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1/1/2030

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.

Health of Mixed breed vs Purebred dogs: what the study by Forsyth et al got wrong

7/3/2024

Fueled by concerns about the health of purebred dogs, and supported by the growing list of mutations known to cause genetic disease, there has been much discussion about whether purebred dogs are predisposed to health issues compared to dogs that are not purebred.

The latest addition to the discussion (Forsyth et al 2023) is a study coming out of the Dog Aging Project, which took advantage of a large database (27.5k dogs) including both mixed and purebred dogs with extensive information about the health and welfare of each individual.

The project summary states that "purebred dogs...did not show higher lifetime prealence of medical conditions compared to mixed breed dogs". Furthermore, "a higher proportion of purebred dogs than mixed-breed dogs had no owner-reported medical conditions".

In the purebred dog community, this was hailed as a decisive nail in the coffin of the "myth" that mixed breed dogs are healthier than purebreds. There was what I would characterize as glee in what they saw as confirmation of what most breeders have long asserted, despite warnings from the scientific community (and some smaller groups of breeders) that inbreeding is detrimental to health in dogs, just as it is in humans and other animals.

I was very interested in this paper, given that the information available to date supports the notion that inbreeding is detrimental to health. This study seems to present information that flies in the face of the expectations about dog health that come from an understanding of the genetics of animal breeding. So I gave it a careful review.

Motivation of the study
The authors recognize that inbreeding in purebred dogs increases the risk of expressing genetic disorders produced by recessive mutations. This leads to the expectation that purebred dogs are more likely to be afflicted by genetic disorders than mixed breed dogs. However, they note that this is not always the case, and that "simpy being purebred may not necessarily be associated with increased disorder prevalence overall" (Forsyth et al 2023).

From this, they describe a study with goals to "estimate the lifetime prevalence of medical conditions among US dogs", and to "determine whether purebred dogs have a higher lifetime prevalence of specific medical conditions compared to mixed-breed dogs".

What does "mixed breed" mean?
First of all, we must address the groups the study seeks to compare. "Purebred" dogs by definition can trace their ancestry back to a specific number of "founders". But a dog that is "not purebred" might be any of a diverse array of identifiable supopulations of dogs that we might expect to differ in general health. Among these would be "mixed breed dogs" with multiple identifiable breeds in their ancestry, crossbreed dogs that are the result of crossing two purebred dogs, dogs of identifiable type that were developed and remain outside a restrictive breeding program (e.g., the many livestock guarding breeds that are typical of a particular geographic region and have recognizable type), which might be described as land race, and pariah dogs, the so-called "village dog". The categories are not discrete or even universally recognized as useful subgroupings of dogs, but we need to address them in passing because most of the studies addressing the health of mixed breed vs purebreed dogs do not define what is specifically meant by "mixed breed", and we should expect that the genetic background of these individuals is likely to matter.

What is a "medical condition"?
The data for "medical condition" used in the study were not based on veterinary diagnosis. Rather, they used what they termed "ORMC", owner-reported medical condition. This could include whatever the owner considered a "medical condition". The authors report that "For purposes of the study reported here, we do not attempt to refine, combine or otherwise modify participant responses, and present the data as reported by the participant", and within these they filtered the data to the top 10 most commonly reported ORMC (Forsyth et al 2023).

I have listed these issues identified as "medical conditions" in this table (from Forsyth et al, Table 2). A quick scan down the list shows that there was a broad scope to the conditions listed by owners. They include things like fleas, patellar luxation, cataracts, urinary tract infection, broken toenail, corneal ulcer, kidney disease, lameness, seizures, and chocolate toxicity. You can see that this lists includes bacterial infections, parasites, injuries, organ failure, and neurological disorders, among others. This is a list of the array of potential reasons you might take your dog to the vet for some sort of diagnosis or treatment.

Now, if you remember the motivation of the study (above), it was whether it is true that purebred dogs are more likely than mixed breeds to suffer from a genetic disorder caused by inheritance of two copies of a recessive mutation.

A proper test of this would look specifically at disorders caused by recessive mutations. But looking at the list, there is no reason a priori to expect that a purebred dog is more or less likely to have a broken toenail or to have ingested chocolate than a mixed breed dog. By not restricting the list of disorders to those caused by recessive mutations, this study cannot tell us anything about the relative risks to purebred vs mixed breed dogs of suffering from a genetic disorder caused by a recessive mutation.

Many of the "medical conditions" on their list more appropriately fall under the description of "husbandry" issues, and more broadly described as "things that happen to dogs."

Somebody might want to ask if purebred dogs receive better care than mixed breed dogs, or if purebred owners are more likely to participate in a study or respond to a lengthy questionnaire.

But the central question - are mixed breed dogs healthier than purebreds - remains an important one. Indeed, it critical to the defense of breeding within a closed gene pool, and justifying the high levels of inbreeding that result.

So here's the deal. We understand the science, so we understand why mixed breed dogs should be healthier than purebreds - if we consider disorders caused by single recessive mutations. (Read more about this HERE). Indeed, this science is the reason that most available DNA tests are for disorders caused by single recessive mutations. The science tells us why these things are true. If it happened that purebred dogs were LESS likely than mixed breed dogs to suffer from genetic disorders, then we would have to conclude that we don't have the science right, and there would be lots of scrutiny to figure out why we're wrong.

But all indications are that we DO have the science right. If somebody is trying to claim that purebred dogs are just as "healthy" as mixed breed dogs, you can know for a fact that they are not referring to recessive genetic disorders, or they are ignorant of the science.

REFERENCES

Forsyth et al., 2023. Lifetime prevalence of owner-reported medical conditions in the 25 most common dog breeds in the Dog Aging Project pack. Frontiers in Veterinary Science 10: 1140417. DOI
10.3389/fvets.2023.1140417

BREEDER MYTH- Crossbreeding will produce the disorders of both breeds in the puppies

6/16/2024

By Carol Beuchat PhD

In any discussion about crossbreeding (mating two different breeds), somebody will surely claim that the offspring will be afflicted with the diseases of both breeds, or at the very least new mutations hiding in the gene pool will wreak havoc in future generations.

Is this true?

Since breeding is all about genetics, let's see what science can tell us about this.

First, dominant mutations are expressed with only one copy of the mutation, so if either parent is afflicted you should be able to avoid using those dogs.

The tricky mutations are recessive. If a dog only has one copy, it is silent. But if a dog gets two copies, then it can't have any copies of the normal gene. Whatever protein that gene was supposed to code for won't be produced, and whatever the protein was supposed to do won't happen, so that dog will have a genetic disorder.

It turns out that 70% or more of the known genetic disorders in dogs are caused by recessive mutations, so the problem is that the particular gene is homozygous for the mutant, non-functional allele. When you breed within the closed gene pool of a purebred dog breed, all of the dogs are necessarily related, so they will share at least some alleles. More closely related dogs will have more alleles in common, and some of those will be recessive mutations that can produce a disorder. The best way to avoid producing dogs that are affected by a disorder caused by a recessive mutation is to avoid breeding dogs that are likely to have the same ones; that is, mating related dogs is risky, and the more closely related, the greater the risk. This is why inbreeding produces genetic disease, not just in dogs, but in all plants and animals.

The best way to reduce the risk of genetic disorders caused by recessive mutations is to avoid breeding related dogs, which is a problem in a closed gene pool where everybody is related. Because purebred breeds have been bred within a closed gene pool for many generations, the dogs within a breed will share many mutations, but the dogs in different breeds will not. If you are crossing Breed A with Breed B, and the breeds are not closely related (e.g, Wire and Smooth Dachshunds, English and American Cockers), then the risk of producing a disease in the puppies caused by a recessive mutation will be equal to the kinship coefficient of the pair of dogs, which tells you how genetically similar they are. (The coefficient of inbreeding of a dog is the kinship coefficient of its parents.)

So, if a breed cross will produce pups with predicted genomic COI of 2%, then the risk of producing puppies with two copies of the same recessive mutation is 2% - extremely low. As far as genetic disease goes, a breed cross has a very low risk. And because you understand the genetics of dominant and recessive alleles, you know that the risk of the introduced mutations causing a genetic disorder somewhere down the line will stay very low as long as the mutation is rare in the population, AND you avoid breeding to closely related dogs.

