Brief Introduction to Genetics (Part 2 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 and Survival of the Fittest, Cell Division and Chromosomes, and the interaction of genes)
Dominance and Polygenic Traits
We think of chromosomes as strings of pearls, with collections of genes up and down their lengths, and each gene having a specific location (locus) in relation to the others. These loci are given arbitrary letter designations, with the initial letter sometimes standing for a key word in the name or description of the condition. Usually, we use a capital letter to designate a dominant trait, and a subcase letter for a recessive (weaker) trait called for by that location's gene. A characteristic governed "entirely" by one gene pair is commonly called a Mendelian trait, and those traits determined by a large number of genes are known as multifactorial or polygenic. What are commonly called simple Mendelian traits are handy characteristics to use in illustrating the nature of inheritance as regarding dominance, recessives, and other terms you've undoubtedly come across. Probably the easiest of these is the matter of coat color, because of everyone's familiarity with it. Suppose that chromosome #28 is the one that carries the gene for coat color in a Labrador Retriever; when the sperm cell carrying a gene for black enters an ovum carrying a gene for yellow, the pup (fertilized egg) have the normal complement of chromosomes and genes. In this example, the pup will be black in color because the gene for "black Lab" is dominant or "stronger" than the gene for "yellow Lab". In the Shiba, the gene for red is stronger than (dominant over) the gene for black-and-tan (sometimes called "tan-point"). Once you gain some familiarity with inheritance of simple traits, which means those which are determined by a single pair of genes, you can at least appreciate the depth of complexity if not understand the combinations of many genes that we call polygenic traits. Most things breeders are concerned with are polygenic, such as temperament, joint quality, good ears, bite, hunting ability, length of bone, HD, and probably angulation and movement traits. The different numbers of genes involved in different traits gives the impression that some disorders are perhaps 50-100% genetic in expression, while others appear to be primarily due to environmental factors. However, this is an illusion, as environment determines only the expression of the genes, not their presence.
Polygenic traits, those determined by a few or many genes working in concert, are not as predictable as the Mendelian traits, but we can make a broad generalization that "defective genes" are usually recessive in nature. Enough "weaker" recessive genes can outnumber and overpower the dominant genes for correct joint conformation, for example. Thus, if you breed a dog with mostly genes for dysplastic hips to a dog with radiographically normal hips but perhaps 45% bad genes (not enough to make for bad hips), what will you get in the litter? Just maybe one or more that has radiographs like the OFA-certified parent, but more likely most of the offspring will have a preponderance of bad genes.
Further complicating this is the probability that one gene for depth of acetabulum is on one locus, the gene for growth plates' response to over-nutrition is on a different locus, the gene for tightness of certain ligaments is on yet another, etc. As in dealing from a deck of cards, where you have a wide variation in the value of cards ace through king, and each player gets a random collection which may have a favorable or unfortunate combination, the puppies in a litter will have varied collections of genes. Some will have been dealt better hands than others, but if you have previously "stacked the deck" you can assure all of them getting better hands than those dealt by your less-careful competitor. If the high cards represent poorer quality genes (high percentage of defects), and the low cards optimum genes for joint quality, it is obvious that you will produce more "winners" if you start with decks that have fewer high cards and more low cards, then play your game without allowing yourself or anyone else to slip high cards into the deck. Removing high cards as they appear in hands is analogous to the process of culling: removing from the gene pool those dogs with lower-quality genes. Easy in principle, but it takes diligence to accomplish this in a breeding program.
You know that genes and chromosomes operate in pairs. When the half-number in sex cells are united at conception, the physical characteristic called for by one gene may be different than that of its corresponding gene partner, in which case the animal is said to be heterozygous for the trait exhibited (you can see the effect in simple, one-gene-pair, Mendelian traits). If the chemical nature (molecular structure) of the two members of that pair of genes is identical, the animal is said to be homozygous for the trait in question. The prefix homo - means "the same" and hetero - means "different", while "zygo" is the Greek root for "pair".
