Poodle Breeders Should Use DNA Tests to Guide Breeding Decisions
Standard Poodle breeders Gail S. Wolaniuk and Joan E. McFadden took a risk and asked for help. Their proactive approach to dealing with the fatal neurologic disease that affects newborn puppies and is now known as neonatal encephalopathy with seizures (NEwS) was a game changer. Along with other Poodle breeders, they contributed to research that led to a direct DNA test for the autosomal recessive disease.
These 2020 AKC Breeder of the Year award recipients list “health” as their first priority. Over 41 years of breeding white Standards, Wolaniuk and McFadden, of Garnet Valley, Pennsylvania, have produced 112 show champions, including six Best in Show and seven Best in Specialty Show winners that collectively won 34 Bests.
Their journey with NEwS began in 2002 when their bitch, CH Unique No Doubt About It, whelped a litter of nine puppies sired by CH Unique Meant To Be. “We noticed that two newborn puppies weren’t thriving,” McFadden says. “They appeared normal at birth but quickly turned smaller and weaker than their littermates. Our veterinarian tested the puppies for every possible cause of the condition and came up with nothing. Because of their continued deterioration, we had them euthanized at 4 weeks of age.”
Two years later the condition resurfaced in two puppies born from a breeding of CH Unique Practical Magic, a sister of the previous dam, to a half-brother of the previous sire. “A fellow breeder mentioned hearing of pups on the West Coast with similar signs,” Wolaniuk says. “People were calling it ‘Funky Puppy Syndrome.’ This breeder mentioned a veterinary neurologist at the University of Missouri who was interested in breeders willing to participate in a study of the disease.”
Many puppies with the unusual syndrome died in the first week. If they survived longer, they became progressively less coordinated. Puppies that made it to 4 to 6 weeks of age developed severe generalized tonic-clonic seizures. No puppy survived to 7 weeks of age.
The neurologist, Dennis O’Brien, DVM, PhD, the Chancellor’s Chair in Comparative Neurology, and colleague Gary S. Johnson, DVM, PhD, associate professor and molecular geneticist, began processing DNA samples from 20 NEwS affected puppies and 58 clinically normal family members from 12 litters across the country. In 2006, they identified a missense mutation on canine chromosome 36 in the activating transcription factor 2 (ATF2) gene.
The discovery provided a direct DNA test for NEwS in which carrier (N/ES), affected (ES/ES) and normal (N/N) puppies are identified via a cheek swab of their DNA. Importantly, the test enables breeders to selectively choose breeding partners that do not produce affected dogs. As many testing laboratories offer the NEwS genetic test, it is challenging to accurately estimate the ATF2 gene penetrance in the breed; however, based on Poodles registered in the Canine Health Information Center (CHIC) database, the carrier rate is around 18 percent.
“We began testing every dog in our breeding program,” McFadden says. “We do not consider breeding to a dog that has not been tested for NEwS. We try to only breed to dogs that test clear for the mutation, though we understand that the DNA test gives us the flexibility to carefully use an occasional carrier.”
The NEwS test is one of several DNA tests available to Poodle breeders. Here is a review of tests that provide information about diseases affecting Poodles and can be used to guide breeding decisions. Not all are required for CHIC certification (See “CHIC Health Testing Requirements for Poodles” on page 3.)
Genetic Tests for Toy & Miniature Poodles
prcd-Progressive Retinal Atrophy: Progressive rod-cone degeneration (prcd) is an inherited form of late-onset progressive retinal atrophy. Blindness occurs in dogs after 5 or 6 years of age. The cells of the retina involved in low light vision, known as rods, are affected first, leading to night blindness. Subsequently, the bright light photoreceptors, or cones, that are important for color vision, are affected, resulting in daytime visual impairment. Breeders can avoid producing dogs affected by the autosomal recessive mutation by including at least one prcd-PRA clear parent in a breeding. According to the Poodle CHIC registry, about 7.9 percent of Toy and Miniature Poodles are carriers of the prcd gene mutation.
Osteochondrodysplasia (OC): Commonly known as Miniature Poodle dwarfism, this disorder is characterized by extended hind limbs, enlarged joints, flattening of the ribcage, shortened and bent long bones, an undershot jaw, and misshapen paws resembling clubfoot. Affected puppies that appear normal at birth have stunted growth by 3 weeks of age. OC is crippling and painful, thus affected puppies are often euthanized. Moreover, the disorder can occur in a variety of forms and the level of disability is not consistent. Some less affected puppies have survived into adulthood. A partial deletion in the SLC13A1 sulfate transporter gene is associated with the autosomal recessive condition. Breeders can avoid producing affected dogs by ensuring that one parent is clear for the SLC13A1 gene mutation. When the mutation was discovered in 2012, the researchers estimated that 10 percent of Miniature Poodles in the U.S. were carriers.