So, introducing new recessive mutations to a breed from crossbreeding won't be a problem unless you break both of Mother Nature's Breeding Rules:

1) Don't make a bunch of copies of a mutation and spread it throughout the gene pool. (Popular sires, we're pointing at you).

2) Don't breed to your relatives.

Get those two things right, and crossbreeding isn't a problem.

In fact, think about this - it is far riskier to breed within a closed gene pool than to crossbreed to an unrelated breed. Some breeders will claim that they won't crossbreed because "they know what's in their lines". How could they if the "bad genes" are recessive and therefore silent? So, you can reject this claim out of hand because it is inconsistent with what we know about genetics.

If we stick to science, and ignore the arguments and excuses coming from hearts instead of heads, then crossing two breeds will not in fact produce a litter of puppies that is riddled with disease. You might not care for the conformation or other qualities of the puppies, but they will be spared the genetic disorders resulting from inbreeding that normally afflict the breed.

Next time you're at a party with your friends in the dog fancy, grab your favorite adult drink, and when there is a lull in the conversation, boldly claim that crossing two breeds is much less likely to produce genetic disorders in the puppies than inbreeding. Then just sit back, relax, and enjoy your drink.

It's Westminster time again! But still, there's an elephant in the room.

5/9/2024

By Carol Beuchat PhD

Once again, it's time for the yearly pilgrimage to New York for the prestigious Westminster Kennel Club dog show. The airports have an unusually high number of dogs relaxing in the waiting areas, tended to by owners and handlers that look after their every need. It's a big event attended by the elite in the US dog world, and it attracts a large public attendance as well as national television coverage.

Every year, this show predictably renews the debate about the health consequences of inbreeding in dogs. This year's contribution is an article in the New York Times by Alexandra Horowitz. It contains a useful summary of the inbreeding levels of various breeds in terms the average person can understand, like cousins or full siblings. There is also a quick quiz that asks you to identify the relative level of inbreeding in pairs of breeds. (There are probably some surprises here!)

But the meat of the article highlights again this year the consequences of inbreeding on dog anatomy, physiology, behavior, and - of course - health. The point is that, deliberately or not, we are sacrificing health and welfare for certain traits that we deem desirable, like head shape, fur type, and body size.

Horowitz correctly notes that the link between inbreeding and health is not a recent insight. Breeders have been aware of the tradeoffs between inbreeding and health for a century. Yet, many breeders stress a focus on health in their breeding program while inbreeding continues unabated, despite the clear and convincing evidence that inbreeding takes a toll on the health of dogs.

There is no shortage of information about genetic disorders in dogs (Google, of course), and quite a bit about what needs to be done to improve things. Yet here we are again this year, off to an event that celebrates the beauty and function of the purebred dog, and where we will avert our gaze from the genetic issues that slowly erode away the DNA coding that produces every individual of every breed.

I will be watching the WKC Kennel Club dog show this year, to enjoy the beauty and incredible diversity of this remarkable animal, the dog. But once again, I will worry about whether we will heed the warnings of the biologists and breeders of other domestic animals that, with every new generation, we are gambling with the future of a breed by putting short term gain before the obligation to breed in a way that protects the unique genetic package that defines the essence of each breed.

Genetic management of purebred dogs: what you need in your toolbox

3/29/2024

By Carol Beuchat PhD

Breeders want to produce puppies that are healthy, long-lived, and have the type and traits that define the phenotype and behavior of the breed. The main tool used to guide breeding decisions is the pedigree, which records the history of the dogs in the breed. This can be paired with health and trait information to select dogs for mating that are likely to produce the desired offspring.

This is how we have bred purebred dogs for more than 100 years. In the last decade, the development of DNA tests for specific genes has allowed breeders to "see" what they're doing, allowing selection of dogs that have specific genes for traits as well as those carrying deleterious mutations, taking some of the guesswork out breeding for phenotypic traits like coat characteristics (color, long or short, straight or curly, etc) or body size, as well as an ever-increasing list of mutations associated with diseases or disorders.

The ability to know the genotype of specific genes in the DNA of an individual dog represents a potentially huge advance in the ability of the breeder to improve the accuracy of selective breeding. Despite this, breeders still struggle with new genetic issues to manage that arise as a result of the unmasking of recessive mutations by inbreeding.

To control inbreeding and reduce this problem, breeders need good information about the genetic relatedness of individual dogs. They could get at this using a pedigree database, but few breeds have the complete pedigree information necessary because of missing data or errors. Because of this, the information about relatedness that would be enormously helpful in making breeding decisions is currently unavailable to breeders.

Addressing the pedigree problem should be at the top of the list of things breeders should do to improve the ability of breeders to control inbreeding and the expression of genetic disease.

Breeders are familiar with the standard 5 (or more) generation pedigree chart that shows ancestors of a specific dog. However, most breeders are not familiar with the treasure trove of information that can be extracted from a pedigree database. Here are some of the statistics about a breed that can be extracted from a pedigree database and which should be part of every breeder's toolbox for proper genetic management. These terms are "jargon" and likely unfamiliar to you - and they go by somewhat nerdy names - but fear not. Keep the definitions in front of you for reference, and look up definitions as necessary when you review the data for your breeds or others.

To make the best possible breeding decisions, breeders should have these tools in their tool box.

Effective number of founders (fe)
Most breeds go back to a small population of "founder dogs", those individuals that contributed to the allelic variation in the original population. The genes in these founders define the size of the original gene pool. However, some of this original diversity is lost over time due to genetic drift (random chance) and selection, so the current population's gene pool will be smaller.

To estimate the size of the current gene pool, we can compute the "effective number of founders" (fe). This is an estimate of the number of founders that would produce the current genetic diversity of the population if all contributed equally to subsequent generations. This is a measure of the fraction of the genes contributed by the founders that still remain in the population. Alternatively, it represents the fraction of the original genetic diversity of the breed that has been lost due to genetic drift or selection.

Founder genome equivalents (fg)
This is the number of hypothetical founder dogs that could produce the same genetic diversity of the current population if each founder contributed equally and there was no loss of founder alleles through genetic drift.

Effective number of ancestors (fa, fe/fa)
The statistics for the effective number of ancestors, fe, is the minimum number of ancestors - which can be founders or not - needed to explain the genetic diversity of the current population. If there have been no population bottlenecks, fa will equal fe. The number and severity of bottlenecks will be reflected in the ratio of fa and fe. If fe/fa is equal to one, the genetic diversity in the current population is the same as in the ancestors; that is, there has been no loss of genetic diversity due to a bottleneck. Most dog breeds have suffered population bottlenecks as a result of wars, disease, changes in the need for particular types of dogs (e.g., herding), or fluctuations in popularity. The higher the ratio fe/fa, the greater the magnitude of the genetic bottleneck.

Mean kinship (MK)
This is an index of the average degree of genetic similarity or relationship between an animal and other members of the population. An animal with many relatives in the population will have a high degree of genetic similarity to many animals, and its MK value will be high; an animal with few relatives will have a low MK. Animals with no relatives in a population have MK = 0%. Consequently, animals with lower values of MK are genetically more valuable in the population because they carry alleles that are uncommon or rare. Every time an animal is born or dies in the population, the MK of all of the animals change because alleles in the new animals become more common and those in the animals that die become less common. The coefficient of inbreeding of an animal is equal to the kinship of its parents; so the greater the genetic similarity between two animals, the greater the risk of inheriting two copies of the same allele.

Effective population size (Ne)
Effective population size is the size of an "ideal" population of animals that would have the same rate of inbreeding, or decrease in genetic diversity due to genetic drift, as the real population of interest. It is not the same as census size, which is the actual number of individuals in a population. Ne reflects the "genetic size" of the population in that it depends on the number of animals that are breeding, which will always be less than the census size of the population. The rate of inbreeding in a population increases as Ne get smaller, so it tells you about the "genetic behavior" of the population in terms of how fast inbreeding will increase in the future. For a sustainably breeding population, the value of Ne should be at least 100, and some recommend at least 500 (the rate of inbreeding will be slower with higher Ne).

Equivalent Complete generations (EqG)
This is an estimate of the completeness of the pedigree database you are using. Missing data will reduce EqG and result in underestimation of inbreeding calculated from a pedigree database. A more complete pedigree database will have a higher EqG.

