Basic Genetics
The basis for order in life lies in a very large molecule called
deoxyribonucleic acid, mercifully abbreviated to DNA. A related
molecule, ribonucleic acid (RNA) provides the genetic material for some
microbes, and also helps read the DNA to make proteins.
Read?
Yes, read.
DNA has a shape rather like a corkscrewed ladder. The "rungs" of the
ladder are of four different types. The information in DNA comes in how
those types are ordered along the molecule, just as the information in
Morse code comes in how the dashes and dots are ordered. The information
in three adjacent rungs is "read" by a kind of RNA that hooks onto a
particular triad of rungs at one end and grabs a particular amino acid
at the other. Special triads say "start here" and "end here" and mark
off regions of the DNA molecule we call discrete genes. The eventual
result is a chain of amino acids that makes up a protein, with each
amino acid corresponding to a set of three rungs along the DNA molecule.
There are also genes that tell the cell when to turn on or turn off
another gene. The proteins produced may be structural or they may be
enzymes that facilitate chemical reactions in the body.
We now know that chromosomes are essentially DNA molecules. In an
advanced (eukaryotic) cell, these chromosomes appear as threadlike
structures packaged into a more or less central part of the cell, bound
by a membrane and called the nucleus. What is more important is that the
chromosomes in a body cell are arranged in pairs, one from the father
and one from the mother. Further, the code for a particular protein is
always on the same place on the same chromosome. This place, or
location, is called a locus (plural loci.)
There are generally a number of slightly different genes that code
for forms of the same protein, and fit into the same locus. Each of
these genes is called an allele. Each locus, then, will have one allele
from the mother and one from the father. How?
When an animal makes an egg or a sperm cell (gametes, collectively)
the cells go through a special kind of division process, resulting in a
gamete with only one copy of each chromosome. Unless two genes are very
close together on the same chromosome, the selection of which allele
winds up in a gamete is strictly random. Thus a dog who has one gene for
black pigment and one for brown pigment may produce a gamete which has a
gene for black pigment OR for brown pigment. If he's a male, 50% of the
sperm cells he produces will be B (black) and 50% will be brown (b).
When the sperm cell and an egg cell get together, a new cell is
created which once again has two of each chromosome in the nucleus. This
implies two alleles at each locus (or, in less technical terms, two
copies of each gene, one derived from the mother and one from the
father,) in the offspring. The new cell will divide repeatedly and
eventually create an animal ready for birth, the offspring of the two
parents. How does this combination of alleles affect the offspring?
There are several ways alleles can interact. In the example above, we
had two alleles, B for black and b for brown. If the animal has two
copies of B, it will be black. If it has one copy of B and one of b, it
will be just as black. Finally, if it has two copies of b, it will be
brown, like a chocolate Labrador. In this case we refer to B as dominant
to b and b as recessive to B. True dominance implies that the dog with
one B and one b cannot be distinguished from the dog with two B alleles.
Now, what happens when two black dogs are bred together?
We will use a diagram called a Punnett square. For our first few
examples, we will stick with the B locus, in which case there are two
possibilites for sperm (which we write across the top) and two for eggs
(which we write along the left side. Each cell then gets the sum of the
alleles in the egg and the sperm. To start out with a very simple case,
assume both parents are black not carrying brown, that is, they each
have two genes for black. We then have:
| |
B |
B |
| B |
BB (black) |
BB (black) |
| B |
BB (black) |
BB (black) |
All of the puppies are black if both parents are BB (pure for black.
Now suppose the sire is pure for black but the dam carries a
recessive gene for brown. In this case she can produce either black or
brown gametes, so
| |
B |
B |
| B |
BB (pure for black) |
BB (pure for black) |
| b |
Bb (black carrying brown) |
Bb (black carrying brown) |
This gives appoximately a 50% probability that any given puppy is
pure for black, and a 50% probability that it is black carrying brown.
All puppies appear black. We can get essentially the same diagram if the
sire is black carrying brown and the dam is pure for black. Now suppose
both parents are blacks carrying brown:
| |
B |
b |
| B |
BB (pure for black |
Bb (black carrying brown) |
| b |
Bb (black carrying brown) |
bb (brown) |
This time we get 25% probabilty of pure for black, 50% probability of
black carrying brown, and - a possible surprise if you don't realize the
brown gene is present in both parents - a 25% probability that a pup
will be brown. Note that only way to distinguish the pure for blacks
from the blacks carrying brown is test breeding or possibly DNA testing
- they all look black.
Another possible mating would be pure for black with brown:
| |
B |
B |
| b |
Bb (black carrying brown) |
Bb (black carrying brown) |
| b |
Bb (black carrying brown) |
Bb (black carrying brown) |
In this case, all the puppies will be black carrying brown.
Suppose one parent is black carrying brown and the other is brown:
| |
B |
b |
| b |
Bb (black carrying brown) |
bb (brown) |
| b |
Bb (black carrying brown) |
bb (brown) |
In this case, there is a 50% probability that a puppy will be black
carrying brown and a 50% probability that it will be brown.
Finally, look at what happens when brown is bred to brown:
| |
b |
b |
| b |
bb (brown) |
bb (brown) |
| b |
bb (brown) |
bb (brown) |
Recessive to recessive breeds true - all of the pups will be brown.
Note that a pure for black can come out of a mating with both parents
carrying brown, and that such a pure for black is just as pure for black
as one from ten generations of all black parentage. THERE IS NO MIXING
OF GENES. They remain intact through their various combinations, and B,
for instance, will be the same B no matter how often it has been paired
with brown. This, not the dominant-recessive relationship, is the real
heart of Mendelian genetics.
