Genetic Health Testing

 

C3 - Cystinuria Type 3 (Bulldog Type Risk Factor, Variants 2 and 3)

Cystinuria type 3 is an inherited disease affecting kidney function in dogs. Dogs with cystinuria are deficient in a specific protein that is essential for the transport of cystine and other amino acids from urine. Normal kidneys reabsorb cystine so that only small amounts pass into the urine. However, dogs with cystinuria fail to reabsorb cystine, allowing large amounts to pass into the urine. Excessive cystine can form crystals and/or stones in the urinary tract, which can block the ureters or urethra and stop the normal flow of urine. Symptoms of disease include straining to urinate, blood in the urine, frequent urination of small volumes or inability to urinate. Dogs with cystinuria often have recurrent inflammation of the urinary tract and if not treated, urinary stones can cause urinary tract infections, kidney failure and even death. This test examines the genome for two genetic mutations in the SLC3A1 gene (Variants 1 and 2) associated with cystinuria type 3. These mutations are not thought to be the actual mutations responsible for the disorder. They are considered “linked markers” for cystinuria type 3. This means these markers are in close proximity to the mutation responsible for cystinuria type 3, and are predictably inherited along with it, making a test for these linked mutations a useful tool to assess cystinuria risk. In addition, these two markers are also thought to be linked to each other. This means that when a dog carries one copy of either of the markers, the other marker is also inherited. Dogs that inherit one copy of each of the SLC3A1 mutations (Variants 1 and 2) are considered carriers of the disease and will not show clinical signs of cystinuria. Dogs that inherit two copies of each of the mutations are considered at risk for/affected with cystinuria type 3 and may develop clinical signs.

Degenerative Myelopathy

Degenerative Myelopathy is an inherited neurologic disorder caused by a Mutation of the SOD1 gene known to be carried by French bulldogs. This mutation is found in many breeds of dog, though it is not clear for French bulldogs 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. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk.

Hereditary Cataracts

A cataract, in general, is the clouding of the lens of the eye. This cloudiness interferes with the ability of the eye to focus light on the retina which is crucial for clear vision. As the cataract matures and becomes cloudier, vision becomes worse until it interferes with daily living. There are both inherited and acquired forms of cataracts. Age related changes of the lens, chronic exposure to UV radiation from sunlight, injury, and various infections are all common causes of acquired forms of cataracts. However, far more common in dogs are cases of inherited cataracts, such as those known to occur in the French bulldog due to a mutation in the HSF4 gene leading to abnormal changes in lens proteins and subsequent cloudiness.

French bulldogs affected with HC begin to show signs of lens cloudiness in the first weeks or months of life that gradually progress to fully involve both lenses by 2 or 3 years of age, severely inhibiting vision. Surgery to remove or replace the lenses with artificial ones are the only effective treatments for cataracts. Though dogs without lenses can see, they are unable to focus on objects near to them. Replacement of the lens is the gold standard for cataract treatment and is expected to restore a dog’s vision to nearly normal. Given that expensive surgery is the only effective treatment for HC, prevention through genetic testing of breeding dogs and selective breeding practices are a much more cost effective and safer option for dogs.

HC in French bulldogs are inherited in an autosomal recessive manner meaning that a dog must inherit one copy of the HSF4 gene mutation from each parent in order to develop disease. Dogs inheriting a single copy of the mutation are carriers of the disease and will not show clinical signs of cataracts, but can have affected puppies if bred with another carrier of the same genetic mutation. Approximately 25% of puppies from a carrier to carrier breeding will inherit two copies of the mutation and thus, develop cataracts. Carriers of the HC mutation can be safely bred to dogs that have not inherited the mutation without fear of producing affected puppies. However, it should be noted that about 50% of the puppies from this pairing would also be born as carriers

Hyperuricosuria (HUU)

Dogs with this genetic mutation metabolize waste products as uric acid in their urine. The uric acid forms into hard stones in the bladder, causing pain and inflammation as the stone moves through the urinary tract.

 A dog that has difficulty urinating or appears to have an inflamed bladder may have HUU. Other signs can include blood in the urine and frequent urination. If the dog is unable to pass the urate stones without medical intervention, surgery may be required to remove them. And if the urinary tract is blocked, the condition can be life threatening. Even in the best case scenario, HUU is uncomfortable and painful for the dog.

The mutation is autosomal recessive. Both parents will need to be carriers of the mutation to pass it on to their offspring. Carriers will not show any symptoms of HUU and even affected dogs may not show any signs, so it is important to test dogs for HUU prior to breeding.

Multifocal Retinopathy 1

Canine Multifocal Retinopathy Type 1 and 2 (CMR1 and CMR2) is an autosomal recessive eye disorder known to affect Great Pyrenees, English Mastiffs, Bullmastiffs, Australian Shepherds, Dogue de Bordeaux, English Bulldogs, American Bulldogs, Coton de Tulears, Perro de Presa Canario, and Cane Corsos.

 

The mutation causes raised lesions to form on the retina. The lesions alter the appearance of the eye but usually do not affect sight. The lesions may disappear, or may result in minor retinal folding. Symptoms of the mutation usually appear when a puppy is only a few months old, and generally do not worsen over time.

 

CMR is a recessive disorder. This means that a dog must inherit two copies of the mutation in order to exhibit symptoms of CMR. A dog with one copy of the mutation is known as a carrier. If two carriers are bred to one another, there is a 25% chance per puppy born that they will develop symptoms of CMR and a 50% chance per puppy born that they will also be carriers. Therefore, it is useful to test for the presence of the CMR mutation before breeding. Additionally, since retinal defects can be caused by other conditions, testing can verify that a dog actually has CMR rather than some other eye condition.

Progressive Retinal Atrophy, Cone-Rod Dystrophy 4

Progressive Rod-Cone Degeneration, or PRA-prcd, is a form of Progressive Retinal Atrophy (PRA) in which the cells in the dog's retina degenerate and die. PRA for dogs is similar to retinitis pigmentosa in humans. Most affected dogs will not show signs of vision loss until 3-5 years of age. Complete blindness can occur in older dogs. Progressive Rod-Cone Degeneration is a form of PRA known to affect over 40 different breeds.

 

The retina is a membrane located in the back of the eye that contains two types of photoreceptor cells. These cells take light coming into the eyes and relay it back to the brain as electrical impulses. These impulses are interpreted by the brain to "create" images. In dogs suffering from PRA-prcd, the photoreceptors begin to degenerate, causing an inability to interpret changes in light. This results in a loss of vision. Rod cells, which normally function in low-light or nighttime conditions, begin to degenerate first. This leads to night-blindness. The cone cells, which normally function in bright-light or daytime conditions, will deteriorate next. This often leads to complete blindness over a period of time.

 

PRA-prcd is inherited as an autosomal recessive disorder. A dog must have two copies of the mutated gene to be affected by PRA. A dog can have one copy of the mutation and not experience any symptoms of the disease. Dogs with one copy of the mutation are known as carriers, meaning that they can pass on the mutation to their offspring. If they breed with another carrier, there is a 25% chance that the offspring can inherit one copy of the mutated gene from each parent, and be affected by the disease.