These five statistics computed from a pedigree database should be available for every breed as the basic tools that can be used to offer insight into the present genetic status of your breed. The are fundamental to genetic management plans to control inbreeding (and therefore genetic disease) as well as mating strategies to protect genetic diversity. Instead of flipping through piles of printed pedigrees trying to estimate inbreeding and relatedness of individual dogs, these statistics provide quantitative information that can help you make the best possible breeding decisions.

Here are some examples of these statistics for a variety of breeds (from Mabunda et al 2022).

A quick look at these data can tell you about the genetic status of each breed. For example, the Finnish Spitz has the most complete pedigree database of these breeds (EqG = 10.88), so the statistics for this breed will be more reliable than for other breeds with lower EqG. The inbreeding coefficient (F) for the Finnish Spitz calculated from the pedigree data is 6.33%. As explained above, this is much lower than the inbreeding coefficient determined from DNA (F = 28.5; Bannasch et al 2021). The ratio of fe/fa (1.5) indicates a loss of some of the genetic diversity that was present in the founder population. The values of Ne range from 384 (Ca de Bestiar) to only 3.2 (Bouvier des Ardennes), and the value for Finnish Spitz is 75.53.

Ne can be increased by balancing the number of male and females used in breeding. Since fewer males are used than females in most breeds, the simple solution to low Ne is increasing the number of males used in the breeding program.

The data for these breeds can give you an idea of the genetic health of each breed. Some have small founder populations (e.g., fe = 3; based on the pedigree data), and only two populations have gene pools greater than 100 (fe = 117 and 205.5, for Border Collies in Hungary and Australia, respectively). Some breeds have dangerously low Ne (Bouvier des Ardennes), some have experienced a significant bottleneck (Border collie, Hungary), high inbreeding (36.45% and 44.7%, for Czech Spotted dog and Bouvier des Ardennes, respectively.

This information about a breed can give you a "heads up" spot check of a breed's genetic health. Having a large population size can be very misleading, but beyond the number of dogs and maybe an underestimate of the inbreeding coefficient, breeders do not have the basic information about the genetics of the population that is summarized here.

These statistics are essential tools that should be in the breeder's toolbox. Of course, every breed should have a good pedigree database, and if yours doesn't already this should be motivation to remedy this. If you do have a good pedigree database, these statistics can be computed for your current breed population, and refreshed to reveal the consequences of breeding decisions on genetic health.

If your breed does not have a good pedigree database, urge your fellow breeders to work on this. The database should be global and should go back as far as possible.

With a pedigree database in hand, I can generate the statistics I describe here to provide the first window into the current genetic status of your breed. If you are breeding for preservation and health, this information is essential.

REFERENCES

Bannasch et al 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.

Mabunda et al 2022 Evaluation of Genetic Diversity in Dog Breeds Using Pedigree and Molecular Analysis: A Review. Diversity 14:1054. https:// doi.org/10.3390/d14121054.

Does your breed need genetic rehabilitation? Here's where to start

3/17/2024

By Carol Beuchat PhD

I am often contacted by breeders that are concerned about inbreeding and loss of genetic diversity in their breed. They recognize that these things matter over both the short and long term, and that they affect the burden of genetic health issues in the breed. The question from the breeder is "What do we do about this?"

Invariably, they bring up the issue of what dogs they should cross to, either individuals in the breed, or other dogs that are completely unrelated (e.g., another breed, mixed breed, etc.)

Breeders always want to discuss this right from the start. But, for a genetic rehabilitation project, you need to identify the specific problems you need to solve before you make decisions about what to do. The "What do we do" questions will get answered after we first ask "What are the genetic problems that need to be solved?"

The first thing you need is information about the genetics of your breed. At the top of list will be information about the inbreeding and genetic diversity of the breed. You can determine these using either pedigree databases or DNA genotypes.

To make a decision about whether to analyze pedigrees or genotypes, you need to know what information each can produce. Both have limitations and advantages, and there are also considerations of cost and whether the information is even available.

When you get to this step, it's worth evaluating both options very carefully so you make the best decision to suit your purposes. In fact, however, having information from both pedigree and DNA analyses will be more powerful than either alone. If you are expecting to do the "whole enchilada" analysis, then you can simply prepare to do both.

The Norwegian Lundehund is undergoing genetic restoration through a crossbreeding program that is now producing dogs of good type that are healthy and fertile. (Melis et al 2022).

Genetic analyses, whether from pedigrees or DNA, will produce information containing a bunch of terms you are probably not familiar with. To use this information, you will need to understand the vocabulary and what the data produced can tell you. Do not think you can learn this stuff from chats in Facebook groups. If you're going to put in the time and make an investment in doing these analyses for your breed, please take the ICB online courses. I am not aware of any other educational resources that are developed specifically for dog breeders and that cover the essential information while requiring no background in science. You need to invest some time in your own education or you won't know how to use the information from data analyses. Remember, the goal here is to figure out what breeders need to do to solve specific genetic problems in the breed. For this, you will need to understand the information provided. Take the courses.

I have created a table (below) with some information about the types of basic information that you can extract from both pedigree data and genotypes. In general, I would advise breeders that only intend to use data from one of these sources to use pedigrees. It might seem that DNA should be better because it uses "high tech" techniques to provide information about chromosomes and genes. But, in fact, you will find that a pedigree analysis provides all the information you need to do a good job of genetic management of a breed. It requires no effort (or cost) from breeders to keep it up to date, and it will provide critical information for you generation after generation, forever. There is some overlap in what can be extracted from pedigree versus DNA data, but pedigrees might be better for some things and DNA better for others. Again, if you have the option of doing both, that is the most useful thing to do.

If you want to use DNA genotype data for your breed, you should use SNP (single nucleotide polymorphism) analysis, not microsatellites (or single tandem repeat markers, STR). Embark uses the most popular, research grade analysis based on high-density SNPs. Their output can be combined with data produced by any research lab using the same chip (e.g., data from a study). Wisdom also uses SNPs but they have a lower resolution chip of their own design and their data cannot be combined with Embark's. Also (and more importantly) they do not make the genotype data available to the user, so third-party analysis (as I am describing here) is not possible. Microsattelite data cannot be combined with SNPs, and they do not provide the resolution needed for planning a genetic rehabilitation program for a breed. However, STRs can provide data for the genes for the immune system (DLA, dog leucocyte antigen), and this is useful to know so you can breed for high diversity in these genes specifically.

The table below includes some additional information about the convenience and logistics of obtaining and managing data from pedigrees versus DNA genotypes.

Armed with the information from analysis of your pedigree database or DNA genotyping, you are ready to start summarizing the issues that need to be addressed. For this, you will also need to know some other things - the actual number of living dogs, how many of these can be used in a breeding program (i.e, not spayed or neutered), and how many breeders there are and where they live (e.g., country). This is also the time to pull out all the information you have about phenotypic traits that you care about (e.g., coat color, variety, etc.) as well as known health issues and associated genotypes when known.

All of this is information that should be available about your breed anyway, but usually the motivation for getting things together is the realization by breeders that there are issues about genetic health that need to be addressed. With some information extracted from pedigrees or DNA genotypes, we can take a lot of the guesswork out of making breeding decisions. A little effort invested now in data preparation will yield benefits for the breed far into the future.

I have provided the reference for a nice paper by Mabunda et al (see References) about using pedigree and molecular data to evaluate genetic health of dog breeds. It contains a useful summary of the information provided by pedigree and genotype analyses and how to use it. You will see some jargon that might be new to you, so you can start here to become familiar with meanings and concepts. There is much more to know about how to set up a genetic rehabilitation program for your breed, but this is the place to start.

If you would like to know more about the genetic status of your breed and what can be done to improve it, contact me and we can discuss where to start.

Watch this space for more information about genetic rehabilitation of dog breeds coming soon...

REFERENCES

Mabunda et al 2022. Evaluation of genetic diversity in dog breeds using pedigree and molecular analysis: a review. Diversity 14: 1054. https://doi.org/10.3390/d14121054.
https://www.mdpi.com/1424-2818/14/12/1054

Melis et al 2022. Genetic rescue of the highly inbred Norwegian Lundehund. Genes 13: 163. https://doi.org/10.3390/ genes13010163.
https://www.mdpi.com/2073-4425/13/1/163

What level of inbreeding is "safe"?

