Autosomes: Basic Conformation and Common Faults

A dog breeder’s life isn’t simple. You have to be trainer, vet assistant, nutritionist, beautician, long-haul truck driver, stevedore, accountant and animated poop scoop. And now, with all the advances in genetics, you also need to be a molecular biologist. And what was your grade in high school biology? Don’t even think about it!

Not to worry. You, too, can understand how chromosomes are put together and how they perform. You already have a thorough knowledge of the finer points of breed conformation, performance and character. You only need to remember a few more little (as in sub-microscopic) dog parts.

Like dogs, chromosomes also have "proper conformation" and "faults." Canine chromosomes, like those of all vertebrates, come in two basic types: autosomes and sex chromosomes. We’ll take a look at the ins and outs of the latter on another occasion. (Sex complicates matters even on the molecular level).

Virtually all members of the animal kingdom, including dogs, are diploid, which means their chromosomes come in pairs. Dogs have 38 pairs of autosomes. Humans, by contrast, have 21. (They also each have a pair of sex chromosomes). This doesn’t mean dogs have more genes than people do, only that the genes are arranged differently.

These different chromosome arrangements are why it is possible to interbreed some closely related species, say a dog and a wolf, and get breedable offspring. Dogs and wolves have the same chromosome count, and their chromosomes are very similar—so similar that some scientists consider dogs and wolves to be a single species.

If the chromosomes have greater differences, things might not work out as well as with wolf/dogs. (Assuming that you consider large, agile, sharp-toothed beasts with strong predatory instincts and no fear of people to be a good idea). A horse, for example, can be bred with a donkey, but the resulting mule is rarely fertile.

Species more distantly related will not produce offspring at all. All those half-Earthling, half-alien characters that populate science fiction are just that—fiction. If some far-future dog breeder wants to establish a new breed by mating his earth bitch with some alien stud with high intelligence and pointy ears or a hard temperament and bumpy brow, he’ll be in for a big disappointment. He’d have a better chance of producing a litter by breeding his bitch to a rhododendron, which at least has chromosomes that developed on Earth and therefore will have a few (very few) similarities.

Chromosomes are long strings of deoxyribonucleiac acid (DNA). Most of the time these strings are too fine to see with even the strongest microscope, but when a cell is ready to divide the chromosomes duplicate themselves and fold up into compact, visible packages. The duplicate parts are called chromatids. They are joined somewhere along their length by a structure called a centromere, resulting, in the case of a dog, in 38 pairs of little X and V shaped things. A pair of chromosomes will always have their centromeres in the same place, so each set of pairs will appear, on this (still microscopic) large scale, to be exactly alike. This is sort of like the way two Australian Shepherds look alike, or two Laboradors, or Chihuahuas. They look alike at first glance, but closer inspection will reveal significant differences.

When the cell divides, during a process called mitosis, the chromatids will split apart, leaving a single strand in each daughter cell. This way the daughter cells wind up with a set of chromosomes that duplicate what the parent cell had before it started to split.

However, if the ultimate purpose of cell division is to make sex cells (sperm or eggs), there will be another division that separates the pairs. Through a process called meiosis, one half of each chromosome pair is parceled out to each sperm or egg cell. The proper number will be restored when the sire’s sperm fuses with the dam’s egg.

You know you can name dog parts as well as any junior handler. The following will let you master the parts of a chromosome.

Genes. Each autosomal chromosome carries a set. Its pair partner has corresponding genes, so every cell will have two of each. The genes are arranged along the length of the chromosomes like beads on a string, with each being positioned at exactly the same place its mate is located on the other chromosome of the pair. This placement is referred to as a locus (loci, if plural).

Telomeres are positioned at either end of the chromosome. They are short sequences of DNA which are repeated over and over. They serve the same purpose as the words "The End" that appears at the end of old movies.

Micro-satellites are DNA sequences that separate one gene from another. It is these little beasties that are being used for the Australian Shepherd Club of America’s DNA paternity testing program.

Chromosomes are made of DNA. DNA is a complex molecule consisting of two sugar-and-phosphate chains linked by bonded pairs of bases. The two chains twist around each other in a double spiral, or helix. (See front page of this newsletter for a picture of this).

The bases that bond the two chains form the genetic code, which includes "words" and "punctuation"—collectively referred to as exons (no relation to the oil company)—and segments that appear to do nothing at all, called introns. Every gene will have some of each.

DNA has only four kinds of bases: Adenine, cytosine, guanine and thymine, or A, C, G and T, for short. A bonds with T and C bonds with G. The order in which these pairs occur forms the code.

Four bases forming two mutually exclusive pair bonds may not seem like much of a code for making things as complex as dogs or rhododendrons or even single-celled critters like bacteria. However, if you consider that computers use two-digit codes to perform a wide variety of complex functions, a four-digit code could have endless possibilities.

