left of the panel, next to the floppy disk, printer, and light bulb icons).

A graph will appear with 6 lines of different colors, one for each of our 6 loci. The frequency of all alleles is at 0.5 when the simulation starts, then the frequencies of each vary independently to simulate genetic drift. Repeat the simulation several times (just keep hitting "View").

If a colored line goes off the bottom of the graph before the last generation, that allele has been lost from the population because of genetic drift. If a line gets to 1.0, it become fixed in the population (it is homozygous) and will remain there. Loss of an allele is a reduction in genetic diversity.

Run the simulation 10 times and for each trial record how many alleles become fixed and how many are lost from the population. Record your data in this table, then repeat with everything the same except the populations sizes, which will be 500, 100, 50, 25, and 10.

After you have collected your data, take the average of each column. Then using the graph grid below plot the averages for number of alleles that became fixed versus population size and connect those dogs. Then do the same with the averages for the number of alleles that were lost.

Then one last thing - for each of those points, put a dot on the chart for the highest value in the series of 10 and the lowest value, and connect those dots through the point with a vertical line. This now shows you how variable the data were for each population size.

Is genetic drift really the "breeders hidden enemy"?
So, looking at the graph you made, you should be able to say something about how the population size of your breed affects the risk of losing a neutral allele just by chance. Think about these questions:

How does population size influence the genetic stability of the gene pool?

If we consider that only the reproductive animals in the population matter for this, what do you think this means for the genetic stability of your own breed?

Has your breed gone through fluctuations in population size (population explosions or bottlenecks)?

What could you do to reduce the loss of genetic diversity by genetic drift in your breed?

Because there is greater loss of genetic diversity at lower population sizes, how would this affect subpopulations in your own breed - e.g., in bench vs show populations, in different countries, different kennels, etc? How would this affect how similar they are to each other? Can you think of a way you could make use of the phenomenon of genetic drift to improve your breeding strategy?

If you would like to learn more about genetic drift, I recommend you have a look at Jeffrey Bragg's article that I mentioned at the top.

These non-genetic influences on the expression of phenotype are collectively called "environmental" factors. For may inherited traits, the phenotype you observe is a consequence of both genetic and and environmental influences.

Phenotype = Genetics + Environment
or
P = G + E

When you're evaluating a trait in a dog, you need to remember that some of the variation you observe among individuals, and even among litter mates, will be the result of genetics and some will be a consequence non-genetic or environmental factors. For example, a dog might have great genes for hips but a bad hip score because it was over-exercised as a puppy. If you're trying to improve the hips in your offspring, you would want to know the difference between dogs with bad hips because of environment and those with bad hips because they have the genes for bad hips. One would be safe to breed from, the other wouldn't. What you need to know is the "heritability" of that trait.

Heritability is the fraction of the variability in a trait among animals that can be accounted for by genetics; that is, we're looking at the G in the equation above. Let's say you raise an entire litter of puppies under conditions that are identical in every way. If the "environment" term in our equation is zero (i.e., there was no effect of environment), then the heritability of that trait in those puppies is 100%; all of the variation among puppies can be accounted for by differences in genetics. On the other hand, you might measure the same trait in 300 puppies raised in different households. The environment in this case will make a difference and will be different for each litter (and maybe different for each puppy), so genetics will account for less of the variation you see from pup to pup. Heritability is not about how a trait is inherited, but about how much of the variation in a trait from dog to dog an be accounted for by genetics.

Because every group of dogs could experience different environmental factors, an estimate of heritability is specific for a particular group of animals measured at a particular time. If a trait has been measured on many groups of animals under different circumstances, it's possible to determine an average or a range of heritability values that can be used to characterize that trait in general. So for example, estimates of the heritability of subaortic stenosis in the Newfoundland range from 0.17 to 0.45. Heritabilty of lymphoma in Golden Retrievers is 0.44, and of osteosarcoma in Deerhounds is 0.7. Behavioral traits are also heritable: heritability of various hunting traits in Finnish Hounds range from 0.12 to 0.15. (See the table HERE for heritability estimates of various traits.)

It's important to understand heritability because traits with low heritability are more difficult to improve by selection. The phenotype of the trait less reliably reflects the genotype of the dog (so it's harder to select the dogs with the best genes), plus the genes account for less of the improvement you would gain from selection. It is easier to improve traits with high heritability, and you could waste a lot of time and effort trying to improve through selection a trait that is strongly influenced by non-genetic factors.

If you have a rough idea of the heritability of a trait and it's high enough to respond well to selection, then what you wish you knew were the actual genes in a particular dog. A trait might have good heritability, but you won't get very far if the dog you want to breed doesn't have the genes you're trying to select for.

Of course, your best sources of information about the genes in a particular dog are that dog's relatives - the parents it inherited the genes from, the siblings that would also carry some of the same genes, and the progeny that the genes would be passed to. This is where long-time breeders have a definite advantage; knowing the history of a particular line, knowing the parents, grandparents, aunts and uncles, and knowing what a dog produced are all clues to the genetics packaged inside a particular dog. If you don't have this wealth of experience, or you don't know much about a particular line, what information would be most useful for you to collect?

These are graphs that display the relationship between how reliable a particular group of relatives would be in selecting for a particular trait and how this varies with the heritability of the trait. [In these graphs, the environmental effects are not a factor.  Reliability is the relationship (as a percentage) between the genetic merit of the dog being evaluated and the phenotype being selected for.]