2/4/2024

By Carol Beuchat PhD

When you select a pair of dogs for your next litter, one of the things many breeders consider is the level of inbreeding expected in the resulting puppies. Most recognize that "lower is better", but how low, and better than what? If you poll a group of breeders, some will respond that inbreeding should be kept less than 5%, or less than 10%, but what's so special about those numbers? Is 5% fine but 6% is not? Is 10% okay, but 12% death and destruction?

To address these questions, you must know what the coefficient of inbreeding (COI) is and what it tells you. (Here and elsewhere, I always mean the actual level of inbreeding, as you would get from genomic DNA or a pedigree database that is complete back to founders.)

The inbreeding coefficient was originally devised to give animal breeders a way of estimating the degree inbreeding in their stock. But what is inbreeding? Animal breeders figured out long ago that if you repeatedly bred related animals together, the quality of the offspring began to decline, something they termed "loss of vigor". They knew that a cross with an unrelated animal restored normal vigor to the animals. What they needed was a way to determine the level of inbreeding in their animals so they could determine the "tipping" point,
in the tradeoff between benefits and costs of inbreeding. In populations of animals with complicated pedigrees, it could be difficult to do this. What was needed was a way to derive inbreeding quantitatively based on the relationships of the animals in the pedigree.

The coefficient of inbreeding was devised specifically for this purpose. If an animal inherits two copies of an allele that is passed on down both sides of a pedigree from a common ancestor, this produces homozygosity at this locus. This specific form of homozygosity, where two copies of the same allele are "identical by descent", is the definition of inbreeding.

The inbreeding coefficient reflects the fraction of loci that are homozygous because of two copies of the same allele were inherited from a single ancestor. (It is also the probability that a specific locus will have two copies of the same allele inherited from a common ancestor.)

By definition, inbreeding is the inheritance of two copies of the same allele inherited from a common ancestor, so this risk should be zero if there are no shared ancestors in the maternal and paternal lines. However, if the parents are related, they will have some genetic similarity, and the more closely the relationship the greater the similarity. So from the breeding of unrelated dogs, which would produce a COI of 0%, to increasing degrees of relatedness of the parents (e.g., distant cousins, near cousins, nephews, half-siblings, etc), you would expect to see an increasing level of inbreeding, i.e, the fraction of homozygous identical alleles. For example, a cross of first cousins results on average in a COI of 6.25% in the offspring. Mating half siblings produces inbreeding of 12.5%, and crossing of full sibs results in 25% inbreeding. You can get even higher levels of inbreeding if the parents themselves are inbred, as you might see with consecutive full sibling crosses generation after generation.

So here's the burning question: Why do we need to worry about inbreeding? What exactly is the problem caused by homozygosity of alleles that are identical by descent?

The first thing you need to understand is that nature favors heterozygosity over homozygosity. Imagine a gene with multiple variants (alleles), each of which confer some different degree of resistance to a bacterial infection. Those with the alleles providing the least resistance might get sick and die, those with the best resistance will survive infection with little negative effects, and animals with a third allele might get sick and survive, but with lower fertility. The allelic diversity in the population of animals prevents entire populations from being wiped out. The animals that survive are more likely to have the alleles that conferred partial or complete resistance, and the population is better able to survive this bacterial infection in the future.

But what if there is lots of inbreeding in the population? Many individuals might have the same allele, and for some that allele could even be homozygous. If it happens to be an allele that confers resistance, the population will be fine. But otherwise, the population will take a hit, with reduced reproduction or even death of animals with the other alleles.

This is a simple example, but you can image a similar situation for many genes in the genome of a animal, which will be reflected in the allelic diversity of the population. Individuals in healthy populations of wild animals usually have an inbreeding coefficient in the very low single digits, even 0%.

These two charts (below) depict the individuals chromosomes of a wolf (left) and a German Shepherd dog (right) (Wang et al. 2012). The regions on each chromosome that are "low diversity regions" (LDR; i.e., homozygosity) are in dark blue. It is easy to see that the German Shepherd has much more dark blue, indicating regions of homozygosity. A population of wolves like this one with low inbreeding is more likely to have the allelic variation that will allow it to adjust to variations in the environment than a population of inbred Germans Shepherds that has much less allelic variation. This effect is so strong that it tends to keep inbreeding levels of wild populations extremely low as long as the population is relatively large and there is some exchange of individuals from other packs.

Mother Nature prefers heterozygosity, because inbred individuals in a population are less successful. But just how picky is she?

This is the question often voiced by breeders: What level of inbreeding is "safe"?

To address this question, we can look at data for effects of inbreeding on "fitness", i.e., traits that reflect the ability of the animal to grow, reproduce, and survive.

Longevity
Thanks to the tendency of royalty to marry their relatives, we have interesting data for humans on the effects of inbreeding for various traits. One such dynasty was the Spanish Habsburgs, for which we have data for various parameters of interest (Alvarez et al. 2011). These are data for survival of children to at least 10 years of age as a function of the degree of inbreeding estimated from pedigrees. Children with the longest lifespans had inbreeding levels less than about 6%. Above this, survival to 10 years dropped sharply, with less than 50% achieving this age.

There are similarly dramatic effects of inreeding on lifespan in dogs. In Standard Poodles, dogs with inbreeding less than 6% live longer than those with higher COI. The penalty paid for an increase in inbreeding from 6.25% (first cousins) to 12.5% (half sib mating) was about 4 years! At 8 years old, more than 80% of dogs with low inbreeding are alive, while only 60% of dogs with inbreeding > 6.25% survived to this age. In dogs with low inbreeding (< 6%), 80% survived at least to 12 years old; only 30% of inbred dogs survived to that age.

There is a similarly dramatic effect of inbreeding on lifespan in Bernese Mountain Dogs, many of which fail to live beyond 6-9 years old (Klopfenstein et al 2016). This chart (Long & Klei, Bernergarde) shows that each 10% increase in COI reduces lifespan by 200 days. That is, lifespan is reduced by 20.6 days for each 1% increase in inbreeding (Long & Klei, 2009). For a dog with a COI of 30%, that's a reduction in lifespan of almost two years.

Abbreviations for breeds: Bernese Mountain Dog (BMD), Basset Hound (BSH), Cairn Terrier (CAI), Epagneul Breton (EPB), German Shepherd Dog (GSD), Leonberger (LEO), and West Highland White Terrier (WHW).

The effects of inbreeding on longevity have been compiled (Leroy et al 2014) for a group of breeds that include Bernese Mount Dog, Basset Hound, Cairn Terrier, Epagneul Breton, German Shepherd Dog, Leonberger, and West Highland White terrier. This chart shows longevity of each breed at three levels of inbreeding, with signifiant effects indicated by asterisks.

Consequences of inbreeding can be manifested at a very early age. These data for Beagles show that there is more than 20% mortality of puppies at 10 days of age at COIs up to 25%. (The data from 0% to 25% are pooled, so we can't determine how mortality was affected by inbreeding levels less than 25%). As inbreeding increases above 25%, the mortality increases significantly, to about 30% for dogs with COI between 25-50%, and about 50% for inbreeding of 50-67%.

Reproduction
Inbreeding reduces reduces fertility and effective length of reproductive period in humans (Alvarez et al 2015).

Inbreeding affects various aspects of reproduction in dogs as well. These are data for litter size as a function of inbreeding coefficient for six breeds of dog from the Swedish Kennel Club database. The top graph is litter size in number of puppies, the graph below is the decline in litter size from the value at the lowest level of inbreeding (litter size as a 5 of maximum), so all breeds start at 100% and decline from there.

Effects of inbreeding on dog fertility. Swedish Kennel Club.

The slopes of these lines tell us about the "cost-benefit" ratio on inbreeding. For these breeds, the slopes are about 0.1, which means that an increase in inbreeding of 10% reduces litter size by about 1.

If normal litter size is about 6, a COI of 30% - which is not uncommon in many breeds would reduce the litter size by HALF. That is half as many offspring from which to choose your "pick", and on top of this realize that these puppies will have reduced fitness in the ways noted by Wright - they are likely to be smaller, less vigorous, have more birth defects and higher mortality, grow more slowly, have shorter lifespan, and of course increased incidence of genetic disorders caused by recessive mutations.

These are data from the same study of longevity by Leroy et al. mentioned above. The data show that higher levels of inbreeding in both the dam and the litter negatively affect litter size. (Leroy et al 2014).

