12 28/2020  How hips form and Wolff's Law
12/27/2020  The basics of hip dysplasia in dogs
    1/3/2020  Do your puppies have enough traction in the whelping box÷
  8/23/2019  Why do mixed breed dogs have so many mutations?
  8/15/2019  About pithy statements vs knowledge
    7/9/2019  Let's kill the breeder myths!
    7/5/2019  What is "heritability" and why do you need to know?
  6/17/2019  Facts vs fear mongering
  4/29/2019  Is health problem X in my breed caused by inbreeding and/or loss of genetic diversity?
  4/19/2019  No, we have NOT found the mutation that causes breathing problems in brachycephalic dogs
  4/21/2019  An update on hip dysplasia in dogs
​  4/20/2019  Addison's Disease and those doggone DLAs
​  3/26/2019  Genetic rescue and rehabilitation: I. Restoring genetic diversity of a breed
  3/12/2019  The key requirement for preservation breeding
  2/28/2019  The genetics of canine behavior goes molecular
  2/14/2019  The messy science of assessing working ability in dogs
    2/5/2019  A new ICB course that will use the DNA data from YOUR dog!
  1/20/2019  How to breed dogs that are better than their parents: the genetics of continuous traits    
    1/7/2019  The right - and wrong - way to use DNA tests
​    1/6/2019  Are breeding restrictions putting your breed at risk?
12/31/2018  More on "Simple strategies to reduce genetic disorders in dogs"
12/29/2018  Simple strategies to reduce genetic disorders in dogs
12/24/2018  Celebrating the preservation breeder!
11/27/2018  On preserving the purebred dog.
11/23/2018  Is the Ky allele in Wirehaired Pointing Griffons evidence of cross-breeding?
    9/7/2018  Cool tricks with Kinship Coefficients, part 4: How closely related are the dogs in my breed?"
    9/6/2018  Cool tricks with Kinship Coefficients, part 3: "How can I manage a disease without a DNA test?"
    9/4/2018  Cool tricks with Kinship Coefficients, part 2: "Should I breed this dog?"
    9/4/2018  Cool tricks with Kinship Coefficients, part 1: "Is this dog really an outcross?"
  8/22/2018  The easy way to understand inheritance of recessive alleles
  8/10/2018  The amazing secrets hiding in your pedigree database
  7/21/2018  We can reduce the risk of hip dysplasia NOW!
  7/12/2018  Is BetterBred better?
    7/7/2018  Assessing genetic diversity and relatedness in dogs using DNA
  6/30/2018  Using genomics to manage genetic disease. You don't need to find the genes
  6/28/2018  How much does outcrossing improve genetic diversity?
  6/26/2018  Are you improving genetic diversity, or just pushing the peas around?
​  6/25/2018  NEW: ICB Genetic Management Workshops
  6/21/2018  A DNA Primer for Dog Breeders. Genetic Diversity: Inbreeding (Fis)
  6/21/2018  A DNA Primer for Dog Breeders. Genetic Diversity: Inbreeding (ROH)
  6/21/2018  A DNA Primer for Dog Breeders. Genetic Diversity: Heterozygosity
  6/21/2018  A DNA Primer for Dog Breeders. ICB Breeder Tool Quick Start Guide
​  6/21/2018  A DNA Primer for Dog Breeders (You have your dog's DNA data. Now what?)
  6/17/2018  No pedigree? No problem!
  5/31/2018  A key innovation in dogs: diet
​    5/1/2018  The lesson(s) from SOD1and degenerative myelopathy
10/27/2017  Update on Newfoundlands
10/26/2017  Please don't ruin the Newfoundland
  8/26/2017  The amazing dog nose: can you smell me now?
​  8/24/2017  The complexity of cancer
  8/12/2017  Are preservation breeders preserving the Doberman? (No.)
    8/5/2017  Hip laxity and the risk of degenerative joint disease
    8/2/2017  Making better decisions about hip and elbow dysplasia: the era of genomics is here
  4/29/2017  New insights into the development of dog breeds
  4/27/2017  The genetic status of the Bernese Mountain Dog
    4/3/2017  How to win The Health Test Game
  3/12/2017  An update on the genetic status of the Doberman Pinscher
    3/9/2017  Lessons from wolves
​    3/6/2017  Why "vulnerable breeds" are vulnerable
​    3/3/2017  Inbreeding and the immune system: unintended consequences
​    3/1/2017  The questions PUPscan won't answer. Part 2: The answers
  2/28/2017  The questions PUPscan won't answer. Part 1
    2/5/2017  Latest OFA statistics for hip dysplasia (Dec 2016)
​    2/2/2017  Why didn't Antarctic sled dogs have hip dysplasia?
  1/23/2017  Your handy DNA testing crib sheet
​  1/18/2017  Rescuing the Norwegian Lundehund: an update from Milo
    1/3/2017  Comparing levels of inbreeding in dogs and horses
12/26/2016  Inbreeding of purebred dogs determined from DNA
​12/15/2016  NEW: ICB Genetic Diversity Certification
  12/9/2016  Why we need a more wholistic approach to managing canine genetic disorders
  12/7/2016  A simple new tool for genetic disease management
​  12/4/2016  The ICB Breeder Tool: Overview 
11/26/2016  Dog breeding in the era of genomic selection
11/23/2016  The new ICB Genomic Breeding Tool: the Genomic Relationship Coefficient
  9/18/2016  How to develop effective strategies for the genetic management of your breed
    9/2/2016  Preventing transmission of infectious disease at dog shows and sporting events
  8/31/2016  Gone too soon? Enough already.
  8/27/2016  Hip dysplaysia facts, fallacies, and fairy tales
​  8/16/2016  Why you should care about effective population size
  8/14/2016  The world's oldest cancer...in dogs 
    8/7/2016  Introducing a new course: The Biology of Dogs
  7/29/2016  Bulldog breeders: a call to action
​  7/23/2016  Try these breeding games!
    7/4/2016  Genes and the amazing mind of the dog
    7/2/2016  A game-changer for breeders: the ICB Breeder Tool
  6/30/2016  Understanding the heritability of behavior in dogs
  6/24/2016  Certificate of Completion: Genetics of Behavior & Performance course
    6/5/2016  Are we watching the extinction of a breed? (part 2)
    6/4/2016  Are we watching the extinction of a breed?
  4/15/2016  A broader view of extinction risk of dog breeds in the UK
    4/2/2016  A call for preservation breeding
​  3/29/2016  Twenty key elements of a successful breeding program
  3/28/2016  Breeds with the BEST & WORST genetic diversity 
  3/25/2016  What are we going to do about Terriers?
  3/20/2016  Evaluating the genetic status of a breed using both pedigrees and DNA
  3/15/2016  Reprise: The Pox of Popular Sires
​  3/13/2016  That purebred vs mixed breed thing again
    2/7/2016  Do you know what you don't know?
​  1/31/2016  Do you REALLY need to take a genetics course?
  1/27/2016  Three key strategies to reduce genetic disorders in dogs
  1/17/2016  Is it Nurture or Nature?
    1/2/2016  Managing risk factors for hip dysplasia
​12/23/2015  How do hips become dysplastic?
​12/21/2015  Reliability of DNA tests for inherited diseases in dogs
12/16/2015  Virtual tours of the canine hip and pelvis
12/11/2015  The 10 most important things to know about canine hip dysplasia
  11/4/2015  Coming soon: Course Certifications!
  11/2/2015  Brachycephaly: it's more than just the pretty face
10/24/2015  The poop about dog diets
​10/12/2015  Is (raw) diet the problem?
10/10/2015  Do dogs have more cancer than other mammals? 
  9/29/2015  Myths and mysteries about hip dysplasia  
  9/21/2015  Genetic status of purebred dogs in the UK
  9/16/2015  Bigger puppies develop hip dysplasia
  9/14/2015  The Mongolian Bankhar Dog Project
    9/5/2015  Citizen Scientists: Let's do something about hip dysplasia!
    9/1/2015  Major 2015 epilepsy consensus report
  8/26/2015  Genetics, behavior, and puppy temperament testing
  8/24/2015  The problem with the immune system: if you break it, it's yours  
  8/22/2015  Managing genetic disorders: "Just eliminate the bad gene"
    8/9/2015  Is the dam more important than the sire?
    7/8/2015  Decoding the genetics of behavior in dogs
  6/23/2015  Looking for early pedigree data?
  6/14/2015  For genetic improvement, it's the mix that matters
  6/12/2015  The relationship between inbreeding and genetic disease
    6/9/2015  Putting dogs to work for conservation
    6/4/2015  COI FAQs: Understanding the Coefficient of Inbreeding
    6/2/2015  Solving the problem of genetic disorders in dogs
  5/14/2015  Visualizing inbreeding on the chromosome  
  4/30/2015  The trouble with Terriers
  4/29/2015  Vulnerable breeds: how small is too small?
    4/1/2015  A bright future for purebred dogs
  3/29/2015  Health of purebred vs mixed breed dogs: the actual data
  3/27/2015  Finding genes without DNA
  3/26/2015  Tracing the paths of drifting genes
  3/24/2015  If knowledge is power, know every puppy
  3/19/2015  Lush on linebreeding
  3/12/2015  Why all the fuss about inbreeding? (Or "Why are there so many genetic disorders in dogs?")    
    3/7/2015  What does "health tested" really mean?
    1/9/2015  The history of purebred dogs in the UK
    1/5/2015  Genetic test for renal dysplasia (Caution advised)
    1/2/2015  A better way to pick 'em: using EBVs to reduce genetic disorders in dogs
    1/1/2015  Estimating the breeding value of a dog
12/31/2014  Why do dogs get cancer?
12/28/2014  Cryptorchidism is complicated
12/26/2014  Silent secrets in old dog bones
12/22/2014  The myth of hybrid vigor in dogs...is a myth
12/17/2014  Hitting the bottle: the genetics of boom and bust
  12/4/2014  More on tending the genetic pantry
  12/1/2014  Using inbreeding to manage inbreeding
11/25/2014  Why dogs are sloppy drinkers (and cats aren't)
11/21/2014  The complexity of coat color
11/18/2014  Epilepsy incidence and mortality in 35 dog breeds
  11/9/2014  Reducing genetic risk
  11/7/2014  Take the breeder quiz!
  11/6/2014  Dealing with those pesky mutations
10/31/2014  It's not always as simple as dominant and recessive
  11/9/2014  The fiction of "knowing your lines"
10/24/2014  Is your breed drifting?
10/23/2014  Who's tending your genetic pantry?
10/15/2014  How breeding the best to the best can be worse
10/10/2014  When Should You Spay or Neuter Your Puppy?
  10/3/2014  Genetic disorders in dogs: breaking the machinery of life
  9/25/2014  Get Started Using Estimated Breeding Values (EBVs)
  9/19/2014  The Costs and Benefits of Inbreeding
  8/27/2014  A bit of sheepish fun
  8/20/2014  How many generations of pedigree data should you use to estimate inbreeding?
  7/23/2014  Me, jealous?  Never!  But my dog, on the other hand...
  7/20/2014  Population Size & Inbreeding
  7/19/2014  Avoiding inherited genetic diseases in dogs
  6/18/2014  Wright’s Coefficient of Inbreeding
    6/5/2014  Why DNA tests won't make dogs healthier
    6/1/2014  Eliminating genetic disorders in dogs - too little, too late?
    5/2/2014  Better hips and elbows?  Maybe.
    5/1/2014  Cancer Surprises
  2/21/2014  Genetic Management of Dog Breed Populations
    2/2/2014  What Does Population Genetics Have To Do With Breeding Dogs?
  12/5/2013  The Pox of Popular Sires
  10/5/2013  A bit more about Poodles
  9/24/2013  An open letter to the Canadian Poodle clubs and others that love the breed
  7/23/2013  Why do dogs have so many genetic disorders?
  7/19/2013  Primary lens luxation is WIDESPREAD among dog breeds - are you testing?
  7/18/2013  Inherited myopathy in Labradors is found worldwide - the legacy of a popular sire
    7/2/2013  Finally, a scientific journal about Dogs!
    3/9/2013  How molecular genetics will change dog breeding
    7/6/2012  Locating the genes for hip dysplasia in dogs (Psssst! Look in the kibble bag)
  4/19/2012  Population genetics suggests dire straits for Tollers and Heelers

If the head of the femur conforms to the shape of the socket with no looseness, the hip will develop normally and hip dysplasia will not occur. But any looseness in the hip joint triggers the vicious cycle of bone deformation and remodeling that results in hip dysplasia. Laxity in the hip joint is the basis of the "distraction index" (DI), one of the statistics used by PennHip to evaluate hip phenotype (xxxx).

