Vestibular Deafness Mutation Discovery Is Expected To Help Reduce Incidence
The recent discovery of the causative gene mutation for vestibular deafness in Doberman Pinschers, and the subsequent development of a direct DNA test to identify carriers, is expected to have an impact on reducing the suspected 13 percent of Doberman puppies born with the disorder.
Besides having congenital deafness in one or both ears, puppies show signs of vestibular dysfunction including head tilting and loss of balance as early as 1 to 2 weeks of age. Although vestibular deafness (DVDob), commonly called “dings,” was identified in the early 1980s, breeders often have not realized that affected puppies had the condition.
Ann Ramsbottom of Holton, Ind., who breeds Dobermans under the Cambria prefix, says, “The more experience you have dealing with dings, the earlier you will notice it. You can detect differences as the puppies’ senses develop, usually by the time they are 2 weeks old. These puppies have a hard time finding their dam’s nipples to nurse, and she often pushes them away. They cry constantly and can’t seem to get comfortable. I think breeders are not aware of what the problem is.”
Aubrey Webb, D.V.M., Ph.D., a veterinarian with a doctorate degree in neuroscience who practices at CullenWebb Animal Eye Specialists in Riverview, New Brunswick, Canada, recalls examining a litter of Doberman Pinscher puppies in 2010, in which two puppies were affected by DVDob. The litter was brought in by their breeder who wanted to know the cause of their condition.
Familiar with the vestibular deafness disorder described in the breed and that it was thought to be an inherited condition, Webb asked Mark Neff, Ph.D., head of the Laboratory of Canine Genetics & Genomics at Van Andel Research Institute to work with him to identify the mode of inheritance. Neff agreed to study the disorder in Doberman Pinschers.
The research efforts led to identification of a candidate gene for DVDob in 2011 based on DNA samples from 24 affected dogs, and the researchers validated the autosomal recessive mutation in 2012. Affected Dobermans inherit a copy of the gene mutation from both their sire and dam. Carriers can be bred to clear dogs to avoid producing affected puppies.
Although the research is yet to be published in a peer-reviewed scientific journal, the DNA genetic test already is available to breeders through projectDOG, a recently founded nonprofit genetic testing and research organization in Albany, Calif. “One purpose for offering the genetic test prior to publication is to allow the test results to be included in the manuscript,” says Alison Ruhe, director of projectDOG.
“An expanded set of test data will help us to define the frequency of carriers within the population,” Neff explains. “Our research found two outlier dogs that tested ‘affected’ but do not show clinical signs. This could be the result of a different gene mutation or variable penetrance in which not all dogs with the mutation are affected.”
Identifying DVDob Phenotype
The phenotype for vestibular deafness in Dobermans was characterized in 1980 by Cheryl Chrisman, D.V.M., a veterinary neurologist at the University of Florida College of Veterinary Medicine. Chrisman described dogs as having a bobble-head appearance due to a tilted head and lack of coordination.1 A detailed phenotypic description of the condition by Margaret K. Wilkes, VETMB, Ph.D., and Anthony C. Palmer, Ph.D., ScD, DACVIM, FRCVS, was published in 1992.2
Affected dogs can appear normal by a routine physical examination, though a neurological examination detects signs of bilateral vestibular disease and BAER (brainstem auditory evoked response) hearing testing can identify deafness. Pathological findings show degeneration of the cochlear portion of the inner ear.
The cochlea, responsible for hearing by receiving and amplifying sounds, and the vestibular system are located in a dog’s inner ear. Vestibular function contributes to balance and a sense of spatial orientation. Some puppies with DVDob may improve over time without treatment due to the neurological system compensating for deficits. Mildly affected dogs can lead relatively normal lives despite being deaf and appearing to have a permanently cocked head. More commonly, puppies are euthanized due to complications raising them.
Conditions similar to DVDob have been anecdotally reported in other breeds. These include Akita, Beagle, English Cocker Spaniel, German Shepherd Dog, and Tibetan Terrier. Researchers have not compared the conditions to learn whether they have the same recessive causative gene mutation.
