Brief Introduction to Genetics(Part 1 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"
...English scientist Francis Galton in the late 19th Century.
Natural Selection & Survival of the Fittest
Hip dysplasia is not common in wild animals because of the continuous processes of natural selection and survival of the fittest. In an environment where society removes or inhibits these means of selection, the host of ills of which HD is but one example is denied full effect and allows the least fit to survive and breed as well, and in some instances makes it easier. The hunter bags the biggest game; we cut the best trees down, and so forth.
The hypothetical young elk with hip dysplasia will be one of the first ones caught by the wolf pack, and such will not live long enough to impregnate as many elk cows as stronger, healthier ones could. Conversely, any wolf with weakness such as HD will not have the stamina of its normal packmates and, bothered by arthritis and coxo-femoral pain, is probably going to lose any leadership challenge as well as the concurrent privilege of fatherhood to a younger, more agile, normal-hipped male. In human society and in those animal societies we influence, these natural safeguards are often lost. In the wild, there are no hospitals or welfare systems.
A colony of Dingos (wild dog breed in Australia) has been reported which had been bred, fed, reared, and protected in captivity for some 40 years. When radiographed, a substantial portion of these zoo animals was found to be dysplastic. However, newly-captured Dingos were free of the disorder. During one of my lecture-judging tours in that continent a couple of decades later, I visited a private Dingo breeding and preservation farm and found the operator practicing selective breeding which included rejection of dysplastic animals from the reproducing groups, just as any responsible breeder of more domesticated canines would do.
Canine hip dysplasia, a multifactorial, developmental, quantitative condition, is genetically controlled. Early in the 1960s and even before, HD was thought to be due to one or more dominant genes with incomplete penetrance, which meant it varied from individual to individual, or even between one hip and the other in the same dog. It is now widely held that HD is basically recessive (the word does not mean unnoticed or diminishing). To understand the difference between dominant and recessive, and to gain a working knowledge of the inheritable nature of HD, with an eye toward genetically controlling it in one's kennel or breed, a brief biology lesson and simplified examples of inheritance modes would be helpful.
One of the principal tenets of education is that understanding is best attained if you start with the simple before progressing to the complex. Starting with atomic physics in order to understand breeding and orthopedic disorders may not seem like it fits that description, but let's start near there anyway, and try not to get lost. We'll go along in that direction a short distance before getting back to structures smaller than cells. You remember from your grade school science classes that "everything is made of atoms", a simplification, to be sure, but good enough for our purposes. An element is a substance that cannot be separated into simpler parts, and whose atoms are all the same kind. Oxygen, gold, and diamonds (pure crystalline carbon) are examples of elements. A molecule is a new arrangement of atoms that are so "glued together" that they seem almost as indivisible and unique as atoms. A compound is a collection of identical molecules; water, salt, and carbon dioxide are examples of simpler compounds, while proteins, nylon, and perhaps even viruses are examples of complicated molecules or compounds. Some of the very highly developed molecules such as viruses and cell nucleus parts have the ability to reproduce themselves by building copies out of the raw materials available in the "cell soup" they are immersed in.
Getting back to the medium level of complexity, though, we see that most living organisms are composed primarily of a fantastic variety and innumerable combinations of compounds of oxygen and hydrogen atoms attached to carbon-chain "backbones" with smaller numbers of other elements such as sulfur, nitrogen, calcium, phosphorus, etc. Exactly how and where they are part of specific carbohydrate (carbon/hydrogen/oxygen) molecules determines their function. Proteins have more nitrogen atoms, bone has more calcium and phosphorus, blood has more iron, and so on, than other molecular structures in the various parts of the body.
Cells are units often likened to building blocks because in so many instances, they are arranged side-by-side to make up larger structures. The next step up in complexity as far as body organization is concerned is a collection of cells grouped together to perform a specific function; this is called a tissue, and examples include hair, bone, and muscle fiber. Tissues of similar or dissimilar types are associated in collections called organs, such as the heart, eye, and skin. Sometimes we use the same word to mean several things, as in the case of "bone", which could refer to specific types of bone cells; bone tissue as compared to cartilage; or bone as an organ containing marrow, cartilage, and harder tissues. Organs work together for the benefit of the organism (body and psyche).
