A Detailed Examination of Coat Color Genetics
in the Labrador Retriever
Why do yellow Labs have variations
of shading? What causes the fox-red
color in yellow Labs? Why do some
Labs have white spots on their
chests? What causes some Labs to
have white at the base of the hair
shafts on their tails? Why do many
Labs develop gray hairs as they get
older? The answers to these
questions and many others pertaining
to coat color can be found in the
canine genes that influence
production of pigment, also known as
melanin. These same genes determine
the black, chocolate or yellow coat
color found in the Labrador breed,
however, to address these former
questions, one must explore beyond
the genes responsible for simple
solid coloration. The following
article presents a detailed
examination into the factors
responsible for inheritance of coat
color including an explanation of
the modifying genes responsible for
unique coat-color attributes.
DNA... Chromosomes... Genes:
The Ancestral Legacy
In 1944, experiments conducted by
Oswald Avery and colleagues
identified DNA (deoxyribonucleic
acid) as the material in the cell
responsible for carrying genetic
information. Thereafter, DNA was
aptly referred to as "the thread of
life." The sequences of nucleotides,
small molecules linked together that
form two complimentary chains to
compose the native double-helix form
of the DNA molecule, are responsible
for encoding specific proteins
required for many cellular functions.
These proteins are critical for
proper function for organs that, in
turn, are required for the normal
function and life of the whole
organism.
In canine somatic cells-- cells
responsible for composing the
body--, the DNA is packaged into 78
chromosomes. Thirty-nine of the
chromosomes contain DNA passed on,
or inherited, from the sire's germ
cell (sperm) and the other 39
contain DNA inherited from the dam's
germ cell (egg). Each chromosome,
therefore, has a partner-chromosome
inherited from the other parent so
that the 78 chromosomes form 39
pairs. Germ cells differ from
somatic cells in that they have
divided through a process known as
meiosis. As a result of meiosis,
each germ cell receives one of the
partner-chromosomes so that it has
one chromosome of each type.
Meiosis, therefore, provides the
means by which offspring may inherit
genetic information from each parent,
while maintaining the same number of
chromosomes in its somatic cells as
found in the somatic cells of each
parent and in other individuals
within its species.
When germ cells fuse during
fertilization they produce a single
somatic cell from which the
offspring will develop. This somatic
cell will divide to produce more
cells by the process of mitosis.
During mitosis, before a somatic
cell divides, each chromosome will
be duplicated so that a canine cell
just prior to dividing will have 156
chromosomes (or 78 chromosome pairs).
When the somatic cell divides, each
new cell will have the same amount
of genetic information as the former
cell. Mitosis, therefore, provides
the means for a single fertilized
cell to develop into a whole
organism, while maintaining the same
chromosome number and amount of
genetic information in each cell
throughout the body.
Composing each of the chromosomes,
the DNA for encoding specific
proteins that are responsible for
producing individual genetic traits,
or characteristics, are called
genes. Each gene encoding a specific
protein is located at a particular
site on the chromosome called a gene
locus. The location of the gene
locus for a trait on one chromosome
will match the location of the gene
locus for that same trait on its
partner-chromosome. However,
although the location of a gene
locus is identical for each partner-chromosome,
the nucleotide sequence of the gene
may be different on each of the two
paired-chromosomes. When this occurs
and the nucleotide sequence of the
DNA to encode a specific protein is
altered, a condition referred to as
a mutation, the resulting protein
may physically and functionally
differ from the normal protein. For
this reason, because more than one
nucleotide sequence of a gene may be
present at a gene locus on partner-chromosomes,
alternate sequences controlling one
particular trait are referred to as
alleles.
Offspring may inherit the same
allele at a particular gene locus
from each parent. In such an
instance, the offspring is
considered homozygous for the
particular trait governed by that
gene locus. Alternatively, offspring
may inherit one allele from one
parent but a different allele from
the other parent. In this instance,
the offspring is considered
heterozygous for the particular
trait. When offspring are
heterozygous at a particular gene
locus, often the characteristic of
only one of the alleles will be
expressed by the offspring. In such
an instance, the allele that results
in expression of the trait is
considered dominant over the other
allele which is considered recessive.
A simple example of dominant and
recessive alleles, respectively, in
Labrador coat color genetics are the
"B" allele for expression of black
and the "b" allele for expression of
chocolate. Black Labradors may be
homozygous for black (BB) or
heterozygous (Bb). In the latter
instance, the dog carries an allele
for the chocolate coloration, but
its expression is masked by the
dominant allele for black.
