Compiled from various sources by Lisa Frankland
Part 1: Frequently asked questions about PNA
What is PNA?
PNA stands for progressive neuronal abiotrophy, also referred to as cerebellar
cortical and extrapyramidal nuclear abiotrophy, or simply abiotrophy, a genetically
transmitted, fatal disease in Kerry Blue Terriers. It is characterized by
head tremors and stiffness in the hind legs, similar to distemper, that gets
progressively worse until affected dogs are unable even to stand or eat.
MRI scans and necropsies performed on affected dogs show lesions in a part
of the brain called the cerebellum. PNA normally shows up before 16 weeks
of age, though there are at least two recent confirmed cases, and a couple
of less recent unconfirmed ones, where affected dogs did not show symptoms
until they were 6-8 months old.
How is it transmitted?
PNA is believed to be a autosomal (or simple) recessive genetic disorder.What
does this mean? The term autosomal means that the disorder is controlled
by a single gene pair (out of thousands, if not millions), as opposed to
polygenic, which means controlled by many genes. Recessive means that, in
order for the dog to exhibit the disorder, both genes in the gene pair have
to code for PNA. A dog that has one normal and one PNA gene is called a carrier.
A carrier appears perfectly normal and healthy, but can produce puppies with
PNA if it is mated to another carrier.
In genetic shorthand, gene pairs are represented by letters, with a capital
letter representing the dominant gene and lower case representing the recessive
gene. Thus, if "A" is chosen to stand for normal and "a" for PNA, an affected
dog would be symbolized "aa," normal would be "AA," and a carrier would be
"Aa." Everybody have that straight? Good, because here's where it gets complicated.
Each gene in a gene pair is on separate paired chromosomes. When eggs and
sperm are produced through a process called meiosis, each egg or sperm only
receives one of each chromosome pair, and therefore only one of each gene
pair. Then when an egg and sperm meet during fertilization, the newly created
individual (future puppy in this case) once again has two of everything--one
from each parent.
A PNA puppy (aa) is produced only when a carrier (Aa) is mated to another
carrier. However, the same carrier to carrier mating will also produce unaffected
puppies, both normal, AA, and carrier. The expected outcome for this particular
throw of the genetic dice is 25% affected, 50% carrier, and 25% normal, though
this can vary tremendously in real life. One source cited a litter in 1973
where 4 of the 6 puppies had PNA! On the other hand, it is also possible
that a carrier to carrier mating could produce no PNA puppies. Carrier to
normal (Aa x AA) matings cannot produce puppies affected with PNA. On average,
half of the offspring will be carriers and half will be normal. For obvious
reasons (I hope!), normal to normal (AA xAA) will only produce normal puppies.
Affected to affected (aa x aa) would produce only affected pups, affected
to normal (aa x AA) would produce only carriers, and affected to carrier
(aa x Aa) would produce on average half affected and half carrier pups. However,
since affected pups usually die before they reach breeding age (not that
anybody in their right mind would breed them anyway), these are probably
Is PNA known to occur in other breeds?
Similar cases have been reported in a French Bulldog, Boston Terriers, a
Scottish Terrier, Fox Terriers, Airedales, Bern Running Dogs, Finnish Harriers,
Jack Russell Terriers, Swedish Lapland dogs, and a Gordon Setter. In
Smooth Fox Terriers and Swedish Lapland dogs, there were enough affected
animals to confirm that their problem is most likely a simple recessive disorder,
just like it is believed to be in Kerries
Why didn't PNA attract notice in Kerries until about 25 years ago?
Probably thanks to a phenomenon known as a genetic bottleneck or the founder's
effect. A gene that is relatively rare in the general population (in this
case, all dogs) can become much more common among a smaller, linebred or
inbred population (one breed of dog) when an individual carrying that gene
is in the pedigrees of most or all of that population. As a result, carrier
to carrier matings, and affected offspring, are much more likely to occur,
and the problem seemingly appears out of nowhere. One example of this in
humans is the higher than normal incidence of polydactyly (extra fingers
and toes) and dwarfism among the Amish. In one breed of dog from the Working
Group, a fatal disorder called cardiomyopathy is attributed to two German
imports that about 80% of all American dogs of that breed trace back to.
Although problems with closely related individuals having offspring occur
only very rarely, the jokes about cousins marrying can be attributed to the
Among Kerry Blues, the scarlet letter of being branded the founder goes to
Ch. Melbee's Chances Are, who was the number one show dog of all breeds in
the nation in 1968, and the all time top winning dog in our breed until recently.
He was very widely used as a stud, siring 66 champions and recently being
named by the United States Kerry Blue Terrier Club as the breed's most influential
sire for a short piece in the AKC Gazette. Chances Are apparently carried
PNA, because the disorder first attracted notice in the early 70's when affected
pups began turning up in litters linebred on Chances Are, his sire Ch. Tregoad's
Vicky's Victor and a litter brother of Victor's named Ch. Tregoad's Vicky's
Cappy, as well as the Tregoad brothers' dam, Ch. Bhoy's Brigid of the Bog.