The first graph below shows that the dog itself provides the most reliable information compared to parents, parents plus grandparents, and the complete pedigree. This graph also shows that the higher the heritability of the trait you are selecting for, the more reliable the dog becomes as a predictor of what will be produced in a particular mating. For traits of low to modest heritability like aortic stenosis in Newfoundlands (0.17-0.45), the phenotype of the dog will predict about 45-65% of the dog's actual genetic merit for that trait. Knowing that a Deerhound suffers from osteosarcoma (heritability of 0.7) would allow you to predict the dog's genotype for that trait with a reliability of about 85%, whereas having that information about parents or grandparents is much less reliable (about 60%). So the information about the dog itself is most informative, and the higher the heritability the more reliable it is. (These data about heritability are from the table in "A better way to pick 'em: using EBVs to reduce genetic disorders in dogs".)

What about information about siblings and half-siblings? These two graphs show how reliability varies if you have information about 2, 4, or 6 full siblings or half-sibs.  As you might expect, the more littermates and half-sibs you have information about, the more reliable your assessment of a dog's genotype. Also, full siblings are more informative than half-sibs. Two full siblings provide about as much information as parents for a trait with a specific heritability; for instance 2 siblings and parents have a reliability of about 20% for a trait with a heritability of 10. For traits with higher heritability, the parents are a bit more informative. So information about siblings is very useful, and that from half-sibs is modestly so.

The most reliable information, however, comes from progeny, each of which carries half the genes of that parent. Again as you would expect, the more offspring you have information about, the more reliably you can estimate the actual genetic merit of a dog for a trait, and the gain from additional offspring is most pronounced for traits with low heritability. This graph depicts reliability for 10, 20, 40, 80, and 120 puppies (the legend is in the lower left corner), and for traits with high heritability puppies are the most reliable reflection of the genetic merit of a dog. So for traits with low heritability, the more information you can gather about the trait in offspring the better; reliability of selection improves by about 50% if you have information for 40 puppies instead of just 10, and reliability almost doubles with 80 puppies.

The take home lesson here is that having information about the progeny of a dog is extremely useful in the assessment of a dog's genetic merit for a particular trait. Every breeder evaluates their puppies, but how many keep systematic records of the information for every trait of interest and for each puppy? Probably not many, and as the graph just above shows, the ability to assess the merit of a dog can be improved substantially with information about more offspring. For polygenic traits in which assessment of quality based solely on phenotype will be confounded by environmental factors (many of which you might know nothing about), being able to predict more reliably the traits a dog will pass on to offspring will make selection all that more efficient.

Data from -

• Willis MB. 1989. Genetics of the dog. (table 92)
  

By Carol Beuchat PhD

Although Gregor Mendel is the father of modern genetics, Jay Lush is the fellow who brought genetics to animal breeding. Lush was a student of Sewall Wright, who devised the coefficient of inbreeding, and a background in both genetics and mathematics allowed him to develop animal breeding into a quantitative science. Perhaps his most important contribution is a book first published in 1937 called Animal Breeding Plans, in which he laid the foundations on which the scientific breeding of both animals and plants still rest today. While parts are necessarily outdated now, much of what he wrote is as useful today as it was then. 

Most breeders know about inbreeding and linebreeding but find it difficult to clearly distinguish between them. Usually inbreeding is considered to be breeding among first-order relatives (e.g., sibling to sibling, parent to offspring), and linebreeding is a fuzzy version of "not as close as inbreeding". When Lush discusses linebreeding in his book, though, he clearly distinguishes between linebreeding and what he calls "other forms of inbreeding", which he simply defines as breeding between relatives.

Lush describes linebreeding as a very special form of breeding.

"Linebreeding, more than any other breeding system, combines selection with inbreeding. In a certain sense, linebreeding is selection among the ancestors rather than among living animals... It is accomplished by using for parents animals which are both closely related to the admired ancestor but are little if at all related to each other through any other ancestors. If both parents are descended from the animal toward which the linebreeding is being directed, they are related to each other and their mating is a form of inbreeding in the broad sense of the word."

This is worth saying again. According to Lush, linebreeding pairs animals that are related to a specific ancestor, but which are little if at all related to each other.

To illustrate his point, he offers some simple pedigrees.

He says, "the parents of X are double first cousins, having the same four grandparents. The parents of Y are half brother and sister. Z is produced by mating a sire to his own granddaughter. W is produced by mating a sire to his daughter out of one of his own daughters. The intensity of the inbreeding is the same for X, Y, and Z. Yet X would rarely if ever be called linebred. Its sire and its dam are related through four different ancestors which, so far as the pedigree shows, may belong to four unrelated strains. If a breeder were to call X linebred, he would have to say that it was linebred to four different lines at once, which is something of a contradiction in terms. He would call Y linebred to M because K and L are related only through M, and Y has been kept almost as closely related to M as it parents were. Z is even more clearly a case of linebreeding because it is more closely related to M than Y is, although no more intensely inbred. Many breeders would call W inbred instead of linebred because the intensity of its inbreeding is so high. Others would call it "intensely linebred to M," since all of its inbreeding is focused on M and it contains 87.5% of the blood of M - a relationship of 75% after allowing for W's inbreeding."

Lush saw linebreeding as a way to preserve an exceptional ancestor's influence. For every generation that passes between the ancestor and the present, its influence is reduced by half. To avoid this progressive dilution, "linebreeding takes advantage of the laws of probability as they affect Mendelian inheritance to hold the expected amount of inheritance from an admired ancestor at a nearly constant level...Linebreeding provides, so to speak, a ratchet mechanism for holding any gains already made by selection, while attempting to make further gains."