​The key to preventing hip dysplasia, then, is to prevent the development of laxity in the joint.

This ligament is very short and tight at birth, restricting the range of motion of the femur by keeping the head of the femur well-seated in the cup of the hip socket. This is why a newborn puppy on its back will hold the legs a bit to the sides with the stifles bent. As the puppy grows, this ligament gradually lengthens and the range of motion of the legs increases until the femur can be extended parallel to the axis of the body. (The same ligament is present in humans, which is why a baby on its back also holds its legs at rest in the same flexed position.)

To solve the joint laxity problem, we need to understand what is causing the joint to be loose. This would probably still be a mystery if not for some observations about the occurrence of hip dysplasia in different populations of humans.

Hip dysplasia is more prevalent in some cultures than others. It is rare in African cultures (0.06 per 1000 live births; Loder & Skopelja 2011), while the recorded incidence in Navajo Indians is among the highest, ranging from 10.9 per 1,000 population (Rabin et al. 1965) to 76.1 per 1,000 (Blatt 2014). It would be tempting to attribute these population differences in the incidence of hip dysplasia to genetics. However, some animal studies  revealed that there could also be non-genetic (environmental) causes. In particular, animal studies showed that hip dysplasia could be induced simply by prolonged (days or weeks) extension of the back legs (Wang et al. 2012).

An association between hip dysplasia in infants and the way they were swaddled was highlighted by the results of an educational campaign to reduce dysplasia in Japan (Yamamuro & Ishida 1983). The incidence of hip dysplasia in infants in Japan prior to 1965 was high, estimated at 1.1%-3.5%. An educational campaign begun in 1975 encouraging parents to reduce prolonged extension of the legs while swaddled achieved a marked reduction in the incidence of hip dysplasia, to about 0.2%.

​

POTENTIAL CONSEQUENCES OF TERES LIGAMENT DAMAGE
Orthopedic
  Hip dysplasia
  Legg-Calves-Perthes
  Luxating patella
  Pes varus
  Cruciate ligament rupture
  Flat chest / Swimmers
  Elbow dysplasia?

Neurological
  Wobblers
  Spinal compression (e.g., pug myelopathy, degeneratiove myelopathy)
​  

​NEUROLOGICAL
Pug myelopathy
​

OTHER ANIMALS

Cats
Rabbits

Captive wildlife
 - Snow leopard
 - Panda

Domestic animals
 - pigs ("spraddle leg")
 - birds

REFERENCES

Loder RT & EN Skopelja. 2011. The epidemiology and demographics of hip dysplasia. ISRN Orthopedics, Vol 2011, Article ID 238607. ​doi:10.5402/2011/238607.

Mahan ST & JR Kasser. 2008. Does swaddling influence developmental dysplasia of the hip? Pediatrics 121:177-178. DOI: 10.1542/peds.2007-1618.

Rabin DL, CR Barnett, WD Arnold, RH Freiberger, & G Brooks. 1965. Untreated congenital hip disease: a study of the epidemiology, natural history, and social aspects of the disease in a Navajo population. Am. J. Public Health Nations Health 55 (Suppl 2): SUPPL: 1-44.
 
Blatt SH. 2015. To swaddle, or not to swaddle? Paleoepidemiology of developmental dysplasia of the hip and the swaddling dilemma among the indigenous populations of North America. Am. J. Human Biology 27: 116-128.

Wang e, T Liu, J Li, EW Edmonds, Q Zhao, L Zhang, X Zhao, & K Wang. 2012. Does swaddling influence developmental dysplasia of the hip? J. Bone & Joint Surgery 94:1071-1077.

Yamamuro T & K Ishida. 1984. Recent advances in the prevention, early diagnosis, and treatment of congenital dislocation of the hip in Japan. Clinical Orthopaedics and Related Research 184 4:40. 
​

Dr Carol Beuchat PhD

This is a basic but good video about hip dysplasia. I like it because it makes a clear point that puppies are not born with dysplastic hips, and that the development of the socket as the puppy grows is not genetically programmed.

You can learn more about the genetics of dogs in ICB's online courses.

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By Carol Beuchat PhD

It's tempting to assume that bad hips are the result of "bad hip genes", and that you can improve hips through selective breeding by breeding away from the troublesome hip genes.

But nobody can find those genes for bad hips. We can identify genes associated with hip phenotype (normal vs dysplasia) in a Labrador, for example, but those genes are not predictive of hip phenotype in German Shepherds. If there are different genes associated with hip dysplasia in each breed, we have a real mess - a genetic disease that is caused by different genes in every breed. This seems very unlikely.

You can learn more about the genetics of dogs in 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

Joint laxity (looseness) is a primary risk factor for the development of hip dysplasia. Laxity is the result of stress on a ligament inside the joint, the teres ligament, that attaches the head of the femur to the wall of the hip socket.

If the teres ligament is damaged, the round head of the femur is not held snugly in the cup of the hip joint. Because normal development of the hip is a response to the biomechanical forces on the socket during growth of the puppy, abnormal position of the ball in the socket can result in damage to the rim of the hip socket and the development of hip dysplasia. Proper development of the hip joint depends critically on the head of the femur being properly seated in the center of the hip socket. (You can read more about this in "The 10 most important things to know about canine hip dysplasia.")
​

​How is the teres ligament damaged? Some information about the cause of hip dysplasia in humans can illustrate.

​The hip sockets of dogs and humans are very similar. The head of the femur is firmly held in the hip socket by muscles and tendons. These are so tight, and the teres ligament so short, that at birth, the legs are held apart and slightly bent. If the legs are pulled together, the head of the femur is pulled away from the hip socket as in the illustration below. This puts abnormal stress on the teres ligament and can cause damage that results in laxity in the hip joint. 

The movement of the legs that puts stress on the teres ligament is called extension and adduction - straightening the legs and pulling them together. This is the reason why hip dysplasia is more common in cultures where babies are tightly swaddled than in those that carry infants on the back with the legs around the mother's waist. With this knowledge, new mothers are advised not to wrap up newborns like little burritos but instead swaddle them loosely with room for spread legs and bent knees. 
​

How does this matter to dogs?

The hips of newborn puppies are similar to those of humans.  The hip joint at birth is mostly cartilage, and it will be converted to bone over the first 5 months of growth. At birth, the teres ligament is very short and strong, and it becomes longer as the puppy grows, allowing more freedom of movement in the joint. Also like humans, a newborn puppy on its back will generally hold the legs apart and bent.

However, when a newborn puppy is placed on a surface with inadequate traction, its feet slide right out from under it just as yours do if you walk on ice in street shoes. In the case of the puppy, it tries to walk by pushing backwards with the hind legs, and if traction is not adequate, the legs and even the feet will extend to the maximum. You will notice this happening if you watch puppies in the whelping box and see the pads of the rear feet facing the sky instead of the floor. A puppy (and you) moves forward by pushing backwards. If there is inadequate traction, the legs will extend and adduct, exactly the position that results in damage to the teres ligament in human babies.

Most people that I ask tell me that their puppies are whelped on some material that has good traction. Vet bed, rubber mats, carpet, whelping pads, and many other things are routinely used in whelping boxes. I have tested all of them and more, and none provided adequate traction for every breed I tested or for the duration of the first few weeks of life as the puppy gains weight. 

How did I evaluate traction? I looked for the single give-away - extension and adduction of the back legs, looking like little puppies on popsicle sticks. If I saw pads facing the sky, the mat failed.

To be fair, I did find one mat that provided terrific traction. It was made from coconut fibers sticking straight up like broom bristles. It provided great traction, but it also took the delicate skin off the newborn puppy's foot pads. That too was considered a fail.

Here are some examples of what I observed watching puppies, and there are many similar examples to be seen in the volumes of puppy videos on YouTube if you care to browse (try searching on "newborn puppies nursing or crawling).

If you've been paying attention, you are probably wondering if the puppies in your whelping box ever reveal their rear foot pads because they're facing the sky instead of the ground. To give you some practice spotting the extended-adducted leg position (before you dash off to look at your photos!), check out these very busy puppies. At a casual glance, they look like they are getting around pretty well. But watch closely; these pups on this surface would fail the traction test.
​

I have made observations of hundreds of litters of puppies on all manner of surfaces, and so far the ONLY surface that provided adequate traction for all puppies (i.e., back legs were never fully extended and straight) was that coconut fiber mat that could take the skin right off the bottom of your feet. These are the mats you see inside large hotels in areas where it snows, so you can brush the snow off the bottom of your shoes with the bristles. They're designed to be harsh.

Now, this raises the obvious question. Is hip dysplasia the result of inadequate traction for newborn puppies in the whelping box? If it is, we could eliminate hip dysplasia now, simply by providing good traction that prevents slipping. It seems far-fetched, but if we haven't eliminated hip dysplasia after 60 years of strong selection, it's worth entertaining a new explanation.

​I've been working on solving this problem for the last few years. Finally, after fussing and fiddling with various types of surfaces, I have finally come up with one that prevents slipping and the damage to the teres ligament that can result in hip dysplasia. I am currently testing this surface on litters of various breeds of dogs, and so far it has worked well. I need to look at many more breeds and also observe the puppies over the first several weeks when their weight increases dramatically with growth. Of course, the acid test will be seeing if these puppies have sound hips, so some of these puppies will be scored at four months using PennHip, which quantifies hip laxity with the "distraction index." Will this ultimately solve the hip dysplasia problem in dogs? Time will tell. But I'm very optimistic.

​You can learn much more about hip dysplasia in ICB's online course, Understanding Hip and Elbow Dysplasia. 

By Carol Beuchat PhD

As we accumulate data from DNA testing, some interesting patterns are starting to emerge.

​A recent study has accumulated data for about 100,000 dogs, including about 83,000 mixed breed dogs and 18,000 purebred dogs representing 330 breeds (Donner et al 2018). For testing, the authors used a SNP array that tests for 152 known mutations, or "variants," at the same time. These tests cannot identify all mutations, only the ones that have been identified and localized at a particular SNP. So the data represent only a fraction of the actual number of mutations in the entire gene pool.

They organized their results in a Venn diagram, which identifies the number of mutations found in mixed breeds, purebreds, both, and not found in this population of dogs.

The data reveal that 34 mutations were only seen in mixed breed dogs, 13 were only seen in purebreds, and 25 were not found in this sample population. Of the mutations identified, 80 were found in both mixed and purebred dogs. If we add up the numbers for mixed and purebreds, we find that a total of 114 mutations (34 + 80) were found in mixed breed dogs, and 93 occurred in purebred dogs.

These results are very clear. More mutations were found in mixed breed dogs than in the purebreds. 

You might look at these data and conclude that this is proof that purebred dogs are healthier than mixed breeds. Would you be correct? 

Let's remember a few things. Recessive mutations are usually not expressed (i.e., they have no effect) unless the dog is homozygous for the mutation; i.e., to be affected, the dog must inherit two copies of the defective allele, one from each parent. A dog with only one copy of the mutation would be called a "carrier" and, for most recessive mutations, carriers suffer no ill effects.

One consequence of this behavior of recessive mutations is that a dog can be a carrier of many mutations but suffer no ill effects from any of them. In fact, because of this, recessive mutations can be passed from parent to offspring generation after generation without affecting the health of the dog.

Dogs that inherit two copies of a mutation (called homozygous, affected, or "at risk") are likely to display some negative effects like blindness, exercise collapse, a nervous disorder, or some other disturbance to a body function. If the consequences are severe enough, natural selection or the breeder will remove the dog from the population of breeding animals and those mutations are not passed on to offspring.