Heterozygous Labs may produce
chocolate offspring only if they are
bred to another heterozygous Lab or
a Lab homozygous for the recessive
"b" (i.e. a chocolate Lab). For a
Labrador to appear chocolate, it
must inherit the "b" allele from
both parents.
The Basis of Dominant and
Recessive Alleles
Though many individuals are familiar
with the terms dominant and
recessive, some, if not most of
these individuals are unaware of the
underlying mechanisms that make some
alleles dominant and others
recessive. To understand these
mechanisms, one must go back to the
DNA sequence of the gene.
The DNA of each gene locus is
responsible for producing a single
protein. As mentioned earlier, DNA
is composed of molecules called
nucleotides. When these nucleotides
are arranged in specific order they
encode for amino acids, which are
molecules that make up proteins. The
sequence of amino acids, in turn,
will determine protein structure and
function. Therefore, for normal
cellular function, the correct
sequence of DNA all the way through
to the sequence of amino acids must
be conserved. When mutations occur
in the DNA nucleotide sequence, the
resulting amino acid sequence may be
altered. As a result, the protein
for that gene locus will either not
be produced, or will be different
from the normal protein. In the
latter instance, the alternate
protein may function adequately but
produce some physiological changes
not seen in the presence of the
normal protein. Therefore, different
alleles occur as a result of
mutations in the DNA for a
particular gene locus.
In many cases, recessive alleles are
those that produce no protein. In
other cases or in cases where there
are more than two possible alleles
for a gene locus (discussed below)
usually there is a rank order of
dominance. In such an instance, the
DNA mutation results in a structural
change in the protein that
influences its reactivity. Put more
simply, those alleles that produce
proteins with the greater capacity
to function will be more dominant to
alleles that produce weakly-functional
or non-functional proteins.
Therefore, in the case of a
heterozygous (Bb) black Lab, the
black producing allele produces a
protein that functions more
efficiently than the protein encoded
by the chocolate producing allele.
Melanin: one molecule, many
shades of coat color
Despite the fact that the B locus on
a chromosome may be occupied by
either the "B" or the "b" allele,
the same molecule responsible for
the black coloration in the Lab is
also responsible for the chocolate
coloration. Melanin, or pigment
molecules, are produced by and
packaged into small organelles
called melanosomes. Within the
melanosomes are enzymes called
tyrosinase, which are proteins
needed to make melanin from
molecules called tyrosine, and
structural matrixes upon which the
melanin is organized after it is
made. The actual color of the
melanosomes is determined by the
amount of melanin it contains.
Melanosomes are produced by
specialized cells called melanocytes.
Melanocytes are distributed
throughout various areas of the body
including the eyes, the hair, and
the skin where they transfer the
melanosomes into the cells that
compose these structures. Color of
each structure will be determined by
both the color of the melanosomes it
contains as well as the distribution
of the melanosomes within its cells.
In hair comprising the coat of dogs,
two types of melanin have been found.
Eumelanin is responsible for black/brown
pigment, and phaeomelanin is
responsible for red/yellow pigment.
Phaeomelanin is formed by a
modification of the pathway that
leads to production of eumelanin
from tyrosine. It is important to
know that phaeomelanin has only been
found in cells composing hair and
not in cells composing the skin. In
Labs, eumelanin and phaeomelanin
production are controlled by the E
locus. The protein product of other
gene loci will determine the level
of pigment expression. For example,
in the instance of black versus
chocolate coat color, color
appearance is actually determined by
the B locus. The B locus controls
pigment not by controlling changes
in the actual eumelanin molecule,
but rather by controlling number,
size, and pattern of the
distribution of melanosomes in the
hair shafts. Therefore, Labs that
are homozygous for black at the B
locus have large eumelanin-producing
melanosomes that are evenly and
densely packed throughout the hair
shaft. Labs that are homozygous for
chocolate have melanomsomes that are
less tightly packed into the hair
shaft.
The Function of the E Locus
and the A Locus in the Labrador
Retriever
The E gene locus in Labs determines
whether the dog will be black/brown
(eumelanin) or red/yellow (phaeomelanin).
This locus encodes the melanocyte
stimulating hormone receptor (a.k.a.
the melanocortin 1 receptor; Mc1r).
Labs that are homozygous for the
dominant E allele have a
constitutively active, mutant form
of Mc1r; that is, the receptor is
always "turned-on", even in the
absence of melanocyte stimulating
hormone (MSH). As such, eumelanin is
constantly produced and the dog
appears black or chocolate. Labs
that are homozygous for the
recessive "e" allele also have a
mutant form of Mc1r. This mutant,
however, is a "loss of function"
receptor that cannot produce
eumelanin, even in the presence of
MSH. Therefore, Labs that are
homozygous for the "e" allele can
only produce phaeomelanin and,
therefore, will appear yellow.