A recent study (Chu et al 2019) has taken advantage of the data from the Golden Retriever Lifestudy sponsored by Morris to show that inbeeding reduces litter size in Goldens. The average level of inbreeding in 93 dogs used in the study averaged 31.6%, and ranged from 18.7% yo 49.9%. A quick look at the levels of inbreeding in the various studies mentioned above makes clear that the inbreeding in these Goldens is extremely high, with all individuals higher than the 12.5% COI that would result from a cross of half siblings. While they did find a negative effect of inbreeding on litter size, note that we would expect to see a substantial reduction in litter size over the range from 0% to 20%, for which they have no data.

Diseases
The detrimental effects of inbreeding can be manifested as increased incidence or risk of disease.

In humans, inbreeding increases the prevalence of multiple disorders including cancer, Schizophrenia, and epilepsy Alvarez et al 2011). In the chart below, asterisks indicate significant difference from the prevalence at the lowest level of inbreeding (0.6%). Note that the highest level of inbreeding in these data is only 3.6^%, far less than we would be worrying about in a dataset for purebred dogs. It's also clear that the relationship between prevalence and inbreeding appears to be roughly linear, potentially allowing prediction of disease incidence at much higher levels of inbreeding.

You know that there is a long list of genetic disorders in dogs that can be linked to recessive mutations. For these, animals with only a single copy of the mutation are considered to be "carriers" without detrimental effects. However, crossing two carriers runs a risk of approximately 25% of offspring inheriting two copies of the mutation, resulting in expression of the disorder. We could reduce the risk of producing puppies that are homozogous for a particular mutation by avoiding pairings that are closely related. The problem, of course, is that the loss of genetic diversity and high levels of inbreeding have resulted in populations of dogs that are extremely similar genetically. Trying to reduce the incidence of disease by selective breeding in such populations might be possible if considering only one or two mutations, but for breeds with multiple known mutations that need to be avoided, avoiding known risks might be impossible. Of course, we don't know all of the mutations hiding in the gene pool of a breed, so testing for and avoiding the documented mutations does not mean a dog is clear of deleterious mutations - only the ones we know about. Doing DNA testing to prevent a 25% risk of genetic disease from a known mutation, then doing a cross with a 25% risk of producing homozygosity for some other yet-to-be-identified mutation, demonstrates a failure to understand the notion of inbreeding and its consequences.

You have seen here some actual data for the effect of inbreeding on various traits in humans and dogs. Based on this, what level of inbreeding would you argue is "safe"? Truth is, we need to define "safe". If by this we mean there are no deleterious effects of any sort, the answer is clearly 0% - in general, NO level of inbreeding is without negative effects. Furthermore, the effects of inbreeding on quantifiable traits or diseases is generally linear; that is, as inbreeding increases, the magnitude of inbreeding depression (the negative effects) on a trait increases in proportion. There is no "5% threshold", below which inbreeding is "safe", nor is there a 10% cutoff above which there are horrible consequences. The effects of inbreeding on individual animals with the same COI will vary (because no dogs are genetically identical and each will have it's own pattern of homozygosity), but across a range of inbreeding levels, the effect will be linear.

These are data for plants, but it illustrates the pattern of change in a trait as inbreeding increases seen in the data for humans and dogs above. When the COI is zero, fitness is at its maximum and there is no and prepotency and uniformity are at their lowest. As inbreeding increases, variation in the offspring goes down but so does fitness.

What else?

I have pulled out data above for humans and dogs because I could find examples of data for both and the particular traits are familiar to breeders.

But don't think that the scanty data presented here is flimsy justification for arguing that we do need to worry about the negative effects of inbreeding, even at very low levels. In fact, there are mountains of data for the consequences of inbreeding in livestock and other domestic animals, because the profitability of commercial breeding hangs on getting the best level of inbreeding to balance benefit with detriment.

This takes us back to the livestock breeders we mentioned above. They recognized that there were some benefits produced by inbreeding, including more predictable, consistent traits in the offspring. But they also realized that more of a good thing didn't make things even better. Breeders needed a quantitative estimate of inbreeding so they could know the level of inbreeding at which the costs began to outweigh the benefits. Hence, the development of the coefficient of inbreeding. They explicitly embraced the realization that there were negative consequences to inbreeding, but in some instances the risk might outweigh the particular negatives. With a way to estimate COI for any animal and any potential cross, and data for how the traits they were interested in were affected by increeding, they could fine tune their mate selection to have the greatest likelihood of maximizing benefit relative to detriment.

This is a table of data for effects of inbreeding on various traits for dairy cattle, using inbreeding estimates from both pedigrees and genomic data (Gutiérrez‐Reinoso et al. 2022). The numbers are the regression coefficients for the slope of each effect when graphed on level of inbreeding. This is the "inbreeding depression" indicated in the graph just above (right) as the slope of the line on of the trait on inbreeding coefficient. With data like this, a breeder could figure out what level of inbreeding will provide the most benefit with a tolerable detrimental effect.

To be able to do this, they have carefully collected the trait data to use in an analysis like this from thousands or even millions of animals over many generations. Dog breeders are not likely to do this, but the point is that we are entirely casual about inbreeding, and we should assume that just because we don't have the data to show that there are deleterious effects doesn't mean there aren't any. Notice also that this paper considers both pedigree and genomic estimates of inbreeding, and advocates that breeders should use both to get the best information to use in breeding. Notice that with data like this, they can estimate the effects of very small differences in levels of inbreeding on a trait, even as little as a 1% increase in inbreeding coefficient.

What level of inbreeding is "safe"?
From the information presented here, it is clear that inbreeding at any level has consequences, and that even very small changes can be relevant. In a litter of puppies, no two puppies will be genetically identical, so even if they have the same level of inbreeding, the homozygosity will likely be at different loci on the chromosomes. So you can have a puppy with 5% COI that is robust and healthy, and another also with 5% inbreeding that happened to be homozygous for loci that produced a negative effect. For this reason, COI is not an index of "health". It is a prediction or estimate of homozygosity, and that homozygosity might be either good or bad. But we know that in general, homozygosity has deleterious effects and should be avoided when possible for that reason. The bottom line is that NO level of inbreeding is "safe" or without consequences.

If there are negative effects of even very low levels of inbreeding on a wide variety of traits, you might assess the inbreeding levels of your own breed with a new perspective. Knowing what we do now, these data for dogs should be shocking. Livestock breeders worry about single digit increases in inbreeding, and begin to panic when inbreeding increases above 6%. The data for dogs show that most breeds have an average level of inbreeding higher than a population of half-sibling crosses (the yellow line), and about 60% of breeds are even higher than the level for a full-sibling cross (red line). From data for other animals, we should expect that dogs should suffer from reduced fertility, shorter lifespan, higher puppy mortality, greater risk of genetic disorders, blood and immune system disorders, and many other things that we aren't even aware of.

Find the data for your breed on the charts below. If your breed is not on the first set of graphs, download the file just below labeled "Bannasch et al 2021", which contains some additional breeds.

If your first response on finding the data for your breed is to assume that the data must be from some non-representative population, because "inbreeding in my breed is nowhere near that high", I can assure you that these data are indeed representative of your breed. These are averages of a sample of dogs, so some individual dogs will have lower than average inbreeding, but at the same time some individuals will be higher. The point is that the livestock breeders try to keep inbreeding lower than about 5%, because at levels higher than this the detrimental consequences of inbreeding outweigh the benefits. These breeders demonstrate that you can have levels of uniformity and consistency in a group of animals at very low levels of inbreeding, so it is simply not the case that (as often claimed by dog breeders), high inbreeding is necessary to "fix type" produce consistency. This is nonsense. We CAN have both health and breed quality, but not at the levels of inbreeding typical of most purebred breeds.

Breeders that are serious about preservation of their breeds will recognize the fix we're in right now and take steps to remedy a really bad situation. It is possible to accomplish genetic "rehabilitation" of a breed, to restore it to health and preserve the traits that make each breed unique.

But this will require these breeders to step out of the bubble of ideology and misinformation that has justified ridiculous and completely unnecessary levels of inbreeding, and use the tools and information of science to return to breeding strategies that maintain type without compromising health.

There are additional data in the paper by Bannasch et al that I have displayed in this graph (below).

bannasch_et_al_2021_cavaiers_fadj.png
File Size:	593 kb
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Download File

REFERENCES

Alvarez et al, 2009. The role of inbreeding in the extinction of a European royal dynasty. PLoS ONE 4:e5174. doi:10.1371/ journal.pone.0005174.