So we have two situations: in one, a dog carries a single copy of the mutation and suffers no ill effects (heterozygous), and in the other the dog carries two copies and the mutation is expressed as a genetic disorder.

Now look back at our Venn diagram. There are more mutations found in the population of mixed breed dogs. But what we need to know is whether they are homozygous and affect the dog, or heterozygous and are harmless.

This pair of graphs show the proportions of mixed breed and purebred dogs in which the mutations were heterozygous (left). The graph on the right shows the proportion of dogs in which the mutations were homozygous (right). Mutations in the heterozygous state on the left were found in both mixed and purebred dogs, but as we would expect from the Venn diagram above, more of the mixed breed dogs were carrying mutations (yellow arrow). The graph on the right shows what we really need to see: both mixed and purebred dogs had homozygous mutations, but they were much higher in purebred than mixed breed dogs.
​

​Here is what the study's authors had to say:

In a nutshell, here's what they found:

a) The collective population of mixed breed dogs contains more recessive mutations than that of purebreds, but those mutations are more likely to be heterozygous and therefore harmless.

b) On the other hand, there are fewer mutations found in purebred dogs, but they are far more likely to be homozygous, and therefore expressed as a genetic disorder, than in mixed breed dogs.

The fact that mixed breed dogs have so many mutations does not make them more prone to illness. In fact, they are less likely to be affected by a genetic disorder than purebred dogs, because the mutations are more often found in the harmless, heterozygous state. The mutation load in purebred dogs is smaller than in mixed breeds, but it is far more dangerous, because the mutations are much more often homozygous.

It is this simple property of recessive mutations, of only being expressed when homozygous, that results in the higher rate of genetic disorders in purebred than mixed breed dogs. 

This comparison of the health of mixed and purebred dogs is oft debated, and breeders usually argue that purebred dogs are just as healthy as mixed breed dogs. For problems caused by non-genetic disorders (broken bones, allergies, and the like), this could be true. But, for genetic disorders, the purebred dogs fare far worse than mixed breed dogs. It's a simple matter of the genetics of recessive mutations.

Why are there more mutations hanging around in the huge gene pool of mixed breed dogs? It's because recessive mutations are harmless if they are heterozygous, so they are not eliminated from the population by selection. The frequency of a specific mutations in the population is usually very low (< 1%, with a few notable exceptions, like the mutation associated with degenerative myelopathy, DM). The chances of any two random mixed breed dogs having the same mutations is low. Although a mixed breed dog can be affected by a genetic disorder caused by a recessive mutation if it inherits two copies, the chance of this happening is very low.

Breeding purebred dogs in a closed population means that all of the dogs in a breed are related and therefore share many genes in common. Some of these shared genes will be mutations. The more closely related the sire and dam, the more likely the puppies are to be afflicted with a genetic disorder caused by a recessive mutation.

This is why the best strategy for reducing the incidence of genetic disorders in purebred dogs is not endless DNA testing. To control the risk from all mutations, the ones you know about as well as the ones you don't, the best strategy is to reduce the relatedness of the parents. Reducing genetic disease in dogs boils down to reducing the risk of a puppy inheriting two copies of the same recessive mutation. The way to accomplish this is to reduce the relatedness of the parents. 

Mixed breed dogs have more mutations than purebreds. But they are less likely to be affected by genetic disorders because they are more likely to be heterozygous; i.e. have only one copy of the mutation.

REFERENCES

Donner J, H Anderson, S Davison, AM Hughes, and others. 2018. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. PLOS Genetics 14(4):31007361. https://doi.org/10.1371/journal.pgen.1007361

As breeders become more aware of the importance for genetic management to control potential genetic disorders, there are more and more discussions in groups about the best ways to do this. Little bits of information, packaged as what I think of as "pithy statements", are put forth as rules of thumb, and these are advocated as best practices. 

Somebody told me the other day that their group was thinking about making a rule prohibiting breedings that would produce COI > 10%, because they heard that 10% was the threshold of the "extinction vortex". She asked me if I thought this was a good idea.

This 10% extinction vortex statement is one of those pithy statements.

I advised her that breeders should NOT make a rule about this. Not because it's not true, but because "it's complicated."

Genetics can be complicated. The more you know about what's going on under the hood, the better decisions you will be able to make the next time you plan a litter. 

This would seem obvious, but in fact there are many nuggets of old "wisdom" that get passed around and around that are, well...not true. Yet, like a fly in the kitchen, it seems no amount of swatting at these untruths will get rid of them. 

Breeder! Unburden yourself of these myths! Embrace truth and science! Read on!

Common Breeder Myths
You've probably heard all of these. You've probably even repeated some of them. We will examine each of them. 
​

Breed only BEST to BEST
Look, don't breed the dogs that have no good points. But, just like in school, realize that there can be a lot of merit in "above average". In fact, if the parents of a litter were quality dogs, then the offspring inherited quality genes, but perhaps not always in the best combination. Don't toss out those valuable genes - mixed a bit differently, they could produce the next superior animal. Remember: Improvement through selection requires genetic variation. Keep a good variety of ingredients in the genetic pantry to choose from!

Inbreeding is required to fix type
The genes for breed type should be fixed in the first few generations after breed formation. Once the breed has the qualities that define it, further inbreeding simply increases homozygosity in the other "dog" genes, for things like toenails and kidneys and glucose metabolism and saliva. If there are some mutations among the thousands of genes in the dog (and of course, there are!), then inbreeding will inadvertently produce paired (homozygous) mutations for some genes. For these, whatever the normal gene is supposed to do will be broken.

​Other domestic animals have clearly recognizable breeds with much lower levels of inbreeding than are typical in dogs. Most purebred dog breeds have average inbreeding in excess of 12%, and about half of the breeds are greater than 25%. In horses, most breeds are less than 12%.

Close the stud book to protect the breed
If the stud book is closed, genes will be lost from the gene pool through selective breeding and "genetic drift" (chance). If you start a breed with a founder gene pool, then lose genes every generation that cannot be replaced, eventually the gene pool will be depleted. You can easily test this with a bowl of M&M's on the coffee table. Grab a few when you need that chocolate fix, but don't put any back. Eventually, the bowl will be empty. 

The rule of thumb here: Animals in closed gene pools go extinct.

Really? Is this always true???

In fact, no. There is a very famous herd of cattle in England, the Chillingham cattle, that has survived for centuries as a closed gene pool. They are the iconic exception.

But every other closed population has gone extinct, and yours will too. You can count on it.

I know what's in my line
You probably know about dominant alleles. They mask the expression of recessive alleles. You cannot know what recessive alleles are lurking in your gene pool as long as expression is masked by a dominant allele. You could unmask recessives using inbreeding, because as we saw above, inbreeding breaks things. Or you could avoid inbreeding, not worry about the recessive lurkers, and keep that doggy working like a well-oiled machine.

Outcrossing introduces new diseases
Outcrossing does not "introduce new diseases". It introduces new alleles, some of which will probably be recessive mutations. But single mutations do not usually produce disease. In fact, as noted above, most recessive mutations are masked by dominant, normal-functioning alleles and produce no ill effects. Eliminate this problem by following a simple rule of genetic management: keep recessive mutations rare. So no popular sires! 

And remember from above: Inbreeding breaks things.

Hybrid vigor doesn't apply to dogs
Hybird vigor results when you "undo" inbreeding by mating two animals that are relatively unrelated. Inbreeding applies to dogs. So hybrid vigor applies to dogs. 

No, it hybrid vigor not require different species. In fact, most interspecific hybrids are infertile and not terribly vigorous.

Nothing will make you look dumber than declaring that hybrid vigor doesn't apply to dogs.

Do yourself a favor. Look this one up. So you never forget.

If you're a dog breeder and you believe in genetics (of course you believe in genetics!), you know that there is a certain predictability in breeding that is the result of genes being passed from parent to offspring. You take advantage of your understanding of the process of inheritance when you breed for certain colors, or you use a taller sire to put a bit more leg under your next litter. 

On the other hand, as most breeders will tell you, "breeding is a crap shoot". You are trying to breed for one a particular trait in your puppies and get instead a litter of puppies with something else or, even worse, a mish-mash of variety that beggars your belief in genetics.

Of course, the problem here isn't that understanding genetics is worthless. It's that you are trying to select a breeding pair based on the genes you would like them to pass on to their offspring. You are trying to select for particular genes, but you are assessing the genetic merit of a dog for a particular trait based on its phenotype - how those genes are expressed in a dog. This method of selection - evaluation of phenotype - only works well if phenotype is a good indication of genotype. As anybody who has ever bred a litter of dogs knows, for some traits phenotype is a good indication of genotype, and for other traits it isn't.

The most important concept in selective breeding is "heritability". If you ask 10 breeders to define heritability, I can almost guarantee that most will get it wrong. Most people will define heritability as the inheritance of a particular trait by a dog.

​But actually, heritability is a concept from population genetics. Heritability tells you how much of the variation in a trait in a group of dogs is the result of differences among them in their genes.

Now, let's say we could create an exact clone of each of those puppies and raise that duplicate litter separately. Each puppy goes to a different home, is fed differently, exercised differently, and raised under conditions that are unique to that puppy. Now when you measure the weight of each puppy at 1 month, you will probably get different numbers compared to each pup's clone, and there will probably be more variation in the litter. The pups have exactly the same genes, but ended up at 1 month with different phenotypes. We know that genes are important to weight, but in this case there are clearly effects of environment.

Here is where most people get tripped up on the definition of heritability. In the first example, the heritability of weight will be equal to 1. In the second example, the heritability of weight will be less than one, perhaps something like 0.3. Same trait, different heritabilities. Why? Because heritability is not about a particular trait in an individual, but rather tells us about the trait in a population of dogs. Here's why.

The phenotype of most traits depends on both genes and environment. We could write this in shorthand as

So for our example of weight in puppies above, the puppies in first litter were raised in identical environments, so the "E" term in our little equation is 0; there is no effect of environment on puppy weight, and all the variation you see among the puppies is due to genetics. So for these puppies, the heritability of weight is 100%.

I don't want to get into the details of heritability and how it is determined (these are things we discuss in the ICB courses). Rather, I want to make a simple but extremely important point. 

When you assess particular breeding combinations, you use whatever information you have about phenotype of the parents or relatives to make assumptions (or guesses, really) about the genes each parent is likely to pass on to each puppy. If the heritability of weight at 1 one month is 1.0, as for the first litter, you know that 100% of the variation in weight from pup to pup is due entirely to genetics. If you wanted smaller size in your next litter, you should keep one of the smaller puppies to breed and you should also get the genes for smaller size.

But what about the second litter, for which heritability of weight was only 30% because there was lots of variation in how they were raised? If you want smaller pups in your next litter, you can't assume that you are correctly selecting the genes you want for size just by the weight of the puppies. Some pups might have had more to eat, some might have been couch potatoes and put on some puppy fat, some might have been slow eaters and never got as much to eat as the others. In this case, phenotype is not a very good indication of genotype; there is lots of variation in phenotype because the "E" term in that simple equation above is not zero.

Okay, here's the rub. For most of the traits you want to select for (or against), there will be multiple genes involved as well as non-genetic factors that will affect phenotype. If you select the pick of the litter based on phenotype alone, you will not necessarily be selecting the puppy with the best genes for that trait. For puppy weight with a heritability (in our example) of 0.3 (30%), most of the variation in phenotype (70%) is because of things that have nothing to do with genetics. If your strategy for selection relies heavily on the phenotype of the dog, you are more likely to be wrong than right. 

If you don't know the heritability of a trait you are trying to select for or against, you are likely to make a lot of incorrect decisions based on phenotype alone. If you're assuming the heritability of a trait is 1.0 - i.e., what you see is what you get - you are going to have a lot of those "breeding-is-a-crap-shoot" experiences, selecting for one thing and getting something else. On the other hand, if you know that the heritability of a trait in dogs raised in uncontrolled conditions (different households, various diets, variable amounts of exercise) is 0.15, then you should understand that phenotype is not a very good reflection of the genes for that trait in an individual puppy and that you will not be very good at selecting the puppies with the genes you want. On the other hand, if the heritability of trait is typically 0.8, then phenotype will be a decent reflection of the genes for that trait inherited by that dog.