A significant advantage of linebreeding over ordinary inbreeding is that, while it also increases homozygosity and prepotency, "the homozygosis produced by linebreeding is more apt to be for desired traits than is the case with undirected inbreeding. Linebreeding tends to separate the breed into distinct families, each closely related to some admired ancestor, between which effective selection can be practiced." 

Don't miss the significance of this last point. Lush is saying that if there are multiple lines of animals linebred to a common ancestor, the breeder can manage inbreeding by using those groups as a source of animals for outcrossing while still maintaining the strong genetic influence of the ancestor. And because these groups of animals have not been interbreeding, they can be used to produce offspring that will have a lower rather higher inbreeding coefficient, and thus will benefit from hybrid vigor (a reduction in inbreeding depression) as well as a diminished risk of genetic disorders caused by recessive mutations. 

There are dangers to linebreeding, one of which is that if too intense it will result in fixation (homozygosity) of undesirable genes. Lush was very clear on the deleterious effects of inbreeding, which he called "inbreeding degeneration". He advises breeders to avoid all inbreeding that is not necessary for maintaining the relationship on the line bred animal so that the inbreeding intensity remains modest. Indeed, he points out that the gains to be made by linebreeding to a mediocre ancestor might not balance the loss of quality (his "degeneration") expected to result from inbreeding.

To linebreed successfully to a particular animal, it must have enough offspring so that linebreeding to its own descendants can be avoided. For a dog breeder to be able to do this, it might require keeping around more dogs than one breeder can accommodate, but a group of breeders with common goals can cooperate in breeding towards the same line and using each other's kennels for the occasional mild outcross.

Lush transformed the science of animal breeding over 70 years ago, and the revolution he started has stood the test of time. The advent of reproductive technologies and DNA analysis have changed the processes of breeding and selection considerably since his day, but his insights into genetics were sound and are still the basis of animal breeding to this day.

You can download a free pdf copy of Lush's classic book HERE.

By Carol Beuchat PhD

Animal breeders figured out a long time ago that inbreeding was a marvelous tool. Done carefully, it could mould an animal to suit the needs of the breeder, "fix" the desired traits, and make breeding more predictable. But despite these advantages, there were some significant disadvantages, and one of the most unfortunate was an increase in the number of genetic disorders.

Breeders know that they can use inbreeding to concentrate the genes for the traits they prefer and to increase the predictability of a breeding by reducing variation in the offspring. But breeders have no way to increase the good genes but not the bad ones through inbreeding. (There are ways this can be done, but not using inbreeding.)

But what about dogs that don't have any bad genes? You will hear people say that their lines are "healthy", or that a particular problem is "not in my lines". Can this be true?

It's for this reason that recessive mutations are more dangerous in a sense than dominant mutations. Dominant mutations have consequences; the problem might not be obvious, or it might only occur late in life, but by definition it will be expressed. If detected, these genes can be managed by removing the dog from the population before spreading it far and wide. Recessive mutations, on the other hand, are like a virus with a long incubation period such as measles. By the time people start turning up sick, they've been virulent for days already and leaving a trail of viruses everywhere they go that will infect the next unwitting generation of victims. Those new infectees will similarly pass the virus on before they have symptoms, and things can get out of hand pretty fast.

Recessive alleles are very similar. A dog with one copy is fine, but it will pass a copy to half of its offspring - who will also be fine if they have only one copy. And they will make more new copies of the mutation that get passed to half of the next generation, and the dispersal continues. If it's a huge population of animals, and each of these carriers only has a few offspring, then in a randomly breeding population the chances that carriers might run into each other will be low. But if related dogs are being bred to each other, then they will share some genes, and the more closely related they are the greater the overlap. The most efficient way to produce puppies that will be homozygous for a recessive allele is by breeding closely related dogs. In a population of registered, purebred dogs, ALL the dogs are related if you go back far enough, and the more recent ancestry they share, the more genes - good and bad - they will have in common.

So genetic disorders are a predictable - even guaranteed - consequence of inbreeding in dogs, and in fact in any animal with two sexes. There is always a risk, and you can know that level of risk by calculating the inbreeding coefficient.

Okay, you say, I get it. But it's not like dogs have zillions of recessive mutations to worry about. In fact, they do - maybe not zillions, but certainly hundreds. In fact, there are FAR more recessive mutations lying in wait than dominant mutations. The OMIA website lists the disorders in dogs and also reports mode of inheritance if it is known. (Note that you don't need to know what the actual defect is to know mode of inheritance, because you can determine this from the pattern of inheritance among a group of related animals in a pedigree.)

Why are there so many more disorders caused by recessive mutations than dominant or x-linked ones? Three reasons:

   1) recessive mutations can accumulate in an animal's genes because they can be inherited without detriment;

   2) recessive mutations are not selected against unless they are expressed; and

   3) inbreeding increases homozygosity, which increases the expression of recessive mutations.

Breeders can't do anything about reason #1, and they can't do much about #2. But reason #3 is the reason why the other two reasons matter - 

- Inbreeding increases the expression of recessive mutations because it increases homozygosity.

Expressed another way -

- A high incidence of genetic disorders is a predictable consequence of inbreeding.

In several places on the ICB website there is information about genetic disorders that occur in different breeds of dogs. But the relevant question for our discussion here is how many of these disorders are caused by genes that are recessive?

