Genetic Defects
DOG BREEDERS WORRY a lot these days about genetic defects, and rightly so. It can reasonably be said that the purebred dog fancy is in the grips of an overall genetic crisis. Those who know a bit about population genetics understand why this is so. The dog breeders themselves, for the most part, do not. To put it in a nutshell, a gene pool is rather like a bank account. You cannot go on making withdrawals year after year without ever making a new deposit. Yet that's what the purebred dog fancy tries to do. Most of our familiar dog breeds were established sixty to a hundred or so years ago. The major kennel clubs have been around for a century or so. In most cases, the stud book for a given breed was opened back when the kennel club was founded, or when the breed was first recognised by the kennel club in question. Foundation stock was registered for maybe a year or so. Then the stud book was closed -- forever! It didn't happen quite that drastically or dramatically, because for awhile it was possible to register new stock on inspection; that is to say, a "knowledgeable person" (usually a dog show judge) could inspect an unregistered dog, give a written statement that the dog appeared to be a reasonable specimen of such-and-such a breed, and the dog would be registered in that stud book. In most of the major kennel clubs that has not been possible for the last fifty or sixty years.
As the available genetic diversity decreases and dominant genes disappear through selection over time, recessive genes begin to surface. They are only expressed in the homozygous state, so it may not be obvious that a particular recessive defect has become widespread until very late in the game, when enough individuals have one copy of the defect gene for homozygous progeny to become a frequent occurrence. (Why are we talking about recessive defects? Because dominant defects are always expressed in the phenotype, are therefore vulnerable to selection, and would tend to be largely self-eliminating since every individual with that gene would have a disadvantage in terms of fitness for survival. But individuals with a single copy of a recessive defect may not have any fitness disadvantage.) By the time the problem is obvious, a recessive defect can be so widespread in a breed population that it can hardly be eliminated without eliminating the breed itself, at least within the terms of the closed stud book.
Screening programmes (like the OFA and OVC programmes for canine hip dysplasia) may only detect the defective phenotypes without revealing the individuals that carry just one copy of the defect gene. Or the gene may have "variable penetrance and expressivity" which is just the screening veterinarians' way of saying that they don't understand why some animals suffer from the defect and other don't. Let's just say that screening programmes are slow, cumbersome and expensive, and often seem to work rather poorly. What is worse, screening programmes mean that breeders must undertake additional selection based on the screening results. If a breed suffers from half a dozen common defects, and many breeds do, is the breeder then to undertake a six-way screening and selection programme? And if so, will he then have any remaining scope to select for other characteristics, after the screening is done? The answer to that for most small kennel operations is probably, "no."
That leaves the sleddog breeder with an unhappy choice: either ignore sleddog selection or ignore genetic defects. It's a Hobson's choice that is inescapable as long as the breeder accepts the conventional wisdom about breeding, selection, and how to handle genetic defects. But the conventional wisdom has misunderstood the nature of so-called genetic defects.
Genetic Defects -- Why They Exist
THE DOG BREEDING COMMUNITY are usually so caught up in reproaching one another over genetic defects, on the premise that if one's dogs have defects it must be due to "bad breeding," that it seems never to occur to anyone to ask why or how it can be that these things occur at all! Yet to ask this question, and to answer it, may give us the clue we need to deal with the problem.
Obviously most breeders have been selecting against genetic defects for a long time. Nobody intentionally breeds defective stock. Where did these genes come from, anyway? We're told that the domestic dog developed from the timber wolf, Canis lupus. The wolf has been an extremely successful predator species in the wild for tens of thousands of years, if not hundreds of thousands. Operating as he does in hostile environments and harsh climatic conditions, you'd think that the wolf would have had his genetic defects eliminated through natural selection a long time ago. And that's our clue.
If a gene, that in its homozygous form causes a defect affecting the animal's fitness for survival, is nevertheless retained for thousands of years, there has to be a reason. The gene cannot be neutral, even in its non-expressive heterozygous state; it would still be eliminated by natural selection over time. So it must confer an advantage in its heterozygous state. And this is exactly what evolutionary biologists and wildlife geneticists believe takes place. They call it overdominance or heterozygote superiority. What has to be happening is this: the so-called "defect" genes are defective only when paired as homozygous recessives. When they are paired with another allele that is dominant, together the heterozygous gene pair confer a fitness advantage to the animal over either the dominant homozygous type or the recessive homozygote. That is the only possible way that these genes could be retained for thousands of years in a wild population subjected to constant natural selection.
