Basic Genetics IV:
the relationship of genes to traits (single locus)
With the exception of the few DNA tests available, we cannot know the
genetic makeup of our dogs, only the physical makeup, or phenotype. We
tend to break that phenotype up into traits, some breed specific, some
more general. For instance, we might know that a Sheltie is 15" tall, a
black-nosed sable merle with full white collar, feet and Teletype and a
narrow face blaze, OFA good, is missing one premolar, has natural ears,
and had double rear decals. All of these "traits" are defined by human
beings. Very few of them actually refer to single genes that might be
inherited as dominant, recessive, incompletely dominant or co-dominant.
In some cases we can break down a trait into a specific combination
of genes. In the case of color, for instance, we know of a considerable
number of genes that affect color through specific processes. In some
cases, this knowledge has fed back on what we consider to be traits.
Thus in the case given, the dog is:
- Sable ay- (as opposed to black with or without
tan-point markings).
- Black (as opposed to brown) B-
- Merle Mm
- Irish-marked sisi or sisw
- Possibly a face-marking gene
In addition, the dog's color can be affected by minor genes (such as
the modifier genes determining how much of the dog is white) by random
factors (which probably influence the exact pattern of both white
spotting and the location of the dark patches in the merling) and by
environmental factors (such as uterine environment, nutrition or
excessive exposure to the sun.) The point is that very few of the traits
that humans have chosen are in fact due solely to the effect of a single
pair of alleles at a single locus. We have looked at some such simple
traits as regards
color.
However, the height of the dog, the ears, the hip rating, the missing
premolar, and the double rear decals are probably not single-gene
traits, but rely on the interaction of several pairs of genes, with
perhaps some influence from the environment.
In general I am using dominant, recessive, co-dominant or
intermediate to refer to genes at the same location on a single pair of
chromosomes, i.e., alleles at the same locus. There are cases where
genes at one locus can "hide" genes at another locus. An example in dogs
is recessive yellow, ee, in which recessive yellow, although a recessive
at its own locus, can hide whatever the dog carries at the A locus and
the proposed K (dominant black) locus. This type of relationship among
different loci is called epistatic. The locus that is hidden is referred
to as hypostatic. In some cases (e.g., E at the E locus) an epistatic
locus has an allele that allows the hypostatic locus to show its
effects.
We will consider a number of types of inheritance. The first group
actually refer to single-gene traits. Any of these types of inheritance
may also be involved in the inheritance of multiple-gene traits.
Single-locus inheritance
More complex inheritance will be covered on the next page, and
includes
- Modifier genes
- Polygenic additive
- Threshold traits
- Variable expression
- Incomplete penetrance
- Polygenic recessive or dominant
- Mixed polygenic
Dominant-recessive inheritance
Black and
brown provide a clear example of a dominant-recessive relationship
among alleles. Every dog has two genes at the black/brown locus. If both
genes are for black, or if one is for black and one is for brown, the
dog is black, most readily identified by nose color. If both genes are
for brown, the dog is brown, again most readily identified by nose
color. BB cannot be distinguished from Bb without genetic tests or
breeding tests.
Many genetic diseases, especially those that can be traced to an
inactive or wrongly active form of a particular protein, are inherited
in a simple recessive fashion. van Willebrand's disease (vWD) for
instance, is inherited as a simple recessive within the Shetland
Sheepdog breed.
Intermediate inheritance
Warning! Although this type of inheritance is common, it has a
variety of names (incomplete dominance and overdominance are two common
ones) some of which are also used for other things entirely. Here I will
use it to refer to the type of inheritance in which the animal carrying
two identical alleles shows one phenotype, the animal carrying two
different identical alleles shows a different phenotype, and the animal
carrying one copy of each of the alleles shows a third phenotype,
usually intermediate between the two extremes but clearly
distinguishable from either.
In dogs, merle color is a good example of this type of inheritance.
If we define M as merle and m as non-merle, we find we have three
genotypes:
- mm non-merle, with normal intense color
- Mm merle, with normal color diluted in a rather patchy fashion
- MM homozygous merle, extreme dilution, dog mostly white if a
white-spotting gene is also present, and often with anomalies in
hearing, vision and/or fertility.
Note that there is really a continuum between dominant-recessive and
intermediate inheritance. In Shetland Sheepdogs, for instance, sables
carrying one gene for tan-point have on average more dark shading than
dogs with two sable genes. However, the darkest shading on dogs pure for
sable is probably darker than the lightest shading on dogs carrying a
gene for tan-point. In practice, intermediate inheritance is often
treated as if it were a special case of dominant-recessive inheritance,
as can be seen by the symbols used for merle and non-merle - usually the
capital letter refers to a dominant gene and the lower-case letter
refers to a recessive gene. I think a separate name is justified because
it could be equally well argued that homozygous merle is an undesirable
recessive for which the merle color is a marker that the dog carries the
merle gene.