Chondrodystrophy (CDDY): The genetic mutation that causes CDDY also puts dogs at risk for paralysis from Type 1 intervertebral disc disease (IVDD). Dogs with the CDDY gene mutation may experience cellular degeneration of the discs, which predisposes them to herniation of the discs into the spinal canal later in life. As the discs press on the nerves of the spinal cord, a dog may experience pain, nerve damage, loss of bladder and bowel control, and/or paralysis. Many dogs that carry the mutation will never have herniation.
A functional fibroblast growth factor 4 (FGF4) retrogene insertion on canine chromosome 12 is the causative variant attributed to the CDDY phenotype and susceptibility to Type 1 IVDD. The FGF4 mutation impacts the IVDD phenotype with a dominant inheritance, thus dogs require only one copy of the retrogene insertion to be predisposed. Largely occurring in Toy and Miniature Poodles, the CDDY variant affects 57 percent of Toy Poodles and 61 percent of Miniature Poodles, based on findings from a small sample tested at the University of California-Davis where the gene mutation was discovered in the lab of Danika Bannasch, DVM, PhD, the Maxine Adler Endowed Chair of Genetics. Comparatively, Standard Poodles are virtually exempt from having a copy of the gene allele. Breeders of Toy and Miniature Poodles are advised to use the FGF4 retrogene test cautiously to avoid reducing genetic diversity and to share test results with their veterinarian if a dog is at risk for IVDD to assist in clinical decisions, says Dr. Bannasch.
Genetic Tests for Standard Poodles
Neonatal Encephalopathy with Seizures (NEwS): Described on pages 2-3.
Von Willebrand Disease (vWD Type 1): An inherited bleeding disorder, this disease is caused by abnormally low levels of von Willebrand coagulation factor (vWF), an essential protein needed for normal blood clotting. Spontaneous bleeding from the mouth, nose and urinary and reproductive tracts may occur as well as uncontrollable bleeding after an injury, surgery or giving birth. Most affected dogs have a normal life span, but it is important to identify affected dogs due to the risk of excessive bleeding and to avoid producing affected dogs. An autosomal recessive disease, vWD affects some dogs mildly and others severely. Dogs must receive two copies of the gene mutation — one from each parent — to develop the disease. When carriers, or dogs having one copy of the gene mutation, are bred together, 25 percent of their offspring will develop the disease, 50 percent will be carriers, and 25 percent will be unaffected. According to CHIC registrations of Standard Poodles, about 2.8 percent of dogs are carriers.
Day Blindness/Retinal Degeneration (DB/RG): Puppies with DB/RG show signs of poor vision in bright light but initially retain normal to subnormal vision in low light levels. Unlike other forms of day blindness in other breeds, the DB/RG mutation causes a more complete retinal degeneration in which affected Standard Poodles eventually lose both cone and rod cell function that results in blindness under all lighting conditions. It is a variable disorder in which some affected dogs at 2 years of age are indistinguishable from dogs with end-stage progressive retinal atrophy, yet in other dogs the retina appears to remain clinically intact for several years using standard clinical examination methods. However, using more advanced imaging modalities such as optical coherence tomography (OCT), which is performed under general anesthesia, the degeneration of the photoreceptors is evident. The autosomal recessive DB/RD mutation has been identified and a DNA test is available. This will enable breeders to selectively choose breeding partners in which one mate is clear for the mutation to avoid producing affected dogs.
Genetic Test for All Poodle Varieties
Degenerative Myelopathy (DM): All varieties of Poodle are among over 40 breeds and mixed breeds affected by DM, a devastating neurologic disease that impairs a dog’s hind limbs. Dragging or scuffing of the legs typically begins around 9 years of age. This progresses to decreased muscle control and weakness causing frequent falls and difficulty getting up. Within 9 to 12 months, dogs are paralyzed as DM spreads through the nervous system, damaging the spinal cord, brain, nerves, and muscles. An autosomal recessive mutation in the superoxide dismutase 1 gene (SOD1) contributes to a dog’s risk to developing DM, though the disease has an age-related incomplete penetrance. The longer an at-risk dog lives, the higher the likelihood of developing signs of DM. The risk for dogs having two copies of the mutant SOD1 variant to developing DM is not known. The DNA test helps breeders make breeding decisions, yet it has diagnostic limitations because it is testing for a risk factor and does not provide definitive diagnosis. Breeders can use genetic testing to breed dogs that carry the SOD1 mutation to clear, healthy dogs to avoid producing affected dogs without reducing genetic diversity.