A Novice's Guide to PNA

Compiled from various sources by Lisa Frankland
2000 Update

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 iscontrolled by a single gene pair (out of thousands, if not millions), as opposed to polygenic, which means controlled by many genes. Recessive meansthat, in order for the dog to exhibit the disorder, both genes in the genepair have to code for PNA. A dog that has one normal and one PNA gene iscalled 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'swhere 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 moot points.

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 founder's effect.

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 linebreeding 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." Linebreeding 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 linebreeding 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 Maryanne Schaefer at (413) 525-4997, or e-mail her at WWKerry@aol.com.

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 witchhunt 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 in
perspective.

 

Essentially, 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 an
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 is
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. In a 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
recognised 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 Aa dogs if they are of moderate quality. One has to assess
failings against virtues and Kerry Blues will not be helped by hysterical
witchhunts 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 witchhunts will not eliminate PNA in our beloved Kerry Blues. Education, honesty, and cooperation will.

Sources:

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 of Blueprints.

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.

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