Here's the (current) list of about 160 disorders caused by recessive genes from OMIA:

• Achromatopsia (cone degeneration, hemeralopia), AMAL
  
• Achromatopsia (cone degeneration, hemeralopia), GSPT
  
• Acrodermatitis enteropathica
  
• Alopecia, colour mutant
  
• Amelogenesis imperfecta
  
• Ataxia, cerebellar
  
• Ataxia, cerebellar, in Old English Sheepdogs and Gordon Setters
  
• Ataxia, cerebellar, Malinois
  
• Ataxia, cerebellar, progressive early-onset
  
• Ataxia, spinocerebellar
  
• Black hair follicle dysplasia
  
• Bleeding disorder due to P2RY12 defect
  
• Brachydactyly
  
• C3 deficiency
  
• Cardiomyopathy, dilated
  
• Cataract, early onset
  
• Cerebellar abiotrophy
  
• Cerebellar cortical atrophy
  
• Cerebellar hypoplasia
  
• Cerebellar hypoplasia, VLDLR-associated
  
• Chondrodysplasia, disproportionate short-limbed
  
• Chondrodysplasia, Labrador
  
• Ciliary dyskinesia, primary
  
• Cleft lip and palate
  
• Cleft palate 1
  
• Coat colour, albinism, oculocutaneous type IV
  
• Coat colour, saddle tan vs black-and-tan
  
• Collie eye anomaly
  
• Coloboma
  
• Cone-rod dystrophy 1
  
• Cone-rod dystrophy 2
  
• Cone-rod dystrophy 3
  
• Cone-rod dystrophy 4
  
• Cone-rod dystrophy, Standard Wire-haired Dachshund
  
• Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis
  
• Craniomandibular osteopathy
  
• Cricopharyngeal dysfunction
  
• Cystinuria, type I - A
  
• Deficiency of cytosolic arylamine N-acetylation
  
• Degenerative myelopathy
  
• Dwarfism, hypochondroplastic
  
• Dwarfism, pituitary
  
• Early retinal degeneration
  
• Ectodermal dysplasia/skin fragility syndrome
  
• Encephalomyelopathy and polyneuropathy
  
• Epidermolysis bullosa, dystrophic
  
• Epidermolysis bullosa, junctionalis, LAMA3
  
• Epilepsy
  
• Epilepsy, benign familial juvenile
  
• Episodic falling
  
• Exercise-induced collapse
  
• Exfoliative cutaneous lupus erythematosus
  
• Factor VII deficiency
  
• Fucosidosis, alpha
  
• Gangliosidosis, GM1
  
• Gangliosidosis, GM2, generic
  
• Gangliosidosis, GM2, GM2A deficiency
  
• Gangliosidosis, GM2, type I (B variant)
  
• Gangliosidosis, GM2, type II (Sandoff or variant 0)
  
• Generalized PRA
  
• Glaucoma, primary open angle
  
• Glomerulonephropathy
  
• Glossopharyngeal defect
• Gluten-sensitive enteropathy
  
• Glycogen storage disease Ia
  
• Glycogen storage disease IIIa
  
• Glycogen storage disease VII
  
• Golden Retriever PRA 1
  
• Goniodysplasia, mesodermal
  
• Hyperekplexia (Startle disease)
  
• Hyperkeratosis, epidermolytic
  
• Hyperkeratosis, palmoplantar
  
• Hypomyelination of the central nervous system
  
• Hypothyroidism
  
• Ichthyosis
  
• Ichthyosis, Golden Retriever
  
• Intestinal cobalamin malabsorption due to AMN mutation
  
• Intestinal cobalamin malabsorption due to CUBN mutation
  
• Kartagener syndrome
  
• Krabbe disease
  
• L-2-hydroxyglutaricacidemia
  
• Leber congenital amaurosis (congenital stationary night blindness)
  
• Lens luxation
  
• Leukocyte adhesion deficiency, type I
  
• Leukocyte adhesion deficiency, type III
  
• Leukoencephalomyelopathy
  
• Malignant hyperthermia
  
• Mucopolysaccharidosis I
  
• Mucopolysaccharidosis IIIA
  
• Mucopolysaccharidosis IIIB
  
• Mucopolysaccharidosis VI
  
• Mucopolysaccharidosis VII
  
• Multidrug resistance 1
  
• Multifocal retinopathy 1
  
• Multifocal retinopathy 2
  
• Multifocal retinopathy 3
  
• Multiple system degeneration
  
• Musladin-Lueke syndrome
  
• Myasthenic syndrome, congenital
  
• Myasthenic syndrome, congenital, Labrador Retriever
  
• Myoclonus epilepsy of Lafora
  
• Myopathy, centronuclear
  
• Myopathy, Great Dane
  
• Myotonia
  
• Narcolepsy
  
• Nasal parakeratosis
  
• Neonatal encephalopathy with seizures
  
• Nephritis, autosomal recessive
  
• Nephropathy
  
• Neuroaxonal dystrophy
  
• Neurological syndrome
• Neuronal ceroid lipofuscinosis, 1
  
• Neuronal ceroid lipofuscinosis, 10
  
• Neuronal ceroid lipofuscinosis, 12
  
• Neuronal ceroid lipofuscinosis, 2
  
• Neuronal ceroid lipofuscinosis, 4A
  
• Neuronal ceroid lipofuscinosis, 5
  
• Neuronal ceroid lipofuscinosis, 6
  
• Neuronal ceroid lipofuscinosis, 8
  
• Neutropenia, cyclic
  
• Oculoskeletal dysplasia 1
  
• Oculoskeletal dysplasia 2
  
• Osteochondrodysplasia
  
• Osteogenesis imperfecta_Dachshund
  
• Persistent Mullerian duct syndrome
  
• Photoreceptor dysplasia
  
• Platelet receptor for factor X, deficiency of
  
• Polyneuropathy
  
• Prekallikrein deficiency
  
• Primary hyperoxaluria type I (Oxalosis I)
  