So guess what? The veterinary professors and the breed clubs who prate about the "elimination" of various genetic defects are talking nonsense! They encourage us to engage in a fruitless struggle to eliminate something that nature herself has not seen fit to eliminate. It is not the gene that is at fault -- our breeding methods and our closed stud books are to blame! We have stripped away the natural canine dominant genes, leaving a residue of homozygous recessives that never should be expressed in the phenotype, because they should never occur in the homozygous state.
So why is it that we never hear this mentioned? You guessed it, for the usual reason: it's to somebody's financial advantage that these facts should go unmentioned. Someone is making money out of our naïve belief that we can "eliminate genetic defects" by screening. Doubtless CERF, SHOR, OFA, OVC and other various screening programmes provide lucrative and secure employment for professors of veterinary medicine, lab technicians and foundation administrative staff, and the system even has attractive spinoff benefits for local veterinarians. Yet should these peoples's vested interests take precedence over the long-term health of our dogs?
Genetic Defects in Seppalas
It is never possible to produce a definitive list of the "genetic defects" found in any one canine breed or bloodline, for several reasons. One is that it is far from certain whether quite a few serious disorders are predominantly of genetic origin or not! Take hip dysplasia, for example. At first it was assumed that this syndrome had to be genetic in origin. But decades of screening have not removed it, although in some breeds the incidence has been decreased. Veterinarians are now convinced that hip dysplasia is at least partly a developmental disorder of domestic animals, brought on in large measure by fast growth, overfeeding, and lack of exercise. It is pointed out that wild canids are very seldom afflicted by hip dysplasia, largely because they are usually forced into a developmental pattern of slow growth through limited food resources, and because they get huge amounts of exercise in the pursuit of those limited resources.
Another source of uncertainty is that new "genetic diseases" seem to be brought to light regularly. Only a few decades ago, canine health was not so closely studied as it now is, and canine ailments were accepted as a part of life and given symptomatic treatment at best, without much searching for underlying causes. Then, too, as inbreeding coefficients continue to rise inexorably, more and more problems seem to emerge. This has certainly been the case with Seppalas. Ten-generation COIs, that normally ran around 20% in the 1970s (certainly a serious enough situation even then) now stand at an average 30% for pure-strain Markovo-Seppalas. It should be no surprise that problems now emerge that were not previously known, or that previously known problems now seem more frequent.
Several problems deserve mention. Probably the best-known is primary
glaucoma. This buildup of pressure within the eyeball
(leading quickly to blindness) is caused by
anomalies in the drainage structures within the eyeball that bleed off
intraocular fluid; there are two separate aspects to these anomalies:
(1) abnormally narrow angle at the juncture of the iris and the cornea
where drainage takes place, and (2) mesodermal dysgenesis
in which the normal pectineal ligaments that should form a
storm-drain kind of grating are replaced with sheets of tissue perforated
irregularly with small round holes. This problem is endemic in northern
breeds generally; it is found in Samoyeds, Eskimo dogs and Malamutes
as well as mainstream Siberian Huskies. Some mainstream Siberian
Husky breeders have tried to depict glaucoma as a problem only for
Seppalas. That is simply untrue: one of the Eva B. Seeley foundation
litter, Cheeak of Alyeska, produced several progeny that were put down
due to primary glaucoma in the 1930s.
Many Seppalas, when examined by gonioscopy
(examination of the iridocorneal angles, a special test that is NOT a part
of the regular CERF tests) will be found to have either narrow angles,
mesodermal dysgenesis, or both. That does not mean that these same
dogs will have glaucoma. At one point we tested two dozen Seppalas
in the hope of finding some useful genetic pattern; no such pattern was
observed. A few dogs were "clear"; others were affected in varying
degrees with either or both anomalies. One "clear" bitch later produced
two progeny with clinical primary glaucoma. To deal with this problem
through testing and selection is likely to be a long and fruitless effort;
it is more likely that it will prove responsive eventually to increased
genetic diversity and reduced COIs.
There are other known eye disorders in Seppalas,
all of much less seriousness than glaucoma. Some of them are
pigmentary keratitis, corneal dystrophy, juvenile-onset cataract, and
persistent pupillary membrane. None are seen with any degree of
frequency.