The critical point here is that heritability tells you how much of the variation in a trait is due to variation in genetics. If heritability is low, efficient selection will be difficult because phenotype is a poor reflection of genotype. If heritability is high, more of the variation in the trait among individuals is a result of genetics, so selection based on phenotype will be more effective.

There are ways to get around the limitations of selection when heritability is low. One is to use information about the relatives of a particular dog. If the heritability of hip dysplasia in a breed is usually about 0.2, and you found a sire you like but his hip score is mediocre, have a look at the hip scores of his litter mates, his parents, and, if he has already been bred, his own offspring. All of this information will provide clues about the genotype of that sire you like. If his relatives have good hips and he is the outlier, you can have more confidence that he probably has good genes, but perhaps he had an unfortunate experience as a puppy or was overindulged by an owner who fattened him up by rewarding everything he did with a cookie. You can do this assessment statistically using something called "estimated breeding values" (EBVs), which does some fancy math and comes up with a number that tells you about the quality of genes in a dog for a particular trait. (Some kennel clubs now provide EBVs for hip dysplasia.)

Hate that "crap shoot" part of breeding? You can reduce the guesswork in breeding by understanding heritability. Know the typical heritability of the trait you are selecting for, and take that into consideration when you evaluate phenotype. And also make use of information available from the ancestors, siblings, and descendants of a dog, because those animals share many genes and can help you decide how much weight to put on your assessment of phenotype when you are trying to select for particular genes.

Breeding will always have an element of chance, because that's how genes are inherited. But it doesn't have to be a crap shoot. Understanding how to use some simple tools like heritability can help you make better decisions and result in more predictability and consistency in your puppies.

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

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​

Breeding strategies should not be ideologies. They are the means to achieve a genetic end, and the savvy breeder will use them appropriately. Breeds with small gene pools that can no longer produce healthy dogs have to use breeding strategies to fix that problem, and in many cases cross-breeding is be necessary. This is the case with the Norwegian Lundehund, a breed on the brink of extinction that is bouncing back thanks to a scientifically managed cross-breeding program. There are other genetic rehabilitation projects ongoing that involve cross-breeding, all under the guidance of scientists with appropriate expertise. Cross-breeding is not a philosophy. It is a breeding strategy, and one I would point out was used routinely by "purebred" dog breeders 100 years ago because they understood that a strictly closed gene pool was unsustainable. They didn't do it because they were "pro" crossbreeding; they did it because it prevented the deterioration in health of their animals that resulted from too much inbreeding. Modern dog breeders have forgotten that lesson, and the long list of genetic disorders in dogs is the predictable result.

I do not have a "personal stance" about any aspect of dog breeding. I am not a dog breeder; I have no opinion about how to do it. I understand the science of breeding and the role of population genetics in determining the health of the gene pool and the population of animals. Everything I say is based on facts.

This isn't the first time somebody has rushed around fear-mongering about me. I am happy to tell you completely, clearly, exactly who I am and what I am doing. My "alignment" is to science, and to the professional scientists whose expertise and research is essential to understand how we can improve the breeding of dogs. I communicate with them, I collaborate with them, and I respect them. I get my information from them and the army of other scientists that are working towards improving the health of dogs, not from people on Facebook with opinions and no expertise. I suggest you do the same.

As a final note:
The International Partnership For Dogs (IPFD) is an organization of kennel clubs, canine health organizations, scientists, genetic testing organizations, and others involved in improving the health of dogs. They met just a few weeks ago in the UK to discuss issues affecting the health of purebred dogs. The producer of Pedigree Dogs Exposed was there, as she was for all of the previous meetings of IPFD. A committee was formed to address issues of genetic diversity in dogs, and she was placed on that committee. She has the respect of the people at that meeting, and if they respect her, so do I.

So stop the fear-mongering. Do your homework. Read the science. Learn something. Align yourself with the people that have the passion and expertise to do right by dogs and are working towards better health based on science.

​A paper has just been published that is being grossly misinterpreted by the press, and even by the Institute where the study was done (Marchant et al. 2019). This is the title of the study:

​These are the critical points of the study:

A) Norwich Terrier

• This is a study about breathing problems in the Norwich Terrier.
• The study found a gene that causes swelling of the airway tissues of Norwich Terriers, which iinterferes with breathing.
• The Norwich Terrier is not a brachycephalic breed.

B) Other breeds

• They also found the mutation in most Bulldogs.
• They found the mutation in only a few French Bulldogs.
• They did not find the mutation in Pugs.
  
  

C) Brachycephaly

• The Norwich Terrier is not brachycephalic, so the effect of this mutation is not linked to brachycephaly.
• Most French Bulldogs do NOT have the mutation.
• The mutation is absent in Pugs.
• Therefore, this gene is NOT the main cause of breathing problems in Bulldogs, Frenchies, and Pugs..

From these points, it is obvious that the press release issued by the Roslin Institute, where the study was done, is incorrect. This is what they said:

​"Dog DNA find could aid breathing problems
Scientists have discovered a DNA mutation linked to breathing problems in popular dog breeds.

Breathing difficulties are most often associated with flat-faced breeds, such as French bull dogs and pugs, but scientists have found the mutation is also carried by Norwich terriers, which have proportional noses.
​
The finding could inform future genetic tests that could help vets identify animals at risk, and help breeders avoid producing affected pups."

Read the points above. This study did not find a mutation that causes breathing problems in brachycephalic breeds. Only a few Frenchies had the mutation, and it is completely absent in Pugs. The mutation was found in Norwich Terriers, where it has NOTHING to do with brachycephaly because the Norwich Terrier is not brachycephalic.


This article is also wildly incorrect. The gene was not found in Pugs. So no, this is not the gene that makes Pugs wheeze. The gene does occur in Bulldogs, but this study did not examine whether it is a cause of breathing problems in this breed, for which there is much evidence that the brachycephalic head shape is a major risk factor for breathing issues. This piece doesn't even mention the Norwich Terrier. In fact, this headline should have said something like "Mutation that causes breathing problems in Norwich Terriers is not the cause of problems in brachycephalic breeds."
​

I repeat AGAIN:

​No, we have NOT found the mutation that causes breathing problems in brachycephalic dogs.

This is NOT a breakthrough for health issues in brachycephalic dogs. In fact, it essentially rules out this particular gene being a significant cause of the problem because it is absent in Pugs and relatively rare in Frenchies, both brachycephalic breeds, and it is linked to the breathing problems in the Norwich Terrier, which is NOT a brachycephalic breed. 

Only a day after publication, the social media groups for owners and breeders of brachycephalic breeds are all a'twitter with news of this terrific research development which (they claim) vindicates flat faces as the cause of breathing problems in their breeds. This study does not do that.  

REFERENCES
Marchant et al. 2019. An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.
PLoS Genetics 15: e1008102. https://doi.org/10.1371/journal.pgen.1008102

Hip dysplasia remains one of the most significant causes of pain and disability in dogs despite decades of research into the causes and diligent efforts by breeders to reduce risk through selective breeding. A new review article aimed at veterinarians provides a useful summary of the current state of our understanding of its causes (Witte 2019). The comments here are detailed in that review.

A number of non-genetic (environmental) factors are known to affect the risk of developing hip dysplasia, and some of these appear to be especially critical to manage properly in the puppy. Housing on a slippery floor, access to stairs, and some types of exercise can significantly increase risk in puppies. Higher weight at birth and while growing elevates risk. On the other hand, dogs raised on farms and those born in spring and summer are less likely to develop hip dysplasia. Aside from nutritional deficiencies, or overconsumption that leads to overweight, there is no evidence that the type of the diet plays a role in development of dysplasia. Although exercise in the adult might lead to clinical signs of pain or lameness, there is little evidence that the amount of exercise alters the progression of development of osteoarthritis once the dog matures. Dogs neutered before 6 months have a higher risk of developing hip dysplasia.

Managing the risk of hip dysplasia remains a challenge for breeders and dog owners. Breeders must consider both genetics in mate selection and environmental factors, especially when the puppies are young. When puppies go to their new homes, owners must be educated about the factors that elevate the risk of developing hip dysplasia, especially weight, stairs, and unsuitable exercise and activities.
​
​

REFERENCES
Witte PG, 2019. Hip dysplasia - understanding the disease. Companion Animal 24:77-81.

The adrenal cortex is the outer layer of the adrenal gland, which is a small organ near the kidneys. It secretes hormones that are part of the stress response (e.g., cortisol), and it also produces aldosterone, a hormone essential for maintaining normal levels of minerals involved in the regulation of blood pressure.

In some dogs (and in humans), the immune system fails to recognize the tissue of the adrenal cortex as "self" and destroys it. The result is Addison's disease, which can be fatal. Addision's is especially common in some breeds, including Standard Poodles, Portuguese Water Dogs, Cocker Spaniels, Nova Scotia Duck Tolling Retrievers, and Bearded Collies. The frequency in Poodles is relatively high, estimated at 5-10% (Famula et al. 2003).

Studies looking for a genetic basis for Addison's have identified SNPs that might be associated with the disease, but causative genes have not been found. Because Addison's is an auto-immune disease, we might expect to find relationships between risk and the genes of the immune system. In dogs, these genes are called the dog leukocyte antigens (DLA), and they come in combinations called haplotypes. There has been some success in identifying DLA haplotypes that confer risk of disease in several breeds (Hughes et al. 2010, Massey et al. 2013, Pedersen et al. 2015). 

A study just out takes a closer look at the association between DLA haplotypes and Addison's Disease in Poodles, using a larger sample size than previous studies and also looking for potential associations related to sex of the dog (Treeful et al. 2019). The results are both interesting and sobering. While the data are for Poodles, the implications are relevant for every breed, so you should read this even if you don't have Poodles.

​Furthermore, haplotypes 2-8 and "other" are uncommon in the breed, which means that the options for "breeding away" from haplotype 1 to reduce the incidence of Addison's in male dogs will be limited by the paucity of dogs to breed to.  Haplotype 5 is a risk for females, presenting similar problems.

The problem here is that we know very little about the DLA genes and how they work. In mammals, the immune system genes have the highest diversity because the individuals with the most diversity also have the highest rates of survival. This tells us that high diversity is important, and we can surmise that low diversity will compromise the function of the immune system. In dogs, limited diversity from a small number of founder dogs, together with inbreeding and loss of diversity through selection and genetic drift, has resulted in both reduced diversity and uneven representation of haplotypes as seen in the Poodle, where haplotype 1 is overrepresented.

Breeders are likely to be strongly tempted to use information about DLA haplotypes to inform breeding decisions, based on the perception that the frequencies of some allele should be increased and others decreased. Dr Lorna Kennedy, who has studied the canine DLA genes for many years, cautions against this. (Note that Kennedy uses the term MHC, which stands for "major histocompatibility complex,"  the broad class of immune system genes to which DLA belong.)

The one recommendation Kennedy makes is to avoid producing puppies that will be homozygous for DLA haplotypes. Otherwise, as she notes, because the interactions among genes are complex and the workings of the immune system poorly understood, breeders should not attempt to alter haplotype frequencies through selective breeding. At the very least, if there is a serious problem in a breed, breeders could consult with experts that can advise on the best course of action.
​

Perhaps the best strategy, once again, is to protect the existing genetic diversity in your breed and avoid producing homozygosity by inbreeding. 

Breed Status

1. Breed history
2. Current number of dogs and locations
3. Pedigree information
4. Health information

Threats to sustainable breeding

1. Small population size
2. High inbreeding
3. Inbreeding depression
4. Small effective population size (Ne)
5. Health issues
6. Not enough breeders
7. Inadequate guidance for breeders

Breed-specific concerns

1. Iconic Norwegian dog of high cultural importance
2. Preservation of unique anatomical and behavioral traits​

​

• Increase the size of the population
• Reduce breeding age of bitches to 15 months
• Breed at least one litter from every healthy bitch
• Develop methods to assess breed-specific traits
• Develop methods to assess temperament and breed-typical behaviors
• Use DNA genotyping to assist mate selection
• Develop a comprehensive strategy for data collection on dogs, litters, health, etc.
• Develop an efficient breeding strategy using population genetic analyses
• Assess efficiency of breeding strategies using appropriate computer models

​

From the start, the Norwegian breeders progressed step by step following a planning strategy, the major outline of which was developed for general goals (e.g., increase the size of the breeding population), with tweaks and adjustments as necessary as the plan progressed. These breed-specific breeding plans are called "Rasespesifikk Avls-Strategi" (RAS) in Norwegian.