In some other breeds, the Agouti
locus is responsible for determining
yellow color. Some of the recessive
agouti alleles produce molecules
that inhibit the activation of Mc1r
by interfering with binding of MSH
to the receptor. In these dogs, Mc1r
is a normal receptor type (called
wild-type; E+); that is, it will
only produce eumelanin when
activated by MSH and will only
produce phaeomelanin when the
receptor is inhibited. As such,
these breeds often display a
combination of black as well as tan
(yellow) coloring resulting from
production of both eumelanin and
phaeomelanin. The Agouti genes are
often ignored in the Labrador with
most writers stating that all Labs
are As at the agouti locus. This
information is based solely on the
observation that agouti will cause
both black and tan banding of the
hair shaft and since the black
banding is not present in Labs, Labs
must be As (the allele that encodes
the agouti suppressor). This
argument, however, fails to take
into consideration the presence of
the mutant "loss of function"
receptor in yellow Labs compared to
these other breeds. The Mc1r in
yellow Labs is unable to produce
eumelanin pigment under any
circumstances. Instead, the effects
of the recessive Agouti alleles in
yellow Labs cause banding of
phaeomelanin pigment in the hair
shafts and as a result, provides the
shading effects observed in yellow
Labs. Conversely, agouti has no
effect on the black/chocolate Lab
because Mc1r is always turned on in
black/chocolate Labradors, even in
the absence of MSH. Therefore, the
recessive Agouti alleles will have
no effect on the black/chocolate
coloration. It is for this reason
that one only observes the effects
of the Agouti alleles in the yellow
Labrador. If the yellow Lab carries
the dominant Agouti supressor gene,
As, phaeomelanin production will be
inhibited, and since eumelanin
cannot be made, the dog will appear
very pale yellow (nearly white). In
contrast, ay or as agouti will
inhibit MSH from binding to the
receptor and phaeomelanin production
will increase.
Some Agouti alleles, such as as,
also produce pigmentation patterns
that result in more phaeomelanin
production on the the dog's back and
less phaeomelanin production on the
dog's belly. Interestingly, the as
allele was not originally proposed
by C.C. Little but was later
introduced to explain an allele that
would encode for the phaeomelanin
saddling effect in some breeds that
only have tan pigmentation variation
on the back and stomach, as opposed
to the black and tan saddling effect
caused by the at allele in some
other breeds. At that point in time
that the as was proposed, the
prospect of the "loss of function"
receptor ("e") had not been explored.
However, the aw allele (the "white-bellied"
allele) was identified as
influencing the expression of Agouti
at different concentrations in
different locations of the body.
Primarily, dogs carrying aw express
more agouti protein (for expression
of phaeomelanin) on the dorsal
surface (the back) and less agouti
is produced on the ventral surface (the
stomach). The result of aw in a Lab
homozygous "e" at the Extension
Locus would have the same effect as
the proposed as. Therefore, it is
possible that as and aw are one and
the same allele but expressed
differently dependent on whether the
breed carries the mutant "E" allele
(for eumelanin production only), the
"E+" allele (for normal expression/inhibition
of eumelanin) or is homozygous for
the "e" allele (loss of function
receptor/phaeomelanin only). Further
modification of phaeomelanin
intensity (concentration) will be
determined by the products of the C
locus which control levels of
tyrosinase, an enzyme required in
the process of pigment synthesis
which preferentially acts upon
phaeomelanin. The dominant C allele
encodes higher levels of tyrosinase
resulting in full intensity of red
pigment. Other less dominant alleles
encode for less tyrosinase and have
the effect of diluting the red
pigment to yellow.
Getting Down to Business: The Gene
Loci for Canine Coat Color and their
Many Alleles
The American Kennel Club
acknowledges only three coat colors
for the Labrador Retriever breed:
black, chocolate, or yellow. The
actual color appearance of the dog
is said to be its phenotype.
Simplistically, however, there are
at least nine combinations of
alleles just to determine which of
the three colors the Lab will
appear. This combination of genes is
referred to as the genotype.
In the canine, geneticists studying
coat color have proposed that there
are eleven gene loci controlling
coloration. Additionally, each of
these loci have multiple alleles.
