Here's how working with DNA can allow breeders to eradicate any genetic defect within 3 generations without ever removing a dog from the gene pool!
A Brave New World Of Canine Genetics
Diane Klumb / © TheDogPlace.org
I'm a self-confessed cover-to-cover Gazette reader, always have been. Next to ShowSight (Joe made me say this!) it's my favorite dog publication. It's funny, but everybody reads the Gazette in different order, I've found. Most people start with their breed column. Me, I start with the Secretary's Pages. Always. I find out the most fascinating stuff that way… Which is how I originally found out about the MULTIPLE SIRES thing.
For those of you who don't traditionally start with the Secretary's Pages, this is a pretty controversial topic. It involves the registering of puppies from a litter with multiple sires, based on DNA-testing of the offspring. Lord knows it happens, even to good breeders occasionally, and sloppy breeders a lot.
Assuming you were aware of it - That's like when the guy hollers “Oh, hell, Marge, Rufus jumped the fence again- he's in with Blossom! No! no, Rufus… off! Down! Off!… Damn!” while he's tearing out the door in his BVDs - under the old system, you either placed the resulting litter in pet homes without papers or put down the sire whose name looked best on the pedigree, depending upon your own personal Code of Ethics. (Now, with the advent of DNA testing, Option Number Two is, to say the least, ill-advised.)
Unfortunately, most of the controversy surrounding the issue seems to be based on that scenario at best, and the validation of truly sleazy pack-breeding at worst. I say: who cares about any of that? Fine the accident victims to make them more careful, keep after the real scum of dogdom as best we can, whatever.. but quit missing the point! Registration of multiple-sired litters is an incredible tool, and has the potential to do more good for the canine world than anything else heretofore dreamt.
You have no idea what I'm talking about, right? That's OK, happens to me all the time...
Follow along: I have spent the last year doing the pedigree research in a single breed for an autosomal recessive disease as part of a CHF study, the ultimate goal of which is to isolate the gene for hereditary cataracts, This involves locating dogs from three groups- Normals (dogs not carrying the gene at all), Carriers (dogs carrying a single copy of the gene, phenotypically normal, but passing the gene to half their offspring) and Affecteds (these dogs have received two copies of the recessive gene, and are very likely to develop the disease, although, for unknown reasons, they may not). DNA from those three groups are then compared in order to isolate the gene. (For the scientifically-challenged, the principle is a bit like the old Sesame Street song... “One of These Things Is Not Like the Other”…for the other three of you, it includes homozygosity mapping and linkage analysis study ..)
Now, the only problem is, we've had a hard time coming up with any Normals. In a year of scouring the country, and testing the offspring of any likely candidates, we've come up with two. One is a neutered twelve-year-old male, and the other was a thirteen-year-old bitch, who unfortunately has since died. What this indicates is a gene pool that is pretty thoroughly contaminated. And this breed is not alone!
What appears to be happening is that by the time the causative gene or gene marker for a disease is discovered, it's also discovered that it's pretty well spread throughout the population. The chart on the next page shows clearly how that happens. It is virtually impossible to eradicate a recessive gene from a population without a DNA test. It will only get progressively worse. If the disease is late onset, as many are, it is even harder (harder than virtually impossible?) because affected animals are unwittingly bred, and pass the gene to all their offspring. Copper toxicosis, Von Willebrand's, and PRA are all examples of diseases that have frighteningly high incidence rates in their respective breeds. Once the gene for hereditary cataracts is isolated, it is likely to be the same story. The reason for the high rates of contamination is the same reason we have quality dogs- we linebreed. So be it. That's not an indictment of the practice, it's just a fact. And we tend to linebreed off the same quality animals. If one of them is carrying a recessive gene, it's gonna get around...
What most breeders don't realize is this: With an autosomal recessive disease, for each affected dog in a pedigree, every one of his offspring, both his parents, half his siblings, at least half his parents' siblings, at least two of his four grandparents and at least half their siblings are carrying the gene. That's a lot of carriers. So if you have an incidence rate of, say 25%, you'll be lucky if 25% of the of the breed is Normal. Yet people are always surprised....
OK, here's the good news: Once you have a DNA test, be it a linkage-analysis (gene-marker) test or a direct test, the disease can be completely wiped out of that breed in three generations without ever removing a single dog from the gene pool or producing a single affected dog ever again.
This is a critical fact to understand, because it is that particular fear that has kept breeders from co-operating in the past. Historically, only the most courageous of breeders have stood up and said "My stud dog is affected," or "My stud dog is a carrier." It is the single most devastating thing a breeder ever has to do, and many of us are simply incapable of it. So we either don't look, or we don't tell. Ethically, there is very little difference between the two. "I can't expect my pet owners to test their dogs!" is a euphemism for "I don't want to know my dog is a carrier because then I'll have to stop using him!" and there is no way around that, kids.