Alvarez et al, 2011. Inbreeding and genetics. Advances in the study of genetic disorders.

Alvarez et al 2015. Darwin was right: inbreeding depression on male fertility in the Darwin family. Biol. J. Linnean Soc 114: 474-483.

Armstrong JB, 2000. Longevity in the Standard Poodle. The Canine Diversity Project.

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

Charlesworth & Willis. 2009. The genetics of inbreeding depression. Nature Reviews: Genetics 10:783-796. doi:10.1038/nrg2664

Chu et al 2019. Inbreeding depression causes reduced fecundity in Golden Retrievers. Mammalian Genome 30: 166-172. https://doi.org/10.1007/s00335-019-09805-4.

Klopfenstein et al 2016. Life expectancy and causes of death in Bernese mountain dogs in Switzerland. BMC Veterinary Research 12: 153. DOI 10.1186/s12917-016-0782-9.

Leroy et al 2014. Inbreeding impact of litter size and survival in selected canine breeds Vet. J. 203: 74-78.

Long P & B Klei, 2009. Inbreeding and longevity in Bernese Mountain Dogs.

Gutierrez-Reinoso et al 2022. A review of inbreeding depression in dairy cattle: current status, emerging control strategies, and future prospects. J. Dairy Research 89: 3-12. doi.org/10.1017/ S0022029922000188.

Rehfeld 1970. Definition of relationships in a closed Beagle colony. J. Am. Vet. Res. 31:723-732.

Wang et al 2012. The genomics of selection in dogs and the parallel evolution between dogs and humans. Natre Communications 4:1860. DOI: 10.1038/ncomms2814.

Treating heat stress in dogs based on science

7/18/2023

By Carol Beuchat PhD

We are entering a new time as residents of earth. As of a few days ago, we are breaking global heat records every day, and this will continue for the forseable future. Just yesterday, a biker in California stopped to help a group of overheated and dehydrated hikers, and while they all made it home safety, the hero biker died.

Reasonable people that make a small mistake while outside in extreme temperatures can die in this heat.

Our dogs are at even higher risk, because it's easy for us to underestimate how the environment affects them. If you find youself with a heat-stressed dog, it is critical that you make the correct decisions immediately.

There is all sorts of "advice" on how to treat a hyperthermic dog, most of it based on little more than something somebody read someplace on Facebook. If your dog is in distressed, you need information based on science and medicine.

Here is a very timely publication with FACTUAL information about how to respond to heat stress in dogs. It debunks some of the common, but incorrect, recommendations you have probably heard. We need to displace those incorrect suggestions bouncing around on the internet with FACTS and DATA.

Read this paper. Share it with your friends with dogs.

The key information:

"Heat-related illness (HRI) is a potentially fatal disorder that can occur in dogs following exercise or exposure to hot environments. While many risk factors can affect the probability of HRI occurring, the priority for treating dogs with HRI is early and rapid reduction in their core body temperature to limit disease progression. Cold-water immersion (conductive cooling) and water spray with air movement (evaporative cooling) are the recommended treatments for dogs with HRI, with cooling attempts in dogs with HRI being strongly advised to take place prior to transportation for veterinary care."

The bottom line:
COOL FIRST. TRANSPORT SECOND.

Download a copy of the paper for yourself and to share here -

https://www.mdpi.com/2306-7381/10/7/465

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

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

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

We can prevent neonatal puppy mortality

4/22/2023

By Carol Beuchat PhD

Rates of Mortality in Puppies

Neonatal mortality is a significant problem in dogs, with rates generally averaging from 5-30% (Gill 2001; Tonnessen et al 2012). After eliminating individuals with developmental abnormalities or other apparent issues, most of this mortality is due to uterine inertia, in which the strength and frequency of contractions are not sufficient to expel the puppy. This results in protracted labor, with the result that puppies run out of oxygen before birth, resulting in stillborn puppies that die of asphyxia. Some puppies are born live but physiologically compromised as a result of hypoxia during parturition; these may die in the days or weeks after birth.

The data in the table below are for the disposition of 2,574 puppies of 44 breeds that were produced by 125 breeders in Australia from 1991 to 1998 (Gill 2001). Most of the mortality in this cohort (61.5%) was due to puppies that were stillborn or died in the first 24 hours. About 65% of whelpings required no assistance for delivery, while dystocia occurred in 35.6%. Emergency cesareans were necessary for 18% of the litters. In 48.6% of the litters, there were no mortalities; 14.8% of litters had stillbirths, and in 6.6% the entire litter died, although about half of these were singleton litters.

Gill 2001; Table 2.2

The charts below show data compiled from the records of the Swedish Kennel Club for 58,439 puppies from 10,810 liters whelped in 2006 and 2007 (Tonnessen et al 2012). The data are reported as 1) puppies that were stillborn and 2) as perinatal mortality (the percentage of all puppies born that did not survive past 7 days, including stillbirths). (Only breeds with data for at least 10 litters.)

What is evident in these data is the wide range of values across breeds. There are a few breeds in which stillborn or perinatal mortality is very low or did not occur in this sample (e.g., Basenji, German Spitz). But for most breeds, it is clear that puppy mortality is unacceptably high, even greater than 10% in many breeds.

Tonnessen et al, 2012

The exceptional rates of mortality in puppies have been a significant veterinary concern for several decades. While attributed to uterine inertia, the cause of uterine inertia has not been determined. Suggestions include uterine fatigue, over-stretching of the uterine muscle (e.g., from large litters), and inadequate levels of oxytocin. Treatment of uterine inertia generally involves administering calcium or oxytocin, although these have either limited effectiveness or none at all in improving uterine contractility and expulsion of puppies (Bergstrom et al 2006; Prashantkumar & Walikar 2018).

The relative rates of mortality of puppies might seem low (i.e., as a percentage of puppies produced). But the toll in number of puppies lost at birth or shortly thereafter is substantial. The mortality in Tonnessen's study represents deaths of 4,684 puppies over just the period from 2006 to 2007 in Sweden. That's a lot of puppies to lose, year after year after year in one country, but you have to appreciate that the toll worldwide would be in the many tens or hundreds of thousands.

With the cause of uterine inertia remaining undetermined, there are no recommended procedures for breeders to prevent the high rates of neonatal mortality. Without a cause for uterine inertia, it cannot be prevented, and the huge number of puppies that are perfectly formed but do not survive their first week in this world will continue to accrue.

Uterine Inertia in Dogs is Caused by Light

While observing the whelping of litters of more than 50 breeds of dogs over the last few years, I have inadvertently discovered that uterine inertia in dogs appears to be caused by light.

When the whelping room was kept dark, bitches were calmer and more relaxed, and puppies were expelled easily and without straining. Visible abdominal contractions were infrequent. The intervals between puppies were generally short, ranging from 10-30 minutes. When darkness was maintained through whelping of the entire litter, there were no stillborn puppies or pups born in distress. The puppies were vigorous as soon as they were released from the membranes and were able to find and attach to teats without assistance. Between puppies, the bitch cared for the puppies but was relaxed and without signs of stress.

If the bitch was exposed to any light during whelping, as for example by turning on a light or even a cell phone, the appearance of the bitch changed. She appeared less relaxed and abdominal contractions began. This usually lasted for about two hours after the light event and the whelping room was again completely dark. All of the stillborn puppies we observed were born after periods of exposure of the bitch to light with one exception, in which the last puppy in a litter of 15 was stillborn.

I am not the first to observe that light shuts down uterine contractions during labor. In humans, contractions are suppressed if a light is turned on, and they resume when darkness is restored (Olcease 2015). This is so effective that there is a patented medical device designed to prevent premature labor by suppressing uterine contractions with light (Olcease 2015).

One human patient (Olcese 2015)

The Case for Whelping in the Dark

There is every reason to suspect that ambient light is the cause of uterine inertia during whelping in dogs. If this is true, the solution to high puppy mortality in dogs is management of light during the few hours when the bitch is whelping. My experiences controlling light during whelping indicate that this is the case.

It makes sense that the physiology of the dog is designed for whelping in the dark.

