A Brave New World Of Canine Genetics
Diane Klumb / © TheDogPlace.org
|Normal Parent + Normal Parent
||4 Normal Offspring
|Normal Parent + Carrier Parent
||2 Normal, 2 Carrier Offspring
|Normal Parent + Affected Parent
||4 Carrier Offspring
|Carrier Parent + Carrier Parent
||1 Normal, 2 Carrier, 1 Affected Offspring
|Carrier Parent + Affected Parent
||2 Carrier, 2 Affected Offspring
|Affected Parent + Affected Parent
||4 Affected Offspring
No dog with unknown genotype will be bred. ALL dogs must be DNA tested for this to work!
An affected dog is bred with a DNA-tested Normal dog. All puppies will be carriers, but none will be affected.
The carrier pups are bred to another DNA-tested Normal dog. Half the
litter will be Normal, half will be Carriers. All pups must be DNA
tested to determine which is which, as they do not come with labels,
unfortunately... The carrier pups can be placed as pets, or if they
are spectacular, Step 3 may be repeated, but it will slow down the
The Normal pups are then bred to another DNA-tested Normal dog. All
pups will be Normal! Voila! If the dog you start with is a carrier
rather than an affected, you can omit Step #2.
Heart Breeders Open Registry
This is what one dedicated
club can do for its breed. Others have tried to accomplish the
seemingly impossible task of open, i.e. shared, genetic information.
They have failed due to lack of breeder participation. Many clubs
throw money at "health testing" and research but members fail to test
their dogs for fear of the results. The Havanese people have shown
that it doesn't have to be that way. If everyone shares,
and if breeders quit throwing stones at each other, and if the
scientific community revises its often accusatory stance on breeding
from carriers or even from affected dogs, H.E.A.R.T proves it can
be done. Real progress at a time when many breeds are facing total
ruination, possibly even extinction as a distinct breed is within the
grasp of those who care enough to take the first step.
Diane leads the way with the firm conviction that this is the "most
exciting time to be in dogs." From her point of view and with the
logic of science to affirm it, we agree. We therefore support
Heart Breeders and hope you will take time to study this article and
visit their website.
Your club can do it too. Study the model!
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