Tollers are generally healthy. However, like almost all dog breeds, they have specific potential genetic disorders. Breeding stock should be tested for the following:
- Hip Dysplasia – an abnormal formation of the hip socket that can lead to severe arthritis and lameness.
- Cardiac – A check for any malformation of the heart or great vessels.
- Eyes (CAER) – A check for any inherited eye disease.
- Collie Eye Anomaly (CEA) – an inherited disease causing defects in the formation of the eye.
- Progressive Retinal Atrophy (PRA) – a group of diseases that cause the retina of the eye to degenerate slowly over time.
- Juvenile Addison’s Disease (JADD) – a rare, early onset, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones.
- Cleft Palate (CP1) – a birth defect whereby a hole in the roof of the mouth develops while the puppy is in utero.
- Degenerative Myelopathy (DM) – A debilitating disease that causes gradual paralysis
- Degenerative Encephalopathy (DE) – a new neurodegenerative disease
THE DYSPLASTIC HIP JOINT
Hip Dysplasia is a terrible genetic disease because of the various degrees of arthritis (also called degenerative joint disease, arthrosis, osteoarthrosis) it can eventually produce, leading to pain and debilitation.
The very first step in the development of arthritis is articular cartilage (the type of cartilage lining the joint) damage due to the inherited bad biomechanics of an abnormally developed hip joint. Traumatic articular fracture through the joint surface is another way cartilage is damaged. With cartilage damage, lots of degradative enzymes are released into the joint. These enzymes degrade and decrease the synthesis of important constituent molecules that form hyaline cartilage called proteoglycans. This causes the cartilage to lose its thickness and elasticity, which are important in absorbing mechanical loads placed across the joint during movement. Eventually, more debris and enzymes spill into the joint fluid and destroy molecules called glycosaminoglycan and hyaluronate which are important precursors that form the cartilage proteoglycans. The joint’s lubrication and ability to block inflammatory cells are lost and the debris-tainted joint fluid loses its ability to properly nourish the cartilage through impairment of nutrient-waste exchange across the joint cartilage cells. The damage then spreads to the synovial membrane lining the joint capsule and more degradative enzymes and inflammatory cells stream into the joint. Full thickness loss of cartilage allows the synovial fluid to contact nerve endings in the subchondral bone, resulting in pain. In an attempt to stabilize the joint to decrease the pain, the animal’s body produces new bone at the edges of the joint surface, joint capsule, ligament and muscle attachments (bone spurs). The joint capsule also eventually thickens and the joint’s range of motion decreases.
No one can predict when or even if a dysplastic dog will start showing clinical signs of lameness due to pain. There are multiple environmental factors such as caloric intake, level of exercise, and weather that can affect the severity of clinical signs and phenotypic expression (radiographic changes). There is no rhyme or reason to the severity of radiographic changes correlated with the clinical findings. There are a number of dysplastic dogs with severe arthritis that run, jump, and play as if nothing is wrong and some dogs with barely any arthritic radiographic changes that are severely lame.
Progressive retinal Atrophy, progressive Rod-cone degeneration (PRA-prcd) is a late onset, inherited eye disease affecting Nova Scotia Duck Tolling Retrievers. PRA-prcd occurs as a result of degeneration of both rod and cone type Photoreceptor Cells of the Retina, which are important for vision in dim and bright light, respectively. The age of onset varies between individual Nova Scotia Duck Tolling Retrievers with PRA-prcd. For most breeds, evidence of retinal disease in affected dogs can first be seen on an Electroretinogram around 1.5 years of age, but most affected dogs will not show signs of vision loss until 3 to 5 years of age or later. The rod type cells are affected first and affected dogs will initially have vision deficits in dim light (night blindness) and loss of peripheral vision. Over time affected dogs continue to lose night vision and begin to show visual deficits in bright light. Other signs of progressive retinal atrophy involve changes in reflectivity and appearance of a structure behind the retina called the Tapetum that can be observed on a veterinary eye exam. Although there is individual and breed variation in the age of onset and the rate of disease progression, the disease eventually progresses to complete blindness in most dogs. Other inherited disorders of the eye can appear similar to PRA-prcd. Genetic testing may help clarify if a dog is affected with PRA-prcd or another inherited condition of the eye.