Wolves and free-living dogs whelp their puppies in underground dens, and the puppies remain in the den for several weeks. Our household pets seek out dark places as whelping nears, disappearing under the bed, in a closet, or behind a piece of furniture. We assume they are looking for a place that is protected, quiet, and cozy, and this might be true. But the key attraction for the dog might be darkness.

Nevertheless, bitches whelping in the house are typically provided a box in a location convenient for monitoring, such as a bedroom, family room area, or even by a window. Because breeders generally supervise and assist with whelping, lighting is at least sufficient for the breeder to see even if it is dim.

This arrangement, however, is very unsuitable for whelping. With the ambient light suppressing uterine contractions, the bitch must expel the puppies with strong abdominal contractions instead. The result is inefficient and protracted labor, and the long intervals between births greatly increase the risk of stillbirth (Cornelius et al 2019).

The unintended consequence of the way we generally whelp puppies is that the difficulties encountered during labor that motivate close supervision by breeders are, in fact, caused by that very supervision, because it requires ambient light for the breeder to see. The best of intentions result in making whelping significantly more difficult.

But we should be able to dramatically reduce mortality of newborn puppies.

We need to give the bitch access to the conditions that her instincts tell her are best suited for whelping and raising her puppies, instead of what suits our convenience. The physiology of dogs and many other mammals is designed to give birth in the dark. We need to give her darkness.

This is routinely done by keepers of zoo animals, who carefully consider the biology and natural history of an animal in its natural environment in designing its habitat in captivity. Staff supervise by video and intervene if necessary, but, more often than not, birth proceeds without complication or intervention.

Dogs are quite good at reproducing themselves if left to their own devices. We should have fewer complications and much greater success with a simple strategy: just give her what she needs and get out of her way.

Dark Whelping

We need a new approach to whelping dogs that is better suited to their biology. I am calling it "dark whelping".

Breeders are asking me questions about dark whelping:

How dark does it have to be?
Does it need to be dark only during labor, or before (or after) as well?
Is turning a light on very quickly okay?
What about a really dim light?
Is a red heat lamp ok to use?

Unfortunately, the answer to these questions like these is usually "I don't know".

The dark whelpings I have done have been in absolute darkness (i.e., can't see your hand in front of your face), because this is a light level that can be replicated by every breeder (as opposed to various unknown levels of dimness). Under these conditions, with total darkness and no unplanned "light events", our puppy mortality has been zero.

Total darkness is difficult to do in the typical household. It takes planning and working out critical bits of the logistics ahead of time (e.g., how to retrieve the puppies for weighing without introducing light to the whelping room). But we have been doing it with success, and the extra trouble over a more convenient whelping box in the living room or bedroom is well worth the prevention of mortality.

I can't provide you with a protocol to set up dark whelping yourself. Every breeder's setup is different, and there will be different issues to resolve for the ideal setup for each litter. I can tell you that the process seems to be extremely sensitive to light, and getting it wrong often results in dead puppies.

However, if you would like to whelp a litter in the dark, you can contact me for assistance. I have experience with enough litters now to have worked out at least some of the problems you are likely to encounter.

Creating a Protocol for Breeders

We have been whelping dogs for decades the same way, in a box in the house. We know nearly nothing about doing it in the dark beyond the fiddling I have done so far. For dark whelping, we will need research to nail down the necessary and sufficient conditions for success.

The sooner we can figure out how to do this right and provide breeders with a protocol they can follow, the sooner we can reduce the tragic loss of puppies that simply run out of oxygen before they make it out into the real world.

It won't take millions of dollars and many years to learn more about this. I just need breeders with upcoming litters and some financial support for my time to assist with logistics and guidance for breeders, and to record the outcome of a whelping event so I can prepare a protocol breeders can follow. There is lots of compelling research that will come out of this new information about whelping dogs, but for now my priority is to reduce puppy mortality as quickly as possible.

We can prevent puppy mortality from uterine inertia in your very next litter.

Research Project: Uterine Inertia and Neonatal Mortality in Dogs

You can learn more about our project to prevent uterine inertia and reduce puppy mortality in our Facebook group, Uterine Inertia and Neonatal Morality in Dogs.

If you are interested in supporting the development of a protocol for dark whelping that breeders can use to reduce puppy mortality, please contact me.

REFERENCES

Bergstrom A, et al. 2006. Primary uterine intertia in 27 bitches: aetiology and treatment. J Small Anim Pract 47: 456-460.

Cornelius AJ et al. 2019. Identifying risk factors for canine dystocia and stillbirths. Theriogenology 128: 201-206.

Gill MA, 2001. Perinatal and late neonatal mortality in the dog. PhD Thesis, University of Sydney.

Olcese J, 2015. Using light to regulate uterine contractions. US Patent No US 8,992,589

Prashantkumar, KA and A Walikar. 2018. Evaluation of treatment protocols for complete primary uterine inertia in female dogs. Pharma Innov J 7:661-664.

Tonnessen R, et al. 2012. Canine perinatal mortality: a cohort study of 224 breeds. Theriogenology 77: 1788-1801.

Why do so many puppies die?

4/14/2023

By Carol Beuchat PhD

Anyone that has been breeding very long has had the experience of excitedly welcoming a new litter of puppies into the world, only to have a beautiful, perfectly-formed puppy born dead. Oftentimes, there are puppies with signs of life but are struggling. Some of these can be revived but, sadly, some cannot despite the best efforts of the breeder.

Perhaps the worst is loss is a puppy that seems to be doing well for several days, then without warning is found dead in the whelping box.

This mortality represents a very significant loss of the puppies produced by breeders. In fact, the statistics are shocking.

In a large study that included 2,574 puppies from 500 litters of 44 breeds (Gill 2001), the total puppy mortality from birth to six weeks averaged 18.5%, with 7% of puppies stillborn. About 10% of liveborn puppies died within the first 7 days.

There is detailed information about this study (Gill 2001):

What is causing such high rates of mortality in puppies?

Excluding the puppies with evident abnormality, the necropsy information for the puppies in Gill's (2001) study (see below) shows that the stillborn puppies suffered from in utero hypoxia - they ran out of oxygen before they were born. In fact, even the puppies that were born live and lived for days also often show evidence of hypoxia (inadequate oxygen) in utero (from Gill 2001). (See necropsy reports below)

Using data for the time of birth of each consecutive puppy, you can compute the "inter-pup interval" as an estimate of how long it takes each puppy to be born (assuming that the placenta was detached at the beginning of that period).

This graph shows that a longer interval between puppies increases the risk of stillbirth. (The first point on the graph represents puppies with inter-pup intervals from 0 to 60 minutes; the marker is placed at 30 min.)

So, as the time between births increases, the proportion of stillborn puppies increases.

But why does birth of puppies take so long?

The pace of labor is determined by the contractile behavior of the uterus. Prolonged labor is the result of "uterine inertia", which is a failure of the uterus to contract with sufficient strength and frequency to expel the puppy.

If we could prevent uterine inertia, we could potentially greatly reduce puppy mortality, both as stillbirths and for puppies that survive for days or even weeks but ultimately die.

So finally, we can ask the critical question:

What causes uterine inertia and how can we prevent it?

When I ran into this issue of high puppy mortality, I was surprised that it had not been resolved long ago. After all, we can determine cause of death, and for most puppies it seems to be a matter of physiology (hypoxia), not a mysterious pathogen or anatomical abnormality. The high mortality of puppies has been well documented, but several studies that searched for a cause came up empty.

If puppies are suffocating in utero because of uterine inertia, then that's the problem we need to solve.

I found various suggestions of possible causes (e.g., overstretching of the uterine muscle, exhaustion of the uterus), but no explanation in the canine or veterinary literature.

However, I stumbled on what I think is the answer.

Uterine contractions during labor are affected by light.

Here are some representative data for uterine contractions during labor in a human. Starting in a dark room, the frequency of contractions increases by the hour. If a light is turned on for an hour, the contraction rate drops dramatically to only 1/hr. When the light is turned off, contractions recover slowly.

But does this also happen in dogs? In fact, it looks like it does.

My colleagues and a group of cooperative breeders have found that bitches kept in a room with lights on typically produce a couple of puppies, but then there is often a prolonged interval before the next puppy appears. In the meantime, the bitch is typically restless and producing strong abdominal contractions. When puppies are produced, the intervals between them can be protracted - an hour or two, or sometimes many hours or even the next day.