Many Lab breeders and enthusiasts
are familiar with the standard
method for indicating a Lab's
genotype by use of the B/b, E/e
nomenclature (refer to A Guide To
Coat Color Inheritance In the
Labrador Retriever). This standard
form indicates only the gene loci
responsible for producing the black
or chocolate coloration (the B
locus) and the yellow coloration
(the E locus). For the most part,
this system is adequate to predict
the expression of simple color
traits in offspring produced by two
Labs. However, when one wishes to
understand more about variations in
color intensity or shading within
yellows, or the reason for other
coat phenotypes that may occur less
commonly in Labs, analysis of the
other gene loci are required. These
other gene loci are the sites for
producing modifiers of coat color;
that is, their protein products may
alter the size and synthesis of
melanin (modifiers) or influence the
distribution of melanocytes
(distributors) to bring about color
patterns.
The following table indicates the
eleven gene loci and their
respective alleles currently
accepted as influencing coat color
in canines and whether or not they
influence phenotypes of the Lab.
The Yellow Labrador Retriever: A
Model for Discerning Effects of Gene
Loci other than "B"
The E locus and its "e" allele
encodes the mutant receptor that can
only produce phaeomelanin (red
pigment as observed in the Irish
Setter). The product of the A locus
and the C locus will determine the
location and extent to which this
red pigment is diluted to yellow.
Therefore, although the "e" allele
provides the basis by which the
yellow color is apparent, the actual
yellow appearance is dependent on
the alleles present at both the A
locus and the C locus.
Fox-reds
Breeders of "true fox reds" will
quickly point out that some yellow
Labs professed to be "fox-red" are
really more dark tan than red and
are therefore, not "true fox-reds".
The difference in concentration of
red color (determined by the "ay" or
"as" allele of the A locus) is
dependent upon the alleles at the C
locus. The "C" allele allows for
full expression and intensity of red
tones, while the "cch" allele will
dilute the red to a clear tan color.
Therefore, the genotype of each
color variation is:
ay_B_ C_ee = True Fox-Red
as_B_C_ee * = True Fox-Red with
Saddling**
ay_B_ cch _ee = Pseudo Fox-Red
as_B_cch_ee = Pseudo Fox-Red with
Saddling**
* the underline denotes that the
gene locus may be homozygous or
heterozygous with a less dominant
allele present at the
partner-chromosome gene locus
** Labs with this genotype
demonstrate the red coloring
localized to certain areas of the
body.
The "as" allele produces the
"saddling effects" seen in many
yellows in which there appears
darker yellow pigmentation on the
back,
ears, legs, etc. compared to areas
of light yellow on the shoulders,
neck, and underside. The "as" allele
also increases intensity of
phaeomelanin, but restricts its
production to the former mentioned
areas on the Lab.
The observation that there appears
to be no solid fox-red or solid
"pseudo" fox-red Labs may be
explained by Little's hypothesis
that the combination of an "ay" in a
homozygous "e" (yellow) dog is
lethal. If Little's hypothesis is
correct, then this would mean that
all fox-red or "pseudo" fox-red Labs
must be: as_B_C_ee or as_B_cch_ee,
respectively.
Medium to light shades of
Yellow
Medium yellow is probably the most
common yellow coloration observed in
Labs. The ranges in the shades of
the yellow coloration, however, can
be quite extensive. Medium yellows,
listed from darkest to lightest, are
produced by the following genotype
combinations:
AsasB_ C_ee
AsasB_ cch_ee
AsAsB_ C_ee
AsAsB_ cch_ee
Those yellows heterozygous "As" "as"
will produce less phaeomelanin
because the As allele encodes a
phaeomelanin suppressor. However,
the alleles of the A locus are
incompletely dominant, so some
phaeomelanin will be produced
because of the as allele. The
phaeomelanin intensity will be
further controlled by the "C" locus,
hence the intensity of the yellow
may be stronger in these
heterozygotes carrying the "C"
allele and lighter in those carrying
the "cch". The homozygous "As" Labs
do not produce red pigment at all
because the suppressor will
completely block phaeomelanin
production by the mutant Mc1r
encoded by the homozygous "e"
allele. As a result, the coat will
appear a cream color and will appear
almost white if the "cch" allele is
the most dominant allele at the C
locus. Additionally, Labs homozygous
"As" will show an even distribution
of yellow color devoid of shading.