The first step in the development of a sound breeding strategy is determine what you have to work with, and a review of history to understand how past events have shaped the current population of animals. For this, they did a comprehensive review of history, documenting the historical use of the breed for Puffin hunting, events that affected population size and breeding such as disease outbreaks, legislation, changes in culture, kennel fires, and replacement of dogs with other hunting methods. They developed a pedigree database that was as complete and error-free as possible. They documented fertility, litter size, mortality, and disease when information was available. They also summarized historical changes in the level of inbreeding, number of sires and bitches in the breeding program, offspring per individual, and imports and exports.

​Threats to sustainable breeding
After assessing these data, they identified the problems that needed to be addressed and articulated the goals to solve them. For this, breeders worked closely with animal breeding experts and population geneticists at NordGen who assisted in developing and testing the particulars of the plan.

These were summarized as:
​ 

​Breed-specific concerns
There's no point in doing a genetic rescue if the dogs produced at the end aren't the breed you started with. A critical part of any program is to have a clear picture of the critical traits of type that make the breed unique so the breeding program preserves those in the dogs that result. These traits would include physical features like size, color, coat type, proportions, shape of ears, tail, feet, and muzzle, and also instinct and behaviors, temperament, features specific to purpose, conformation including gait, shape of eye, proportions and planes of the head, and so on. A special consideration for the Lundehund is the preservation of their extreme flexibility in the shoulder and neck joints, polydactyly, ability to fold the ears, rotary front movement, and double coat that is waterproof and warm. Overall, the goal is to produce dogs with good Lundehund type that are healthy and fit for function.
​

​Development of a breed-specific breeding plan (RAS)
The specifics of the RAS planning schedule are in their document (download below), which is broken up into sections that focus on specific aspects of the breeding plan. You can review that document, but here are some of the highlights: 

​The size of the breeding population affects critical aspects of genetic management. As for the Condor, the success of the breeding population will hinge on increasing the census number of individuals as rapidly as possible. This will improve genetic stability (chance fluctuations of gene frequencies) and broaden the options for breeding. A top-level concern for the short- and long-term goals of the program was to increase the effective population size (Ne), setting a goal of Ne = 200 (90 males and 110 females) by 2020-2025, as well as increasing the total census size of Lundehunds in Norway to 1,000 by 2025.  It was stipulated that the highest recommended inbreeding coefficient is 3.25, based on a 5 generation pedigree.

You can download these two RAS documents, which lay out the information and goals for the Lundehund breeding program. Note that the date ranges are a bit different, which I suspect reflects updates in the plan as they progressed
​
Download RAS Schedule (2014-2025):  Breeding strategy for the Norwegian Lundehund
Download RAS data summary (2014-2018):  RAS – breeding strategy for the Norwegian Lundehund

Many dog breeds are struggling to manage a growing list of genetic disorders at the same time as the options for managing inbreeding are becoming more and more difficult. Avoiding problems with the known mutations and lines producing complex diseases only shifts selection away from one corner of the gene pool and towards another, producing an ever-narrowing bottleneck that ultimately only makes matters worse.

The holy grail is discovery of a population of dogs that has been isolated for generations and contains genetic diversity long lost in the main population of dogs. Failing this, however, many breeds do in fact retain enough genetic diversity to improve health and open up new options for breeding. But when a breed reaches the limits of improvement using the diversity remaining in the breed, the only other option is to restore the genetic diversity that has been lost to selection and genetic drift. ​

The goal here is to outline a basic program to rehabilitate or rescue a dog breed that is facing challenges due to inbreeding, small population size, low genetic diversity, or other factors that make sustainable breeding difficult. The path to genetic improvement will be different for every breed, but the considerations are generally the same, so this can provide a rough template for the rehabilitation or rescue of any dog breed.

​
Genetic assessment of the breed from pedigree & 
​DNA data

Central to the development of a plan for genetic rescue is information about the current
genetic status of the breed. The pedigree database is a primary source of historical genetic
information, and DNA analysis can now be used to supplement this with much detail about
actual genetic diversity, gene frequencies, inbreeding, relatedness, etc.

Historical Information From Pedigree Data

1. Number and identity of founder dogs
2. Changes in population size over time
3. Loss of genetic diversity
4. Changes in effective population size
5. Average inbreeding over time
6. Average kinship over time
7. Genetic contributions of founders
8. Addition of unrelated dogs (new founders)
9. Fraction of dogs used for breeding

Genetic Information From Pedigree Data
The pedigree database can provide a significant amount of critical data about the current genetic status of the breed, including several measures of genetic diversity, genetic composition of current dogs, size of the gene pool, relatedness of dogs in the population, etc.:

1. Level of inbreeding (coefficient of inbreeding, F, or "COI")
2. Genetic relatedness (mean kinship, mK, and average mK for the population)
3. Effective number of founders (fe)
4. Eeffective number of ancestors (fa)
5. Founder genome equivalent (fg)
6. Effective population size (Ne)
7. Origin of genetic variation

​

Genetic assessment of the breed from DNA data

Genotyping using high-density SNP chips (e.g., Illumina CanineHD SNP chip; > 170k markers) can provide a wealth of information about the genetics of the current animals in the population, and it can also be used to estimate historical trends in effective population back hundreds of generations. Information from DNA analysis will be "realized" instead of "estimated" or predicted, because it is based on DNA marker status and not on probability of allele inheritance from pedigree data. 

Genetic information from DNA genotype analyses (SNPs)

1. Genetic diversity (observed and expected heterozygosity, Ho & He)
2. Genetic structure(Fst)
3. Current and historical effective population size (Ne)
4. Genomic inbreeding (as F)
5. Genomic inbreeding relative to the population (Fis)
6. Genomic kinship coefficients and kinship matrix
7. Fraction of polymorphic loci
8. Population genetic structure (e.g., principal components analysis, cluster analysis)
9. Genealogical relationships determined from DNA and cluster analysis
10. Assessment of disease risk without knowledge of the genes involved or mode of inheritance
11. Localization of inbreeding on individual chromosomes (runs of homozygosity, ROH)
12. Genetic relatedness to other breeds
13. Across-breed comparisons of patterns of homozygosity on the chromosomes (ROH)​

​

Assessment of Potential Breeds for Crossing

The goal of a genetic rescue is ideally to restore a breed to its original genetic state. We rarely know what that is, but 

​Phenotype Information

1. Size and weight
2. Conformation (e.g., proportions, topline, tailset, head size, athleticism)
3. Specific features of type (e.g., ears, skull, coat  type)
4. Temperament and behavior
5. Purpose

Genetic Information

1. Inbreeding and mean kinship within cross breeds
2. Haplotype sharing of cross breeds with other breeds (indicating historical relatedness or crossing)
3. Genetic relatedness to rescue breed
4. Shared blocks of homozygosity with rescue breed
5. Potential to produce genetic diversity in F1 crosses

By Carol Beuchat PhD

Okay, what other things do we need to think about in the process of getting from generation 1 to 2, and from 2 to 3, and onward?

If we had a population of dogs that were healthy and terrific examples of their breed, and we wanted to replicate that in the next generation, what should we do? We should make copies of all of the genes in all of the dogs of our founding populations, mix those genes up, and package them into puppies that will become the healthy dogs of the next generation.

And for the next generation? We want to do the same thing. Gather up all the genes in that first generation, replicate every single one, give them a good mix, and distribute them in the puppies of the next generation.

Of course, we might want to change something about the dogs - make the legs longer, or produce more dogs of a particular color. We can use our skills as a breeder to preferentially breed the dogs with the traits we want, using the magic of selective breeding. We make more copies of the genes we want by breeding more of the dogs with those genes, and this changes the mix of genes in the gene pool in the direction of creating dogs with the traits we want.

In a perfect world, we could continue like this forever.

But our world is not perfect. Not every gene in the current generation will end up in a new puppy, either because we have chosen not to breed some of the animals (selecting for longer legs or whatever), or simply by chance. Over time, selection and random chance will shape the nature of the gene pool, changing the frequencies of genes little by little with each generation.

If we started with founder dogs of perfect health, we want to make sure all the critical genes for health get passed from generation to generation so we continue to produce healthy dogs. But what happens if we lose a few of those, either by selection or chance? The Dalmatian, for instance, inadvertently lost a critical gene for nitrogen metabolism, with the result that the dogs suffered from the formation of urinary stones. How did breeders fix that problem? They put the critical gene back in the gene pool. They did this by crossing a Dalmatian to a breed similar in structure (the pointer), then selected the offspring that inherited that critical gene, which is identical in all dogs. It was a brilliant and simple fix. With each backcross into the breed population, with selection of the offspring that inherited that gene, the frequency of the new gene increased, the fraction of pointer genes in the gene pool dropped exponentially, and in a few generations the dogs were genetically pure Dalmatian.

Now, we have technology that might someday allow us to go in and replace that single lost gene using something called CRISPR. But it was easily restored, not with technology, but with clever breeding in a single cross.

Back to our hypothetical breeding program. If we have been randomly (by chance) or deliberately (by selection) losing genes every generation, and all the genes in our founder dogs were essential for some function, we can expect some things are not going to not work like they're supposed to. These broken things become genetic disorders - allergies, temperament problems, low infertility, cancer, kidney disease, heart failure, and any of a very long list of canine maladies.

We understand why this happens.

If we start with a population of healthy dogs and want to keep them that way, there's one critical thing we need to do - make sure every single one of the "dog" genes - the ones necessary to build a healthy dog - is passed on to dogs in the next generation, generation after generation after generation. ​​Fiddle with the genes for type all you want, but you have to protect that original collection of "dog" genes that are necessary for building dogs that are healthy and fit to do what they were bred for.

This is the critical feature of preservation breeding. If we don't do this, we will break things.

Reality
To be fair - and realistic - it's nearly impossible to get all the genes of one generation into the next one, even if that was our sole aim as breeders. It certainly doesn't happen if we breed in a way that guarantees that some genes will be lost, and the two obvious ways this can happen is just by chance (an inescapable property of genetic inheritance) and by selection. Dogs that are bred will pass on only some of their genes; and dogs that are not bred pass on none.

If we replaced each critical "dog" gene lost like they did for the Dalmatian, we could keep a healthy population of purebred dogs forever. But if those critical genes are not replaced, there will be a deterioration in the health and function of our dogs over time. We should expect this; it's an inescapable consequence of losing genes from the gene pool each generation.

As purebred dog lovers, this is where we are. We have dogs with great genes for type - the particular traits that make each breed unique - but we have all sorts of problems with function, even to the point where breeding has become difficult in some breeds. We are hoping to cope by indentifying the critical genes that have been lost (by looking for the broken genes that have taken the normal gene's place), and we are spending millions studying the diseases that have resulted from loss of a particular critical gene. But neither of these efforts is solving the problem because we are still missing the normal copies of those critical genes.

What else could we do to solve this problem of missing genes? Why not the obvious? Why don't we just put those lost genes back, or make more copies from the dogs that have them? For some problems, it will be just a single gene as it was in the Dalmatian. In some cases, it might be multiple genes that together are necessary for some important function. But if we understand that every gene in those founder dogs played an essential role in building a healthy dog, it should be obvious that the only solution to a problem caused by missing genes is simply to put them back. In fact, this is really the only solution to the problem. Without that critical gene for nitrogen metabolism, the Dalmatian will produce urinary stones - in fact, any dog missing that gene will produce urinary stones. To solve the problem, put the normal gene back in the gene pool.