But we have found that when the whelping box is in a dark room - a VERY dark room - the bitch is relaxed and calm, and the puppies are expelled quickly and easily, without straining and abdominal contractions. The pups are vigorous as soon as they emerge from the membranes, and the bitch tends to each without assistance.

Most notably, as long as the whelping room stays dark, there are no stillborns or puppies needing reviving.

However, if a light are turned on, even very briefly, the strong abdominal contractions resume, but there are long intervals between puppies. Some of these puppies are born with fluid in the respiratory tract or need to be revived, and some can be stillborn.

Could reducing puppy mortality be as simple as whelping in the dark? I think it can be.

After all, dogs left to their own devices dig a den for their pups, and they are typically born at night. When we bring dogs indoors to manage their reproduction, they are denied this opportunity, although who hasn't found their pregnant bitch under the bed or in the back of a closet when the time comes near for whelping. For tens of thousands of years, dogs have produced their puppies in the darkness of an underground den, and we should expect that their reproductive physiology is suited for this. The consequence of whelping in the light instead of darkness is high puppy mortality. Natural selection would weed out the non-conformers rather quickly.

ICB Uterine Inertia and Neonatal Mortality

If you are interested in following the progress of this study or would like to participate with your own upcoming litter, please join the Facebook group created for this project at -

https://www.facebook.com/groups/uterineinertiaindogs

If light is the key to reducing puppy mortality, it could have huge implications for canine husbandry. Not only would there be fewer losses to morbidity and mortality, there would also be fewer emergency c-sections to recover puppies trapped by unproductive labor, and less risk of losing a bitch because of a difficult labor.

The significance of this doesn't escape me. We will need to do some careful studies to verify the effects of light and darkness on whelping, and there is a long list of questions about effects on physiology and behavior that should be addressed. But as problems go, this one is potentially very easy to solve. And it will result in more puppies. That's definitely a win.

VIDEO: Bernese Mountain Dog, dark whelping.

This is typical for bitches whelping in the dark. The bitch is relaxed and not straining. The puppy emerges quickly and mom takes caresof it to remove membranes and lick clean. (Watch carefully!)

NECROPSY REPORTS

Pathology of Stillborn Puppies

Pathology of puppies that survived up to 10 days

Pathology of Puppies That Survived < 48h

Column labels for table of breed statistics below (Tonnessen et al 2012).

REFERENCES

Cornelius AJ et al, 2019. Identifying risk factors for canine dystocia and stillbirths. Theriogenology 128: 201-206.

Gill, MA, 2001. Perinatal and late neonatal mortality in the dog. PhD Thesis, University of Sydney.

Tonnessen R et al, 2012. Canine perinatal mortality: a cohortt study of 224 breeds. Theriogenology 77: 1788-1801.

Please don't swing the puppy

11/13/2022

Carol Beuchat PhD

The transition from fetus to neonate is physiologically strenuous for a puppy. Like an astronaut at the space station, working outside the station requires a transition from an environment with the adequate air pressure and oxygen for normal respiration, to one completely lacking these things. To survive a space walk outside the vehicle, the astronaut needs a suit that can be pressurized and provides oxygen. A failure of those systems to work properly is catastrophic.

A puppy faces similar challenges in its transition from fetus, where the placenta is its lifeline and supplies all of its needs, to a world in which its own physiological systems need to take over all of the processes necessary for life. The complexity of this transition is not physiologically trivial.

In a perfect world, every puppy would be fully mature, with all systems go, at the moment of birth. But as many of you know, the reality can be very different. Dogs have surprisingly high neonatal mortality. It varies considerably from litter to litter, but the average frequency of stillborn puppies that are fully mature with no evident defects is variously estimated as 5-30%. Some of these puppies respond to resuscitation efforts by the breeder; in fact, puppies are fairly tolerant of short periods without respiration or a heartbeat.

In addition to the stillborns, a significant number of puppies are born alive and breathing, but are struggling with fluid in the lungs. You can hear this liquid crackling as the pup struggles to breathe. For the oxygen in inhaled air to reach the blood, it needs to pass through the thin membranes lining the alveoli of the lungs, but fluid in the lungs prevents this. Removing this fluid so oxygen transport to the blood can occur is a matter of life or death for a newborn puppy.

One of the techniques that has been used to remove the fluid from lungs of a puppy immediately after birth involves holding the puppy in the hand with arm extended and "swinging" the puppy, head down, in an arc. This will often successfully clear the fluid in the lungs so the pup can begin to breathe normally. I have seen many breeders do this, and there are videos and instructions online for those unfamiliar.

But swinging puppies to clear the airways is a really, really bad idea.

I have to confess that the first time I saw this done, it literally took my breath away (not a pun). Swinging might move the fluid out of the lungs, but it causes ALL of the fluids in the body to move towards the head of the puppy - blood, cerebrospinal fluids, stomach contents, and any other fluids in the body. This is NOT a good thing, and I will explain why.

Perhaps you have seen how astronauts are trained to tolerate the g-forces produced in space flight. They use a huge centrifuge with a capsule at the end of a long arm. The test subject is in the capsule, and as the centrifuge rotates, the g-force experienced by the human in the capsule increases; the faster the rotation, the greater the force.

Take a few minutes to watch this video of the human centrifuge in action.

The expressions on that fellow's face tell you something about what you look like when the force of gravity is higher than your body is designed to tolerate. There is great pressure on the body, making it difficult to breathe, but, perhaps worse, the body fluid want to rush to the head. In an adult humans (and dogs), the physiological systems that control blood pressure kick in immediately to try to maintain normal fluid pressures in the organs and vessels.

Now think about the puppy with fluid in the lungs. (In a newborn, this will ilkely be amniotic fluid, but it can also be milk that is aspirated when nursing or being hand fed.) A newborn puppy is not a small version of an adult dog. Many of the organs are not mature at birth (e.g. eyes, kidneys), nor are the systems that control blood flow and regulation of blood pressure. In the newborn puppy, the circulatory system has a much lower pressure than in the adult dog, and the immature nervous system has very limited ability to control it (Grundy et al 2009).

Your body does a good job of regulating your blood pressure by changing the diameter of blood vessels (constrict or dilate) and increasing or decreasing the heart rate to keep blood pressure from going too high or too low. If you have ever stood up quickly and started to black out, this is your body momentarily failing to maintain the blood pressure in your head; in just a second or two, everything will return to normal as your body automatically adjusts blood pressure and heart rate to restore adequate oxygen delivery to your brain.

The systems to control blood pressure and tissue perfusion in the dog are essentially the same as your own, but they are not fully functional in the newborn puppy. A puppy is more like a premature human infant at birth, with organs systems and regulation not yet fully developed. Because of this, insults that would be handled easily by an adult dog can be much more challenging to the newborn puppy. Control of blood pressure is one of these.

This is a real problem if the puppy is swung in an arc to remove fluid from the lungs. Watch this fellow (a veterinarian, apparently) demonstrate.

Raise your hand if you gasped when you watched this. Or maybe you even stopped breathing. Think about that astronaut in the centrifuge. Try to imagine what would be happening inside the body of a tiny puppy. That puppy is being swung HARD.

Yes, swinging might help remove fluid from the lungs of a newborn puppy. But it can also cause brain damage.

What happens to the brain of a puppy that has been swung to clear its airways?

The puppy might have no obvious signs of physical trauma; there are no surface lesions and few behavioral changes (after all, the puppies only have two activities, nurse and sleep). There can be seizures, which might be the only significant outward evidence of serious damage (Grundy et al 2009). However, examination of the brain tissues will reveal evidence of trauma manifested as subdural and intracerebral hemorrhage.

There is nothing known about the consequences of swinging newborn puppies, but it would be naive to assume that there are none. Breeders should be educated about the potential damage done to the delicate tissues of the brain by swinging to remove fluid from the lungs. There are a number of devices that can be used to facilitate removal of fluid from the airways effectively and safely (Grundy et al 2009).

Always remember that a puppy is like a premature infant, not a tiny adult, and it has very limited physiological reactions in response to the stresses that are handled easily by the adult dog.

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REFERENCES

Grundy SA, 2009. Clinically relevant physiology of the neonate. Vet. Clin. Small Anim. 36: 443-459.

Grundy et al 2009. Intracranial trauma in a dog due to being "swung" at birth. Topics in companion animal medicine 24: 100-103.

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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)

NECROPSY REPORTS

Archives

Categories

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)