Many of the standard color genes normally treated as
dominant-recessive do in fact have intermediate inheritance, the
heterozygote generally much more similar to one homozygote than the
other, between at least some alleles in the series. Coat color gene loci
with at least some allele pairs leaning toward intermediate inheritance
include A (agouti, patterning of black and tan), C (color, intensity of
color), and S (white spotting). I suspect the same is true for T
(ticking), G (graying) and even D (dilution) if another diluting gene,
such as merle, is present. This may be much more generally true than is
recognized.
Co-dominant inheritance
The dividing line between intermediate inheritance and co-dominant
inheritance is fuzzy. Co-dominance is more likely to be used when
biochemistry is concerned, as in blood types. Co-dominance means that
both alleles at a locus are expressed. Co-domininance in X-linked genes
is a special case that will be treated under sex-linked inheritance.
Sex-limited autosomal inheritance
Please, don't confuse sex-limited inheritance with sex-linked
inheritance. They are two totally different things. Sex-linked
inheritance is discussed below. I do include sex-influenced traits under
the sex-limited heading, though some genetics texts separate
sex-influenced and sex-limited traits.
A classic example of a sex-limited trait in dogs is unilateral or
bilateral cryptorchidism, in which one or both testicles cannot be found
in their usual position in the scrotum. Since a bitch has no testicles,
she cannot be a cryptorchid - but she can carry the gene(s) for
cryptorchidism, and pass them to her sons. Likewise, genes affecting
milk production are not normally expressed in a male. The main problem
with sex-limited inheritance is that it is impossible to know even the
phenotypes of the unaffected sex in a pedigree, which makes it difficult
to determine the mode of inheritance.
In sex-influenced inheritance, the genes behave differently in the
two sexes, probably because the sex hormones provide different cellular
environments in males and females. A classic example in people is male
early-onset pattern baldness. The gene for baldness behaves as a
dominant in males but as a recessive in females. Heterozygous males are
bald and will pass the gene to about 50% of their offspring of either
sex. However, only the males will normally be bald unless the mother
also carries the pattern baldness gene without showing it (female
heterozygote.) If the mother is affected with baldness (homozygous) but
the father is not, all of the sons will be affected and all of the
daughters will be non-affected carriers. A bald man may get pattern
baldness from either parent; a bald woman must have received the gene
from both parents.
Sex-linked inheritance
In order to understand sex-linked traits, we must first understand
the genetic determination of sex. Every mammal has a number of paired
chromosomes, that are similar in appearance and line up with each other
during gamete production (sperm and eggs). In addition, each mammal has
two chromosomes that determine sex. These are generally called X and Y
in mammals. Normal pairing of chromosomes during the production of
gametes will put one or the other in each sperm or ovum.
In mammals, XY develops testicles which secrete male sex hormones and
the fetus develops into a male. An XX fetus develops into a female. Thus
sperm can be either X or Y; ova are always X. Sex linked inheritance
involves genes located on either the X or the Y chromosome. Females can
be homozygous or heterozygous for genes carried on the X chromosome;
males can only be hemizygous.
X-linked recessive:
The most common type of sex-linked inheritance involves genes on the
X chromosome which behave more or less as recessives. Females, having
two X chromosomes, have a good chance of having the normal gene on one
of the two. Males, however, have only one copy of the X chromosome - and
the Y chromosome does not carry many of the same genes as the X, so
there is no normal gene to counter the defective X.
An example of this type of inheritance is color blindness in human
beings. Using lower case letters for affecteds, we have
- Affected male: xY Color blind
- Non-affected males XY Normal color vision
- Affected female xx Color blind
- Carrier female xX Normal color vision
- Clear female XX. Normal color vision
Now the possible matings:
xY to xx (both parents affected) xx females and xY males, all
offspring affected.
xY to Xx (affected father, carrier mother) half the females will be
xX and carriers, half will be xx and affected. Half the males will be XY
and clear, half will be xY and affected.
xY to XX (affected father, clear mother) all male offspring XY clear,
all daughters Xx carriers.
Note that the daughters of an affected male are obligate carriers or
affected. The unaffected sons of an affected male cannot carry the
problem.
XY to xx (father clear, mother affected) xY males (affected) and xX
daughters (carriers.)