Collie Eye Anomaly (CEA), also known as choroidal hypoplasia (CH), is an inherited disease affecting several dog breeds including the Nova Scotia duck tolling retriever. The choroid is the layer of tissue in the eye responsible for supplying blood and nutrients to the Retina. In dogs affected with CEA, the choroid does not develop properly and is therefore thinner than normal. The severity of the condition can vary from dog to dog. In mild cases, affected dogs may only show signs of collie eye anomaly on eye exam between about 5 and 12 weeks of age, just prior to normal, age-related pigmentation of the retina which often masks the characteristic, disease-related changes. After this time period, mildly affected dogs may be impossible to distinguish from normal dogs on eye exam (a phenomenon often referred to as “going normal”) and may not display obvious vision deficits. In more severely affected dogs, clinical signs include malformations of the eye and/or optic nerve (colobomas), retinal detachment, intraocular bleeding, and subsequent blindness. Both mild and severe forms of CEA are associated with the same NHEJ1 gene Mutation. Therefore, predicting the potential severity of the disease in an affected puppy is difficult as mildly affected parents may produce offspring that are severely affected.
JUVENILE ADDISON’S DISEASE (JADD) IN THE NOVA SCOTIA DUCK TOLLING RETRIEVER
Addison’s disease (hypoadrenocorticism) occurs when the adrenal glands stop secreting the natural steroid hormones (glucocorticoid) and hormones (mineralicorticoids) necessary for the regulation of sodium and potassium levels in the blood. Addison’s disease can occur in any breed of dog and it has an average age of onset of 4 years. Addison’s disease is diagnosed by a veterinarian using a blood test called an ACTH stimulation test. The clinical signs of Addison’s disease can include lethargy, inappetance, vomiting and diarrhea.
In the NSDTR, a genetic form of this disease, called JADD, occurs in much younger animals. The average age of puppies affected with JADD is 5 months; however, puppies as young as 8 weeks and as old as 12 months of age have been identified.
Treatment of puppies affected with JADD requires both mineralicorticoid and glucocorticoid replacement therapy. Puppies can have other concurrent diseases including eye problems (corneal edema, conjunctivitis or uveitis) that may require specialized treatment.
Scientists from the Bannasch Laboratory at the University of California, Davis have developed a DNA test to identify carriers ofJADD in the Nova Scotia Duck Tolling Retriever. The juvenile form of Addison’s disease is genetically distinguishable from the adult onset form in that all dogs who develop the juvenile form have two identical copies of a specific region within their genome. Our lab has identified numerous markers within this region and we have compiled these markers into a haplotype based test in order to identify dogs that carry JADD. We believe that in addition to the markers that distinguish affected puppies from unaffected ones, the actual mutation responsible for JADD is included in this haplotype test.
The mutation responsible for JADD causes a change the amino acid sequence in a highly conserved region of a protein. This mutation is not present in any other breeds of dogs based on testing of over 250 individual animals in 80 different breeds. However, additional research is needed to demonstrate how this mutation causes JADD in Tollers. We offer the test now to help breeders avoid producing affected puppies while we continue to understand the mechanism of the mutation.
THE MODE OF INHERITANCE
This form of the disease is inherited as an autosomal recessive disease meaning that affected puppies inherited one mutant copy of this gene from each of their parents. In addition, JADD is not completely penetrant meaning that not all puppies with two copies of the mutation will go on to develop the disease. Based upon our research, approximately 75% of puppies with two copies of the mutation and haplotype will develop Addison’s disease.
- JADD Probable N/N This dog has two normal copies of the JADD region
- JADD Probable N/A This dog has one mutant (abnormal) copy of the JADD region
- JADD Probable A/A This dog has two mutant (abnormal) copies of the JADD region and has a 75% chance of developing Addison’s disease by 1 year of age.
In order to keep the costs of this test low it will be run in batches of 48 samples which could affect the turnaround time for results.