The other serious known problem with probably genetic origins is idiopathic epilepsy (that is, epilepsy without a traumatic cause). This is supposedly caused by a complex of about six different genetic factors, the presence of any three of which will result in clinical epilepsy. Therefore, like glaucoma, epilepsy is not likely to be very responsive to testing and screening-selection. This problem is seen regularly enough to be taken seriously, but the rate of incidence is not high. Lines of ancestry known to have produced it are candidates for outcross or outbred matings.
One hears from time to time of other problems, or veterinarians from time to time diagnose them, but not with enough consistency to make them worth reporting here. Examples are allergies (which can have any number of causes, some of them environmental) and hypothyroidism (caused usually by autoimmune thyroiditis and not that simple to diagnose positively). Another that is not very serious but DOES turn up across a wide spectrum of bloodlines is zinc malabsorption syndrome, resulting in hair loss and dermatosis, primarily around the eyes, ears and muzzle but also in patches on the body in some cases. It is both diagnosed and cured by dietary zinc supplementation, preferably using a chelated, bio-available zinc compound. As it's known to be a Siberian problem, presumably there is a genetic predisposition involved.
There is a tendency for any breeder who experiences a serious genetically-related problem within his kennel to go off the deep end with respect to that particular problem! Having a dog suffer (and perhaps in the end be put down) due to epilepsy or glaucoma is a traumatic experience for any dog owner. But it should be underlined that this is no justification for a root-and-branch campaign to "eliminate" the problem. The nature of Seppala lineage, with its extreme degree of interrelatedness and pedigree similarity, coupled with the very limited number of dogs making up its population, means that such campaigns are counterproductive, doomed to failure from the outset. The answer to the few genetic problems that are known to be endemic in Seppalas is for all of us to work together to bring down the COIs and to bring about a gradual and sustained increase in genetic diversity. The Seppala Siberian Sleddog Project has already done a great deal in this regard; it is to be hoped that others in turn will now find it possible to bring in additional stock from Siberia that can be put to use to continue the trend towards "diversity breeding."
Generation Time
AN IMPORTANT AND TRADITIONAL aspect of Seppala breeding is the use of thoroughly proven senior stock in breeding. The generation time for a particular litter is the average of the age of the sire and the dam at the time of the litter's birth. The average generation time for a kennel is the grand average for its litters; at Seppala Kennels the average generation time is about six and one half years. In most show-dog kennels the average would probably be around two years. That means that the show kennels are breeding three times as rapidly, and therefore inevitably undergoing three times as much genetic drift and attrition of genetic diversity in the process! My feeling has always been that the close connection with the original Siberia imports and the Leonhard Seppala dogs is worth preserving. One way to accomplish that end is to breed senior stock. Our current best leader and broodbitch, TONYA OF SEPPALA, is as little as eight generations removed from TSERKO the 1930 Siberia import, and nine generations from his brother KREE VANKA. Keeping the generation time long has another benefit: it restrains you from breeding that young hotshot yearling you think is showing so much stuff in training (mostly because he's young and ignorant and has yet to find out what real work is all about). All too often the young hotshot never fulfils his early promise once he has matured. At that point probably you'll be relieved you don't have several litters of his pups hanging around the place.
Genetic Diversity
WHETHER WE LIKE IT or not, the system that has given rise to dogs, people, birds and other living creatures on this Earth is ruled by natural selection. That means that when living organisms compete with one another for limited resources, or when organisms must struggle to survive hostile environmental conditions, some survive while others don't. The ones that survive, do so because they are in some way better equipped for survival; scientists call that fitness. Fitness traits are genetically determined. But which traits are most conducive to survival depends upon the particulars of place and time, and those particulars are subject to change. When climate changes occur, or new viral diseases turn up, or population pressures drive living creatures into new and unfamiliar habitats, the genetic patterns that were formerly best adapted for survival, most fit, may no longer be so. If the creatures involved in such a situation cannot produce progeny that are different from themselves, their line may die out. The potential for variability must be there in their genes, constantly producing new combinations of traits, if evolutionary change is to occur in response to environmental change. Genetic diversity makes the difference! If insufficient diversity remains in the genome of a species or a variety of creature, then change will threaten it with extinction; it won't have the genetic capability to produce progeny with different combinations of survival traits.
You think that's irrelevant to sleddogs? Well, better think again. In one century (not long by evolutionary standards) Siberian dogs have migrated from the east Siberian peninsula into the North American continent, and from there to Europe, Australia, and as far as Patagonia! From an environment that was largely dominated by natural selection in a harsh environment, they have moved into an environment of artificial selection in temperate environments. That's a BIG change, right there! They are facing (as the human race, too, is facing) new viral diseases and a host of environmental pollutants, none of which they had to cope with two centuries ago. And what are we doing to help them cope with these massive changes? We are inbreeding them like crazy in closed kennel club stud books, reducing their genetic diversity as fast as we can! Clever, huh?
