The number of genetic tests for inheritable diseases in Tollers is quite remarkable, due to the dedication and commitment of breeders.

Here is a list of the tests available to breeders and information to help explain the disease and mode of inheritance.

 Most breeders test for these diseases and will use them in their decision making when selecting mating pairs to reduce the likelihood of producing known diseases.

When selecting a breeder, please feel free to ask them for confirmation that the parents of the pups they are selling are tested, or at least cleared by parentage.  Clear by parentage is only guaranteed by one generation, ie the grandparents of the pups.

The breeder should have copies of all their dog's clearances, that they should be sharing with you, if not, ask.


PRA, Progessive Rod Cone Degeneration

Progressive rod-cone degeneration (PRCD) is an inherited form of late-onset progressive retinal atrophy (PRA) that has been identified in many dog breeds.

Phenotype: PRCD affects the photoreceptor cells in the eye involved in both night and day vision. The cells of the retina involved in low light vision, known as rods, are affected first, resulting in night blindness. Subsequently, the bright light photoreceptors known as cones, which are important for color vision, are also affected, resulting in daytime visual deficit. The age of onset and rate of progression vary among breeds, but retinal changes can be identified by screening performed by a veterinary ophthalmologist from adolescence to early adulthood. Most PRCD-affected dogs have noticeable visual impairment by 4 years of age, typically progressing to complete blindness.

Mode of Inheritance: Autosomal recessive

Alleles: N = Normal, PRCD = Progressive rod-cone degeneration

Breeds appropriate for testing: Many breeds including but not limited to: American Eskimo Dog, American Hairless Terrier, Australian Cattle Dog, Australian Cobberdog, Australian Shepherd, Black Russian Terrier, Barbet, Chesapeake Bay Retriever, Chinese Crested, Chihuahua, Cockapoo, American Cocker Spaniel, Coton de Tulear, English Cocker Spaniel, English Shepherd, Entlebucher Mountain Dog, Field Spaniel, Finnish Lapphund, German Spitz, Giant Schnauzer, Golden Retriever, Golden Doodle, Jack Russell Terrier, Japanese Chin, Lab/Golden Cross, Labradoodle, Australian Labradoodle, Labradoodle/Goldendoodle Cross, Labrador Retriever, Miniature American Shepherd, Norwegian Elkhound, Nova Scotia Duck Tolling Retriever, Pomeranian, Poodle (Standard, Medium, Miniature and Toy), Portuguese Water Dog, Puli, Silky Terrier, Schipperke, Spanish Water Dog, Standard Poodle, Swedish Jamthund, Swedish Lapphund, Tibetan Terrier, Xoloitzcuintle, Yorkshire Terrier

Explanation of Results:

  • Dogs with N/N genotype will not have this PRCD form of progressive retinal atrophy and cannot transmit this variant to their offspring.
  • Dogs with N/PRCD genotype are not expected to be affected by this PRCD form of progressive retinal atrophy, but are carriers. They may transmit this PRCD variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% PRCD-affected puppies.
  • Dogs with PRCD/PRCD genotype are expected to develop this PRCD form of progressive retinal atrophy and will transmit this variant to all of their offspring.

CLPS, Cleft Lip/Palate and Syndactyly

Phenotype: The phenotype of affected puppies can vary from only a cleft palate (hole in the roof of the mouth) to cleft palate and cleft lip (split in the lip that can occur on one or both sides of the mouth). In both cases puppies may also have syndactyly (fusion of the middle two digits of the feet).

Mode of Inheritance: Autosomal recessive

Alleles: N = Normal, A = Cleft lip/palate and syndactyly (CLPS)

Breeds appropriate for testing: Nova Scotia Duck Tolling Retriever

Explanation of Results:

  • Dogs with N/N genotype will not have this form of cleft lip/palate and syndactyly and cannot transmit this CLPS variant to their offspring.
  • Dogs with N/A genotype will not have this form of cleft lip/palate and syndactyly, but are carriers. They will transmit this CLPS variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% CLPS-affected puppies.
  • Dogs with A/A genotype will be affected to varying degrees by cleft lip/palate and syndactyly. They will transmit this CLPS variant to all of their offspring.

CP1, Cleft Palate

Phenotype: 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.

Mode of Inheritance: Autosomal recessive

Alleles: N = Normal, A = Cleft palate (CP1 variant)

Breeds appropriate for testing: Nova Scotia Duck Tolling Retriever

Explanation of Results:

  • Dogs with N/N genotype will not have this form of cleft palate and cannot transmit this CP1 cleft palate variant to their offspring.
  • Dogs with N/A genotype will not be affected by this form of cleft palate, but are carriers. They will transmit this CP1 cleft palate variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% CP1 cleft palate-affected puppies.
  • Dogs with A/A genotype will have this form of cleft palate and will transmit this CP1 cleft palate variant to all of their offspring.

