Brief Introduction To Genetics (Part 3 of 3)
By Fred Lanting Mr.GSD@juno.com
(Thanks to Mr. Lanting for again allowing us to draw on his experience to further our education)
"Nature prevails enormously over nurture"
(Part I of this series addressed the topics of Natural Selection & Survival of the Fittest, Cell Division and Chromosomes, and the interaction of genes. Part II focused on Dominance and Polygenic Traits, Effects of the Bitch on HD in the Offspring, and Polygenic Selection).
Perhaps someday the mysterious chemical nature of the inheritance of defects will be understood, and a simple chemical correction made or gene therapy performed for most of them. Until then, we must use what tools we have and do what can be done to control the genetic disorder known as hip dysplasia. OFA, GDC, and PennHIP are excellent diagnostic and control "helps", and AKC's slowly-awakening sense of responsibility to animal soundness and owner is commendable, partially making up for a history of neglect and greed in letting puppy mills flourish for the sake of litter registration dollars. The AKC is cooperating with OFA and the Morris Animal Foundation in a search for genetic markers in the chromosomes of dysplastic dogs and their (probably) carrier relatives. As a popular advertising phrase goes, "Watch This Space".
Are Orthopedic Disorders Such As HD Inherited?Literally speaking, traits themselves aren't inherited; the bits of chemicals making up the genes are reproduced and distributed among sperm and egg cells for transmission to the next generation. But we can use the terminology just as we use the word "bloodlines" when blood has nothing to do with inheritance. Knowing that a trait is hereditary does not necessarily mean that equal knowledge is to be had about the manner in which it is so.
Numerous noted experts in the field have commented about the hereditary nature of HD, adding tons to the weight of evidence. Dr. U. V. Mostosky of Michigan State says, based on actual results in breeding programs involving many breeds, HD "is principally a genetic disease which may be modified by diet and exercise". Dr. Donald Patterson, chairman of Medical Genetics at University of PA School of Veterinary Medicine, states that some dogs with radiographically normal hips but a large number of hidden dysplasia-producing genes, if mated together, will produce at least some dysplastic offspring. Dr. Sheldon Gerstenfeld, author of "Taking Care of Your Dog", writes, "hip dysplasia has a polygenic mode of inheritance". Dr. George Lust of Cornell talks of "eliminating genes responsible for abnormal hip joint conformation". In another place he says flat out, "Canine hip dysplasia is a hereditary disease". Dr. E. A. Corley, in an OFA report, says in a section headed Findings of the OFA, "Hip dysplasia is an inherited trait". Dr. Frederick Hutt, author of a notable text on genetics, wrote of "genetic selection to reduce the incidence of hip dysplasia" and HD as "a good example of a defect that is polygenic". Allow me here also to quote Dr. Malcolm Willis who states the increase in proportion of better hips "provides ample proof to those doubters who still argue that HD is not inherited." Hedhammar, Olsson, and many scores of others have proven beyond any reasonable doubt that incidences of orthopedic disorders are reduced when genetic selection is used. The rare voice putting the blame for HD and other problems on a lack of vitamins or on some other nutritional or environmental cause will always find a few itching ears, but it is or should be absolutely astounding that anyone would give it the least credence.
Variation in Polygenic Traits
The reason you might not get a litter of exactly the ratio calculated when you breed two heterozygous dogs (Labs with genes for both black and yellow, for example) is that the mating of sperm and egg cells is a random event. It could easily be that the eggs are coincidentally surrounded by sperm cells carrying the black gene, in which case the "yellow genes" can't get to the eggs in time, and the litter will be all black, as if the sire was homozygous black. Well, if this can happen once in a while with only two alleles, imagine the random nature of mating perhaps dozens of eggs with millions of sperm cells. A great deal of variety exists in the wiggle-tailed suitors for Ms. Ovum. Some may have a bad gene for one specific trait in the hip joint design, some may have a bad gene for another trait, some may have both (in different genes or loci, of course, since there are no pairs in sex cells), and some sperm may have a whole bunch of defective genes (for many separate features in the joint). This is why you can get a very wide distribution of joint quality when you mate a dog with bad genotype to one with either good or bad overall genotype (we're talking hips here, but it could apply to any polygenic disorder/trait). When there are more genes involved, and when the genotypes of the parents are disparate, you can expect much of what geneticists call "continuous variation".
To narrow the distribution of genotypes in the litters, and insure that it will be much closer to the ideal, "good end of the spectrum", mates must be chosen who have those properties themselves, and ideally ones who have already proven their genotype through their progeny.