The "White" Form of Yellow
Although the "white" color is
considered by most Lab breeders to
be a very light shade of yellow,
this color may be quite distinct
from the yellow shade that may
represent cream-colored yellows
represented as genotype [As_B_
cch_ee] above. In fact, the "white"
color may be represented by another
allele that may be found at the C
locus. The "cd" allele is
responsible for producing white hair
in other breeds of dogs, like the
West Highland White Terrier, while
allowing full expression of dark
nose and eye pigment. Though this
white color may be distinct from the
yellow coloration, it should still
be grouped with the other yellow
variations since its expression is
also controlled by both the E and C
loci.
Black Puppies Produced from
Two Yellow Parents?...Or From Two
Chocolate Parents?..."Impossible!"
You Say?...Maybe Not!...
Geneticists recognize that there are
two gene loci that are capable of
controlling production of the yellow
color in the dog. In Labradors,
homozygous "e" at the Extension loci
is considered the predominant
genotype for producing yellow.
However, in some other breeds,
homozygous "ay" at the Agouti loci
is recognized as being responsible
for producing the yellow (tan/sable)
color in dogs with the wild-type
(E+) Mc1r, such as in the Basenji,
Collie, Dachshund, etc.
The yellow (buff) color of the
Cocker Spaniel was once believed
only to be determined by homozygous
"e" just as in the Labrador.
Interestingly, however, upon
occasion when two yellow Cocker
Spaniels are bred, a black puppy
will be produced. This observation
was first made by Clarence Little in
1957 and later confirmed by Burns
and Fraser in 1966. Because these
test breedings were controlled
studies, the possibility of
mismating as an explanation was
ruled out and a new hypothesis was
postulated: There are two kinds of
"yellow" Cocker Spaniels, an
AsAsB_ee Cocker Spaniel that is
usually buff-colored and an
ayayB_E+E+ Cocker Spaniel that is
usually sable-colored. When these
genotypes are crossed, one possible
resulting genotype of the offspring
will be AsayB_E+e: a black Cocker
Spaniel!
This scenario may not be limited to
the Cocker Spaniel breed.
Occasionally, black puppies are
produced from yellow Lab X yellow
Lab crosses. Some Lab breeders
immediately cry "mismating",
however, mismating is clearly not
the only explanation since many
times mismating is ruled-out by
virtue of circumstance (ie. the
bitch was exposed only to the
intended stud and there was no
opportunity for breeding to occur
with any other male). In addition to
what has been observed for the
Cocker Spaniel, there may be
additional indications supporting
this theory. One author has
suggested that the way to
distinguish between a homozygous "e"
yellow and a homozygous "ay" yellow
is to examine the whiskers: If the
whiskers are cream or straw colored
the dog is homozygous "e", if the
whiskers are black then the dog is
homozygous "ay" (refer to: "Canine
Color Genetics" by Sue Ann Bowling).
It is possible that like the Cocker
Spaniel breed, the Labrador has two
genotypic "kinds" of yellow dog: one
that is homozygous "e" (more common)
and one that is homozygous "ay"
(less common) with the wild-type
Mc1r (E+). As such, crossing these
two different genotypic types of
yellow Lab could produce an
occasional black puppy from two
yellow parents. This may also
explain why occasionally a black
puppy is whelped in litters from a
chocolate to chocolate cross. It is
also conceivable that some of these
ayay Labs, especially if they are
homozygous "C" at the C locus may
appear to be chocolates rather than
yellows (albeit with a more red-tone
than a brown tone). As such,
crossing of one of these
chocolate-appearing yellow Labs with
a true chococlate would produce
AsayBbEE+: a black Lab.
While on the Subject of
Yellow Labs…
Why is it that the yellow Labs' ears
are always darker than their bodies,
even when they have no shading on
their bodies? And what causes the
noses of yellow Labs to fade during
winter months?
The answers to both these questions
can be found by examining the
tyrosinase enzymes responsible for
producing melanin from tyrosine.
Some forms of these enzymes are
temperature-unstable mutants that
only produce melanins under ideal
temperature conditions. Some
tyrosinase enzymes work more
efficiently in colder temperatures.
Extremities, like the ears, are
usually a cooler temperature than
other parts of the body and as a
result, the tyrosinase is able to
produce more pigment in this region.
Conversely, the tyrosinase enzyme
responsible for producing the dark
nose pigment in yellows is unstable
at low temperatures. Under
conditions of low temperature, the
tyrosinase enzyme stops driving the
chemical reaction, and tyrosine
conversion to eumelanin in the skin
will occur at a much slower rate. As
a result, pigment will fade.
Though certain drugs may also
produce pigment fading, this latter
cause for reduction in pigment
occurs because these drugs will bind
to dopa (an early precursor to
melanin in the reaction from
tyrosine to melanin) and inhibit the
further chemical reactions that
result in melanin. This condition
will also cause fading of pigment in
the Lab.