But once that fear is removed, there is no reason not to rid a gene pool of a recessive disease. If the disease is not lethal or debilitating and doesn't affect his sperm count, there is NO – I repeat: NO-reason that an affected dog cannot be bred. Now, geneticists will gag a little over this, as they currently recommend breeding only a percentage of carriers, and certainly not affecteds, yadayadayada, but they are not breeding showdogs, either. Breeding off the affecteds will slow down the process by a single generation, because all the offspring will be carriers, but it will also allow breeding programs to continue without sacrificing years of work in the areas of breed type and soundness and movement, which are fairly alien concepts to molecular biologists. These guys do not understand the complex psychology that keeps breeders from using an available DNA test that they spent years developing. They are frankly baffled by the ridiculous excuses breeders are coming up with, when they slaved long and hard over their electron microscopes to come up with these tests. They think breeders are idiots...
I, on the other hand, understand completely. Let's look at the English cocker. (I had Engies, by the way, for fifteen years, and I have more than a passing personal familiarity with PRA, so get off my back…) They've got a DNA test for PRA. I have heard every conceivable excuse for why breeders are not using it. “It's just a gene marker. It's not 100% accurate.” SO? Although there is a possibility that a carrier may actually be normal, or an affected dog may in reality only be a carrier, as long as a normal is a normal, it doesn't matter! “We don't know if it really will work.” Not until you try, that's for sure ... "Some dogs are turning up as affected, but aren't going blind.” I'd say be happy for them-but it doesn't change their genotype. Or my personal favorite: “Optigen is just making money off us breeders.” Yeah, well, last time I looked, so were Iams and Pedigree and Purina, but that's hardly a good reason to quit feeding your dogs ... who GIVES a damn?
NO, the real reason, although all the nonparticipators will deny it, is in the results of the tests that have been done. Only twenty percent of the English Cockers tested last year were Normal...
Which means if you have your dog DNA tested, odds are good he won't be Normal, and there go your hopes, dreams, years of work and reputation. But that is bullshit, pure and simple. That's applying 16th Century morality (stoning, witch-hunting and the like) to 21st Century molecular biology. If we want to achieve perfection in purebred dogs, which is the holy grail of dog breeding, we have to stop being stupid. New Rules apply, and we, as ethical breeders, must write them as we go. No one can write them for us, because no one else understands what we are about.
Study the two charts carefully. They are instructions for permanently removing a recessive disease gene from any population of dogs without removing a single dog from a breeding program. And no affected animals will be produced in the process, which is important. Nothing need be sacrificed-not type, nor soundness, nothing.
Now, there is one problem with this program. Let's assume that 20% of your breed tests Normal. Those dogs become "universal donors" and are largely responsible for eradicating the gene. Now, Nature being what it is, half of those animals will likely be bitches and half will be males. And the odds are good they will not be young animals, either, if you're looking at those percentages, because as the gene pool becomes more contaminated with each generation, the number of Normals decreases.
Logic tells us Normal males, even older ones, comprising 10% of the population, can easily service 40% of the total population, which would be your carrier and affected bitches. Geography is not a huge problem, either, because of the avail- ability of chilled and frozen semen.
But where does that leave the carrier and affected males? These males would also make up 40% of the population, but can only be safety bred to 10% of the population, and these will likely be bitches approaching or past middle age, with a limited number of litters left in them. This problem is going to create a genetic bottleneck, and those bottlenecks are generally what got breeds into this mess in the first place ... it is imperative that these dogs make a genetic contribution for the overall health of the population, because when a gene pool is bottlenecked, the possibility of introducing a gene more deadly than the one you are trying to get rid of often rears its ugly head. But there aren't enough Normal bitches to go around.
OK, guys, have the lights gone on yet? Did the term Multiple Sires just pop into your head?
As more DNA tests become available in more and more breeds (and they will) and as breeders learn how to use them to eradicate genetic disorders, the concept of Multiple Sires will come to be a viable, everyday tool in creating a healthy gene pool. A single Normal bitch could be artificially inseminated with the semen from four quality males, thereby quadrupling her genetic contribution, as well as maintaining the contribution of those four males, three of whom would otherwise be excluded from the gene pool for lack of a "safe" mate, without forcing her to have four litters.
This is 21st Century dog-breeding, guys. Finally, with the tools available to us, we truly won't have to throw out the baby with the bathwater ever again.
Now, if in order to do this we have to put into place a program that will let sloppy breeders register a litter out of two sires because 0l' Rufus jumped the fence again, so be it. I've got a News Flash for you-he was gonna register that damn litter anyhow. He's been doing it for years ... at least this way the integrity of the Studbook is maintained. Slap him with a big fine and he'll just go back to his old method, because it was cheaper, and he's unlikely to get caught anyway.
We cannot expect the AKC to legislate stupidity, sloth or greed out of this sport, much as we may badger them to do so. But we can expect them to lead in the quest for better, healthier dogs. And this is a big step forward. If you are a breeder, and all this was news to you, go buy Future Dog, Breeding for Genetic Soundness, by Patricia J Wilkie. It's available from CHF. Old Breeders can learn new tricks, and if you're not part of the solution, my dears, you know the rest of the line....
reprint courtesy ShowSight Magazine, Instant Information ii THERAPY vs. CURE~ ii Legal Health Disclaimer ~ ii luxating patellas
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