JADD is inherited as an autosomal recessive disease meaning that animals have only one mutant copy of the region (N/A) are normal but they are carriers of the disease and they can produce affected puppies if bred to an affected dog (A/A) or another carrier (N/A). At the time that this test was released approximately 20% of Tollers carry JADD (N/A); however, the number of carriers can change with each generation. Dogs that are carriers (N/A) are normal themselves and can be safely bred to N/N dogs in order to maintain diversity within the breed and select for other positive attributes in carrier dogs.
CLEFT PALATE (CP1) IN THE NOVA SCOTIA DUCK TOLLING RETRIEVER
A cleft palate is a birth defect whereby a hole (cleft) in the roof of the mouth (palate) develops in a puppy during gestation. Puppies born with cleft palate can experience difficulty nursing which will greatly increase their risk of developing aspiration pneumonia – a serious life threatening condition. There are multiple genetic causes of cleft palate within the NSDTR breed; however, the most common form has been identified as CP1.
The mutation test we have developed identifies carriers of CP1 within the NSDTR breed. It does not apply to any breed other than the NSDTR. If you have a puppy of a different breed with cleft palate and you wish to participate in the identification of the gene(s) responsible please contact the Bannasch Laboratory at the University of California at Davis (firstname.lastname@example.org).
Scientists from the Bannasch Laboratory at the University of California, Davis have discovered the genetic cause of ONE FORM of cleft palate in the Nova Scotia Duck Tolling Retriever. Dogs with this form of cleft palate have a large insertion into a gene known to affect the proper development of the palate. This mutation is not present in any other breed based on testing conducted on over 300 individual animals of over 80 different dog breeds.
THE MODE OF INHERITANCE
Cleft palate caused by CP1 is a simple autosomal recessive disease meaning that an affected puppy has inherited one mutant copy of the gene from each parent.
- CP1 N/N This dog has two normal copies of CP1
- CP1 N/A This dog has one mutant (abnormal) copy of CP1
- CP1 A/A This dog has two mutant (abnormal) copies of CP1
In order to keep the cost of this test low the test will be run in batches of 48 which could affect the turnaround time for results.
CP1 is an inherited autosomal recessive disease. Animals that have only one mutant copy of CP1 (N/A) are normal but they are carriers of the disease. When two carriers are bred to each other the resulting puppies can be affected. At the time that this test was released, approximately 15% of Tollers were carriers of CP1 (N/A); however, the number of carriers can change with each generation.
Veterinary neurologists in Europe and America have recently recognized a new neurodegenerative disease in the Nova Scotia Duck Tolling Retriever (NSDTR). The disease is called Degenerative Encephalopathy with Sleep Disorders and Caudate Necrosis or simply Degenerative Encephalopathy (DE) for short.
The term encephalopathy comes from the Greek words encephalo- (the brain) and pathy (disease) and simply refers to a disorder of the brain. In this encephalopathy there is degeneration of a region of the brain called the caudate nucleus. The caudate nucleus is a part of the brain that is important in controlling movement and some aspects of behavior. In DE, this portion of the brain undergoes necrosis or complete destruction. One of the manifestations of caudate necrosis is a very unusual change where the dogs vigorously act out their dreams, and are difficult to awaken. Hence the name Degenerative Encephalopathy with Sleep Disorders and Caudate Necrosis. Though this is a devastating disease, it does not appear to be common in the breed.
Researchers at the University of Missouri have found a genetic mutation that is highly associated with DE. A DNA test for this mutation will permit the detection of dogs that have inherited two copies of the mutation and are at risk for developing the disease, and dogs that have inherited one copy of the mutation and have the potential of producing puppies that will develop the disease.
From the University of Missouri research team, THANK YOU to all the breeders, pet owners and veterinarians who contributed to this effort. We could not have done this work without your help!
Dogs with DE show neurologic signs beginning at a young age. These signs become progressively worse with age and most affected dogs have been euthanized due to poor quality of life by 3-5 years of age. Some of the reported signs include:
- More anxious than normal after weaning but learn basic obedience
- Swimming in a more upright posture that does not improve with experience
- Increasing anxious behavior and difficulties learning with age
- Coordination loss: difficulty jumping, choppy gait, falls when making sharp turns
- Abnormal tail position
- Difficult to arouse from sleep and excessive running movements during dreams
- Hyper-vigilant behavior with obsessive barking at vehicles or other inanimate objects
- Excessive fixation on food
- Inappropriate aggression towards other dogs or people.