This type of dominant-recessive inheritance is common (and at times
frustrating if you are trying to breed out a recessive trait, as you
can't tell by looking which pups are pure for the dominant and which
have one dominant and one recessive gene.) Note that dominant to
dominant can produce recessive, but recessive to recessive can only
produce recessive. The results of a dominant to recessive breeding
depends on whether the dog that looks to be the dominant carries the
recessive. A dog that has one parent expressing the recessive gene, or
that produces a puppy that shows the recessive gene, has to be a carrier
of the recessive gene. Otherwise, you really don't know whether or not
you are dealing with a carrier, bar
genetic testing or test
breeding.
One more bit of terminology before we move on - an animal that has
matching alleles (BB or bb) is called
homozygous. An animal that has two different alleles at a locus (Bb)
is called heterozygous.
A pure dominant-recessive relationship between alleles implies that
the heterozygous state cannot be distinguished from the homozygous
dominant state. This is by no means the only possibility, and in fact as
DNA analysis advances, it may become rare. Even without such analysis,
however, there are many loci where three phenotypes (appearances) come
from two alleles. An example is merle in the dog. This is often treated
as a dominant, but in fact it is a type of inheritance in which there is
no clear dominant - recessive relationship. It is sometimes called
overdominance, if the heterozyote is the desired state. I prefer
incomplete dominance, recognising that in fact neither of the alleles is
truly dominant or recessive relative to the other.
As an example, we will consider merle. Merle is a diluting gene, not
really a color gene as such. If the major pigment is
eumelanin, a dog with two non-merle genes (mm) is the expected color
- black, liver, blue, tan-point, sable, recessive red. If the dog is Mm,
it has a mosaic appearance, with random patches of the expected
eumelanin pigment in full intensity against a background of diluted
eumelanin. Phaeomelanin (tan) shows little visual effect, though there
is a possibility that microscopic examination of the tan hair would show
some effect of M. Thus a black or black tan-point dog is a blue merle, a
brown or brown tan-point dog is red merle, and a sable dog is
sable
merle, though the last color, with phaeomelanin dominating, may be
indistinguishable from sable in an adult. (The effect of merle on
recessive red is unknown, and I can't think of a breed that has both
genes.) What makes this different from the black-brown situation is that
an MM dog is far more diluted than is an Mm dog. In those breeds with
white markings in the full-color state the MM dog is often almost
completely white with a few diluted patches, and has a considerable
probablity of being deaf, blind, and/or sterile. Even in the daschund,
which generally lacks white markings, the so-called double dapple (MM)
has extensive white markings and may have reduced eye size.
Photographs of Shelties with a number of combinations of merle with
other genes are available on this site, but the gene also occurs in
Australian Shepherds, Collies, Border Collies, Cardiganshire Welsh
Corgis, Beaucerons
(French herding breed), harlequin Great Danes, Catahoula leopard dogs,
and Daschunds, at the least.
Note that both of the extremes - normal color and double merle white
- breed true when mated to another of the same color, very much like the
Punnett squares above for the mating of two browns or two pure for
blacks. I will skip those two and go to the more interesting matings
involving merles.
First, consider a merle to merle mating. Remember both parents are
Mm, so we get:
| |
M |
m |
| M |
MM (sublethal double merle) |
Mm (merle) |
| m |
Mm (merle) |
mm (non-merle) |
Assuming that merle is the desired color, this predicts that each pup
has a 25% probability of inheriting the sublethal (and in most cases
undesirable by the breed standards) MM combination, only 50% will be the
desired merle color, and 25% will be acceptable full-color individuals.
(In fact there is some anecdotal evidence that MM puppies make up
somewhat less than 25% of the offspring of merle to merle breedings, but
we'll discuss that separately.) Merle, being a heterozygous color,
cannot breed true.
Merle to double merle would produce 50% double merle and is almost
never done intentionally. The Punnet square for this mating is:
| |
M |
M |
| M |
MM (sublethal double merle) |
MM (sublethal double merle) |
| m |
Mm (merle) |
Mm (merle) |
Merle to non-merle is the "safe" breeding, as it produces no MM
individuals:
| |
m |
m |
| M |
Mm (merle) |
Mm (merle) |
| m |
mm (non-merle) |
mm (non-merle) |
We get exactly the same probability of merle as in the merle to merle
breeding (50%) but all of the remaining pups are acceptable full-colored
individuals.
There is one other way to breed merles, which is in fact the only way
to get an all-merle litter. This is to breed a double merle (MM) to a
non-merle (mm). This breeding does not a use a merle as either parent,
but it produces all merle puppies. (The occasional exception will be
discussed elsewhere.) In this case,
| |
M |
M |
| m |
Mm (merle) |
Mm (merle) |
| m |
Mm (merle) |
Mm (merle |
The problem with this breeding is that it requires the breeder to
maintain a dog for breeding which in most cases cannot be shown and
which may be deaf or blind. Further, in order to get that one MM dog who
is fertile and of outstanding quality, a number of other MM pups will
probably have been destroyed, as an MM dog, without testing for vision
and hearing, is a poor prospect for a pet. In Shelties, the fact remains
that several double merles have made a definite contribution to the
breed. This does not change the fact that the safe breeding for a merle
is to a nonmerle.
Thus far, we have concentrated on single locus genes, with two
alleles to a locus. Even something as simple as coat color, however,
normally involves more than one locus, and it is quite possible to have
more than two alleles at a locus. What happens when
two or more
loci are involved in one coat color?
