Genetic Heath Testing

Gene – A part of an organism’s DNA that is passed down from its parents and codes for a specific function.
Allele – A form of a gene; it can be dominant or recessive.
Dominant gene – A gene that will show its effects even if an organism also has a copy of a different allele (the recessive allele).
Clear By Parents (CBP) - Both parents are "clear" and offspring are designated CBP for two generations - mutations may happen at any time, so two generations is the logical cutoff for a CBP designation.
Genotype (set of alleles) determines phenotype (observable features/traits)

Mode of Inheritance

Dominant - only a single copy of an allele is necessary to express the trait.

Recessive - two identical alleles are necessary for the trait/disease to be observed

Incomplete Dominance - only one copy of a given allele is necessary to produce the trait - example "S" which may produce white hairs or spotting and which needs only be inherited from one parent.

Responsible breeders look at more than just hip and elbow scores. Dr Malcolm Willis, the late leading authority on canine hips while speaking during a health seminar sponsored by the Flatcoated Retriever Society stated the following: "Don't struggle for perfect hips! Hips need be no better that what will give a dog an active pain free life, and to struggle for better can/WILL mean losing other dogs from the gene pool who have good things to offer, such as temperament. A dog is a whole animal, not just a pair of hips!”

With this expert opinion and with the science showing that owners are as responsible as Breeders in ultimately limiting hip and elbow dysplasia in mind, genetic testing for diseases is of equal or even greater value in the Breeder's toolkit for responsible breeding. That toolkit includes normal hips and elbows, low coefficient of inbreeding and testing for Genetic Diseases as well as traits which include temperament and adherence to the physical breed standard.

Many of the inheritable diseases require that both parents pass on a copy of the gene responsible for disease to a puppy. To avoid breeding dogs that could pass on these genes and have affected puppies, one or both parents are genetically tested; to keep a puppy from a carrier's litter, puppies are tested before choosing to ensure that this new generation is clear of the mutation. Carriers who bring other excellent traits to the breeding are not removed from breeding programs. Rather, to "improve" the next generation and avoid narrowing the gene pool, offspring are tested to be clear of the mutation before being used in a breeding program.

Many breeders are now using Embark Panel testing to genetically test for diseases; please see this article for why we still use GenSol single disease gene testing.

Accuracy: Direct versus Indirect Genetic Testing

Diseases Relevant to Labradors

There may be other causes of these conditions in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait. Breeder testing can only eliminate the TESTABLE inherited form of any disease. It is also important to understand that a gene may mutate from one generation to the next causing a "Carrier" status for a puppy produced by two "Clear" parents. For this reason, many Kennel Clubs are restricting "Clear By Parents" to two generations.

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Hereditary nasal parakeratosis (HNPK)

Mode Of Inheritance - Recessive This is a (disfiguring) disease that affects Labrador Retrievers and related breeds and leads to dry, rough, discolored crusts on the edges of the dog’s nose. The disease results from a mutation that causes the nose to dry out and can lead to chronic irritation and inflammation of the skin on and surrounding the dog’s nose. Symptoms of the disorder appear in young dogs typically between the ages of around 6 months to 1 year of age. PAW PRINT GENETICS

Exercise Induced Collapse (EIC)

Mode Of Inheritance - Recessive - Dogs will collapse after 5 to 10 minutes of high-drive, trigger activities, such as chasing a ball or hunting. Though a large majority of these cases recover completely within a short timeframe (less than 30 minutes), some dogs have been known to die of the condition.

Canine Degenerative Myelopathy (DM)

Mode Of Inheritance - Recessive - This mutation is found in many breeds of dog, though it is not clear for Labrador retrievers whether all dogs carrying two copies of the mutation will develop the disease. The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age. The disease affects the White Matter tissue of the spinal cord and is considered the canine equivalent to amyotrophic lateral sclerosis (Lou Gehrig’s disease) found in humans.