Many of the signs of DE, such as anxiety, barking at cars, and aggression toward other dogs, could be considered somewhat normal behaviors for a young dog still being trained. These behaviors in a dog with DE, however, take on characteristics where it appears the dog is losing control of its actions. The problems running, swimming or jumping that the dog shows also occur in other neurologic diseases that affect coordination. The sleep disorders that owners of affected dogs describe are not commonly seen with other neurologic diseases. This is why they are highlighted in the name of the disease and warrant further discussion.
When a dog or a person sleeps, there are different phases to sleep. When we first fall asleep, our sleep is fairly light and we are easily awakened. With time, we go into a much deeper sleep that periodically gives way to dreams. The dreaming phase of sleep is called REM sleep. The REM stands for Rapid Eye Movements because if you watch the eyes of a person or dog during this phase, they are darting around beneath the eyelids as if they are watching the action of the dream. A dog cannot tell us what they experience, but everything about REM sleep in dogs suggests that they are also dreaming. During REM sleep, our brain is every bit as active as it is when we are awake. To prevent us from acting out our dreams, the brain blocks communication to the areas that control body movements. In people, the only part of the body that is not blocked is the eye, and hence the rapid eye movements. In dogs, this blockage is not as complete, and thus it is not unusual for dogs to have some small twitches of their paws or little yips as well as the eye movements during REM sleep. The caudate nucleus, that part of the brain that degenerates in DE, is a critical player in blocking the translation of our dreams into movement. Thus, people with diseases that affect this area commonly experience sleep disorders such as sleep walking or violent movements during sleep. In dogs with DE, we see violent kicking and paddling movements during REM sleep.
How is Degenerative Encephalopathy diagnosed?
Many of the clinical signs of DE can be seen with other diseases of the nervous system such as liver shunts, back injuries or infections of the brain. The sleep disorder seen in DE, however, is not often seen with other diseases. Thus the combination of coordination loss, personality changes, and a sleep disorder would suggest a diagnosis of DE. A veterinary neurologist would be able to evaluate a dog showing such signs and ensure that some other condition was not the cause.
The degeneration of the caudate nucleus is the most specific finding that would confirm a diagnosis of DE. These changes can be readily seen on an MRI scan of the brain. Thus an MRI would be indicated in any NSDTR showing signs of DE. We know that these changes can be found in the dogs by 3 years of age, but we do not know what the earliest age that they can be detected is. This degeneration is also readily identified on a post-mortem examination of the brain.
The DNA test will identify dogs at risk for developing DE but appropriate clinical signs would need to be present for the veterinarian to confirm the diagnosis.
What are the treatment options for DE?
Until the underlying mechanism of the degeneration of the brain is better understood, only symptomatic therapy is available.
What is the prognosis?
Most of the affected dogs have been euthanized by 3-5 years of age due to poor quality of life and worries about aggression.
Are there any risk factors (age, sex, genetic lines, etc..) for Degenerative Encephalopathy?
DE is an autosomal recessive hereditary disease. In a recessive disease, both parents of an affected pup can be normal. All animals have two copies of each gene, one that is inherited from the mother and one inherited from the father. A dog that has one normal gene and one bad (mutated) copy of a gene associated with a disease is a carrier of the trait. They show no symptoms because the one good gene is enough for their brain to function normally, but they will pass that bad gene on to about half of their offspring. If a carrier dog is bred to another carrier, then some of the pups (25% on average) may get a bad gene from each parent. Without one good gene to carry the day, the brain cannot function normally and the unlucky pup has the disease.
All the dogs with DE were born to normal parents and both sexes are equally affected. Several dogs have undergone extensive neurologic evaluations including MRI, spinal fluid analysis, tests for metabolic disease and post-mortem examination of the brain. No evidence of any other cause such as infection, trauma, brain tumors, toxicity or metabolic disease has been found in any of the dogs with DE.
Is there a DNA test for Degenerative Encephalopathy?