Part of the reason for the success in identifying the mutation in Dobermans is due to breeders working together to submit DNA samples and provide information about affected puppies. “Doberman breeders have always been leaders in research participation for us,” Ruhe says. “They are really driven to solve health and genetic issues, and their involvement is crucial for learning more about genetic conditions, such as dings.”
A catalyst in the effort was Kathy Davieds, D.V.M., of Floyd, Va., who serves as the liaison between researchers and breeders for the Doberman Pinscher Club of America. “There is growing support within the Doberman community for health testing as well as openness about health conditions,” Davieds says.
A request to Doberman breeders and owners for DNA samples to study a variety of health conditions — including dings — resulted in 3,800 samples submitted within three weeks to the Neff laboratory for projects specific to the breed. Select samples are run on a commercial gene chip (Illumina Canine HD BeadChip) that allows for the screening of 170,000 genetic markers per dog.
“In total, costs can exceed $500 to run one dog,” Ruhe says. “However, once a dog has been tested by this dense marker screen, the data may be used in many studies at no additional cost. This enables us to investigate multiple conditions simultaneously and provides an efficient, cost-effective way to do research.”
The DNA from Dobermans will be used to study disorders such as cervical vertebral instability, or wobbler’s syndrome, chronic active hepatitis and osteosarcoma. Behavioral disorders, such as obsessive compulsive disorder (OCD) and pica, in which dogs eat non-food items, also will be studied.
“Preliminary data suggests that as many as 60 to 65 percent of Dobermans exhibit habitual flank or blanket sucking behavior,” says Ruhe. “OCD behavior is hard to assess in dogs. Although no genes have been identified, even narrowing down the search to a specific area of the genome could have a tremendous impact on understanding this behavior and similar disorders in people and dogs. Researchers have hypothesized that OCD and pica could be the result of the evolution of the breed from its original purpose as a guard dog.”
Breeders today strive to produce Dobermans that have a temperament suited for families and companionship. “Originally, this breed was bred to be an alert, high-drive guard and protection dog,” Ruhe says. “As breeders breed dogs to be less driven, it is possible they redirect their innate drive into other areas, including compulsive behaviors.”
On a trial basis, projectDOG is offering the DVDob DNA test at a requested donation amount to cover costs. Donated laboratory space and equipment from Quintara Biosciences, plus generous private donations, make this possible.
The testing laboratory plans to add genetic marker tests as they become available. “These are tests in which we have a good idea of the genetic markers but are not ready to publish our research results,” says Ruhe. “Our goal is to provide accurate, affordable genetic tests to breeders as soon as they are available.”
“The potential of projectDog is great,” Davieds says. “They need two resources: funding and DNA samples. The ability to unravel the mysteries of countless genetic diseases of purebred dogs is almost limitless.”
The importance of the DVDob DNA test is that it allows breeders to be informed about the selection of dogs they wish to use for their breeding programs. A breeder can work toward retaining the traits of valuable dogs that carry the dings mutation by crossing them with unaffected, healthy dogs.
“With our genetic test for the dings mutation, the production of affected dogs can be prevented,” Webb says. “Breeders can use lines that have produced dings without fear.”
1 Chrisman CL. Vestibular diseases. Veterinary Clinics of North American Small Animal Practice. 1980;10:103-129.
2 Wilkes MK, Palmer AC. Congenital deafness and vestibular disease deficit in the Doberman. J Sm Anim Prac. 1992;33:218-224.
Purina appreciates the support of the Doberman Pinscher Club of America and particularly Dr. May Jacobson, chair of the DPCA Health Research Evaluation Committee, and Judith Brown, past chair, who helped to identify this topic for the Purina Pro Club Doberman Pinscher Update newsletter.
How to Test Doberman Pinschers for Dings
Doberman Pinschers may now be tested for vestibular deafness (DVDob), which also is known as dings. A new genetic testing laboratory in Albany, Calif., projectDOG, offers the direct DNA test that identifies carriers of the recessive inherited disorder.
For information, go to projectdog.org and click on “Doberman DVDob ‘DINGS’ Test Available Now” on the right side of the home page or call 510-900-3899. For a trial period, projectDOG is offering testing at a requested donation rate of $20 to $40 per dog, based on the number of dogs tested.