2022 Embark Canine Health Summit

Chondrodystrophy is a term used in veterinary medicine to indicate a dog with a combination of shorter legs and intervertebral disc disease. Prior to the discovery of the mutation that causes chondrodystrophy, many breeds were classified as chondrodystrophic just based on their short-legged phenotype. It turns out there are two major variants that cause short legs in dogs and only one affects the intervertebral discs. The genetic variant that causes chondrodystrophy is a special type of variant called a retrogene. It is an extra copy of the gene (FGF4) that is important in early development. This extra copy makes too much FGF4 in the wrong places. It only takes one extra copy to have an effect on development and thus the FGF4 retrogene, called FGF4L2 is dominantly inherited.

The intervertebral discs express FGF4 when the retrogene is present and this causes the inner portion of the disc to be replaced by cartilaginous tissue as early as 10 weeks of age. Later this inner portion can degrade further and mineralize. All of the changes to the intervertebral discs makes them prone to move or herniate from their normal location as shock absorbers in the vertebral column. Acute intervertebral disc herniation can result in severe pain and paralysis in its worse form. Even though FGF4L2 causes all the discs to be abnormal, they only occasionally herniate causing spinal cord compression.

FGF4L2 is found in many breeds of dogs, including the original chondrodystrophic breeds where it is very common. It also occurs less commonly in a long list of other breeds and has been identified as a region under selection across dog breeds due to its effects on leg length and other parts of the body. Many dogs with FGF4L2 never experience clinical problems associated with this variant and the other effects of FGF4L2 are desirable in some breeds. Since FGF4L2 is dominantly inherited and predisposes dogs to intervertebral disc herniation, it presents unusual challenges to breeders.

Hip dysplasia (HD) is a non-congenital and multifactorial disorder that affects several canine breeds. HD is chronic and often painful, and can significantly lower the quality of life. It usually develops during rapid growth in juvenile dogs. The increased laxity destabilizes the joint leading to a progressive complex phenotype. Different sub-traits include, e.g., joint incongruency, shallowness of the acetabulum, deformation of the femoral head, varying degrees of subluxation, erosion of the articular cartilage, sclerosis in the subchondral bone and formation of osteophytes. HD is evaluated by aggregating several sub-traits from hip-extended ventrodorsal radiographs. The clinical signs vary from occasional stiffness to severe chronic pain and impaired mobility of the joint.

The breed-specific frequency of HD varies from 0 to 71% [The Orthopedic Foundation for Animals]. Differences in growth rate, obesity, exercise habits and muscle condition, and in biomechanical, nutritional and hormonal factors have been suggested to contribute to the risk of developing HD. Heritability (h2) estimates vary typically between 0.15 and 0.80 indicating a significant genetic component. Individual loci have a rather limited contribution to the overall genetic risk. Further, there have been great difficulties to validate the observed associations using independent cohorts.

We conducted a case-control study using a cohort of 769 German Shepherds. We found significantly associating SNP-markers in chromosomes 1, 9 and 28 with genes such as NOX3, ARID1B, NOG and NANOS residing nearby. We also found deletion variants upstream NOG and showed that they affect reporter gene expression in vitro. Using a 1572 dog cohort from ten breeds we validated the association of 23 previously identified markers across 21 loci in 14 autosomes. Proteins involved in the neddylation protein modification pathway were overrepresented among the >250 protein coding genes residing within one megabase of the 23 markers.

Alaskan sled dogs are a hybrid canine athlete combining traits of arctic adaptation, speed, endurance, and mental and physical fortitude. They were originally developed as working dogs to haul cargo-laden sleds and served as humans’ primary means of transportation, protection, and companionship in arctic regions. With the advent of modern machinery, Alaskan sled dogs transitioned into elite canine athletes, with one subpopulation capable of sprinting 20mph for nearly 30 miles and another subpopulation able to traverse over 1,000 miles of harsh arctic terrain in just 8 days. They are a recognized breed of working / sporting dogs selected solely on performance, rather than appearance, thus setting the breed apart from most others. They have a complex history of crossbreeding and performance selection making them more genetically diverse and hardier than many other dogs. These factors make the Alaskan sled dog a unique model to study the genetics of ancestry, adaptation, and athletic performance. To date, my research has provided insight as to the historical and recent ancestry of modern Alaskan sled dogs and how that ancestry influences performance. We’ve determined the frequency of genetic health variants and identified regions of the genome associated with two distinctive diseases in Alaskan sled dogs. Our current work is aimed at understanding the genetics of various performance measures and the selection of Alaskan sled dogs for sprinting (<30 miles) or endurance (hundreds of miles). With this information, we aim to implement genetic prediction of health and performance traits in Alaskan sled dogs to inform management and breeding programs of sled dogs. This work will in turn establish a foundation to similarly study and implement genetic selection of other working and sporting dogs in the future.