• Progressive retinal atrophy
  
• Progressive retinal atrophy type 3, Tibetan Spaniel and Tibetan Terrier
  
• Progressive retinal atrophy, Basenji
  
• Progressive rod-cone degeneration
  
• Pyruvate dehydrogenase deficiency
  
• Pyruvate kinase deficiency of erythrocyte
  
• Retinal dysplasia and persistent primary vitreous
  
• Rod dysplasia
  
• Rod-cone dysplasia 1
  
• Rod-cone dysplasia 1a
  
• Rod-cone dysplasia 2
  
• Rod-cone dysplasia 3
  
• Rod-cone dysplasia 4
  
• Severe combined immunodeficiency disease, autosomal
  
• Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive
  
• Skeletal dysplasia 2 (SD2)
  
• Spinal dysraphism
  
• Spondylocostal dysostosis, autosomal recessive
  
• Subaortic stenosis
  
• Thrombocytopaenia
  
• Thrombopathia
  
• Trapped Neutrophil Syndrome
  
• Tricuspid valve dysplasia
  
• Urolithiasis
  
• Vitamin D-deficiency rickets, type II
  
• Wilson disease
  
• XX testicular DSD (Disorder of Sexual Development)

That's a lot of genetic disorders to dodge. [Note that OMIA lists not only disorders but traits, which can be benign (coat color) or even breed features (brachycephaly). I tried to weed all of these out, but please don't throw me and my list under the bus if I missed one.]

Many of these disorders might not occur in your breed. But if one of them has EVER occurred in your breed, then the mutation is in your breed too. Unfortunately, this is a depressingly long list and it grows longer every month, so we know (and can expect) that there are many more that we don't know about yet. 

If you're a breeder, you might be thinking about now that that breeding is a genetic crap shoot and that producing healthy dogs is a hopeless mission. But it's not.

Your dogs will never be afflicted with any of these disorders as long as none inherits two copies of the responsible gene. Controlling these genetic disorders is conceptually simple:

You have a terrific tool available - the coefficient of inbreeding - that can tell you about the predicted level of homozygosity in a dog. You can use this information to balance the risks of inbreeding with the benefits. 

The coefficient of inbreeding is equal to the risk of inheriting two copies of the same mutation from an ancestor on both sides of the pedigree.

If the COI is 10%, then the risk of producing one of these disorders if the gene is in your breed is 10%. If the COI is 25%, then the risk is 25%. It's simple. You can even choose the level of risk you're willing to take.

You CAN manage the risk of genetic disorders in dogs. All you need is a pedigree database and some software that calculates the coefficient of inbreeding. The only reason dogs are afflicted with disorders caused by recessive mutations is because people are taking that risk and losing the bet.

By Carol Beuchat PhD

If you're interested in this topic, the first thing you should do is scroll down and download a copy of the review paper by Farrell and colleagues about the management of heritable genetic diseases in dogs (links below). And after you're done here, you should sit down and read it. All of it.

In the downloadable supplementary materials of the paper by Farrell and colleagues, there is a table with information about the number of identified disorders in more than 200 breeds of dogs, as well as the number of available tests. I've generated some graphs from these data, which I've split into breeds with more than 20 disorders (top) and breeds with fewer (bottom). The graphs are large and might be difficult to read here, so you can download copies to view at a larger size. I also provide a link to download a copy of the table on which they are based below.

One problem with these data is that, as the authors point out in the supplementary table, it "is
not an exhaustive list of all inherited disorders in pedigree dogs". In fact, the comprehensive online database of disorders in animals (OMIA, Online Mendelian Inheritance in Animals) lists 651 "traits and disorders" (as of 7 March 2015). To be fair, this includes some normal traits like coat color and genes for breed features like brachycephaly. But certainly the majority are veterinary disorders.

Perhaps a better indicator is the list in OMIA of "Mendelian trait / disorder, key mutation known"; i.e., there is a known gene associated with the trait. For this there are 188 listed, and even discounting a dozen or two as non-disease traits (like coat color), the list is still half again longer than the one used in the Farrell et al. study. Notably, it includes 16 types of progressive retinal atrophy, 26 different lysosomal storage diseases, and 23 heart disorders; those alone amount to 65.

Of course, because the OMIA database is comprehensive, many of the disorders listed are probably very rare. There really isn't any way to know what fraction of the dogs in a particular breed are diagnosed with any of these illnesses in their lifetime, so a list of hundreds of disorders that occur with trivial frequency isn't an accurate reflection of the prevalence of genetic disorders in general. On the other hand, most of the disorders on the Farrell et al. list are familiar to me, so they would not be from incidence reports of only a handful of dogs. Getting better data will require more comprehensive reporting and record-keeping than is regularly done in most countries, although some of the Scandinavian countries are keeping excellent records that might be useful for better analyses.