The key element of preservation breeding
If you want to have a sustainably breeding population of purebred dogs, you have to prevent the loss of the genes necessary for function from one generation to the next, or you have to replace the genes that are lost. We can't do the first if we practice selective breeding (which of course we do), so we have to solve the problem by replacement. To get back to healthy dogs, we need to restore the gene pool needed for health.

If a critical gene has been lost from one subpopulation of the breed (e.g., the dogs in the UK, or the bench lines of a retriever), it can be restored from dogs in another population that have retained that genes. In fact, there are breeding strategies that will reduce the loss of genes from a population over time by taking advantage of the ability to restore a lost gene from another population of dogs in the breed. This strategy is used by animal breeders that want to breed from a particular population of animals for many generations. It involves some clever population management and rotation of dogs among several populations that are maintained by inbreeding. In fact, this is how wild animal populations are able to persist for thousands of generations. Individuals from one population migrate to another, brining with them some of the genes that were lost over time in the new population. If populations are prevented from doing this, if they are isolated on an island for example, they eventually lose so many of the genes necessary for function that they go extinct.

For some dog breeds, critical genes might be lost from the entire gene pool, as the nitrogen metabolism gene was for Dalmatians. To replace those genes will require crossing to another breed that is selected to address the specific genetic problems most efficiently. Crossbreeding is routinely used in animal breeding to change particular  traits or to restore genetic health when there has been a loss of genetic diversity.  Cross-breeding is just one of several strategies breeders can use to achieve particular goals. Inbreeding, linebreeding, outcrossing, and crossbreeding are all used strategically by breeders to "shape" the gene pool so it best serves as the genetic pantry of ingredients you use in your breeding program.

The secret to producing healthy animals generation after generation - not just purebred dogs, but animals of any sort - is to maintain a gene pool that contains all the genes necessary for health. Protect the genes you have, and replace the ones that are lost, and you can breed healthy dogs forever.

It would be fair to say that the pioneering studies conducted by Scott and Fuller using dogs in the 1950s and 1960s gave birth to the modern scientific discipline of behavioral genetics. It has only been in the last decade, however, that dogs have again caught the interest of biologists interested in the evolution and domestication of dogs, and once again research on dogs is pushing forward the fields of animal behavior and cognition.

With the availability of affordable DNA analysis that can provide information about hundreds of thousands - or even millions - of markers, we have started to look for the genetic basis of behavior at the level of the gene. A few genes have been identified that are associated with specific behavioral traits in dogs, like xxxxxxxx (Bridgett). There is also a growing number of studies that looked for the genetic basis of behavioral differences in dog. But as I explained in an earlier post, the associations of behavior with genes have been generally weak and not especially useful for identifying genes of major effect or improving traits through genomic selection. 

A new study, however, is a game-changer (MacLean et al 2019). It has been made available before submission for publication, so it has not been subject to peer review and you should keep that in mind. But what it offers is a tantalizing first look at links between genes and behavior in dogs. 

Previous studies have looked for variation in genes that could account for differences in behavior in a group of dogs. The strength of the association between genetics and a trait is indicated by a statistic called "heritability", and in most studies of behavioral traits in dogs of a particular breed, the heritability was found to be low; i.e., variations in behavior were not associated with genetics.

Instead of focusing on a particular breed, the new study looked for major differences in behavior and genetics across many breeds. And here, they were successful.

In this study, a large set of behavioral assessments from CBARQ testing of > 17,000 dogs was paired with DNA genotyping data for > 5,600 dogs of 141 breeds  by combining information from two separate studies (Hayward et al. and Parker et al.) that used the current gold-standard analysis platform (high density SNP markers; > 100,000). They identified 14 behavioral traits of interest and looked for differences in the behavior of breeds that appeared to be associated with differences in the DNA, which would tell them the heritability of these specific traits.

​What they found was fascinating.

In this graph, the behaviors they looked at are indicated down the y-axis, and the strength of the association between genetics and the trait, i.e., heritability, is on the x-axis. The stronger the association, the higher the heritability. The grey dogs are measurements of heritability made on dogs of the same breed. The green and yellow dogs display heritability of those same traits when the associations are made looking across breeds.

You can see here that heritabilities determined from dogs of the same breed are generally low, less than about 0.3, which means that 30% or less of the variations in behavior can be attributed to variations in genotype.

But when you compare across breeds, the average heritabilities are high, from about 0.4 (40% of variation explained) to more than 0.7 (70% of variation explained.

This is very exciting, because it's the first time we have been able to detect strong links between genes and behavior. 

This is a game-changer. Our understanding of the genetic basis of behavior in dogs has gone molecular.

We now have large databases for both behavior and genotype, and these will continue to grow in size because the methodology for both is standardized (CBARQ for behavior and high-density SNP for genotype). These allow us to do analyses like the one below, which is a "heat map" that depicts the behavioral scores by breed displayed along with the dendrogram displaying their genetic relatedness. You can easily find the sporting dogs because they are high in trainability, and the small breeds like the chihuahua, rat terrier, and miniature pinscher stand out for scoring  high in traits that we might describe as reactive or "fiesty" (e.g., aggression, fear). The herding breeds score high in trainability while the hounds are low. And now we are finally able to explore the genetic basis for major breed-specific differences in behavioral traits among dog breeds. 
​

This paper will need to go through peer review, revision if necessary, then publication, so don't expect to see the final version for at least a few months. But I suspect we're about to see a flood of studies that also leverage the large datasets now available for both behavior and genetics. Buckle up!

NOTE: If you are interested in the links between genetics and behavior, now is the time to start boning up on the jargon and concepts you need to understand these studies. You can find relevant articles in the blog posts on the ICB website (just search for a topic or keyword). Even better, ICB has courses designed for dog people with no background in science that will get you up to speed. This genie is out of the bottle. A little homework now to learn the basics will pay off every time you read about an exciting new paper about the genetics of behavior in dogs!

Wow. What on earth is that?

This is not a paper about behavior. It is about measuring something called heritability (h ^2). Here's the translation of that first equation:

Heritability is the fraction of the variation in a trait that can be attributed to variation in genetics.

This study shows that there is a measurable fraction of the variation in a number of behavioral traits in dogs that is due to genetics. 

Heritability doesn't mean "inherited". It doesn't tell you how much variation there is in a trait. It doesn't tell you how likely a dog is to inherit a behavior. None of those things.

Clearly, to understand this paper, you need to be really clear on the meaning of heritability. You can start learning about it by reading some of my blogs on the ICB website, starting with this one:

                Understanding the heritability of behavior in dogs             

There are others if you do a search.

Also, please consider taking the Genetics of Behavior course. We will go through some papers like this one (including this one!) so you have a good understanding of what the information does - and doesn't - mean. There will be more studies like this one. Make sure you get the most out of them by understanding the science.

Check out those blog posts, and consider taking my course that starts (coincidentally) next week, 4 March 2019:

REFERENCES

MacLean EL, N Snyder-Mackler, BM vonHoldt, & JA Serpell. (unpub) Highly heritable and functionally relevant breed differences in dog behavior. BioRxiv preprint accessed 27 February 2019.. doi: http://dx.doi.org/10.1101/509315.

Dealing with the behavioral issues of dogs is a big business. Trainers and therapists abound, as do the professional suffixes tagged after the names of those who took some sort of course or were accredited by an organization.

I have no idea whether the majority of these people know what they're doing. I can tell you, though, that the scientific literature about behavior in dogs is a morass of tangled, insufficient, and often contradictory studies. In fact, in the field of canine behavior, science is marching forward very slowly, even as the ranks of lay behaviorists swell and practitioners claim to become ever more authoritative and confident of their expertise.

How reliable are behavioral assessments of dogs? Are they repeatable, meaningful, and verifiable? This especially matters when dogs are being assessed for working ability, as in breeding programs for service, police, and other types of working dogs. Breeding and training these dogs is time consuming and expensive, and being able to accurately assess the usefulness of a potential working animal is the differences between success and failure.

A recent study evaluated the reliability and validity of various behavioral tests that are used to assess the traits of working dogs (Brady et al 2018). What the researchers found should give pause to anybody that professes to have a deep and true understanding of canine behavior. 

For the selected studies, they evaluated the reliability, repeatability, and predictive validity of the behavioral tests,  both within and among "raters" (the individuals conducting the evaluation). They had an assortment of problems to deal with, like the use of different terminology for the same trait. More seriously, they found that data were often inadequately reported, statistical analyses were misinterpreted, and there was an overall lack of concordance in the various methods used for assessment.

​Ultimately, they concluded that there is "a widespread lack of information relating to the reliability and validity of measures to assess behaviour and inconsistencies in terminologies, study parameters and indices of success...This review indicates that we are still not addressing concerns over the lack of standardisation (sic) amongst research on dog behavioural tests". 

What this means is that we are probably not as good at assessing behavioral traits as we think we are or, at the very least, it's hard to tell how good we are because of limitations of the studies and the lack of standardization in terminology and protocol. Certainly, it should give pause to anybody relying on "experts" for advice, most of whom cannot lean on published studies to support claims about the validity and reliability of their assessments.

Buyer beware.

You can download a copy of the study below.

REFERENCES

Brady, K., N. Cracknell, H. Zulch, and D.S. Mills. 2018. A systematic review of the reliability and validity of behavioural tests used to assess behavioural characteristics important in working dogs. Frontiers in Veterinary Science 5(103);doi: 10.3389/fvets.2018.00103.

By Carol Beuchat PhD
​

Have you ever wondered how scientists figure out the genetic basis of a particular trait? This is especially difficult if the trait is polygenic and many genes plus environmental effects might be involved.

These are called "continuous" or quantitative traits; most of the traits under selection by dog breeders are of this type. For most of us, the process of identifying the markers associated with particular traits is a "black box" from which information mysteriously emerges from huge files of cryptic genotype data. How are scientists able to identify which of the many of thousands of markers play a role in the expression of a specific trait? ​​

In ICB's has a new course, The Genetics of Continuous Traits, we'll take the lid off the box and show you how scientists get from genotype to phenotype using DNA data you provide for your own dogs! For a learning example, we will study the genetics of body size, which is a trait that varies widely and continuously among breeds and mixed-breed dogs.

​We will use the raw DNA data file provided by Embark for your own dog, together with information about the size of your dog that you will provide. If we get data for enough dogs of a single breed, we can also explore the genetic basis of variation within a breed, also for a variety of mixed-breed dogs.

We will review some published studies for comparison with our own results, so you will also get to make comparisons with "real world" information.

This course is a great opportunity for you explore "under the hood" and learn how scientists go from a table of data to new information extracted from the data for your own dog!

Don't miss this great learning opportunity and the chance to analyze the data for your dog!

This unique online course is $125 and lasts 10 weeks, with students free to work along with the class or at their own pace. There are no prerequisites and a scientific background is not required - just your keen interest in dogs!

Class starts 11 February. Register now to join us!
​

Through a series of clever experiments, Mendel opened the black box that held the secret of the gene, which he concluded was responsible for the inheritance of traits in plants and animals. Knowing this, breeders could do some simple breeding experiments to reveal whether the genes for particular traits were dominant or recessive, which allowed them to design breedings that produced predictable traits.

While this took some of the mystery out of breeding for many traits, for other traits prediction remained elusive, and breeders realized that in some cases the genetics of a trait must be more complex. The problem, of course, was that some traits are determined by many genes. How could breeders do selective breeding on these so-called polygenic traits to reliably produce particular traits?

The puzzle was finally solved by a university geneticist named Jay Lush. In the 1930s, Lush realized that, for many traits, there could be lots of variation from individual to individual in a trait. That is, some traits were not "binary".

​For instance, there could be a range of size in a population of cows from small to large and everything in between, and not just two (binary) sizes of large and small. He realized that this was the case for many traits and began to think about how genetics could account for this. What Lush had stumbled upon was the key to selective breeding for traits that can vary continuously - genetic variation.

He described this in his groundbreaking book, Animal Breeding Plans.

Here, Lush is making the two observations that transformed animal breeding in the mid-1900s: 1) that genetic variation provides the raw material for selection, and 2) that some of this variation was "additive". Put another way, the effects of multiple genes acting on the same trait can be added. One large dog bred to another large dog could produce offspring larger than either parent.