Copper is an essential element for a number of metabolic processes in the body. It is provided via diet and drinking water and after absorption in the upper intestine, the liver is responsible for storage, redistribution en excreting excess copper into the bile. Hepatic copper accumulation due to increased intake or metabolic disturbances eventually leads to hepatitis and liver cirrhosis. Copper homeostasis is tightly regulated by a large number of copper-binding proteins. Mutations in genes coding for these proteins result in a disturbance in copper metabolism. In humans, the best described examples are the copper deficiency disorder Menkes disease and copper overload disease Wilson disease which are respectively caused by mutations in the copper transport pumps ATP7A and ATP7B.

In Bedlington terriers, autosomal recessive copper toxicosis is caused by a large deletion in the COMMD1 gene which functions in stabilizing both the ATP7A and ATP7B copper transporters. Mutations in both ATP7A and ATP7B influence hepatic copper levels in Labrador retrievers and Dobermanns (only ATP7B). The allele frequency of the ATP7B mutation in Labrador retrievers is estimated to be ~30% in the Netherlands.

Dietary intake of copper and zinc have a large impact on hepatic copper levels in Labrador retrievers and possibly other breeds. Therefore, canine copper storage disease is caused by a combination of Nature and Nurture.The balance between Nature and Nurture is breed dependent. In Bedlington terriers with the COMMD1- mutation the effect on hepatic copper is highly genetically determined. In genetically more complex forms of copper toxicosis like in Labrador retrievers, Dobermanns and possibly other predisposed breeds, the effect of copper and zinc in diet has a major impact on hepatic copper levels.

Learning Objectives

1. Attendants will have an overview of genes involved in copper metabolism and an understanding of the role of these genes in copper metabolism on cellular level and organism level. 
2. The role of mutations in ATP7A, ATP7B and COMMD1 in different dog breeds will be discussed.
3. The role of diet as an environmental factor in the pathogenesis of copper-associated hepatitis will be discussed.

Canine problem behaviors represent a major burden on society and an unmet clinical need. Until very recently, there was essentially nothing known about common genetic variations associated with dog temperament. This presentation shows how crowd-sourcing of the C-BARQ owner-reported canine behavior questionnaire was used to break that log jam. The findings have biological implications and suggest potential for therapeutic advances for dogs and humans.

Learning Objectives

1. Why study problem behavior in dogs?
2. How to study problem behavior in dogs
3. What have we learned about dog problem behaviors and how can that be exploited?

Generally, coping with disorders in small animal reproduction is a rewarding subspecialty in veterinary medicine. Breeders owning pets with reproductive problems are usually very motivated to achieve resolution. Although a bit demanding of the clinician's time and expertise, the breeder client tends to be very loyal and compliant. A good reproductive practice generates its own referrals, and usually is quite busy. Obstetrics and pediatrics are undeniably rewarding parts of the specialty for veterinarians and their staff. Reproductive practice incorporates the interesting fields of physiology, endocrinology, embryology, genetics, metabolism, nutrition, pediatric and maternal critical care, anesthesia, pharmacology and anatomy. The field is uniquely both medical and surgical.

Unsolved and controversial clinical problems are not uncommon to the reproductive practitioner. Progress in understanding the etiology, pathophysiology and proper therapeutics of such problems has also been hampered by anecdotal information abounding amongst the breeder clientele and often amongst veterinarians as well. The internet frequently becomes an annoyance, used by clients to challenge a clinician's decisions. University residencies and post doctorate programs limited to and promoting advances in small animal theriogenology are uncommon. Collaboration amongst small animal reproductive specialists is developing but remains limited. Discussion of some of the controversial clinical problems familiar to the small animal reproductive practice follows.