DNA tests are becoming less expensive, but they nevertheless can run into hundreds of dollars per dog in many breeds for just the relatively few ones available. Veterinary diagnostics can be much more expensive (e.g., hip radiographs, blood tests, holter monitors). Responsible breeders are diligent about taking advantage of available tests, but you have to wonder about the potential size of the bill if we had tests for even half the disorders in most breeds. There is clearly the possibility that the cost of testing could become prohibitive and breeders would be faced with some very difficult choices.

Perhaps most worrisome about these data is what they reveal about our notion of the "health tested" dog. Dogs are often advertised as health tested, but given the size of the gap between the number of known disorders and the number of available tests, this is clearly quite misleading. Breeders might wish for more DNA tests, but if each one potentially limits breeding options, at some point they will find themselves facing a genetic minefield across which it is impossible to find a clear path. 

The genes for all of these genetic disorders are already out there; they have already affected some animal, which is how we know about them. If they are not now causing a noticeable problem, it is because they are rare, and they will not become a problem if they continue to stay rare. Testing for the (few) mutations we already have tests for does nothing to protect against the risk of some other mutation becoming a problem, and in fact DNA testing as it is widely used today might be reducing the number of affected animals for a known disorder but increasing the risk of producing animals afflicted with one caused by these known but rare mutations (as explained here). Every puppy contains copies of the mutations of its parents. Producing many puppies with the same mutations will cause rare mutations to become common, and some "new" genetic disorder will make an appearance in a breed when the frequency becomes high enough. Even if we had all the necessary DNA tests, they will never eliminate genetic disorders in dogs. There are hundreds of mutations we know about for which we have no test, and even more that we don't yet even know exist. 

Farrell et al. make this key point:

"Doing a genetic test and subsequently eliminating an individual from the breeding population may not be the best strategy, as by targeting a particular allele at one genetic locus for removal from the gene pool of a particular breed, breeders may in fact increase allele frequencies of genetic variants on alternative haplotypes at the same, or a different locus, that are recessively deleterious. In addition, by eliminating some animals from breeding, a reduction in the effective population size will occur, thus risking higher levels of inbreeding, potential founder effects and genetic bottlenecks. in essence, by correcting one problem there is a chance of inadvertently creating a new one."

The game of genetic whack-a-mole could potentially go on forever.

If inappropriate breeding strategies like overuse of popular sires, inbreeding, and strong selection for particular traits is at the root of the problem, then the first and most useful step we can take is to stop doing those things. Since genetic disorders will be rare if the genes that cause them are rare, the most efficient way of managing genetic disorders in dogs should be adoption of the appropriate breeding strategies to accomplish this. We have not been doing this very well.

A "health tested" puppy with a coefficient of inbreeding of 30% is an oxymoron. Preventing the 25% risk of a known disorder, then breeding with a 30% risk of risk of producing a new one, is not a responsible breeding strategy, and certainly not the road to better canine health. Breeders should avail themselves of DNA tests, tools like estimated breeding values that will improve assessment of genetic risk, and be more open and honest about reporting genetic problems. 

But none of these things will prevent or even reduce the overall level of genetic disorders unless breeders also adopt sensible, sustainable breeding strategies that keep the problematic mutations rare in the population and avoid the inbreeding that will bring two together in the same animal.

In the table, there are 47 breeds listed that have more than 20 identified genetic disorders, and 12 of these have 50 or more (in red). The German Shepherd tops the list with 77, and the Boxer is not far behind with 63. I have also plotted the number of tests available for each breed, which includes DNA and other diagnostic procedures (in blue). There is a clear gap in almost all breeds between the number of disorders and the tools to diagnose them. For the German Shepherd, there are tests for only 14% (11) of the known disorders, and for the boxer only 6% (4). Gaps of these magnitudes apply to most breeds. (You will see a few breeds for which the number of available tests is greater than the number of disorders. My guess is that these are tests that are expected to be appropriate for any breed.)

OMIA: Mendelian genetic disorders dogs, key mutation know (as on 7 March 2015)
(Total = 188)