This is what he is alluding to when he says that it's not necessary for a breeder to find the exact traits desired in a potential breeding animal, because genetic variation can be used to create a new mix of genes that will produce a trait not present in the current population. 

Lush's observation launched a new field of genetics, called "quantitative genetics", that was based in mathematics and statistics and applied specifically to traits that vary continuously. The advances in our understanding of quantitative genetics subsequently revolutionized animal breeding and was the basis of the spectacular improvements in production that became the modern system of commercial breeding of livestock and other animals.

One of the best examples of the gains that could be achieved by understanding the basis of additive genetic variation is for milk production in cattle. At the beginning of the 1900s, average milk yield was about 2,000 kg per year.There were no cows to be found anywhere that could produce 8,000 kg of milk per year. However, with the application of selection based on quantitative genetics in the 1940s, milk production soared and by 2000 it averaged more than 8,000 kg of milk per year - a four-fold increase in milk production over a period of about 50 years. Gains in production were made incrementally, a bit more each generation, and the basis for progress was finding advantageous combinations of genes that, added together, would push a trait in the desired direction. Breeders used the genetic variation in the animal population to create new combinations of genes in the next generation, then selected from among those animals the ones that improved on the trait over their parents.

There was one critical thing that was absolutely necessary for this to work: there needed to be genetic variation in the population. Breeders had to protect the genetic variation in their breeding stock, because without it new combinations of genes would not be possible and there would be nothing to select for.
​

The realization that selective breeding could produce animals that were superior to both parents revolutionized animal breeding. The use of additive genetic variation to produce animals with traits not present in the original breeding stock became the fundamental process of selective breeding in domestic animals.

Of course, dogs provide many examples of traits that have been shaped by selective breeding that takes advantage of additive genetic variation.

Body size is an obvious one. Researchers have identified multiple genes that can be associated with variation in body size in dogs. Some of these have a large effect, accounting for a significant fraction of the variation in size. But there is still much variation that is not yet accounted for genetically, and there might be dozens or even hundreds of other genes that have tiny effects individually but collectively account for differences among individuals.

Let's look at another example.

People probably started racing dogs thousands of years ago, and it's fair to suspect that over this time there has been selection to improve speed. 

One option would be to breed only the best to the best. Identify the sire and bitch with the fastest racing times and breed them together. Will some of the offspring be faster than either parent? Perhaps. Might some be slower? Perhaps. So what do we do from here?

We could mate the fastest male in the litter with the fastest female, and again select the fastest of their progeny. 

We might end up with dogs faster than the first two parents, but over the generations of inbreeding and strong selection (breeding only "best to best"), progress will start to level off. We will have eliminated much of the original genetic diversity in the dogs of the first generation. In fact, the puppies in each litter will share a larger and larger fraction of the same genes every generation. We are not going to get faster and faster dogs forever. Why? Apart from the deleterious effects of inbreeding, we have tossed out the genetic variation necessary to produce improvement in a continuous trait by exploiting additive genetic variation. We have bred ourselves into a dead end.

So how can you produce faster dogs from selective breeding and not run into this problem of a genetic dead end?

Redefine what you mean by "best". We do definitely want to select the best animals to breed, but we need to think of it in terms of the genetics of the population. To improve on a polygenic trait, we need genetic variation to select for. Instead of selecting a single best dog, we can select a subpopulation of dogs that are all faster than average. We will then use the genetic variation in those dogs, and the random inheritance of that variation in the offspring, to push racing performance in the direction of higher speed.

Can we keep producing faster and faster dogs forever? Probably not. If we don't run out of genetic variation, at some point we will run up against the limits of design and physiology. But we can definitely use selective breeding in this way to improve most traits that are polygenic in dogs.

So think about this. What traits do you strive for that are polygenic? Size. Temperament. Working ability. Coat quality. Ear length. Muzzle length. Shoulder angulation. Intelligence. The list is long.

Note that there is another issue here that breeding in this way addresses. The phenotype of polygenic traits is likely to be a reflection not just of genetics, but also of a roster of non-genetic factors, some of which might be known but most will not. When you select only the "best" individual to breed, you are selecting for the combination of genes and environment that produced what you perceive to be best. But you really only want to be selecting based on genes, because only that part of a trait can be inherited. Maybe the fourth "best" dog has great genes for the trait you want but was raised in a less than ideal situation. That dog's genes will get tossed if you only select the single best animal. By breeding a subpopulation of the top performing dogs, you preserve the genetic variation you need for selection and also reduce the influence of non-genetic factors in your choice.

You have no doubt noticed that this method of breeding, where the "best" is defined as a subpopulation of individuals instead of a single dog, is not the way dog breeders usually breed. We usually choose to breed only the dog we perceive to be the "best", ignoring the possible effects of environment on our assessment of the other apparently-inferior dogs. Doing this, we narrow the gene pool and increase inbreeding every generation, both of which will limit our ability to continue to improve traits. This applies to health as well as physical and behavioral traits. We can't "breed around" health issues if the necessary genetic variation no longer exists in the population of breeding animals.  

Can we breed better dogs by taking advantage of additive genetic variation? Yes, by changing the way we define "best" during selection. The improvement we can achieve might be significant - in health, in physical traits of importance, in temperament, and many other traits that we care about. 

Let's breed better, healthier dogs. Learn about the quantitative genetics of continuous traits and how you can use this knowledge to your advantage in your breeding program.
​

Since tests for specific mutations have become available in the last few years, the mantra of breeders is that their puppies are from "health tested" parents. To breed without first doing the available DNA tests is considered the height of irresponsibility in the fancy. But there is a right way to use DNA test results and also a wrong way. 

If you are reading this, you probably consider yourself to be a responsible breeder. Let's do some cyber dog breeding using some information from DNA testing and see how you do! All you need is a pen and paper along with your expertise as a responsible breeder.

Okay, we have a bitch we want to breed, and we have selected seven possible sires (S1 to S7). We have ranked these according to how well we think they fit what we're looking for in a sire in terms of conformation, temperament, health, longevity, working ability, or whatever criteria are important to you. We have given three green starts to the dogs we rank the highest and one green star to the dogs ranked lowest. However, we would be willing to breed to any of them. Assume we have done the relevant phenotype tests (e.g., hips, elbows, eyes, heart, etc.) and the results for all of those were acceptable.
​

The first thing we need to do is run the appropriate DNA tests for the recessive mutations known to be in the breed. In this case there is one, for the "red circle" trait. Our bitch is  carrier, as are two of the sires. I have identified the carriers with a red X on the chart, and the dogs that were clear have blue check marks.
​

Now we have our health-tested dogs from which we are going to select the perfect sire for our bitch. Using your rankings for overall quality, together with your information from health testing, rank the sires with 1 being your first choice and 7 your last choice. 

On your piece of paper, make columns for S1 through S7, and in the first row below that write your ranks for each of the potential sires.

​

Let's say you went to a little more trouble before making your breeding decision and you were able to get the  predicted average inbreeding coefficient of the litters that would be produced from our bitch and each of the seven sires. (You can get this information from the kinship coefficient, which is an index of the relatedness of a pair of dogs and can be determined either from pedigree or DNA information. The kinship coefficient of a pair of dogs is equal to the inbreeding coefficient of their potential offspring.)

Let's add the predicted litter COI to our table. With this information to consider as well, again rank the sires from 1 to 7 and add these data to the next row of your table. (Did this alter your first set of ranks?)

This is usually as much information as a breeder has about the dogs they want to breed. 

You did the testing for the "red circle" mutation in our potential parents and discovered that two of the sires were carriers. For both of them, there would be a 25% risk of producing puppies that are homozygous for the red circle mutation. You probably chose to eliminate those two sires from breeding consideration, which reduced the risk of producing affected pups in this litter from 25% to 0%.

You breed using your top-ranked sire and your bitch produces a beautiful litter of puppies. You advertise your pups as being from health-tested parents, keep a lovely pup for your breeding program, and send the rest off to pet homes. Sometime later one of the pet owners contacts you with the report that their puppy has a serious inherited blood disorder, and they ask how this could be if you claimed your pups were from health tested parents?

Indeed. How can this be???

We only know what we can know. We can know if a dog possesses a mutation if we have a test for it. We did our tests so we knew about the status of the red circle mutation in all of the potential parents.

But most dogs have many recessive mutations lurking in their genome for which there is no DNA test, and we have no way to know they are there if they are not expressed. Clearly, there was a mutation in your parents that you didn't know about. You feel horrible, offer to replace the puppy, and bury yourself in pedigrees trying to figure out how you could have produced a puppy with a genetic disease after being so careful.

If there is no DNA test for a recessive mutation, a disease can suddenly appear out of the blue that you have never seen in your lines if you happen to pair two carriers. This is why, if somebody claims that they only breed within their own kennel because they "know what's in their lines", you know that either they don't understand genetics, or they are being dishonest. It is not possible to know what recessive mutations are in your lines if you have no way to detect them.

So this leaves you in a pickle. All dogs have recessive mutations, and there are always going to be some that you don't know about. How do you avoid them? This is like tip-toeing across a mine field in which there are 3 mines that you can't see but are flagged, but you know that there are 28 more hiding out there somewhere. One wrong step and you will meet your maker. If these are mutations hiding in your dogs, this is a pretty hectic way to breed.

What if there were two mine-fields, but you can choose which one to cross. The first minefield has 3 mines you know about and can avoid and 28 that are hidden. The second mine field also has 3 that are flagged, but only 6 more that are hidden. If you're not ready to start your after-life, you would logically decide to cross the second mine field, where the risk of getting blown up is only 25% of the risk in the other one.

​Now we can see the problem. Our bitch has not one but three mutations that are also found in our "health tested" sires. Have a look at your last set of sire rankings. Now that you can see these other mutations, are you still happy with those ranks? If you would like to change your rankings, add another row to your table with these new assessments.

Great, you say. But in the real world, if we don't have tests for those unknown mutations, there is no way for us to avoid them, right?

Actually, there is. You just need one piece of information that in fact you already have - the predicted inbreeding coefficient of the litter.

Remember that inbreeding is defined as the probability of inheriting two copies of the same allele from an ancestor. By definition, then, inbreeding is homozygosity. If the inbreeding coefficient of a dog is 25%, then the probability of inheriting two copies of the same allele from an ancestor is 25%. If that allele happens to be a recessive mutation, then the risk of producing a genetic disorder caused by that recessive mutation is also 25%. Likewise, if the inbreeding coefficient is 10%, then the risk of a genetic disorder produced by a recessive mutation is also 10%.

Think about this. You did mutation testing to eliminate the 25% risk of producing a recessive genetic disorder from two carrier parents. But we just explained that the inbreeding coefficient tells us the risk of producing a genetic disorder from ANY recessive mutation, the ones we know about as well as the ones we don't.

So, we can be clever about this. We can control the risk of genetic disease from all recessive mutations by controlling the inbreeding coefficient of the litter. If we test for red circle and eliminated the carrier sires, it would be dumb to then breed to sire #1. We have paid to eliminate the 25% risk from the known mutation then done a breeding with a 31% risk of producing a disorder from some other mutation we don't know about.

Let's read that again.

We tested, eliminated the carrier sires so there is no chance of producing affected puppies from the known mutation, then we bred to a "clear" dog with a 31% risk of producing puppies with a disorder from some other mutation we don't know about.

You might be breeding "health tested" dogs, but you are still producing puppies with a significant risk of genetic diseases from recessive mutations.

Go back to what we know about the inbreeding coefficient. If our litter has a predicted COI of 10%, then the risk of ANY mutation causing a problem is only 10%, including the one we paid to test for. This is because parents with a kinship coefficient of 10% are less similar genetically than parents with a kinship coefficient of 25%. If the parents have fewer genes in common, there is a lower chance of a puppy getting two of the same mutation from both.

So it's simple. Reduce the risk of genetic disorders in your puppies by reducing the predicted inbreeding coefficient of the litter. 

If you've never thought about this before, this should be your light-bulb moment. All this "health testing" is a waste of time and money if we choose parents that produce a litter with an inbreeding level of 38%.