Learning Objectives

1. Rational approach to the use of medications and supplements in canine reproduction
2. Understanding evidence based vs anecdotal information
3. Appreciate the value of the pre breeding veterinary consultation

This presentation will focus on providing a review of the literature related to the diagnosis and treatment of canine acute intervertebral disc extrusion (IVDE), accompanied by an update on genetic basis of IVDD and discussion of future opportunities for prevention strategies.

Learning Objectives:

1. Described the rational for recommending medical versus surgical management for IVDE
2. Review the prognosis for dogs of various injury severities
3. Discuss the role of the FGF4 retrogene in development of disc degeneration

This program has been submitted (but is not yet approved) for 1.0 hour of continuing education credit in jurisdictions which recognize RACE approval. The RACE section code will be added once approved and a certificate will be made available upon licensee request at the completion of the summit.

Complex diseases are determined by thousands of genetic variants spread in a dog’s genome. The effects of those individual variants are typically small, but summed together they contribute to a genetic predisposition to a given disease. On top of this genetic predisposition, the environment in which a dog has lived may will influence on whether the dog actually displays the symptoms of the disease.

Because there are many genetic targets, and because the environment can obscure the genetic predisposition of the dog, selecting against complex diseases in dogs to date has only achieved modest success. Accurately assessing the genetic merit (the total sum of the effects of the individual genetic variants) of a dog for a complex trait requires advanced statistical tools. Such tools have been developed, and are being used very successfully in all livestock and crop species, across a wide variety of traits with different levels of genetic contribution. These tools are called Estimated Breeding Values (EBVs).

In this talk, we are going to discuss in detail the principles of complex traits, from the difficulties in determining the effects of genotypes, to the impact of the environment. Following, we will talk about the basic methodology behind EBV calculations. Finally, we are going to discuss how EBVs are being used to reduce the prevalence of hip dysplasia in dogs registered with The Kennel Club UK.

While tools such as EBVs are very helpful in honing in on the genetic merit of the animal and so improving the response to selection, they depend on the availability and wealth of data used in calculation. For complex diseases in dogs, this information is sourced from health testing records. As a result, progress in breeding against complex diseases in dogs can only be achieved when scientists and dog breeders work together.

Breeders and veterinarians need to have a great collaborative relationship to succeed in producing the healhiest puppies possible. In this era of new genetic testing, the more we know, the more confusing and expensive appropriate genetic testing can become. This discussion will help sort out how breeders can team up with their veterinary professionals and sort through the overwhelming onslaught of screening for great health.

This program has been submitted (but is not yet approved) for 1.0 hour of continuing education credit in jurisdictions which recognize RACE approval. The RACE section code will be added once approved and a certificate will be made available upon licensee request at the completion of the summit.

In this talk, Dr. Hauser describes how we can measure and quantify inbreeding as the coefficient of inbreeding (COI), the consequences of inbreeding on dog’s health and lifespan, and how we can leverage COI to make the best breeding decisions for our dogs and the breed.

For many of us, dogs are not just pets, they are family members with their own bespoke clothing and therapists and trendy snacks (for example, canine pumpkin spice latte treats). Dogs have become so integrated into our lives that it is difficult to imagine how, for at least 90% of our species’ history, we lived without them. In this talk I will discuss how dogs are best conceived as an emergent property of the interaction between human populations and wolves, and how the union of those two species has intensified over the past 15,000 or so years. Specifically, I will detail how numerous approaches to studying dogs has revealed just how deep our relationship has been, and how that has manifested both biologically and culturally. It is not overstating things to say that dogs are people, and we are our dogs.

This program has been submitted (but is not yet approved) for 1.0 hour of continuing education credit in jurisdictions which recognize RACE approval. The RACE section code will be added once approved and a certificate will be made available upon licensee request at the completion of the summit.

Dr. Evans will discuss genetic investigation of cancer susceptibility in dogs, focusing on her histiocytic sarcoma research, as well as how the results of these studies can be applied to improve canine health.