Cell Division and Chromosomes
In every cell of every living thing, there are submicroscopic strands of protein-like material called "chromosomes", composed of long spiral macromolecules. Macro, meaning large, and molecules are fairly stable combinations of atoms. Examples of macromolecules include DNA, cellulose, rubber and nylon. An electron microscope can differentiate not only the number but also the shapes and sizes of chromosomes when cells divide. The dog has 78 chromosomes, humans normally have 46; always an even number since chromosomes appear in pairs with each cell containing the same number of chromosomes except in sex cells which each have half the number so that the normal number reappears when they get together. The male sperm and female ovum (egg cell) each have just one of each pair that are found in the other cells of the body.
When cells perform that mathematical wonder of dividing to multiply, they create identical "daughter cells". The cell structure is basically cytoplasm, nucleus, and wall. During cell division, strands begin to appear in the nucleus, and soon are distinguishable as chromosomes. Before and after the phases of division, they are not identifiable, but persist in a "distributed" manner, becoming visible again only in the next division. Because each chromosome is composed of a double chromatids entwined about each other, they split lengthwise into two "pieces" which seem pretty identical on casual view. Only upon much closer investigation, such as with electron microscopes, other analytical instrumentation, and deductive reasoning, do we see that they are not truly identical. For the gene on a particular location on one chromosome of the pair could easily have a very slightly different chemical structure than that on the exact same location on the matching chromosome. Just as the chromosomes exist in pairs of strands, the genes on them obviously are paired, also. They too are strand-like in dimension, and are twisted and coiled like knobby rubber ladders made by someone on drugs or devoid of coordination.
Biochemists are able to stir up semi-dissolved cells with certain chemicals in order to separate these chromosomes and make them visible under high-power microscopes. They take pictures of the alphabet-soup dilution, and cut the photos apart so they can pair up "twins". You then have a karyotype and can see some abnormalities such as missing or extra chromosomes (severe defects such as Down's syndrome), or one chromosome fused to another (may produce either obvious or covert defects). Usually such fusions inhibit reproduction ability, so the results are seldom heritable. On the other hand, crossing-over is fairly common and is responsible for much of the variety you see in your litters. A dog can have a great multitude of different sperm cells (none of them quite the same, like snowflakes). The same is true in bitches' ova, but she releases far fewer sex cells at a time than does the male.
A chromosome is composed of numerous chemical units called "genes", and from the same root we get the word genetics. An idea of how complex genetics can be is had when one realizes there may be from 10,000 to 100,000 pairs of genes in mammals. The interaction of many of these genes makes for an almost infinite number of variations, like snowflakes or fingerprints, and no two dogs are exactly alike. Genetic diseases such as HD are results of one or more abnormalities in deoxyribonucleic acid (DNA), the complex macromolecule/chemical of which genes are primarily made.
Most defects cannot be determined by just looking at the chromosomes. The aberrations are in individual genes, and since these are so much smaller, you can't tell much by looking, regardless of magnification. Just how small are these genes? They might be three to seven microns long but only two thousandths of a micron long. (A micron is a thousandth of a millimeter, and a millimeter is about four hundredths of an inch). There are now about six billion humans on Earth, each of us having our physical beginning in a single fertilized ovum (egg). Genes are made of strands of DNA (deoxyribonucleic acid), and if you could measure the entire DNA in 3 billion ova (nearly equal to the half the number of the world's entire population), you could fit it inside a single raindrop! Yet, end to end, the strands could make eight loops to the moon and back! We are talking about some pretty small, narrow strands of molecules.
Certain genes have a primary effect on individual characteristics but other genes, especially nearby ones, influence them as well. Depending on the proximity on the chromosomes and the strength of the chemical attractions between different genes, minor to major differences will appear in genotypically very close relatives. One dog may have slightly larger white areas than a littermate with mostly similar gene arrangements; one pup may have a slightly different degree or appearance of HD than a littermate inheriting basically the same major genes. The nearest-neighbor theory holds that the greatest mutual effect may be between two adjacent genes.
Part 2 will focus on Dominance and Polygenic Traits, Effects of the Bitch on HD in the Offspring, and Polygenic Selection.
(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.")