POODLE Update - DNA DISEASE TESTING Tools to Guide Breeding Decisions - Purina Pro Club
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POODLE Update
A PURINA PRO PLAN PUBLICATION DEDICATED TO POODLE ENTHUSIASTS VOLUME 19 | SUMMER 2021
DNA DISEASE TESTING
Tools to Guide Breeding Decisions
SUMMER 2021
POODLE BREEDERS SHOULD USE DNA
TO GUIDE BREEDING DECISIONS
TESTS
Standard Poodle breeders Gail S. for their Unique Standard Poodles.
Wolaniuk and Joan E. McFadden Over 41 years of breeding white
took a risk and asked for help. Their Standards, Wolaniuk and McFadden,
proactive approach to dealing with of Garnet Valley, Pennsylvania, have
the fatal neurologic disease that produced 112 show champions, including
affects newborn puppies and is now six Best in Show and seven Best in
known as neonatal encephalopathy Specialty Show winners that collec-
with seizures (NEwS) was a game tively won 34 Bests.
changer. Along with other Poodle Their journey with NEwS began in
breeders, they contributed to research 2002 when their bitch, CH Unique
that led to a direct DNA test for the No Doubt About It, whelped a litter
autosomal recessive disease. of nine puppies sired by CH Unique
These 2020 AKC Breeder of the Meant To Be. “We noticed that two
Year award recipients list “health” newborn puppies weren’t thriving,”
as their first priority. “Focusing on McFadden says. “They appeared
the health, temperament, structure normal at birth but quickly turned
and longevity of Standard Poodles smaller and weaker than their litter-
involved in conformation, agility, mates. Our veterinarian tested the
obedience and companionship” puppies for every possible cause
appears at the top of the home page of the condition and came up with
Joan McFadden, left, and Gail Wolaniuk,
the 2020 AKC Breeder of the Year
award recipients, are shown with, from
left, Unique Sparking Rays of Hope,
4 months old, CH Unique The Queen
of Everything, 5 years old, and her
daughter, Unique A Sky Full of Stars,
6 months old.
COVER PHOTO: LESLIE NEWING
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POODLE Update
nothing. Because of their continued
PHOTO: LESLIE NEWING
deterioration, we had them eutha-
nized 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. CHIC HEALTH TESTING REQUIREMENTS FOR POODLES
Puppies that made it to 4 to 6 weeks
of age developed severe generalized Toy Poodle
tonic-clonic seizures. No puppy • DNA test for prcd-progressive retinal atrophy
survived to 7 weeks of age. • Eye examination by a board-certified veterinary
The neurologist, Dennis O’Brien, ophthalmologist
DVM, PhD, the Chancellor’s Chair in • OFA evaluation for patellar luxation at minimum
Comparative Neurology, and col- age of 1 year
league Gary S. Johnson, DVM, PhD, Miniature Poodle*
associate professor and molecular • Same requirements as listed above for Toy Poodle
geneticist, began processing DNA • OFA or PennHIP evaluation for hip dysplasia
samples from 20 NEwS affected * The PCA Foundation also recommends the DNA test for osteochon-
puppies and 58 clinically normal drodysplasia (Miniature Poodle dwarfism).
family members from 12 litters across Standard Poodle*
the country. In 2006, they identified • OFA or PennHIP evaluation for hip dysplasia
a missense mutation on canine • Eye examination by a board-certified veterinary ophthalmologist
chromosome 36 in the activating • One of these elective health tests:
transcription factor 2 (ATF2) gene. • OFA thyroid evaluation by an approved laboratory
The discovery provided a direct • OFA sebaceous adenitis evaluation by an approved dermapathologist
DNA test for NEwS in which carrier • Congenital or advanced cardiac examination by a board-certified
(N/ES), affected (ES/ES) and normal veterinary cardiologist or basic cardiac examination by a general
(N/N) puppies are identified via a veterinary practitioner
cheek swab of their DNA. Impor- *The PCA Foundation recommends all three elective health tests as well
tantly, the test enables breeders to as DNA tests for neonatal encephalopathy with seizures (NEwS) and
selectively choose breeding partners von Willebrand disease (vWD).