Achromatopsia (cone degeneration, hemeralopia), AMAL
Achromatopsia (cone degeneration, hemeralopia), GSPT
ACTH-independent adrenal Cushing syndrome, somatic
Alopecia, colour mutant
Amelogenesis imperfecta
Anhidrotic ectodermal dysplasia
Arrhythmogenic right ventricular cardiomyopathy
Ataxia, cerebellar
Ataxia, cerebellar, in Old English Sheepdogs and Gordon Setters
Ataxia, cerebellar, progressive early-onset
Ataxia, spinocerebellar
Autosomal dominant PRA
Black hair follicle dysplasia
Bleeding disorder due to P2RY12 defect
Brachycephaly
C3 deficiency
Cardiomyopathy, dilated
Cataract, early onset
Cerebellar abiotrophy
Cerebellar hypoplasia, VLDLR-associated
Chondrodysplasia
Chondrodysplasia, disproportionate short-limbed
Ciliary dyskinesia, primary
Cleft palate 1
Coat colour, agouti
Coat colour, albinism, oculocutaneous type IV
Coat colour, brown
Coat colour, dominant black
Coat colour, extension
Coat colour, grizzle
Coat colour, harlequin
Coat colour, melanistic mask
Coat colour, merle
Coat colour, saddle tan vs black-and-tan
Coat colour, white spotting
Coat colour, white spotting, due to KIT
Collie eye anomaly
Colorectal hamartomatous polyposis and ganglioneuromatosis
Cone-rod dystrophy 1
Cone-rod dystrophy 2
Cone-rod dystrophy 3
Cone-rod dystrophy 4
Cone-rod dystrophy, Standard Wire-haired Dachshund
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis
Craniomandibular osteopathy
Curly coat
Cystinuria, type I - A
Cystinuria, type II - A
Cystinuria, type II - B
Deficiency of cytosolic arylamine N-acetylation
Degenerative myelopathy
Dermoid sinus
Dwarfism, pituitary
Early retinal degeneration
Ectodermal dysplasia
Ectodermal dysplasia/skin fragility syndrome
Elliptocytosis
Epidermolysis bullosa, dystrophic
Epidermolysis bullosa, junctionalis, LAMA3
Epilepsy, benign familial juvenile
Episodic falling
Exercise-induced collapse
Factor VII deficiency
Factor XI deficiency
Fanconi syndrome
Fucosidosis, alpha
Furnishings (moustache and eyebrows)
Gallbladder mucoceles
Gangliosidosis, GM1
Gangliosidosis, GM2, type I (B variant)
Gangliosidosis, GM2, type II (Sandoff or variant 0)
Gastrointestinal stromal tumor
Generalized PRA
Glaucoma, primary open angle
Glycogen storage disease Ia
Glycogen storage disease II
Glycogen storage disease IIIa
Glycogen storage disease VII
Golden Retriever PRA 1
Haemophilia A
Haemophilia B
Hair length
Hyperekplexia (Startle disease)
Hyperkeratosis, epidermolytic
Hyperkeratosis, palmoplantar
Hyperparathyroidism
Hypocatalasia
Hypomyelination of the central nervous system
Hypothyroidism
Ichthyosis
Ichthyosis, Golden Retriever
Improper coat
Intestinal cobalamin malabsorption due to AMN mutation
Intestinal cobalamin malabsorption due to CUBN mutation
Krabbe disease
L-2-hydroxyglutaricacidemia
Leber congenital amaurosis (congenital stationary night blindness)
Lens luxation
Leucodystrophy
Leukemia, chronic monocytic
IA 000595-9615 Leukocyte adhesion deficiency, type I
Leukocyte adhesion deficiency, type III
Malignant hyperthermia
May-Hegglin anomaly
Metabolizer of a cognitive enhancer
Mucopolysaccharidosis I
Mucopolysaccharidosis IIIA
Mucopolysaccharidosis IIIB
Mucopolysaccharidosis VI
Mucopolysaccharidosis VII
Multidrug resistance 1
Multifocal retinopathy 1
Multifocal retinopathy 2
Multifocal retinopathy 3
Muscular dystrophy, Duchenne type
Muscular hypertrophy (double muscling)
Musladin-Lueke syndrome
Myasthenic syndrome, congenital
Myasthenic syndrome, congenital, Labrador Retriever
Myoclonus epilepsy of Lafora
Myopathy, centronuclear
Myopathy, Great Dane
Myotonia
Myotubular myopathy 1
Narcolepsy
Nasal parakeratosis
Necrotising encephalopathy, subacute, of Leigh
Neonatal encephalopathy with seizures
Nephritis, X-linked
Nephropathy
Neuroaxonal dystrophy
Neuronal ceroid lipofuscinosis, 1
Neuronal ceroid lipofuscinosis, 10
Neuronal ceroid lipofuscinosis, 12
Neuronal ceroid lipofuscinosis, 2
Neuronal ceroid lipofuscinosis, 4A
Neuronal ceroid lipofuscinosis, 5
Neuronal ceroid lipofuscinosis, 6
Neuronal ceroid lipofuscinosis, 8
Neutropenia, cyclic
Oculoskeletal dysplasia 1
Oculoskeletal dysplasia 2
Osteochondrodysplasia
Osteogenesis imperfecta
Osteogenesis imperfecta_Dachshund
Pancreatitis, hereditary
Periodic Fever Syndrome
Persistent Mullerian duct syndrome
Polycystic kidney disease
Polycythemia
MIA 001917-9615 Polyneuropathy (LPN1)
Prekallikrein deficiency
Primary hyperoxaluria type I (Oxalosis I)
Progressive retinal atrophy
Progressive retinal atrophy type 3, Tibetan Spaniel and Tibetan Terrier
Progressive retinal atrophy, Basenji
Progressive rod-cone degeneration
Pyruvate dehydrogenase deficiency
Pyruvate kinase deficiency of erythrocyte
Renal cystadenocarcinoma and nodular dermatofibrosis
Rod-cone dysplasia 1
Rod-cone dysplasia 1a
Rod-cone dysplasia 2
Rod-cone dysplasia 3
Rod-cone dysplasia 4
Sensory ataxic neuropathy
Severe combined immunodeficiency disease, autosomal
Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive
Severe combined immunodeficiency disease, X-linked
Skeletal dysplasia 2 (SD2)
Spinal dysraphism
Spondylocostal dysostosis, autosomal recessive
Squamous cell carcinoma of the digit
Tail, short
Thrombasthenia
Thrombocytopaenia
Thrombopathia
Trapped Neutrophil Syndrome
Tremor, X-linked
Urolithiasis
Vitamin D-deficiency rickets, type II
Von Willebrand disease I
Von Willebrand disease II
Von Willebrand disease III
Wilson disease
X-linked PRA 1
X-linked PRA 2

List of Disorders in Farrell et al 2015
(Total = 114)