In a heterozygous situation, one gene will have a greater influence than its partner, but when many genes in many locations affect each other (polygenic), predicting the outcome is not as easy. Thus the importance of lowering the variation or number of different genes by culling.
Effects of the Bitch on HD in the Offspring
At the 1987 conference, "The Dog in Service of Humanity" which was held in Geilo, Norway, Swenson reported on test and retrospective breeding data, matching normal studs with grade-1 dysplastic bitches and vice versa, and compared that to the similar results found by the State Dog Training Centre eleven years earlier. It was discovered that the bitch had more influence on the eventual hip status of the offspring than did the sire, by about 10%. If the bitch were the dysplastic half of the union, about 10% more HD was found in the progeny. To explain, he offered a couple of possible reasons. It could be that the uterine environment or some factors prior to weaning, such as poor "general physiology" or poor milk/colostrum or other undiscovered factor affects HD in a negative direction from the beginning of conception or some time shortly thereafter.
It is also possible that a genetic factor plays a part. You know that the ovum is a cell with a nucleus surrounded by other substances collectively called cytoplasm. You also know that the DNA strands that make up the genes are located on chromosomes in the nucleus, and these chromosomes (and genes) match up with homologous (same shape, size and general make-up) ones from the entering sperm to make the nucleus of the first offspring cell. Well, there is also some DNA in the cytoplasm outside of the nucleus. While not thoroughly investigated yet, this "extra" DNA could explain the conventional wisdom that the bitch contributes more to the pups than the sire does, as well as explain the results of the Swedish studies noted above. The tiny sperm cell apparently does not carry cytoplasmic DNA to the union.
Early research in HD involved the effects of hormones, especially estrogens, and some thought they could initiate or prevent some evidence of dysplasia by manipulating estrogen levels but others found "maternal environment" including estrogens not to be important in the cause or etiology of HD. When I was on one of my lecture/judging tours in Australasia one of the lectures was sponsored by Uncle Ben's, the same company that makes Pedigree and Pal brand dog foods. During my incidental research at Murdoch University and elsewhere I came across work (also partially sponsored by Uncle Ben's) by Queensland and Victoria HD investigators (Goddard & Mason) which found "no differences" but rather a "lack of any breed-of-dam effect", which led them to conclude that "it is unlikely that maternal oestrogen concentration is an important cause of variation between dogs..." and that other maternal environments were likewise insignificant.
That Australian work looked at the possible effect of heterosis (contribution to health or size, sometimes referred to as "hybrid vigor" even though matings within a species perhaps do not really produce hybrids in the usual semantic sense). They used 4 breeds with hip quality ranging from the native Kelpie down through Boxer and Labrador Retriever to the German Shepherd Dog, and cross-bred them in almost all combinations, partly to see if better-hipped candidates for blind guides might be possible. Only the Kelpie and the Shepherd can liberally be considered anywhere near each other on the canine genealogical tree, and that very remote indeed. One breed known worldwide for its connection to relatively high incidence of HD (the GSD), one lightweight breed with generally low incidence (Kelpie), and two with moderate incidence (the Boxers were worse than expected and the Labs better, so they were roughly equivalent) made up the breeding stock. Pups were palpated, later radiographed, and the results analyzed using the least-squares estimate for breed effects. They found more variation within breeds than between breeds.
Tne indication was that selection against HD has occurred "naturally" in times past by selection for "working" qualities (Greyhound for speed, Kelpie for agility and stamina) but earlier reports by Pharr and others show no reduction in HD when Australian Shepherds were chosen on the basis of occupation as working stock dogs. Perhaps we don't work our "working" dogs as rigorously as they did a century ago! While significant heterosis is seen when cross-breeding Greyhounds and German Shepherds, no such significant improvement was seen by crossing the Shepherds to Kelpies.