that do not produce affected dogs. Note: In addition to these health requirements, a dog must be perma-
As many testing laboratories offer nently identified via microchip or tattoo to qualify for a CHIC number.
the NEwS genetic test, it is challeng- For CHIC certification, a dog’s testing results do not need to be normal
ing to accurately estimate the ATF2 but must be made public so that responsible breeders can make informed
gene penetrance in the breed; how- breeding decisions.
ever, based on Poodles registered
3
SUMMER 2021
A BALANCED APPROACH TO BREEDING POODLES
Taking breeding advice from the “Review of the Current for many, sometimes hundreds, of different traits.
State of Genetic Testing in Dogs” helps put in perspec- These reports tend to inform dog breeders and
tive how to breed healthy dogs with quality traits when owners of mutations and disorders that are not
inherited diseases crop up in bloodlines. relevant in their dog since a specific genetic back-
“Poodle breeders must balance their choices to ground may be necessary for that mutation to
produce the fewest affected animals while removing cause disease. If a disease mutation that typically
the fewest animals from the gene pool to avoid a occurs in a different breed is part of your Poodle’s
loss of genetic diversity,” says manuscript co-author panel genetic testing report, these findings should
Anita Oberbauer, PhD, professor at the University of be interpreted cautiously.
California-Davis. “When selecting mating pairs you • To preserve genetic diversity, a quality dog tested
should think about the characteristics of individual as a carrier can be bred to a clear dog free of the
dogs and the puppies you hope to produce but also mutation. Fifty percent of puppies would be clear
consider how you can make choices to improve the and also have the genetic richness of the carrier
breed as a whole for future generations.” parent. Clear puppies from this breeding could be
Published in late 2020, the white paper resource used in the next generation.
was co-funded by the AKC Canine Health Foundation • Insightful knowledge from genetic testing about
and the Orthopedic Foundation for Animals. Liza the likelihood of a dog to develop a hereditary dis-
Gershony, DVM, PhD, an AKC Canine Health Foun- ease is particularly meaningful for disorders that
dation Clinician-Scientist Fellow and postdoctoral develop later in life and for which clinical surveillance
scholar, co-wrote the manuscript with her advisor, and/or lifestyle or dietary modifications could
Dr. Oberbauer. improve the dog’s quality of life. Proper interpre-
Below are key learnings taken from this paper that tation of genetic tests is fundamental to avoid
apply to genetic testing of Poodles. misapplication and negatively impact genetic
• Some genetic tests are breed-specific, such as variability.
those for neonatal encephalopathy with seizures • Breeders should gradually apply selection based
(NEwS) in Standard Poodles and osteochondro- on genetic testing to improve breed health. Most
dysplasia (OC) in Miniature Poodles. Breed-specific importantly, breeders should not depopulate the
tests are not universally relevant or applicable breed and cause a genetic bottleneck from loss of
across all dogs and dog breeds. genetic diversity. Always be mindful of how your
• Large-scale panel genetic testing, also known as choices impact the population of the Poodle breed
multiplex testing, looks at the presence of variants as a whole.
in the Canine Health Information Poodles and can be used to guide
Center (CHIC) database, the carrier breeding decisions. Not all are
rate is around 18 percent. required for CHIC certification (See
“We began testing every dog in “CHIC Health Testing Requirements
our breeding program,” McFadden for Poodles” on page 3.)
says. “We do not consider breeding
to a dog that has not been tested GENETIC TESTS FOR TOY
for NEwS. We try to only breed to & MINIATURE POODLES
dogs that test clear for the mutation, prcd-Progressive Retinal Atrophy:
though we understand that the Progressive rod-cone degeneration
DNA test gives us the flexibility to (prcd) is an inherited form of late-
carefully use an occasional carrier.” onset progressive retinal atrophy.