Unique Variations Occurring
in Labrador Coat Color
The E+ allele: Enter the Potential
for a "Gain of Function" Mutation in
the "e" allele of the Extension
Locus
Color oddities have occurred
occasionally throughout the breed
history of the Labrador Retriever.
Such variations on the typical
black, chocolate or yellow coloring
have included but are not limited to
black-and-tan points, brindling, and
silver-casting. It is important to
recall that during the early and
perhaps mid-history of the breed,
interbreeding with other breeds
occurred. Crossbreeding to breeds
that carry the "wild-type" extension
allele (E+) as well as the
possibility of a spontaneous
mutation resulting in a "gain of
function" (also denoted E+) of the
Mc1 receptor encoded by the
recessive "e" allele, may be
possible explanations for color
oddities occurring in the breed.
The E+ allele (whether wild-type or
"gain of function") would encode a
normal, functional Mc1 receptor that
would be under greater influence of
the alleles at the Agouti (A) locus.
Unlike the E allele mutant found
normally in Labs that does not
require activation by MSH to produce
eumelanin (and therefore is always
"turned-on" producing black or brown
pigment), the Mc1 receptor encoded
by E+ would be dependent upon MSH
for production of eumelanin
(black/brown pigment). Homozygous E+
would allow the effects of the
Agouti locus that would otherwise
not be seen in a Lab carrying the
typical mutant "E" allele (in the
typical Lab, effects of Agouti are
only seen if the dog is homozygous
"e"). Therefore, a Lab that is
homozygous E+ would also have to
carry As to appear solid black (or
chocolate dependent on the allele at
the B locus). If a recessive allele
(ay, at or as) were the most
dominant allele at the A locus, then
the Lab would appear either
red/yellow (ay or as) or
black-and-tan (at). Other Agouti
alleles such as aw (which is
attributed to producing silver in
some breeds) may also be observed.
Labs having Tan Points
Early breeding records indicate that
a Labrador puppy with tan points on
the ears, muzzle, and above the eyes
(as found in the Doberman and
Rottweiler) would occasionally be
whelped to pure-bred Labrador
parents. Breeders attributed this to
previous interbreeding of Labradors
with Gordon Setters during the early
history of the breed. Because this
trait was considered undesirable as
a characteristic of the breed,
breeders chose not to breed
individuals expressing the trait in
hopes of reducing frequency of its
expression in future offspring.
Today, it is recognized that tan
points are controlled by the "at"
allele of the A locus and that it is
recessive to most of the alleles
found at the A locus of Labs.
Because this allele is recessive, it
may be passed through many
generations before a breeder is
aware that the allele is present. In
order for the allele to be
expressed, a carrier would have to
be bred to another carrier of this
same allele and both parents would
have to be carriers of the wild-type
(E+) Mc1 receptor. This explains the
low frequency of expression of this
trait in the current Labrador
population.
Brindling Effects And
"Mosaics" in Labs
Brindling describes alternating
expression of black and red color in
the hair throughout the coat. There
are several possible causes for this
fault that occasionally appears in
Labs. One cause may be attributed to
the "ebr" allele that controls
brindling in many other breeds of
dogs. For expression of this trait,
both sire and dam would have to
carry the mutant "ebr" allele, which
is recessive to the "E" allele, but
more dominant than the mutant "e"
allele for yellow.
Alternatively, brindling in Labs may
be the result of what geneticists
call a mosaic. A mosaic indicates
differences in the somatic tissue of
heterozygotes that come about during
mitotic division of somatic cells
(recall from above that somatic
cells are those that make-up the
body). There are two possible ways
by which an individual may become a
mosaic. The first is called
chromosome nondisjunction by which
during division into daughter cells,
one of the chromosomes fails to
separate from its duplicated
chromosome. As a result, one
daughter cell receives an extra
chromosome and the other receives an
unpartnered-chromosome.
The second way that a mosaic may be
produced is called chromosome loss
by which the chromosome containing
the dominant allele gets left behind
when the daughter cell's nucleus
reconstitutes.
In either situation described above,
the daughter cells of these altered
somatic cells will contain the same
alterations. As a result, one will
observe a mosaic or brindled pattern
of normal color mixed with color
produced by the altered somatic
cells. This condition has been
reported in a Lab showing mosaic
black and yellow coat color. When
this Lab was bred to other Labs of
normal coat colors of black,
chocolate, or yellow, it was
determined that the variation in
color was not due to a mutated E
locus allele (like the "ebr" allele)
because none of the offspring
demonstrated this phenotype. Rather,
this coat characteristic was
attributed to a chromosomal
alteration as described above.