Random Nature of Polygenic Disorders
To illustrate the culling aspect of the selection process in a polygenic disorder, let's start up that game of poker I alluded to earlier. Shuffle a deck of cards, then deal four hands, "up" so everyone can see all cards dealt. Assume that the "face cards" (king, queen, and jack) represent the highest numbers of genes for HD, and that the numbers on the rest of the cards are in proportion to the number of bad genes. Player A might get two face cards in his five "litters", and players C and D might get one face card each. Remove those face cards from play, set them aside, and reshuffle all other cards whether played or still in the deck. Repeat the procedure, and in the next couple of deals, you'll see the number of face cards decline. Become more selective, and remove from play the 10s, 9s, and 8s. After 2 to 4 more hands, which by now look pretty good, you might want to cull the 7s and 6s to get your score down really low in most hands (a hand representing either a bunch of litters or the pups in a single litter). Lo and behold, you'll still come up with an occasional face card or high-number card, which is the nature of our polygenic card game, but the odds against it are greater the longer you play the game and the more strict you become in culling individual dogs from a breeding program.
Because of the polygenic nature of HD and the heritability in most breeds and sub-populations, the breeder can expect much variation, a wide "spectrum" of hip qualities, when using phenotype as the deciding factor in his breeding program. Dogs with normal radiographs, mated together, will produce a range of pelvic quality in their offspring. However, if a dog has a normal (radiograph) phenotype, the chances of it having a genotype to match (normal, and expected to produce such phenotypes regardless of environments) is 1.4 times greater than the chances of it actually having a "dysplastic genotype". This figure comes from Lust's work at Cornell where it was found that, "of the dogs with normal phenotypes, the ratio of dogs with normal genotypes to dysplastic genotypes is 1.4 to 1".
The phenomenon of crossing-over mentioned earlier explains how a dog can inherit its father's ears and its mother's bite, just as in humans, and since there is so much crossing-over in the "plastic" nature of canine genes and chromosomes, we can see how a particular puppy might be unlucky enough to inherit all the bad-hip genes its dam contributes and if it doesn't get enough dominant good-hip genes from its sire to counteract them, can resemble the dam's worst ancestors in the hips, yet resemble the sire outwardly.
Since there are so many genes involved in polygenic traits such as HD, some few dogs with what we call a normal genotype (very few defective genes as evidenced by progeny results, for example) can be "forced" into dysplastic phenotypes if they are overfed and mineral-supplemented during their fast growth period. It is pretty hard to create more than mild signs of HD in a dog with very few bad genes, though, and my litter mentioned earlier which had been fed ad libitum is an example. Thus, some dogs with a certain mild grade of dysplasia have been known to produce better hips than they had themselves. And, as you have seen in the chapter on nutrition, a dog predisposed to HD because of the number of bad genes inherited may appear (phenotype) normal on radiographs if it has had restricted exercise and diet. Its genotype has been masked by manipulating the environment. Such a dog does not have as desirable a genotype as one which has been "forced" into signs of mild HD by overfeeding. Also, overfeeding often gives more signs of osteophytes than of laxity.
The very best dogs for breeding and work, given other things being equivalent, are those with the best pelvic radiograph phenotypes, raised in the most favorable environments. However, in order to establish a line or colony with great genotype, some believe, it may be worthwhile to expose the dogs in the program to the disadvantageous environments in order to force the few bad genes out into the open: feed liberally, especially. Then you could select for breeding only those dogs which, as pups, had such a "strong" genotype (fewest number of defective genes) that they were able to resist environmental forces, and develop normal phenotypes in spite of them. Some have termed this an extreme approach to eugenics.
How Much Is Genetic and How Much Environmental?
Most people like to put labels on others, and those who study characteristics of animals are often categorized as either hereditarians or environmentalists (not to confuse this word with the other meaning, that of conservationist). The latter believe more of an animal's actions are due to culture (training or environment) than do the hereditarians. I always like to exaggerate just a little for the sake of emphasis, and tell people that everything is genetic, even getting run over by a car (because traits of fear or avoidance in dogs who survive would tend to keep them away from the road). A more scientific phrasing might be that genetically-determined diseases and traits are modified to some degree between zero and 99% by forces other than the genes themselves; it has been my observation through many years of intensive experience in dogs that this percentage is usually far lower than the average dog owner believes. One reason you can't find most of the wild animals in the woods is that they have a genetic shyness or flight response to the stimulus of human presence in their home. Of course, environmental forces such as the opening days of hunting season serve to greatly reinforce such inherited traits, so no one is a total hereditarian.
(Fred Lanting is an AKC judge, breeder of German Shepherds, the author of "Canine Hip Dysplasia" and the soon-to-be published "Canine Orthopedic Problems.")