The NEwS test is one of several DNA Blindness occurs in dogs after 5 or
tests available to Poodle breeders. 6 years of age. The cells of the retina
Here is a review of tests that provide involved in low light vision, known
information about diseases affecting as rods, are affected first, leading to
4
POODLE Update
night blindness. Subsequently, the on the nerves of the spinal cord, a
bright light photoreceptors, or cones, dog may experience pain, nerve
that are important for color vision, damage, loss of bladder and bowel
are affected, resulting in daytime control, and/or paralysis. Many dogs
visual impairment. Breeders can that carry the mutation will never
avoid producing dogs affected by have herniation.
the autosomal recessive mutation A functional fibroblast growth
by including at least one prcd-PRA factor 4 (FGF4) retrogene insertion
clear parent in a breeding. According on canine chromosome 12 is the
to the Poodle CHIC registry, about causative variant attributed to the
7.9 percent of Toy and Miniature CDDY phenotype and susceptibility
Poodles are carriers of the prcd to Type 1 IVDD. The FGF4 mutation
gene mutation. impacts the IVDD phenotype with
Osteochondrodysplasia (OC): a dominant inheritance, thus dogs
Commonly known as Miniature require only one copy of the retro-
Poodle dwarfism, this disorder is gene insertion to be predisposed.
characterized by extended hind Largely occurring in Toy and Minia-
limbs, enlarged joints, flattening of ture Poodles, the CDDY variant
the ribcage, shortened and bent affects 57 percent of Toy Poodles
long bones, an undershot jaw, and
PHOTO: LESLIE NEWING
misshapen paws resembling club-
foot. 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 adult-
hood. 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 dis-
ease (IVDD). Dogs with the CDDY
gene mutation may experience
cellular degeneration of the discs,
which predisposes them to herni-
ation of the discs into the spinal
canal later in life. As the discs press
5
SUMMER 2021
and 61 percent of Miniature Poodles,
POODLE BREEDERS & OWNERS CAN HELP ADVANCE based on findings from a small
BREED RESEARCH sample tested at the University of
The Poodle Club of America Foundation is proud to support breed health California-Davis where the gene
research with funding made possible from Poodle lovers. Here are studies mutation was discovered in the lab
currently underway and how you can contribute to the research. of Danika Bannasch, DVM, PhD, the
• Addison’s Disease: A University of Minnesota study in the lab of Maxine Adler Endowed Chair of
Steven Friedenberg, DVM, PhD, DACVECC, seeks to identify the gene Genetics. Comparatively, Standard
variants and other factors linked to this common, life-threatening Poodles are virtually exempt from
disorder that occurs in Standard Poodles. Addison’s disease causes having a copy of the gene allele.
the body’s immune system to destroy the outer layer of adrenal glands Breeders of Toy and Miniature Poodles
that produce hormones critical for energy metabolism, immune system are advised to use the FGF4 retrogene
and kidney function, and intestinal health. The researchers need DNA test cautiously to avoid reducing
blood samples from dogs diagnosed with Addison’s disease and cheek genetic diversity and to share test
swabs from healthy dogs 5 years of age and older. Swabs will be pro- results with their veterinarian if a
vided, and postage covered. Contact Anna Hedger in Dr. Friedenberg’s dog is at risk for IVDD to assist in
lab at hedge042@umn.edu for more information. clinical decisions, says Dr. Bannasch.
• Epilepsy: At the University of Missouri, Gary S. Johnson, DVM, PhD,
is looking for DNA variants in hundreds of epilepsy candidate genes GENETIC TESTS FOR
that contribute to increased risk of this most commonly diagnosed STANDARD POODLES
chronic neurologic disorder in dogs. The goal is to find the changes Neonatal Encephalopathy with
in genes that may increase the risk for epilepsy so breeders can use Seizures (NEwS): Described on
these tools to help reduce the incidence of disease. Blood samples pages 2-3.