Kerry breeders are divided over whether the gene responsible for PNA is limited
to this line, or is present in others as well.
If line breeding caused this problem, why don't we just stop linebreeding?
Linebreeding, or breeding related individuals, is how different breeds and
lines are developed and "fixed." Line breeding increases the percentage of
identical gene pairs, so there is more consistency among offspring. To understand
this, think of those ever popular crosses such as cock-a-poos. A cock-a-poo
is created by mating a Cocker Spaniel with a Poodle. The Cocker-Poodle cross
produces very consistent results which are readily identifiable as cock-a-poos.
However, what happens when Joe Backyard-Breeder decides to mate his two cock-a-poos?
What he'll probably end up with is a mixed bag ranging from almost-looks-like-a-Poodle
to could probably pass-for-a-purebred-Cocker, and all sorts of interesting
variations in between!
While all breeds of dog started out as random or deliberate crosses, developing
them into purebreds that breed true takes years of selecting closely related
individuals with the desired characteristics and breeding them together.
Similarly, this is how we maintain the quality and consistency of our purebreds--selecting
for good structure, proper temperament, and correct breed type. While line
breeding can also fix undesirable traits, ranging all the way from improper
tail carriage or undesirable color to structural problems or PNA, responsible,
educated breeders are prepared for this, and can use outcrosses (breeding
unrelated or more distantly related individuals), culling, and selective
breeding to help eliminate problems from their lines.
Part 2: Identifying Carriers and Controlling PNA
Is my dog a carrier?
Currently, the only way to know for certain if a dog is a carrier for PNA
is if that dog produces a PNA puppy, which of course will only happen if
that dog is bred to another carrier, and still might not happen if the Fates
are kind and especially if there is a small litter. A test to identify PNA
carriers has been discussed for years, and will hopefully become a reality
in the not-too-distant future. Developing any kind of genetic test usually
takes years of research, which requires lots of money and interest in that
problem, as well as the widespread support and cooperation of breeders and
owners. The USKBTC is currently working with several universities who have
shown an interest in looking for a DNA marker for this problem. The Club
will continue working with researchers in looking for a marker for the gene
that carries PNA. Another promising advancement is that PNA can now be diagnosed
with an MRI (Magnetic Resonance Imaging). This means that researchers, breeders,
and owners no longer have to wait for a pup to be euthanized to get a confirmed
diagnosis on a suspected case. The USKBTC strongly encourages breeders and
owners to come forward with any type of health information that may contribute
to this research on PNA. Contact Health and Genetics Committee Chairman.
Dr. Jerold Bell, a veterinarian at the University of Illinois, has proposed
using relative risk assessment to determine the chances of a dog being a
carrier. For an autosomal recessive genetic disorder like PNA is believed
to be, the risk factors would be: Parent of affected=100% chance of being
a carrier; offspring of affected (not likely with PNA)=100% chance of being
a carrier; full sibling to carrier=50% chance of being a carrier; non-affected
full sibling to affected=67% chance of being a carrier. If you knew the risk
factors of every ancestor in your dog's pedigree, you could determine the
relative chances of your dog carrying PNA. For example, if the only known
carrier in your dog's pedigree is his paternal grandsire, then his sire's
risk of having the PNA gene is 50%, and your dog's risk of having it is 25%.
Needless to say, figuring out risk can get complicated fast, especially in
heavily linebred dogs, but generally the more generations there are between
your dog and a known PNA carrier, the less risk he has of being a carrier
himself. However, the success of this system would depend on the complete
honesty and cooperation of all Kerry breeders.
What about "PNA free lines"?
To many Kerry fanciers, this term is synonymous with "no relation to Chances
Are (or the Tregoad brothers)." However, keep in mind that the PNA gene did
not simply pop out of thin air and into these dogs' chromosomes. The
PNA gene was around long before these dogs were, albeit a heck of a lot less
common. There were a couple of reported cases as early as 1941 and 1946 in
pedigrees entirely free of Tregoad dogs, and the PNA gene might even go all
the way back to Ireland, which would make all bloodlines suspect. An affected
1976 litter also was from supposedly clear lines. Blueprints, the official
publication of the USKBTC, has a policy that it will not accept any advertising
claiming that dogs are clear of PNA. If relative risk assessment becomes
widely used among Kerry breeders, perhaps the national club will approve
an acceptable risk threshold and permit breeders with dogs below that threshold
to make that claim. However, although the risk factor can become infinitesimally
small, it never actually reaches zero, so until such time as there is a surefire
test to identify carriers, the claim "PNA free" is, at best, stretching it.
"Believed to be free of PNA" is closer to the truth.
How can we control PNA?
Since PNA is such a devastating disease, discussions among Kerry fanciers
on how to control it can be very heated and emotional. The mere whisper that
there is PNA in somebody's bloodline seems to be enough to seriously damage,
if not ruin a breeder's reputation. One excellent, impartial, third-party
discussion on control comes from the PNA chapter in Genetics of the Dog,
by Malcom Willis.