Researchers at the University of Missouri have identified a mutation in a gene that is highly associated with Degenerative Encephalopathy with Sleep Disorders and Caudate Necrosis. The brain function that would be affected by this mutation is disrupted in similar neurodegenerative diseases in people. Dogs that have two copies of the mutation (homozygous) are at risk for developing DE. In some hereditary diseases, every dog that is at risk develops the disease. Other hereditary diseases show what is called variable penetrance. In diseases with variable penetrance, not every dog that is homozygous for the mutation develops disease. Further research is needed to determine whether this occurs with DE, but thus far, all the dogs with 2 mutated copies of the gene have shown signs of DE.
The DNA test can also identify carriers of the mutation. Continuing to use carriers wisely for breeding will maintain genetic diversity in the breed and thereby preserve desirable traits in that line. To prevent producing an affected pup, a carrier of the mutation should always be bred to a dog that has tested clear of the mutation by the DNA test. Approximately 50% of the offspring of that breeding will be carriers, so the offspring should then be tested for the mutation. Whether the pups are also carriers should then be one consideration when deciding which dogs will be kept as future breeding stock.
How can I DNA test my dog for DE?
A DNA test is available to identify the genetic status of a dog for this gene mutation. The test will determine if the dog has 2 normal copies of the gene (normal), one normal copy and one mutated copy (carrier), or has 2 mutated copies and is at risk to develop clinical signs of DE. Owners of dogs that are suspected to be showing clinical signs of DE will be tested at no charge. Dogs that were sampled specifically for this DE research, or have a DNA sample stored at University of Missouri for any reason (other research, CHIC DNA Bank sent via blood sample, etc.) are eligible to request test results at a reduced fee of $35. For owners who sent samples specifically for this DE research, there is no charge to request an email with results only. (If a report and certificate are desired, the charge is $35.) To request a report on a dog with DNA already at U of MO, please contact Liz Hansen at HansenL@missouri.edu.
Explanation of Test Results
Normal: This dog has tested normal (or clear) for the mutation identified as responsible for development of Degenerative Encephalopathy (DE) in Nova Scotia Duck Tolling Retrievers. It is not at risk for developing DEN. It can only transmit a normal gene to offspring, and current information indicates that dogs with this result can be bred to a dog with any DNA test result without risk of producing affected offspring.
Carrier: This dog has tested as a carrier for the mutation identified as responsible for development of Degenerative Encephalopathy (DE) in Nova Scotia Duck Tolling Retrievers. Carrier individuals are clinically normal, but may transmit either a normal gene or a mutated/affected gene to potential offspring. To avoid risk of producing an affected puppy, these dogs should only be bred to mates which have been DNA-tested normal.
Affected/At-Risk: This dog has 2 mutated copies of the gene identified as responsible for development of DE and is at risk for developing clinical neurologic signs of DE, starting at a young age and becoming progressively worse with age. Most DE affected dogs are euthanized due to poor quality of life by 3-5 years of age.
What research is going on to help us better understand Degenerative Encephalopathy?
The DNA test will allow identification of dogs at risk for developing DE and carriers of the mutation, but the situation in this disease may be more complex. There are reports of dogs showing behavior changes and coordination problems, but not the sleep disorder and necrosis of the caudate nucleus that are the hallmarks of DE. These dogs do not have the mutation associated with DE. Also one of the dogs with DE who had a post-mortem performed had additional changes in the brain that were not seen in other dogs with DE. This raises the question of whether there may be more than one brain disease in the breed. The DNA test will identify dogs with signs related to the mutation that has been identified. Those with signs of neurologic disease that do not have the mutation can then be studied further to determine if there is a second neurologic disease.
Please visit http://www.caninegeneticdiseases.net/Toller for additional information and contact the researchers at the University of Missouri if you think you may have a dog with DE. The researchers will keep all information confidential.
Degenerative Myelopathy is an inherited neurologic disorder caused by a Mutation of the SOD1 gene known to be carried by Nova Scotia duck tolling retrievers. This mutation is found in many breeds of dog, though it is not clear for Nova Scotia duck tolling 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. 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. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected medium to large breed dogs, such as the Nova Scotia duck tolling retriever, can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs.