Each
hair follicle is surrounded by many
melanocytes (pigment cells), which make and transfer the pigment
melanin into a developing hair. Dog fur is colored by two types of melanin:
eumelanin (brownish-black) and
phaeomelanin (reddish-yellow). A melanocyte can be signaled to produce either color of melanin. Dog coat colors are from patterns of: • Eumelanin — black, chocolate brown, grey or taupe pigment; • Phaeomelanin — tan pigment, including all shades of red, gold and cream pigment; and/or • Lack of melanin — white (no pigment). By 2020, more than eight
genes in the canine
genome have been verified to determine coat color. Each of these has at least two known
alleles. Together these genes account for the variation in coat color seen in dogs. Each gene has a unique, fixed location, known as a
locus, within the dog genome. Some of the loci associated with canine coat color are:
Pigment shade Several loci can be grouped as affecting the shade of color: the Brown (B), Dilution (D), and Intensity (I) loci.
B (brown) locus The gene at the B locus is known as
tyrosinase related protein 1 (TYRP1). This gene affects the color of the eumelanin pigment produced, making it either black or brown. TYRP1 is an enzyme involved in the synthesis of eumelanin. Each of the known mutations appears to eliminate or significantly reduce TYRP1 enzymatic activity. This modifies the shape of the final eumelanin molecule, changing the pigment from a black to a brown color. Color is affected in coat and skin (including the nose and paw pads). There are four known alleles that occur at the B locus: •
B = Black eumelanin. An animal that has at least one copy of the
B allele will have a black nose, paw pads and eye rims and (usually) dark brown eyes. •
b = Brown eumelanin - such as chocolate or liver (includes several alleles -
bs,
bd and
bc). An animal with any matched or unmatched pair of the
b alleles will have brown, rather than black, hair, a liver nose, paw pads and eye rims, and hazel eyes. Phaeomelanin color is unaffected. It is unknown whether the different brown alleles cause specific shades or hues of brown.
B is dominant to
b. (standard).
KB for solid eumelanin coat;
b/b for brown eumelanin lightened by
d/d dilution. (non-standard):
KB for solid eumelanin coat;
B/_ for black eumelanin lightened by
d/d dilution. Labrador dogs with the dilute gene often suffer from
color dilution alopecia.
D (dilute) locus The
melanophilin gene (MLPH) at the D locus causes a dilution mainly of
eumelanin, while
phaeomelanin is less affected. This
dilution gene determines the intensity of pigmentation. MLPH codes for a protein involved in the distribution of melanin - it is part of the
melanosome transport complex. Defective MLPH prevents normal pigment distribution, resulting in a paler colored coat. There are two common alleles:
D (normal,
wild-type MLPH), and
d (defective MLPH) that occur in many breeds. But recently the research group of Tosso Leeb has identified additional alleles in other breeds. •
D = Not diluted. Black or brown eumelanin (as determined by Brown locus), reddish or orangish tan phaeomelanin. •
d = Diluted. Diluted fur color: black eumelanin (
B/-) diluted to bluish grey (ranging from light blue-grey to dark steel); brown eumelanin (
b/b) diluted to taupe or
"Isabella". Phaeomelanin is diluted from red to yellowish tan; this phaeomelanin dilution is not as dramatic as the eumelanin color shift. Slight to moderate dilution of the paw pads and eye rims towards bluish grey if
B/- or taupe if
b/b, and slight to moderate reduction of
eye color from brown towards amber in a
B/- animal, or from hazel towards light amber in a
b/b animal.
D is completely dominant to
d. This dilution gene can occur in almost any breed, where blue gene is the most common. Also, there are some breeds that come in dilute but with no specific color, such as the
Weimaraner or the Slovakian Pointer. Some breeds that are commonly known to have dilution genes are "
Italian greyhounds,
whippets,
Tibetan mastiffs,
greyhounds,
Staffordshire bull terriers, and
Neapolitan mastiffs".
Color gene interactions I (intensity) locus The alleles responsible for
pheomelanin dilution (changing of a dog's coat from tan to cream or white) was found to be the result of a mutation in MFSD12 in 2019. and occurs in breeds that do not exhibit dark gold or red phenotypes. Two alleles are theorised to occur at the
I locus: •
I = Non-diluted pigment •
i = Diluted pigment It's been observed that
I and
i interact with semi-dominance, so that there are three distinct phenotypes.
I/i heterozygotes are paler than
I/I animals but normally darker than
i/i animals. •
i results in diluted phaeomelanin such as cream, yellow, and white. Unlike
d/d, it allows the skin and eyes to remain dark. It does not effect eumelanin (black/brown/blue/lilac) pigment, i.e. leaving a cream Afghan with a very black mask. This is not to be confused with the cream or white in Nordic Breeds such as the
Siberian Husky, or cream roan in the
Australian Cattle Dog, whose cream and white coats are controlled by genes in the Extension E Locus. Golden Retriever Sammy.jpg|
Golden Retriever genotype II Golden retriever in play.JPG|Golden Retriever genotype Ii Spicegoldenretriever.jpg|Golden Retriever genotype ii Intermediary inheritance - Gene i.png|
Punnett square: intermediate inheritance Hovawart black and tan.jpg|
Hovawart: black and tan, genotype II) Chihuahua portrait.jpg|
Chihuahua: tan is lightened to creme, genotype Ii CHIHUAHUA DOG.JPG|Chihuahua: same parts are creme-white, genotype ii
Red Pigment Pigment Intensity for dogs who are darker than Tan (shades of gold to red) has been attributed to a mutation upstream of KITLG, in the same genes responsible for coat color in mice and hair color in humans. The mutation is the result of a Copy Number Variant, or duplication of certain instructions within a gene, that controls the distribution of pigment in a dog's hair follicle. As such, there are no genetic markers for red pigment. • Dogs with a higher CNV were observed to have darker, richer colors such as deep gold, red, and chestnut. • Dogs with a lower CNV were observed to have lighter gold and orange colors. This mutation not only effects Pheomelanin, but Eumelanin as well. This mutation does not effect all breeds the same.
Eumelanin vs. Phaeomelanin Pigment Switching Several loci affect coat color by changing whether and where on a dog eumelanin (blacks-browns) or phaeomelanin (reds-yellows) are produced. Tan with black whiskers and varying amounts of black-tipped and/or all-black hairs dispersed throughout. Fawn typically referring to dogs with clearer tan and sable to those with more black shading. •
aw = Wild-type agouti. Each hair with 3-6 bands alternating black and tan. Dorsal hairs are darker, and ventral hairs are paler. Phaeomelanin production is limited to tan points; dark portions of the dog are solid eumelanin hairs. •
a = Recessive black. Loss-of-function ASIP mutation leads to only eumelanin production. Solid black coat. Most texts suggest that the
dominance hierarchy for the A locus alleles appears to be as follows:
Ay > aw > at > a; however, research suggests the existence of pairwise dominance/recessiveness relationships in different families and not the existence of a single hierarchy in one family. •
Ay is incompletely dominant to
at, so that heterozygous individuals have more black sabling, especially as puppies and
Ayat can resemble the
awaw phenotype. Other genes also affect how much black is in the coat. •
aw is the only allele present in many Nordic spitzes, and is not present in most other breeds. •
at includes tan point and saddle tan, both of which look tan point at birth. Modifier genes in saddle tan puppies cause a gradual reduction of the black area until the saddle tan pattern is achieved. •
a is only present in a handful of breeds. Most black dogs are black due to the K locus allele
KB for dominant black.
Border Collies is one of the few breeds that lack agouti patterning, and only have sable and tan points. However, many border collies still test to have agouti genes.
E (extension) locus The alleles at the E locus (the
Melanocortin 1 Receptor gene or
MC1R) determine whether an animal expresses a
melanistic mask, as well as determining whether an animal can produce
eumelanin in its coat. MC1R is a receptor that sits on the surface of a melanocyte; when this receptor is activated, it signals the melanocyte to make black-brown eumelanin instead of red-yellow phaeomelanin. •
E = Normal extension (pattern expressed as per alleles present at A and K loci). •
eh = Cocker sable (if
KB/- and may require
atat, tan with a dark overlay covering the top and sides of the body, head and tail, and the outside of the limbs). •
e = Recessive red. Loss-of-function of MC1R, which results in no eumelanin production in fur. With only phaeomelanin produced, coat is yellow to red. There are three loss-of-function alleles identified, all with the same phenotype. •
e3 = Found only in Nordic breeds, this gene creates the white and yellow coat color.
EG is theorized to have no effect on the phenotype of non-
at/- nor
KB dogs and to be allelic to
Em and
e. • Little information exists regarding the
Ed allele. In behavior and appearance it almost mimics the Grizzle allele found in Sighthounds, however it is not the same mutation. Domino animals of this type will either have two copies of the mutation or have a single copy paired with
e. • The
eh sable extension allele has been studied only in English Cocker Spaniels and produces sable in the presence of dominant black
KB and tan point
at/at. Its expression is dependent upon the animal not possessing
Em nor
E nor being homozygous for
e.
eh is theorized to be on the E locus and to have no effect on
ky/ky dogs. All cocker spaniels are homozygous for
at, so it is unknown how the gene may function in the presence of other A-series alleles.
K (dominant black) locus The alleles at the K locus (the
β-Defensin 103 gene or DEFB103) determine the coloring pattern of an animal's coat. There are three known alleles that occur at the K locus: •
KB = Dominant black (black) •
kbr =
Brindle (black stripes added to tan areas) •
ky = Phaeomelanin permitted (pattern expressed as per alleles present at A and E loci) The dominance hierarchy for the K locus alleles appears to be as follows:
KB >
kbr >
ky. •
KB causes a solid eumelanin coat (black, brown, grey or taupe) except when combined with
e/e (tan or white),
Eh/- (Cocker sable) or
Em/- G/- and appropriate coat type (light eumelanin with dark eumelanin mask) •
kbr causes the addition of eumelanin stripes to all tan areas of a dog except when combined with
e/e (no effect) or
EG/- atat non-
KB/- (eumelanin and sabled areas become striped, tan areas remain tan) •
ky is wild-type allowing full expression of other genes.
Interactions of some pigment-switching genes Alleles at the Agouti (A), Extension (E) and Black (K) loci interact to affect coat color and pattern. Below is a table of some of the more common alleles and their interactions: Below is a table of less-common alleles from the Extension locus:
Patches and white spotting The Merle (M), Harlequin (H), and Spotting (S) loci contribute to patching, spotting, and white markings. Alleles present at the Merle (M) and Harlequin (H) loci cause patchy reduction of melanin to half (merle), zero (harlequin) or both (double merle). Alleles present at the Spotting (S), Ticking (T) and Flecking (F) loci determine white markings.
H (harlequin) locus DNA studies have isolated a
missense mutation in the 20S
proteasome β2 subunit at the H locus. The H locus is a modifier locus (of the M locus) and the alleles at the H locus will determine if an animal expresses a harlequin vs merle pattern. There are two alleles that occur at the H locus: •
H = Harlequin (if
M/-, patches of full colour and white) •
h = Non-harlequin (if
M/-, normal expression of merle)
H/h heterozygotes are harlequin and
h/h homozygotes are non-harlequin. Breeding data suggests that homozygous
H/H is embryonic lethal and that therefore all harlequins are
H/h. • The Harlequin allele is specific to
Great Danes. Harlequin dogs (
H/h M/m) have the same pattern of patches as merle (
h/h M/m) dogs, but the patches are white and
harlequin affects eumelanin and phaeomelanin equally.
H has no effect on non-merle
m/m dogs.
M (merle) locus The alleles at the M locus (the silver locus protein homolog gene or
SILV, aka premelanosome protein gene or PMEL) determine whether an animal expresses a
merle pattern to its coat. There are two alleles that occur at the M locus: •
M = Merle (patches of full colour and reduced colour) •
m = Non-merle (normal expression)
M and
m show a relationship of both co-dominance and no dominance. • On heterozygous
M/m merles, black is reduced to silver on ~50% of the animal in semi-random patches with rough edges like torn paper. The fraction of the dog covered by merle patches is random such that some animals may be predominantly black and others predominantly silver. The merle gene is "faulty" with many merle animals having one odd patch of a third shade of grey, brown or tan. • On homozygous
M/M "double merles", black is replaced with ~25% black, ~50% silver and ~25% white, again with random variation, such that some animals have more black or more white. • Eumelanin (black/etc.) is significantly reduced by
M/m, but phaeomelanin is barely affected such that there will be little to no evidence of the merle gene on any tan areas or on an
e/e dog. However, the white patches caused by
M/M affect both pigments equally, such that a fawn double merle would be, on average, ~75% tan and ~25% white. • The merle gene also affects the skin, eye colour, eyesight and development of the eye and
inner ear. Merle
M/m puppies develop their skin pigmentation (nose, paws, belly) with speckled-edged progression, equally evident in
e/e merles except when extensive white markings cause pink skin to remain in these areas. Blue and part-blue eyes are common. • Both heterozygosity and homozygosity of the merle gene (i.e.,
M/m and
M/M) are linked to a range of auditory and ophthalmologic abnormalities. Most
M/m merles have normal-sized eyes and acceptably functional eyesight and hearing; most
M/M double merles suffer from microphthalmia and/or partial to complete deafness.
Variation on merle allele There are other new discovery on M locus and it would be useful to add the supplementary category on "M(merle) Locus" part. Since the original section only talk about just one allele M, but there are some variation on the one allele and derive a number of new alleles, which will lead to the other production of pigment. • Cryptic merle (Mc and Mc+) One of the variation of M allele is Mc and Mc+. Although just one copy of Mc is not long enough to make visible change on coats, the combination of Mc or more than two copies of Mc would lead to odd shade of black/liver. There is disagreement as to the number of alleles that occur at the S locus, with researchers sometimes postulating a conservative two or, commonly, four alleles. The alleles postulated are: •
S = Solid color/no white (very small areas of white may still appear; a diamond or medallion on the chest, a few toe tips/toes, or a tail tip) •
si = Irish-spotting (white on muzzle, forehead, feet, legs, chest, neck and tail) •
sp =
Piebald (varies from coloured with Irish spotting plus at least one white marking on the top or sides of the body or hips, to mostly white which generally retains patches of colour around the eyes, ears and tail base) •
sw = Extreme piebald spotting (extremely large areas of white, almost completely white) In 2014, a study found that a combination of simple repeat polymorphism in the MITF-M Promoter and a SINE insertion is a key regulator of white spotting and that white color had been selected for by humans to differentiate dogs from their wild counterparts. Based on this research the degree of White Spotting is dependent on the Promoter Length (Lp) to produce less or more color. A shorter Lp creates less white (Solid Colored and Residual White dogs) while a longer Lp creates more white (Irish Spotting and Piebald). What separates Piebald from Irish White and Solid is the presence of a SINE insertion (Short Interspersed Element) in the S locus genes that changes the normal DNA production. The result is Piebald and Extreme Piebald. The only difference between the two recognized forms of Piebald is the length of the Lp. Because of this variability, a dog's Phenotype will not always match their Genotype. The
Beagle for example is fixed for
spsp Piebald, yet there are Beagles with very little white on them, or Beagles that are mostly white. What makes them Piebald is the SINE Insertion, but the Lp length is what changes how their patterns are expressed. • White spotting can cause blue eyes, microphthalmia, blindness and deafness; however, because pigmentation is generally retained around the eye/ear area, this is rare except in SINE White dogs (Piebald) which can sometimes lose pigment in those areas during fetal development. • Some breeds like the
Boston Terrier,
Australian Shepherd, and
Rough Collie have a naturally longer Lp and are considered "Fixed for White". This means even if they are genetically
SS for Solid Color, they will still show White Spotting.
Albinism C (colored) locus People have postulated several alleles at the C locus and suggested some/all determine the degree to which an animal expresses phaeomelanin, a red-brown protein related to the production of
melanin, in its coat and skin. Five alleles have been theorised to occur at the C locus: •
C = Full color (animal expresses phaeomelanin) •
cch = Chinchilla (partial inhibition of phaeomelanin resulting in decreased red pigment) •
ce = Extreme dilution (inhibition of phaeomelanin resulting in extremely reduced red pigment) •
cb,
cp = Blue-eyed albino/Platinum (almost total inhibition of phaeomelanin resulting in near albino appearance) •
ca =
Albino (complete inhibition of phaeomelanin production, resulting in complete inhibition of melanin production) However, based on a 2014 publication about albinism in the Doberman Pinscher and later in other small breeds, the discovery was made that multiple alleles in the C locus are highly unlikely, and that all dogs are homozygous for Normal Color production, excluding dogs who carry albinism.
Theoretical genes for color and pattern There are additional theoretical loci thought to be associated with coat color in dogs. DNA studies are yet to confirm the existence of these genes or alleles but their existence is theorised based on breeding data: ====F (
flecking) locus==== The alleles at the theoretical F locus are thought to determine whether an animal displays small, isolated regions of white in otherwise pigmented regions (not apparent on white animals). Two alleles are theorised to occur at the
F locus: •
F = Flecked •
f = Not flecked (See ticking below, which may be another name for the flecking described here) It is thought that
F is dominant to
f. Two alleles are theorized to occur at the U locus: •
U = Urajiro •
u = Not urajiro It is thought that
U is recessive to
u but due to lack of genetic studies these assumptions have only been made through visual assessment. The
urajiro pattern is expressed in the tan (phaeomelanin) areas of any dog and does not effect black (eumelanin) pigment. ==Miscolours in dog breeds==