and clinical records are needed from affected dogs and their healthy Von Willebrand Disease (vWD
relatives, particularly from Miniature and Toy Poodles. For information, Type 1): An inherited bleeding
contact project coordinator Liz Hansen at HansenL@missouri.edu. disorder, this disease is caused by
• ONH & PMG Eye Disorders: Research at the University of Pennsylvania abnormally low levels of von Wille-
led by Gustavo Aguirre, VMD, PhD, is investigating a rare genetic defect brand coagulation factor (vWF),
known as optic nerve hypoplasia (ONH) that occurs in Miniature and an essential protein needed for
Toy Poodles. The non-progressive congenital defect occurs when the normal blood clotting. Spontaneous
optic nerve fails to develop normally causing blindness or severely bleeding from the mouth, nose and
impaired vision in one or both eyes. A second study is focused on a urinary and reproductive tracts
neurologic condition, polymicrogyria (PMG), in Standard Poodles. may occur as well as uncontrollable
This condition often but not always affects vision. While the brain’s bleeding after an injury, surgery or
surface, or cortex, is normally covered in large folds called gyri, in giving birth. Most affected dogs
dogs with PMG, the cortex has many excessive small folds that disrupt have a normal life span, but it is
normal connections within the cortex. DNA samples are needed for important to identify affected dogs
both studies. Contact Dr. Leonardo Murgiano at leomur@vet.upenn. due to the risk of excessive bleeding
edu or Jessica Niggel at jniggel@vet.upenn.edu for information and and to avoid producing affected dogs.
to submit samples. An autosomal recessive disease, vWD
• Intervertebral Disc Disease (IVDD): A study in the lab of Danika affects some dogs mildly and others
Bannasch, DVM, PhD, at the University of California-Davis aims to learn severely. Dogs must receive two
why some Poodles with chondrodystrophy (CDDY) are more adversely copies of the gene mutation — one
affected with IVDD than others. DNA cheek swabs are needed from from each parent — to develop the
Miniature and Toy Poodles that are healthy and from those with herniated disease. When carriers, or dogs
discs Contact Kevin Batcher at klbatcher@ucdavis.edu for information. having one copy of the gene muta-
tion, 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
6
POODLE Update
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 sub-
normal 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 indistin-
guishable 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 exam-
ination methods. However, using damaging the spinal cord, brain,
more advanced imaging modalities nerves, and muscles. An autosomal
such as optical coherence tomog- recessive mutation in the superoxide
raphy (OCT), which is performed dismutase 1 gene (SOD1) contributes
under general anesthesia, the degen- to a dog’s risk to developing DM, LOOKING TO REPRINT?
eration of the photoreceptors is though the disease has an age-
evident. The autosomal recessive related incomplete penetrance. Poodle Update articles may be
DB/RD mutation has been identified The longer an at-risk dog lives, the reprinted provided the article is
and a DNA test is available. This higher the likelihood of developing used in its entirety and in a positive
will enable breeders to selectively signs of DM. The risk for dogs having manner. To request permission to
choose breeding partners in which two copies of the mutant SOD1 vari- reprint this article, please contact
one mate is clear for the mutation ant to developing DM is not known. the editor at: Barbara.Fawver@
to avoid producing affected dogs. The DNA test helps breeders make purina.nestle.com. Reprints should
breeding decisions, yet it has diagnos- include the following attribution:
GENETIC TEST FOR ALL tic limitations because it is testing Used with permission from the
POODLE VARIETIES for a risk factor and does not provide Poodle Update, Nestlé Purina
Degenerative Myelopathy (DM): definitive diagnosis. Breeders can PetCare.
All varieties of Poodle are among use genetic testing to breed dogs
over 40 breeds and mixed breeds that carry the SOD1 mutation to clear,
affected by DM, a devastating healthy dogs to avoid producing
neurologic disease that impairs a affected dogs without reducing
dog’s hind limbs. Dragging or scuffing genetic diversity. n
of the legs typically begins around
9 years of age. This progresses to Purina thanks Pat Forsyth, president
decreased muscle control and of the Poodle Club of America
weakness causing frequent falls and Foundation board of directors,
difficulty getting up. Within 9 to 12 for helping us to identify this topic
months, dogs are paralyzed as DM for the Poodle Update.
spreads through the nervous system,
7
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