If we want to hang onto the hardiness, vigour and capability of the Original Siberian Dogs, we need to change our approach to breeding sleddogs. Natural selection produced the Original Siberian Dog, but it is not natural selection that governs sleddog breeding and selection now. Hypernutrition, sophisticated veterinary care, and a climate much more moderate than that of Siberia work against the very fitness traits and hardiness sleddogs once had. Dogs survive under our care that would never have made it in Siberia. At the same time, we are eliminating much of the genome, reducing genetic diversity and variability. Every generation is less fit for survival. We need to put something back into the genetic bank account from which we have only made withdrawals for the better part of a century. If we don't pay some attention to restoring genetic diversity, one day some new disease (or a new variation of an old one) may just wipe our dogs out. It can't happen? Well, there was no parvovirus problem until around 1980! And in our own environment, how about AIDS, necrotising fasciitis ("flesh-eating disease"), West Nile Virus, SARS, avian parainfluenza, bovine spongiform encephalopathy, etc.?
SEPPALAS have more genetic diversity than most Siberian Huskies, although that isn't saying a whole lot. (If you look at the photos of show winners for the last decade or so, you'll see that most of them are as alike as peas in a pod.) Seppalas show evidence of a certain amount of diversity, but they also show evidence of inbreeding depression. We ought to all be out scouring eastern Siberia for new breeding stock! At least at Seppala Kennels we managed to get one good dog from Siberia when it suddenly became possible, although you'd think we had done something criminal if you were to go by the reaction from DW and the ISSSC to that single import.
Homozygosity and Heterozygosity
ONE FELLOW AT A FORUM said, "Homozygosity! What's that? Why can't you use layman's language?" OK, here's the explanation! The genes of an animal (basic units of heredity, remember?) are found mostly on the chromosomes, structures within the cell nucleus that are visible only during the process of cell division. The chromosomes occur in pairs, and every organism receives one chromosome of each pair from each parent. In this way a puppy gets half of its nuclear DNA from its sire and half from its dam, each of them contributing thirty-nine chromosomes (a dog has 78 chromosomes in all). Since the thirty-nine chromosomes are paired, an individual gene on one chromosome corresponds to the gene in the corresponding location on the other chromosome of the pair. If these two corresponding genes are identical, the puppy is homozygous for that gene and the trait it controls; if the two corresponding genes are different "versions," then he's heterozygous for that gene. There may be more than just two versions of a particular gene -- there might be four, or six versions, but each animal can have only one or two versions in his genetic material, because he has only two copies of every gene, whether those copies are identical or non-identical. If a particular version of a gene can control the trait in question even though the other copy of the gene is non-identical, then that version is said to be dominant. If it takes two identical copies before a version can express itself by controlling the trait, then that version is recessive.
The dominant/recessive relationship is somewhat relative. Where more than two versions of a gene exist, there may be a hierarchical order of dominance, or the relationship might not be so clear-cut. Geneticists speak of "variable penetrance and expressivity" when the dominant/recessive relationship is less than clear.
It has become apparent in studying wildlife biology that some heterozygous combinations of genes seem to have a survival advantage over the homozygous phase of either gene of the pair. You may recall that this is called overdominance or heterozygote superiority. It is probable that this superiority is the factor that allows the genes of so-called "recessive genetic defects" to be carried in the genome of a species for thousands of years without being eliminated by natural selection. It is factors such as this that create a strong argument for the value of genetic diversity to an animal species or breed.
It should be clearly understood that the more gene loci are homozygous in an individual animal, a breed or a species, the less genetic diversity that animal, breed or species has. The ultimate case of this kind is the cheetah, homozygous at virtually all its gene loci, genetically frozen, unable to respond to environmental change. Unfortunately, whether consciously so or not, this is the goal towards which the closed studbook/inbreeding/selection system of present-day purebred dog breeding is aimed. When next you read an article on "breeding for success," bear in mind that the methods it promotes are those that will ultimately produce dogs that are genetic cheetahs, totally deprived of their natural ability to adapt or respond to changes in their environment (or even in the goals and ideals of their breeders). Many show dog breeds are very close to that point already.