Whether PNA occurs in Kerry Blues or any other breed, it is both undesirable
and illogical for breeders to adopt a witch hunt type of action against it.
They will rightly want to reduce the incidence or eliminate it, if possible,
but they must seek to do this by sound genetic measures and without losing
valuable qualities. This means keeping the PNA problem inperspective.
PNA is a breeder's loss in that it has a fairly early age of onset (on average
11 weeks of age). This means that losses will be met by the breeder since
he must either destroy the dog early in life or, if sold at about 6-8 weeks,
it will quickly develop ataxia and most buyers would have a case in law to
reclaim the costs incurred at having been sold affected animal. This, however,
seems eminently desirable since breeders who make wrong decisions ought to
be prepared to pay for their mistakes.
On the credit side, the very
fact that PNA is an early onset disease means
that breeding information is quickly known and one does not have to keep
a dog for some years before finding out that it has a genetic disease. It
also effectively lethal, so that all PNA affected stock will be dead or destroyed
prior to sexual maturity. There is thus no risk to the breed from
PNA cases. The recessive nature of the condition means that it will be spread
by Aa type animals and the breeder needs to be able to identify
which animals are of this genotype. He cannot do this, as yet, by any physical
means, since Aa type animals will be perfectly normal and indistinguishable from AA animals. Any suggestion that Aa dogs should be
banned from exhibition or destroyed is ludicrous. If we ban these, then there are many other dogs who, for similar clinical reasons, would have to
be banned and, carried to a logical conclusion, all dog showing and
breeding would cease. By the same token, the cry that all descendants
of the Tregoad brothers be destroyed or not bred from is illogical.
simple recessive condition, only 50% of the progeny of an Aa type animal
will carry the defective a allele, the other 50% will be carrying A. If we
were to conclude that the Tregoad stock were of only moderate quality, then
little harm would result from culling their descendants, but it is quite
another thing to dispose of bloodlines which are producing many other virtues.
Kerry Blues are not a breed on which I can speak with any expertise, but
it is well established that the Tregoad line has produced good Kerry Blue
Terriers. The dog Melbee's Chances Are (a known carrier of PNA) was possibly
one of America's greatest sires. To cull him and his offspring might help
to reduce the incidence of PNA, but at too high a price in terms of breed
type. Furthermore, the global disposal of all descendants of the famous
litter will not necessarily eliminate PNA. We still do not know from whence
the PNA allele reached this litter. It is unlikely to be a mutation in the
litter itself, but more likely in a parent. The sire was widely used so is
probably not to blame, and if the dam was in some way involved, then it means
that other lines of British origin may be implicated. Certainly one pup confirmed
by deLahunta as a PNA case had a pedigree entirely free of Tregoad dogs (USKBTC
1976). Then again the 1946 case reported by Mettler and Goss suggests that
the defect goes back to a much earlier point in time and probably to Ireland.
The decimation of top bloodlines advocated by some breeders--whatever
their motivation--is not sensible. What is needed is a dispassionate and
cooperative study of the problem on an international level.
Kerry Blue breeders should begin to compile data on all litters, retaining
pups to three months or selling earlier on a guarantee of replacement if
PNA results. All presumed affected animals should be checked by a recognized
expert and pathology undertaken to ensure that PNA is involved. Test
matings have been advocated but little hope exists in this area. All aa dogs
will die so that test mating must be between suspect carrier (A?) and known
(Aa). . . . This means that three or four litters with a total of 16 pups
[are required] before one can be reasonably sure of the genetic makeup of
the dog under test. If PNA was at a high incidence in the breed,
Aa type dogs would be commonplace, but if PNA is rare, Aa dogs are difficult
to identify. If PNA is rare, then there is no serious problem
anyway. I am not convinced that in this case outstanding specimens
should be disposed of even if they are proven carriers, though I see little
point in using known A dogs if they are of moderate quality. One has to assess
failings against virtues and Kerry Blues will not be helped by hysterical
witch hunts on this or any other defect. A register of known carriers to
which breeders could have access is a useful record which breed clubs could
maintain. (pp. 191-192).
In short, finger pointing and witch hunts
will not eliminate PNA in our beloved Kerry Blues. Education, honesty, and
Bell, Jerold S., DVM. "Identifying and Controlling Defective Genes." Pure
Bred Dogs/American Kennel Gazette, July 1993.
Vite, C.H., Dayrell-Hart, B., Lexa, F., Kerlin, R., Van Winkle, T., and Steinberg,
S.A. 1996. Progress in Veterinary Neurology. Vol. 7 (1): 12-15.
Willis, Malcom W. Genetics of the Dog. New York. Howell Book House, 1989.
Articles, letters, and Health and Genetics Committee reports in various issues
Many thanks to all the Kerry breeders whose knowledge and different perspectives
helped shape this article, especially Susan Meredith Dunivant, Helen Eiden,
Zippy Fleisher, Diane Lee, Maryanne Schaefer, and Lonie Ward.
Last Updated: 11/19/2003, 3:01 pm