This is the WRONG WAY to use DNA testing. The breeder believes they are doing everything they can to produce puppies that will live long, healthy lives. But in fact they mark the known land mines with flags then assume the coast is clear without considering the risk produced by the many unseen explosives.

To produce healthy dogs, we need to get the risk of problems caused by ALL recessive mutations as low as possible, the ones we know about as well as the ones we don't. You can estimate this risk from the kinship coefficients of the potential parents. These numbers can be computed from a pedigree database, or (even better) they can be determined from the genotype data produced by DNA testing.

Don't waste your money on DNA tests then breed in a way that has a high risk of producing disease. Use those tests to eliminate all risk from mutations we can test for, then use kinship coefficients to make sure we have reduced as much as possible the risk from the unknown mutations hiding out in the genome of every dog.

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There are some fun tools we can use to explore the effects on genetics of changes to some of the properties of a population. This is one that we use in my population genetics courses to help students understand how genetics can be affected by changes in various properties of a population such as size or addition of new individuals.

One of these is an online population simulator called Red Lynx. It's easy to use, and if you have access to the internet you can take it for a test drive.

Go the the Red Lynx website at ​http://scit.us/redlynx/. 

On the landing page, click on the button to start the Red Lynx simulator.

This will take you to the simulator and you should see the screen below.

Red Lynx simulates the "behavior" of a single allele, "A1", in populations with various properties. There are two alleles at every locus, so actually A1 has a pair (lets call it A2). But we only need to simulate one allele, because if the frequency of allele A1 in a population is going up, the frequency of A2 must go down. If we model the behavior of A1, we know that A2 will be responding as a mirror image. So, we will run our simulations using only a single allele at a locus.

On the simulation page, you will see a graph, and below that a series of parameters that you can change using some simple sliders. We are only going to play with the first three: number of generations, population size, and initial allele frequency (green arrows). You can change these either by using the slider or just type the number you want in the box. You can ignore the rest of the sliders on the page.

​This line is the predicted behavior of the allele A1 in this population over time, assuming a 50/50 chance of inheriting the allele at each generation in a population under "ideal" conditions - no selection, no migration of A1 alleles in or out of the population, and no mutation. You can see that the initial frequency is 50%, and from there it change in frequency in the population with each generation.

Now, without clearing the graph, do a few more simulations. Each of these lines will be different because the role of chance in inheritance at each generation. If you do enough of these, you might see one of the lines go either all the way to 0% and flat-line (red arrow), or to 100% and stay there (green line). In the first case, all copies of the red allele have been lost from the population; for the green arrow, the alternative allele (A2) has been lost completely, leaving only A1, a situation we call "fixed" for that allele.
​

So what?

I hear you say "That's cool, but so what?".

Let's say the A1 allele was for something like the ability to smell a particular scent. If this isn't something you would be selecting for, this simulation suggests that there is a chance it could be lost from the population just by chance, a phenomenon called "genetic drift". Maybe this scent wasn't important to you, but if it was to the dog (e.g., a pheromone), it would have consequences that might affect some aspect of the physiology or behavior of the dog. Perhaps it is an allele that prevents fearfulness; losing it from the breed would definitely have consequences for the welfare of the dog. Or maybe it is an allele at a locus that is most beneficial when heterozygous - that is, the genotype A1A2 is more beneficial to the dog than either A1A1 or A2A2, something called "over-dominance". If one of the alleles is inadvertently lost from the population, all individuals will be homozygous for the other allele, and beneficial effects of heterozygosity will be unavailable.

So now let's do the fun stuff.

Let's make the number of generations in the simulation 100 so it will be more relevant to dog breeding. Change the population size to 50, and leave the allele frequency at 50%. Use the button to clear the graph, and run some simulations. 

You should find that the frequency of A1 goes to one extreme or the other (0% or 100%) in many of these simulations. 

Now run some simulations with different population sizes, perhaps 100 and 25. How does this affect the graph?

This simulator makes it easy to explore the effect of population size on the behavior of alleles in the population that you might not be paying any attention to. Clearly, the genetic stability of a population is sensitive to the number of individuals.

Why does this matter to your breed?

How big is your breed? What fraction of the puppies produced are used for breeding? Remember, only reproducing animals count when we're considering genetics. What are the effects of breeding contracts or spay/neuter policies on the population genetics of your breed? How stable is it genetically to the chance loss of alleles by genetic drift?

These changes in allele frequency occur in all populations. If a population is divided into closed subpopulations, the same phenomenon will occur in each of them. This will cause them to drift apart genetically over time. Breeders can take advantage of the genetic differences in these subpopulations to use them as outcrosses that can restore alleles that have been lost in another subpopulation. You can simulate this using the slider for "migration". If breeders can work together to monitor the genetic status of these subpopulations in a breed, they can reduce the loss of genetic diversity, slow the increase in inbreeding, and benefit from the hybrid vigor produced by an outcross.

​Is the population of your breed stable, or is it one of the many with registrations dropping off and fewer active breeders than there used to be? The simplest thing you can do to reduce the chance of losing important genetic diversity from your breed is to use more of the dogs produced in the breeding program. If the usual fraction is 20%, increase it to 40% or more. Don't send so many puppies off with contracts that prohibit breeding, or breed once before spaying or neutering. How much of a difference will it make? You can check it out using the Red Lynx simulator. Just remember that the simulator assumes a population with no selection, no migration, and no mutation (unless you stipulate conditions for these using the sliders). Certainly a purebred population will be under selection for the traits for type, but you can assume there is no selection for the "neutral" alleles that have no effect on type.

This simulator can also have a very practical use. Let's say your breed is discussing separating various colors in the breed into separate populations that would not interbreed. Or perhaps it is different sizes, or some feature of phenotype. If the groups are prevented from interbreeding, what will the consequences be for the genetic stability of the resulting smaller populations? There are many examples of breeds being split in the past - Norwich and Norfolk were separated based on ears, Toy and Standard Manchester were separated by size, the Belgian Shepherds are separated in the US based on color (but not in Europe), and perhaps you know of others. Splitting a breed WILL have consequences to the genetics of the separate populations, as you can see here effects of genetic drift on allele frequency. There will also be changes in other genetic properties of the populations such as the rate of inbreeding, and breeders should carefully consider these before deciding to make any changes in the breed.

In a previous post, I showed how inbreeding and strong selection increase the risk of genetic disease (via increased expression of deleterious mutations) and diminish overall health (via inbreeding depression). I also explained how we could improve health and reduce the risk of genetic disorders by making some simple changes in the way we breed. I showed why these things happen using a simple path diagram.

(If you didn't read my previous post, you should do that first and return here: Simple strategies to reduce genetic disorders in dogs)

There are other consequences of inbreeding that might be less familiar to the dog breeder but can ultimately be more important because they also feed into the same cycle of "inbreeding -----> genetic disease".

Below is  the figure from my previous blog post, to which I have added another loop (in green). (I have collapsed the loop that was to the left of health consequences and simply replaced it with the word "health".)

Once again we start with inbreeding in a population of dogs. Mating related dogs produces inbreeding, in which a puppy gets identical copies of an allele from both parents, increasing the fraction of genes that are homozygous. To here, we are following the same steps as we reviewed before.

At this point, we will add a new detail to our path diagram. The homozygosity produced by inbreeding might be scattered over the chromosomes, or it can be in blocks of adjacent genes on a chromosome. 

Blocks of homozygosity on the chromosomes are called "runs of homozygosity" (ROH), and they have two important properties.

a) the blocks of homozygous alleles tend to get longer and longer with inbreeding;

b) linkage disequilibrium increases with inbreeding.

We need to define "linkage disequilibrium". We usually think of inheritance as one of the two alleles at a loci that are passed on to a descendant by random chance. This is a simple and useful way to think about inheritance, but in reality it can be more complicated. In fact, the regions of homozygous loci that form runs of homozygosity tend to be inherited together as a block. This non-random inheritance at adjacent loci in a run of homozygosity is called "linkage disequilibrium". 

So, follow along using the chart below -

In step 4, why do mutations get trapped in blocks of homozygosity? Inbreeding removes genetic variation. To breed "away" from a deleterious allele, the alternative (i.e., normal) allele must replace it. When there is inbreeding to increase homozygosity for genes for type, as well as selection to reduce genetic variation, the normal allele can become rare. Homozygosity of the mutation within ROHs will increase. Now it becomes difficult or impossible to remove or even avoid a mutation, and over time the number of mutations that are "trapped" increases.

5) mutation trapping increases the "genetic load", the number of deleterious alleles in the gene pool

6) the expression of recessive mutations increases

This path now joins the main pathway that we discussed previously.

​You can see that the breeder is now trapped. We are trying to improve type and reduce genetic diseases at the same time as we lose the genetic variation needed for improvement. We are also making it more and more difficult or even impossible to breed away from genetic issues because of linkage disequilibrium. Of course, we continue to select strongly for type, which insures that the blocks containing those genes remain homozygous. The mutations in these blocks are trapped forever.

Now this path feeds back into the larger pathway, where we remove affected dogs or entire lines in an effort to get rid of the genes causing problems. But this reduces the size of the gene pool and throws out valuable genetic variation.

​And so it goes, round and round, the quality of the gene pool deteriorating a bit more with every generation.

This is a real pickle if you're a breeder. What all this means is that the more effort you put into breeding for improved health using the usual strategies of inbreeding and strong selection, the bigger the problem gets. This is where we are.

How do we fix this?

If we breed a very inbred dog to one that is not closely related, we can reduce homozygosity (inbreeding) in the puppies. Less inbreeding means smaller blocks of homozygosity, so linkage disequilibrium is reduced. Mutations and other unwanted genes that were trapped in runs of homozygosity are now "set free", so you can breed away from them. There is also new variation that you can make use for improvement of phenotype, so selection will be more effective.

Note that the most useful dogs for an outcross will likely be the ones that are not what you would choose to breed to on the basis of phenotype. The dogs you gravitate to with good type are likely to have all the same ROH you are battling with already, and there will be little to gain. Paradoxically, dogs with more phenotypic variation, especially as it varies away from the extremes in type, will have the most to offer you in terms of escaping from the feedback loop illustrated above. You probably won't get stunning puppies out of a breeding with a dog with mediocre type, but you will escape the loop that is strangling your breeding program and sending purebred dogs towards the cliff.

I can hear a bunch of people complaining that outcrossing will introduce new mutations to your line. Yep, it might. You would probably know about the dominant mutations in a dog you're breeding to, so the new mutations are likely to be recessive. Look again at the feedback loop and you will see that those recessive mutations are completely harmless as long as you don't breed dogs together that have the same ones. And if you keep inbreeding low, you can eliminate those mutations through selection because they aren't trapped in those blocks of homozygosity. Also put your foot down on popular sires; the last thing you want is to produce dozens of puppies that each carry half the mutations found in the favorite dog. Remember, inbreeding is how we ended up with the current problem in the first place. The solution is simple: don't put two copies of the same mutation together in a puppy.

You can fix this problem. You can eliminate health problems in a generation. You can use selection more efficiently. You can add the variation necessary to produce better dogs than you have now. Lives will get longer. Vet bills will go down. Breeding will get easier. Litter sizes will increase. The health and welfare of dogs will improve.

The secret to improving the health of dogs is not more DNA tests, but sound genetic management. We know what is causing the high burden of genetic disorders in dogs, and we know how to prevent this. Trying to eliminate problems by chasing down pesky mutations will not get us out of the feedback loop that is causing the problem. Breeding ever more selectively won't help either. These things make the problem worse.

The solution is genetic management. Understand how the problems are created. Understand the critical importance of genetic variation and reduced inbreeding for improving health. And breed in a way that will be sustainable into the future.

If you learned something useful from this article, there is much more information out there that will improve the health of dogs and make your breeding program more successful. The best way to increase your knowledge and understanding is through one of the courses offered through ICB. These courses are specifically designed for breeders and they truly are the best way for breeders to learn what they need to know to improve the health and well-being of dogs.

The next course is Managing Genetics for the Future and starts 7 January 2019. You can learn more about it and register here -

​https://www.instituteofcaninebiology.org/managing_genetics.html

I hope to see you there!