Therefore, the brindling phenotype
rarely observed in Labs might be the
result of a stable allele mutation
(such as the "ebr" allele), or a
random somatic chromosome mutation
involving the E or B loci. To view
an example of a mosaic occurring as
a result of a random somatic
chromosome mutation involving the E
locus in the Labrador Retriever
click here.
Silver Labs
The silver coat color in Labradors
has gained much attention recently
and is a very controversial topic
(see The Labrador Coat Color
Controversy: Do Silver Labs Really
Exist?). Reasons for the controversy
stem from the lack of information
available to trace the origins of
this color in the breed as well as
the fact that the AKC standard for
the Labrador breed does not
acknowledge silver as an acceptable
color for a Lab. Some breed
enthusiasts consider the silver
coloration to be a sign of impurity
of the bloodline, however, what
geneticists have come to understand
of recessive alleles is that they
may be passed through many
generations going undetected, such
as the allele for tan points
discussed above.
The range observed in silver
coloration suggests that silver
occurs through a modifying gene.
There have been several possible
outcomes observed for the silver
Lab:
Black Lab + silver modifier =
charcoal gray coat with a
"sparkly"-like appearance. Nose:
dark gray; Eyes: dark to light gray
Chocolate Lab + silver modifier =
"mousy"-brown gray coat. Nose: same
as coat; Eyes: yellow to gray-yellow
Yellow Lab + silver modifier =
platinum to pale silver (yellow with
gray casting). Ears: gray (instead
of red-toned); Nose: dark to pale
gray; Eyes: dark to pale gray.
There are several possible
explanations for the silver coat
color in Labs. The first explanation
would attribute this rare color in
the breed to the D locus. Recall
that the alleles of the D locus
modify the color determined by the B
locus. Therefore, if a dog is
homozygous or heterozygous for black
at the B locus, presence of
homozygous recessive "d" at the D
locus would dilute the black pigment
to appear blue. Alternatively, if a
dog is homozygous for chocolate at
the B locus, presence of homozygous
recessive "d" at the D locus would
dilute the chocolate pigment to
appear silver. The absence of the
corresponding "blue" phenotype in
the breed, however, would seem to
argue against this explanation.
Another explanation for silver coat
color in Labs would attribute this
color to the C locus. There is an
allele mutant at the C locus that
has been determined to cause silver
coat color and blue eyes in dogs.
The "cb" allele is believed to be a
type of albinism. Since alleles at
the C locus influence red pigment
only, effects of the "cb" allele
should only be observed in dogs
homozygous "e" at the E locus.
Therefore, a silver Lab would not
only have to receive the yellow
allele from both parents, but also
receive the silver allele from both
parents (which is recessive to the
common "cch" allele). This allele
would explain the silver-toned
modification of coat observed in
yellow Labs in the presence of the
recessive "e" allele, however it
would not explain the eumelanin
modification in the black or
chocolate-based silvers (since the C
locus alleles primarily dilute
phaeomelanin).
Likewise, the possibility of a
"partial loss of function" mutation
that may have occurred in the
dominant "E" allele resulting in
muted tones of eumelanin would not
explain the modification of
phaeomelanin (yellow).
An alternative explanation for
explaining the modification of both
eumelanin and phaeomelanin again
returns to the
wild-type/gain-of-function "E+"
allele that encodes for a normal
functioning Mc1 receptor. If this
allele either occurred as a
spontaneous mutation or was
introduced into the breed through
interbreeding, this might explain
the modification occurring in all
three colors, particularly when one
considers the following:
When one traces the pedigrees of
some silver Labs, one finds a
history of other color oddities
occurring in some related bloodlines
to the silver Labs. Occurrences of
"black-casting" in chocolates, muted
chocolate coloration ("card-board
box" coloring), as well as the
occasional occurrence of black
puppies being whelped from two
chocolate parents suggests that
these "chocolates" were probably not
chocolate at all but rather E+
yellows. As such, it is conceivable
that the Agouti alleles could
produce an intense red pigment
resulting in deep red (interpreted
as chocolate especially in the
absence of "saddling" modifiers) or
diluted, muted red (card board box
color) due to further modification
by the alleles of the C locus). In
black Labs, an ayayEE+ geneotype
could produce a muted black color
(because of the presence of both
receptor types) especially if the
alleles at the C locus were cch,
thus resulting in a deep charcoal,
silvery coat appearance. This
suggests a possible role of E+ for
the silver coloration as well as for
a multitude of other coat color
variants that occasionally occur in
the breed.