JADD, Juvenile Addisons Disease

Addison’s disease occurs when the adrenal glands stop secreting necessary natural steroid hormones. In the Nova Scotia Duck Tolling Retriever, a genetic form of Addison's disease can occur in puppies.

Phenotype: The clinical signs of Addison’s disease can include lethargy, lack of appetite, vomiting, and diarrhea. The average age of puppies affected by this juvenile form of Addison's disease is 5 months. Puppies can have other concurrent diseases including eye problems (corneal edema, conjunctivitis, or uveitis) that may require specialized treatment.

Mode of Inheritance: Autosomal recessive (incomplete penetrance)

Alleles: N = Normal, A = Juvenile Addison's disease (JADD)

Breeds appropriate for testing: Nova Scotia Duck Tolling Retriever

Explanation of Results:

  • Dogs with N/N genotype are not expected to have this form of juvenile Addison's disease and cannot transmit this JADD variant to their offspring.
  • Dogs with N/A genotype are not expected to have this form of juvenile Addison's disease, but are carriers. They will transmit this JADD variant to 50% of their offspring. If carriers are bred together or to an affected mate, affected offspring can be produced.
  • Dogs with A/A genotype have a 75% chance of developing Addison's disease by one year of age. 

DE, Degenerative Encephalopathy

Nova Scotia Duck Tolling Retriever ONLY

Veterinary neurologists in Europe and America have recently recognized a new neurodegenerative disease in the Nova Scotia Duck Tolling Retriever (NSDTR).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!

Symptoms

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.

Diagnosis

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.

Risk Factors

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.

DNA Tests

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.

Additional Research

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.

Statistics on testing results

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.

DM, Degenerative Myelopathy

Degenerative myelopathy (DM) is an inherited neurologic disorder of dogs characterized by gradual muscle wasting and loss of coordination typically beginning in the hind limbs.

Phenotype: Affected dogs usually present clinical signs of disease in adulthood (at least 8 years of age) with gradual muscle wasting and loss of coordination typically beginning in the hind limbs. Disease progression continues until the dog is unable to walk. Small breed dogs tend to progress more slowly. In late stages of the disease, dogs may become incontinent and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of signs.

Mode of Inheritance: Autosomal recessive, incomplete penetrance

Alleles: N = Normal/Unaffected, DM = Degenerative myelopathy

Breeds appropriate for testing: Many breeds

Explanation of Results:

  • Dogs with N/N genoytpe will not have degenerative myelopathy and cannot transmit this variant to their offspring.
  • Dogs with N/DM genotype will not have degenerative myelopathy, but are carriers. They will transmit this variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% degenerative myelopathy-affected puppies.
  • Dogs with DM/DM may have degenerative myelopathy, a disabling condition, and will transmit this variant to all of their offspring.

CDDY, Chondrodystrophy

Chondrodystrophy, a trait that is characterized by a short-legged phenotype, also impacts the health of dogs by increasing susceptibility to intervertebral disc disease.

Phenotype: Chondrodystrophy (CDDY) includes a short-legged phenotype as well as abnormal premature degeneration of intervertebral discs leading to susceptibility to intervertebral disc disease.

Mode of Inheritance: Autosomal dominant for intervertebral disc disease; semi-dominant for height

Alleles: N = Normal, CDDY = Chondrodystrophy

Breeds appropriate for testing: Nova Scotia Duck Tolling Retriever

Explanation of Results:

  • Dogs with N/N genotype do not have the mutation for chondrodystrophy and therefore are not predicted to be at increased risk for intervertebral disc disease. They cannot transmit this chondrodystrophy variant to their offspring.
  • Dogs with N/CDDY genotype will have leg shortening compared to N/N dogs and are at risk for intervertebral disc herniation. They will transmit this CDDY variant to 50% of their offspring. Matings with N/N genotype dogs are predicted to produce 50% shorter-legged puppies at risk for intervertebral disc herniation.
  • Dogs with CDDY/CDDY genotype will have leg shortening compared to N/N dogs and are at risk for intervertebral disc herniation. If a CDDY/CDDY dog is bred, all of the puppies in the litter will have shorter legs and are also be at risk for intervertebral disc herniation, regardless of the mate's genotype.

The incidence of CDDY in the breed is quite high, due in most part to it being Autosomal dominant, which means even the carrier population is affected.  The incidence of IVDD is increased with CDDY but the understanding to why some dogs herniate and some don't still requires ongoing research.  At this time many breeders are slowly moving forward to try to reduce CDDY in the breed without reducing the genetic diversity as well as affecting the current breed standard.  Not easily done.