XY to Xx (father clear, mother carrier) half the males affected (xY)
and half clear (XY); half females clear (XX) and half carriers (Xx)
XY to XX (father and mother both genetic clears) all offspring clear.
Note that all female offspring of affected males are obligate
carriers (if not affected.) Likewise, any female who has an affected son
is a carrier. Non-affected sons of affected fathers are genetically
clear.
This type of inheritance may be complicated by the sublethal effect
of some X-linked genes. Hemophilia A in many mammals (including dogs and
people) is a severe bleeding disorder inherited just like the
color-blindness above. Many affected individuals will die before
breeding, but for those who are kept alive and bred for other
outstanding traits, non-affected sons will not have or produce the
disease. All daughters, however, will be carriers.
X-linked dominant:
Here I will use X+ for the dominant gene on the X
chromosome, and X for the gene on the normal X chromosome. The actual
possibilities are similar to those for an X-linked recessive, except
that X+X females are now affected. In X-linked dominant
inheritance, more females than males will show the trait. Possible
matings are:
Affected to homozygous affected (X+Y to X+X+):
All offspring affected.
Affected to heterozygous affected (X+Y to X+X):
All daughters affected; half of sons affected.
Affected to homozygous normal (unaffected female): (X+Y to
XX): All daughters affected, all sons normal.
Normal to homozygous affected (XY to X+X+): all
offspring affected, but daughters are heterozygous affected.
Normal to heterozygous affected: (XY to X+X): Half of
offspring affected, regardless of sex. Affected daughters are
heterozygous.
Normal to normal (XY to XX) all offspring clear.
X-linked co-dominant:
Mammalian cells, even in females, get along fine with just one X
chromosome. In fact, more than one X chromosome within a cell seems to
be a problem if both are active. So in female cells, one or the other X
chromosome must be inactivated. This occurs more or less at random, so
any female mammal has patches of cells with one X chromosome
inactivated, and patches with the other not active. If the gene being
discussed codes for an enzyme that is spread throughout the body, it may
not be obvious that the different patches of cells are behaving
differently, and we will get what looks like dominant, recessive, or
intermediate inheritance.
However, if the gene is expressed directly within the cell, the
mosaic nature of the female may become obvious. The tortoiseshell cat
provides an excellent example of this.
In cats, the orange color is on the X chromosome. It is designated as
O, and the "wild-type" gene that allows black (eumelanin) to appear in
the coat is designated +. Note that a cat homozygous or hemizygous
(male) for + may be solid or tabby with the eumelanin pigment showing
only in the tabby stripes, ticks and blotches (in extreme cases only on
the tips of the hairs) and the "black" may just as well be chocolate or
blue. A cat with only O genes will be some shade from cream to deep
red., with no black/blue/chocolate pigment in the coat, but usually with
tabby markings.
However, a cat with the gene for orange on one X chromosome and the
gene for non-orange on the other is neither orange nor non-orange, but
has patches of both colors. This color is known as tortoiseshell, and I
am going to use the broad definition, including blue/cream or
chocolate/yellow tortoiseshells. Most of the time cats with two X
chromosomes are female, and since two X-chromosomes are required for
tortoiseshell, most tortoiseshell cats are female.
Now and then a cell does not divide properly when it is making a germ
cell, and you might, for instance, get an XY sperm cell. This would
produce an XXY male, which would look male (he has a Y chromosome) but
also have two versions of X and thus could be a tortoiseshell. However,
the XXY makeup, corresponding to Klinefelter's syndrome in human beings,
is believed to produce sterility. A similar syndrome involving females
with only one X chromosome but no Y is called Turner's syndrome in human
women, and again appears to produce sterility. We will therefore
consider only matings between animals with two sex chromosomes.
Non-orange male to non-orange female (+ to ++): all non-orange
offspring.
Non-orange male to tortoiseshell female (+ to +O): Males 50% orange
and 50% non-orange; females 50% non-orange and 50% tortoiseshell.
Non-orange male to orange female (+ to OO): all males orange; all
females tortoiseshell.
Orange male to non-orange female (O to ++): All males non-orange; all
females tortoiseshell.
Orange male to tortoiseshell female (O to O+): males 50% orange and
50% non-orange; females 50% orange and 50% tortoiseshell.
Orange male to orange female (O to OO): All offspring orange.
Y-linked inheritance:
The Y chromosome in most species is very short with very few genes
other than those that determine maleness. Y-linked inheritance would
show sons the same as their fathers, with no effect from the mother or
in daughters. In humans, hairy ears appear to be inherited through the Y
chromosome. Padgett does not list any known problem in dogs as being
Y-linked.