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Labrador Centronuclear Myopathy (CNM)

- Mode Of Inheritance - Recessive - Typically occurs in young Labradors between 6 weeks and 7 months of age. Similar to DM, CNM is a disease that will greatly affect a dog’s ability to work or perform physical tasks. Affected dogs typically display an intolerance to exercise, a hopping gait, decreased reflexes, generalized skeletal muscle weakness and atrophy, and an increased likelihood of collapse when in cold temperatures. Many affected dogs also develop a loss of muscle contraction in the esophagus (megaesophagus) resulting in difficulties swallowing. Problems with swallowing can allow food particles and other material to enter the lungs, thus, leading to severe pulmonary infections known as aspiration pneumonia.

Progressive Rod-Cone Degeneration (PRA-PRCD)

- VARIANT 1 Mode Of Inheritance - Recessive - Progressive retinal atrophy (PRA) is a category of different progressive conditions related to retinal atrophy that can eventually lead to blindness. Progressive rod-cone degeneration (PRA-PRCD) is one specific type of PRA that affects many dog breeds. It is an inherited eye disease with late onset of symptoms that are due to degeneration of both rod and cone cells of the retina. These cells are important for vision in dim and bright light.

Progressive Rod-Cone Degeneration II (PRA-PRCD)

VARIANT 2 Mode Of Inheritance - Recessive - Progressive retinal atrophy (PRA) is a category of different progressive conditions related to retinal atrophy that can eventually lead to blindness. . Breeding two carriers with the same mutation is predicted to produce 25% affected puppies and 50% carriers. Mating a carrier of PRA1 (that is CLEAR for PRA2) with a carrier of PRA2 (that is N/N for PRA1) will not produce affected animals.

PYRUVATE KINASE DEFICIENCY LABRADOR RETRIEVER (PKD-LAB)

- Mode of Inheritance Recessive Affects red blood cells due to a mutation in an important enzyme needed for metabolism. This defect leads to red blood cell death that results in severe hemolytic anemia.

Retinal dysplasia/oculoskeletal dysplasia 1(RD/OSD)

Mode Of Inheritance - Recessive - An inherited Collagen disorder affecting Labrador retrievers. Dwarfism and eye abnormalities may be apparent as early as 4 to 6 weeks of age in affected puppies. The dwarfism is characterized by shortened forelimbs that become curved as the dog grows. In puppies, the top of the head may be noticeably dome shaped compared to littermates. A range of eye abnormalities is visible on a veterinary eye exam of which retinal detachment and cataracts are the most common. Carrier dogs do not have skeletal changes but may have mild eye abnormalities, including retinal folds.

Skeletal Dysplasia 2 (SD2)

Mode Of Inheritance - Recessive - Musculoskeletal disease affecting Labrador Retrievers. Affected dogs develop a mild form of “disproportionate dwarfism” consisting of short legs with normal body length and width. The leg bones are shorter, thicker, and slightly curved and the front legs are frequently more affected than rear legs. Joints and eyes are not typically affected with this disease. The causal Mutation shows Incomplete Penetrance meaning that not all dogs inheriting two copies (one from each parent) will display obvious physical characteristics of dwarfism.

The discovery of relevant diseases for breeds is fluid

Early genetic testing offered only single gene testing; recently panel testing became available to both breeders and pet owners. While many breeders are using panel testing the new dogs in their program, you will see single testing for the diseases relevant to their breed for their older dogs. Panel testing is opening the doors to our eventually being able to prove whether a disorder is an inherited one or one that is from random interruption in the gestational process.

Panel testing companies, like Embark and Wisdom, will add a new "relevant" test even if the test is extremely rare within the breed. Typically, any study will have more participants from our breed than any other breed; it is therefore important to weigh the risk in foundation stock for which the disease has not been known/recorded in the pedigrees. As more breeders move to panel testing, the results for these tests will be available for more breeding pairs.

HYPERURICOSURIA (HUU)

Mode of Inheritance - Recessive

This disease is characterized by the excretion of uric acid leading to the formation of urinary calculi (stones).

Incidence is rare. Many breeders do not single test for the gene unless there is an incidence in either ancestry or descendants in a pedigree or before breeding to a known carrier. It is included in Embark's panel testing.

Note: While treated as Pure Bred in sharing the results, the Standard Schnauzers and Labrador Retrievers participating were related to varying degrees (ranging from littermates to separated by > 5 generations); in other words, the Labradors were not all purebred and the gene may have been introduced in mixed breeding.

Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds

Congenital Myasthenic Syndrome (CMS) in Labrador Retrievers (2023)

Phenotype: Neuromuscular disorder characterized by generalized muscle weakness and fatigue, usually induced by exercise. Affected puppies collapse after a few minutes of rigorous exercise, but recover after some rest. Signs usually appear between 6 to 12 weeks of age.

Mode of Inheritance: Autosomal recessive (needs two copies, one from each parent, to be affected.

According to the referenced paper below, only 2 Labrador Retrievers were reported to be affected and homozygous for this mutation but 16 out of 58 (28%) of their relatives were carriers. However, carriers can transmit the recessive allele to their offspring and can thus produce affected offspring if their mate also contributes a recessive allele. No carriers were found among 288 unrelated Labrador Retrievers, which suggests that the mutation is not widespread within the breed. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106425

Modes of Inheritance

Some diseases/traits (i.e. coat color) require only one copy for expression (incomplete dominance). In these cases, neither of the inherited alleles is completely dominant over the other and both alleles can be seen at the same time.

Dogs (and humans) can only have two alleles (one from each parent) for a given gene, however, multiple alleles (3 or more) may exist in a population level, and different individuals in the population may have different pairs of these allele.

Copper toxicosis (Labrador retriever type)

Mode of Inheritance - incomplete dominant - Metabolic disease resulting in a decreased ability to excrete dietary copper from the body resulting in excessive copper storage in tissues and organs, including the liver, which can result in liver damage and subsequent cirrhosis. Dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing the disease. Though copper toxicosis is most commonly seen in dogs having two copies of the mutated gene, Carrier dogs have a lower risk of copper toxicity than dogs with two copies of the Mutation, but have a higher risk of developing the disease than dogs without the mutation. Since there appears to be multiple genetic and environmental factors which play a role in causing copper toxicosis in dogs, a normal result in ATP7B does not exclude copper toxicosis in a pedigree and an at-risk result does not mean that a dog will develop copper toxicosis during its lifetime. It is recommended that dogs inheriting the ATP7B mutation be bred to dogs that have not inherited the ATP7B mutation rather than being removed from breeding programs. It is important to note that removal of all dogs with one or two copies of the ATP7B mutation from the gene pool would drastically reduce genetic diversity within the breed and potentially increase the risk of other genetic diseases in Labradors. Paw Print Genetics

What about the things for which there is no genetic test available?

Congenital Defects:

Just like in humans, sometimes something can go wrong during gestation that affects one or more puppies. Exposure to some form of a toxin can cause birth defects; positioning in the uterine horn in a large litter can affect the development of a limb or the tail, an excess or deficiency in, for example, Vitamin A during gestation can cause developmental issues (i.e. an undeveloped leg or a crooked tail) in one puppy but not in the entire litter. Puppies can be born showing a recessive trait like a shorter tail or a longer tail than we are used to seeing and some puppies are born with mis-markings (white spotting and more rarely mosaic or tan and black points). These puppies should not be used in a breeding program.

In these cases, if a pattern emerges in which several puppies in one or more litters have the same congenital defect, the following questions are asked prior to making a decision as to the future of the parents::

Is the defect cosmetic or does it require medical intervention?
- If cosmetic, then the degree of the defect is considered
- If medical intervention is required, move on to the next question
Is this a repeat breeding of two dogs to each other. If so, the pairing is not repeated.
Has either parent produced this defect more than once with another mate? If so, that parent should be withdrawn from the breeding program.

Next: Genetics of Color