 AMP, Alaskan Malamute polyneuropathy
 ARVC, arrhythmogenic right ventricular cardiomyopathy
 BAER, deafness
 BHFD, black hair follicular dysplasia
 BNA, Bandera's neonatal ataxia
 BTPKD, Bull Terrier polycystic kidney disease
 CA, cerebellar ataxia
 CC/DE, curlycoat/dryeye
 CCN, canine cyclic neutropenia
 CD, cone degeneration
 CEA/CH, collie eye anomally/ choroidal hypoplasia
 CH, congenital hypothyreosis/hypothyroidism
 CL, ceroid lipofuscinosis
 CLAD, canine leucocyte adhesion deficiency
 CM, cobalamin malabsorption
 CM/SM, Chiari malformation/syringomyelia scheme
 CMHM, BVA/KC CMSM Scheme
 CNM, centronuclear myopathy
 COMMD1, Copper toxicosis
 cord1-PRA, progressive retinal atrophy-cone and rod deterioration-1
 cord2-PRA, progressive retinal atrophy-cone and rod deterioration-2
 crd3-PRA, progressive retinal atrophy-cone and rod dystropy-3
 CSNB, congenital stationary night blindness
 CU, cystinuria
 DCM, dilated cardiomyopathy
 DFM, dwarfism
 DM, degenerative myelopathy
 ED, ectodermal dysplasia
 EDS, BVA/KC Elbow Dysplasia Scheme
 EF, episodic falling
 EIC, exercise induced collapse
 ES, BVA/KC/ISDS Eye Scheme (including annual eye testing)
 FN, familial nephropathy
 FS, Fanconi syndrome
 Fuco, fucosidosis
 FVII, factor VII deficiency
 FVXI, factor XI deficiency
 GCL, globoid cell leukodystrophy
 GM1, gangliosidosis
 GN, Greyhound neuropathy
 GSD, glycogenesis type IIIa
 GSDI, glycogen storage disease type I (Pompe's disease)
 GT, Glanzmann's thronbasthenia type1
 HAVIII, Haemophilia A (factor VIII deficiency)
 HBIXl, Haemophilia B (factor IX deficiency)
 HC-HSF4, hereditary cataracts
 HDS, BVA/KC Hip Dysplasia Scheme
 HN, hereditary nephritis
 HNM, hereditary necrotising myelopathy
 HNP, hereditary nasal parakeratosis
 HUU, hyperuricosuria
 IC, improper coat
 ICT-A, ichthyosis
 IRIDA, iron refractory iron deficiency anemia
 JE, juvenile epilepsy
 JEB, junctional epidermolysis bullosa
 L-2HGA, L-2-hydroxyglutaric aciduria
 LD, Lafora's disease
 LOA, late onset ataxia
 LPN1, Leonberger polyneuropathy
 MD, muscular dystrophy
 MDR1, multiple drug sensitivity/resistance
 MLS, Musladin-Leuke syndrome
 MPS, mucopolysaccharidosis type VI
 MPSIIIA, mucopolysaccharidosis type IIIA
 MPSIIIB, mucopolysaccharidosis type IIIB
 MPSVII, mucopolysaccharidosis type VII
 MYO, myotonia congenital
 N/A, No information currently avaliable for this breed
 NCCD, neonatal cerebellar cortical degeneration
 NCL, neuronal ceroid lipofuscinosis
 NE, neonatal encephalopathy
 NHPH4, progressive retinal atrophy CRD
 NPY, narcolepsy
 NTPL1, bitches < 2 yrs not to produce a litter
 NTPL2, bitches not to produce > 1 litter in a 12-month period
 NTPL3, bitches not to produce > 3 litters in a lifetime
 NTPL4, bitches not to produce > 4 litters in a lifetime
 NTPL5, bitches not to produce > 5 litters in a lifetime
 OI, osteogenesis imperfecta
 OSD, retinal/ocularskeletal dysplasia
 PCD, primary ciliary dyskinesia
 pcrd-PRA, progressive rod cone degeneration -progressive retinal atrophy
 PDE, Pug dog encephalitis
 PDP-1, pyruvate dehydrogenase phosphate 1 deficiency
 PFK, phosphofructokinase deficiency
 PH, primary hyperoxaluria
 PHPT, primary hyperparathyroidism
 PHPV, persistent hyperplastic primary vitreous
 PKD, pyruvate kinase deficiency
 PLL, primary lens luxation
 PLN, protein losing nephropathy
 POAG, primary open angle glaucoma
 PRA-D, progressive retinal atrophy-dominant
 PRA, progressive retinal atrophy
 rcd1-PRA, progressive retinal atrophy-rod-cone degeneration-1
 rcd2-PRA, progressive retinal atrophy-rod-cone degeneration-2
 rcd3-PRA, progressive retinal atrophy-rod-cone degeneration-3
 rcd4-PRA, progressive retinal atrophyrod-cone degeneration-4
 RCND, renal cystadenocarcinoma nodular dermatofibrosis
 SAN, sensory ataxic neuropathy
 SAT, sebaceous adenitis testing
 SCA, spinocerebellar ataxia
 SCID, X-linked severe combined immunodeficiency
 SD, Startle disease
 TNS, trapped neutrophil syndrome
 TPA, thrombopathia
 vWD, von Willebrand disease (types 1, 2, 3)
 XL-PRA, X-linked progressive retinal atrophy.
 AF, anal furunculosis
 CMR, canine multifocal retinopathy
 GSDII, glycogen storage disease type II (Pompe's disease)
 VDD, vitamin D deficiency (Rickets) type 2