The genetic code is made up of three-base-pair "words." These DNA triplets create sections of ribonucleic acid (RNA) called "codons," that in turn create specific amino acids. Through a complex chemical process, those amino acids form the proteins upon which all life depends.

RNA is like half a DNA molecule, with a sugar-and-phosphate spine and attached bases. RNA also differs from DNA because it uses adenine-binding uracil (U), instead of thymine.

With four bases there are sixty-four possible three-base codons, but there are only twenty amino acids. So what are all those extras for?

These genetic "words" have "synonyms." There are at least two different codons for most amino acids. Quite a few have four and only a handful have three or one. These redundant forms all have two of the three bases in common. We’ll see why later.

For a code to communicate clearly, punctuation is necessary. When I string words into a sentence, I use a period to show where the sentence stops. Three of the RNA codons form "periods." There is also beginning "punctuation" which signals where RNA should start encoding. These areas are called origins of replication.

A sound chromosome will have health genes made up of DNA:

That produces RNA

Which codes amino acids

That build proteins

Which make our own

Very up-close-and-personal

Worlds go round.

Ideal conformation is a wonderful thing.

But, like dogs, chromosomes have their faults. Mutations are the best known. When you consider how many billions of DNA base pairs have to be lined up in all of a dog’s (or human’s) cells in the course of its life, it isn’t surprising that mistakes happen. (Next time you sit down at your computer, try entering a few billion keystrokes without error—and no fair using spell-check!)

The probability of mutation is one reason for those synonyms—a tiny glitch here or there won’t make much difference and life can go on according to plan.

However, sometimes the errors are large enough to significantly re-write the code. If, for instance, the "typo" occurs because a chromosome in one of the unpigmented skin cells in your dog’s blaze gets too much sun, the result may be a skin cancer. These kinds of chromosome "faults" are a problem for the dog that has them and its owner, who pays the vet bills. But since the cells so affected don’t produce sperm and eggs, they aren’t a concern for a breeder. (Except to the extent that breeding outdoor dogs that have massive white markings might not be too clever).

When the mutation occurs in sex cells—the ones responsible for producing sperm and eggs—the effect can literally be passed on for generations. Most mutations in sex cells are so wrong that no offspring can be produced. Or they will be too faulty to survive pregnancy and birth. If a healthy bitch reabsorbs fetuses, severe genetic faults in those fetuses are a possible reason.

Other mutations are less virulent. As long as the individual has at least one normal gene in a pair, it will be fine, though bad things may be in store for offspring unfortunate enough to get mutated genes from both parents. Collie Eye Anomaly is one example of this. Homozygous merles and Pelger-Huet Anomaly are others.

In a few cases the mutation may have only minimal effect, be benign, or even beneficial. Dogs come in a wide variety of colors, patterns, shapes and sizes because of more-or-less benign mutations which breeders liked.

The word "benign" is used loosely here, since many domestic dogs have structures and coats so bizarre, from Mother Nature’s point of view, that they could not survive without people to take care of them. Even the merle coloring we so prize in our Aussies is a semi-lethal.

Genetic code "typos" are not the only fault chromosomes can have. Sometimes the whole system stutters, causing multiple repeats. These repeated sequences can cause major problems.

Huntington’s Chorea is a lethal genetic condition in humans. Affected individuals usually don’t become ill until middle age, but some get sick much earlier. Recent DNA studies on the Huntington’s gene have revealed that it contains CAG repeats, multiple repetitions of the cytosine-adenine-guanine (CAG) codon. The more of these repeats there are, the earlier the person develops the disease.

Like dogs, chromosomes can have major conformation problems. Sometimes a pair of chromosomes will fail to separate during meiosis, resulting in sperm or eggs with two or none of that particular chromosome. When it becomes part of a fertilized egg, the resulting individual will have either a single chromosome (monosome) instead of a pair, or a triplet (trisome).

In lizards, fish and some other critters, this doesn’t represent a problem, but for mammals—and therefore dog breeders—it does. Monosomy is nearly always lethal. A trisome, however, may survive—though often with severe problems. One of the best known is human Trisomy 21. The designation means that the 21^st "pair" is a triple. This condition is also known as Down’s Syndrome.

Today, selecting the best set of dog chromosomes is largely a matter of educated guesswork. But genetics is one of the fastest-growing areas of scientific knowledge. That far-future dog breeder we mentioned earlier may be making his selections not be looking at dogs, but by looking at their chromosomes.

In the meantime, building your knowledge of how chromosomes are put together, and how they do what they do, will put you a step ahead of the game as researchers around the world make more and more discoveries that will someday directly impact what you do.