Patterson illustrates polygenic inheritance with a balance: one pan contains the "good hip genes", the other contains the "bad hip genes". Each gene is on a different locus, and the pans probably involve more than one chromosome. Each pair of genes has one partner (allele) from the sire and one allele from the dam. Suppose young Rover had radiographically fair hips (but good enough to rate an OFA normal classification), and almost half of his hip genes were defective, the other half okay, and if he is bred to Lady who also has "normal X-rays" but many defective hip genes, what will the puppies of such a union inherit?
Mathematically, you might expect more possibilities than the dam would ever have time to produce, but suppose one of her pups designated "A" inherits all of Rover's bad genes and all of Lady's bad genes (actually half of all the pairs). "A" will then have the same genetic bank. But it is quite possible, even likely, that the hips of pup "A" will look worse on film if environmental forces (nutrition, especially) had more of an effect. Many people consider HD to be a "threshold condition" which means that if there are a certain number of bad genes (even if less than half), the condition will be seen unless covered up by such practices as deliberately keeping Rover and Lady very thin during growth. Also, some of the bad genes affect the acetabulum, some the ligaments, some the shapes of bones, etc., so the combination can be very complex.
Let's further suppose that Rover and Lady (both barely over borderline in hip quality genotype) were bred to each other by a math and statistics instructor (named Matthew Maddox, of course) and the professor kept one of the "average" pups (having both some bad and some good genes, like their parents). He named it "Gordo" and fed it a diet richly laced with calcium/phosphorus/Vitamin D tablets and beefed up that diet with ground meat to stimulate appetite, although keeping the meat supplement to 10% in accordance with advice from his colleague the biology professor who used to work for NRC. Another average pup, "Slim", was sold very early to a student who spent his summers at the Royal Veterinary College in Stockholm, helping researchers compile data on the effects of over-nutrition. Knowing what you do about the effects of diet, especially over-nutrition, guess which of these two average pups will have the greater chance of developing clinical and radiographic HD.
One more supposition: the rest of Lady's large litter (all average) went to loving homes whose masters all made sure they had their shots and vitamins, and ate well of their nice, rich puppy food especially formulated for growing dogs and reeking with appetizing flavors.
By now, you're getting ahead of me. Professor Matthew Maddox who spent a great deal of money for a fancy brood bitch and a stud service, both animals managing to have OFA numbers, has turned out a large litter of pups who have become badly dysplastic before the one-year guarantee ran out, and he has to borrow money to make refunds to many of the unlucky buyers, and stave off the others with a free replacement as soon as he can get another litter out of Lady, sired by some stud other than that nasty defective rascal Rover! Maybe when that student returns from Sweden this fall, just in time to breed Slim when Lady comes in season? What luck! The only dog not sold to a show home has great hips... well, actually, the OFA said "fair", but that's the same as his dam's, and they both have the same beautiful characteristics, so the breeding should be great! Besides, Lady's breeder had said, when he bought her as a pup, that they didn't have HD in their kennel, so it must have been carried by Rover. But you and I know something the professor doesn't: Slim has the same poor hip genotype or genetic bank that his dam, sire, and his moderately or severely dysplastic littermates have. And with such a precarious balance, such a small margin of total good genes over bad, the influence of environment can again be significant.
Unfortunately, "breeding programs" similar to the above extreme example are being conducted in like manner by "breeders" all over the world. The cripples go to the pound or are nursed by longsuffering, disappointed, or embittered owners, and the others like Slim or even some with not as good radiographs or none taken at all, are bred and bred and bred. There are nearly 90 million dogs and cats born each year, thousands every hour! (Dr. Faulkner says 2,000 to 3,000; Humane Society of the U.S. says 10,000; United Humanitarians say 12,500; Roger Caras estimates 15,000.) We have a responsibility to encourage the breeding of genetically better dogs in preference to dogs with relatively more defective genes.
Part 3 (and last) will give us an idea of "What's Ahead" and discuss the whether orthopedic disorders such as HD inherited, the variation in polygenic traits, the random nature of polygenic disorders and how much is genetic and how much environmental.
(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.")