White Hair Conditions in
Labs
There are several conditions that
can produce white hair in Labs. Some
of these conditions are determined
by color genes and others may be
caused by environmental factors that
effect melanin production.
White Spots
To analyze the reason why some black
Labs have only a few,
not-easily-seen, white hairs on
their chests while others have small
white spots, it is best to first
picture that all Labs are white--the
condition of having no melanin
production. The gene loci for color
control both the color of the
pigment as well as the distribution
of melanocytes throughout the body
of the Lab. Therefore, in a black
Lab, although color is determined by
alleles at the B locus, alleles at
the A and E loci determine even
distribution of the color over the
entire surface of the coat. Labs
that carry an allele other than "As"
at the A locus, have a greater
likelihood of expressing more white
hairs than those Labs that do carry
"As". Therefore, although all Labs
should be homozygous for the S
allele at the S gene locus, some may
still express white hairs on the
chest, bottom of the feet and under
the arms and groin areas.
Graying In Labs
Unlike the even distribution of
graying observed in some breeds of
dogs as they get older, graying in
Labs, particularly noticeable in
blacks and chocolates, occurs in
distinct areas such as the muzzle
and paws. Graying may occur as a
result of certain genes or as a
normal process of aging. In regard
to genetic causes, the dominant "G"
allele is responsible for causing
reduction in the number of
melanocytes so that melanin
production is diminished. However,
in the breeds carrying the graying
allele, this effect on pigment is an
early event, therefore, it is
unlikely that the graying observed
in older Labs is a result of this
allele.
Alternatively, the process of aging
is also associated with loss of
melanocytes and reduction in pigment
production. Melanocytes in the
muzzle and paws of the Lab may be
more prone to the aging process and
thus gray more quickly than other
locations of the body. Additionally,
the reduction in blood circulation
and resulting cooling of extremities
in geriatric Labs may reduce
production of melanin under the
control of cold-temperature-unstable
tyrosinase enzymes as explained
above.
Other potential causes for white and
gray hairs include tissue injury
that may destroy the melanocytes in
a particular area as well as dietary
deficiency of copper, which is
required for the production of
melanin. The former would appear as
localized depigmentation, the latter
would appear as an evenly
distributed loss of pigmentation.
White "Ring around the Tail"
and Two-Toned Appearance in Black
Labs
Helen Warwick reported the former
condition occurring in Labs in her
book "The Complete Labrador
Retriever." In one chapter, she
describes that some Labs have white
at the base of the hair shafts on
the tail. This white color is only
discernable when one lifts up the
hairs to view the base of the hair
shaft closest to the skin. Mrs.
Warwick made note that she had
observed this condition primarily in
Labs of English descent.
This condition, which is often not
limited to the tail, is actually
found frequently in both black and
chocolate Labs and most likely
indicates that the Lab is
heterozygous at the Extension (E)
Locus ("Ee") and does not carry the
As allele at the A Locus. These Labs
also can be observed as having red
tones in their coat (occasionally
causing a two-toned appearance
especially obvious during shedding
season). This two-toned appearance
is not attributed to chocolate
undertones, as some breeders may
believe, but is rather due to the
production of the red pigment,
phaeomelanin, in "e" (yellow)
carriers that also carry "ay-" or
"as-".As a result, both Mc1 receptor
types will be present in the dog:
one that continuously makes
eumelanin and one that will only
make phaeomelanin. The receptor
encoded by "E" for production of
black/brown is more efficient,
however, some phaeomelanin will be
produced by the "e" receptor. Since
the recessive Agouti alleles control
synthesis of phaeomelanin during
particular times of hair growth
(with phaeomelanin produced only
during the mid to late portion of
hair growth), phaeomelanin will only
be seen at the base of the hair
shaft. If these Labs also carry the
"cch" as the dominant allele at the
C locus, the red pigment will be
diluted allowing the base of the
hair shaft to appear very light in
color.
Final Remarks
To date, much of the knowledge
pertaining to coat color inheritance
is very limited with most of the
information either derived from
small canine studies or extrapolated
from other species. Therefore, much
of the data is still open to
interpretation. In light of this,
this article presents the current
consensus for inheritance of coat
color based on the previous findings
and interpretations of those in the
field. It is anticipated, however,
that our knowledge of canine
genetics will be greatly enhanced
over the next several years as
scientists conducting the "Canine
Genome Project" draw closer to their
goal of mapping specific genes to
their chromosomes in the canine.
