User:HFHah/sandbox

class="wikitable "

This is the user sandbox of HFHah. A user sandbox is a subpage of the user's user page. It serves as a testing spot and page development space for the user and is not an encyclopedia article. Create or edit your own sandbox here.

Other sandboxes: Main sandbox | Template sandbox

Finished writing a draft article? Are you ready to request review of it by an experienced editor for possible inclusion in Wikipedia? Submit your draft for review!

me messing around with dog gene article structure

Dog coat color is governed by how genes are passed from dogs to their puppies and how those genes are expressed in each dog. Dogs have about 19,000 genes in their genome but only a handful affect the physical variations in their coats. And the usual rules apply—most genes come in pairs, one from the dog’s mother and one from its father. Genes of interest have more than one version, or allele. Usually only one or a small number of alleles exist for each gene. So, at any one gene locus a dog will either be homozygous, that is, the gene is made of two identical alleles (one from its mother and one its father) or heterozygous, that is, the gene is made of two different alleles (again, one inherited from each parent).

To understand why a dog’s coat looks the way it does based on its genes requires an understanding of a handful of particular dog coat genes and their alleles. For example, if you wanted to find out how a black and white greyhound that seems to have wavy hair got its coat, you would want to look into the dominant black gene with its K and k alleles, the (white) spotting gene with its multiple alleles, and the R and r alleles of the curl gene.

Terms to consider

follicular melanocytes

deposition of pigment granules/melanosomes

pigment switching

hair follicle: hair bulb

Genes associated with coat color

Pigment production

Melanocytes localize to the bulb of a hair follicle. These cells produce pigment granules (melanosomes), which are transferred into the growing hair.

Each hair follicle is surrounded by many melanocytes (pigment cells), which make and transfer the pigment melanin into a developing hair. Melanocytes can be signaled to produce either eumelanin (brownish-black) or phaeomelanin (reddish-yellow).

The various 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).

Melanin is synthesized and stored in specialized organelles inside the melanocyte called melanosomes; when mature, these melanosomes are transferred out of the cell and into the developing hair. Melanin synthesis is a multistep process; some enzymes are involved in both the eumelanin and phaeomelanin pathways, while others are used to produce only one of the pigments.^[1]

The process of coloring a hair is complicated, and coat color can be altered at many steps along the way, including:

pigment cell (melanocyte) development and survival.
signaling a melanocyte to produce eumelanin vs phaeomelanin.
melanin synthesis pathway.
transport of melanosomes into the hair follicle. ^[2]

Currently eight genes in the canine genome are 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.

Pigment color loci

Several loci can be grouped as determining a "baseline" melanin color: the Brown (B) and Dilution (D) loci.

B (brown) locus

Genotype B/B or B/b

Genotype b/b

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; alleles at the B locus affect TYRP1 production in the coat and skin (including the nose and paw pads).^[3] Each of the known mutations appears to eliminate or significantly reduce TYRP1 enzymatic activity.^[2] This modifies the final shape of the eumelanin molecule produced,^[4] ????? or dilution????meaning that the pigment is a different color (instead of, for example, changing pigment density).TYRP1 affects the eumelanin synthesis pathway very late, after the split from phaeomelanin has occurred; it is not unexpected that phaeomelanin color would appear unaffected.^[3]

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. Includes several alleles: b^s, b^d and b^c. 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.^[2]^[3] Only one of the alleles is present in the English Setter (b^s), Doberman Pinscher (b^d) and Italian Greyhound (b^c), but in most breeds with any brown allele 2 or all 3 are present.^[5] It is unknown whether the different brown alleles cause specific shades or hues of brown. No obvious differences in the shade of brown have been noted between the different alleles.^[3] ^[2]
- novel mutation/allele in australian shepherd (2017). ^[6]

B is dominant to b.

D (dilute) locus

The melanophilin gene (MLPH) at the D locus causes a dilution of eumelanin and phaeomelanin and determines the intensity of pigmentation. MLPH codes for a protein involved in the distribution of melanin - it is part of the melanosome transport complex. ^[7] Defective MLPH prevents normal pigment distribution, resulting in pigment clumping and a paler colored coat.^[8]

There are two known alleles: D and d.

D = Not diluted. Black or brown eumelanin (determined by Brown locus), reddish or orangish tan phaeomelanin.
d = 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.^[9] 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.

Homozygosity of d is sometimes accompanied by hair loss and recurrent skin inflammation, a condition referred to as either color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD) depending upon the breed of dog.^[10]

Color gene interactions

B/_ D/_

B/_ d/d

b/b D/_

b/b d/d

COLOUR GENE INTERACTIONS^[11]	Not Dilute (D/D or D/d)	Dilute (d/d)
Black B/B or B/b	Black eumelanin Red* phaeomelanin	Blue-grey eumelanin Yellow phaeomelanin
Brown b/b	Chocolate-brown eumelanin Red* phaeomelanin	Taupe or "Isabella" eumelanin Yellow phaeomelanin
* Note that phaeomelanin is frequently diluted by intensity factor of theoretical I locus.

Pigment-type switching loci

Many genes are involved in controlling whether a melanocyte produces eumelanin or phaeomelanin. Time-dependent pigment switching leads to the production of a single hair with bands of eumelanin and phaeomelanin.^[2] Spatial-dependent signaling results in parts of the body with different levels of production of each pigment.

MC1R (the E locus) is a receptor on the surface of melanocytes. When active, it causes the synthesis of eumelanin; when inactive, the melanocyte produces phaeomelanin instead. ASIP (the A locus) binds to and inactivates MC1R, thereby causing phaeomelanin synthesis. DEFB103 (the K locus) in turn stops ASIP from inhibiting MC1R (thereby increasing MC1R activity and inducing eumelanin synthesis). ^[2]

A (agouti) locus

The alleles at the A locus are related to the production of agouti signalling protein (ASIP) and determine whether an animal expresses an agouti appearance, and, by controlling the distribution of pigment in individual hairs, what type of agouti.

ASIP works with other genes to regulate which color of melanin is produced in a hair shaft; ASIP induces the production of phaeomelanin. In wolves and wild-type coloration dogs, each hair has several alternating bands of black and tan. Generally, a mutation that increases ASIP cause more tan (phaeomelanin) and mutations that reduce ASIP cause a darker coat (more eumelanin). ^[12] A non-functional ASIP mutation would result in a coat with no phaeomelanin.

There are four known alleles that occur at the A locus:

A^y = Fawn or sable. Tan with black whiskers and varying amounts of black-tipped and/or all-black hairs dispersed throughout.
- Fawn typically refers to dogs with clearer tan and sable to those with more black shading
a^w = Wild-type agouti (each hair with 3-6 bands alternating black and tan) - also called wolf sable
a^t = Tan point. Black with tan patches on the face and underside - including saddle tan (tan with a black saddle or blanket) ^[13]^[14]
a = Recessive black. Black, inhibition of phaeomelanin.
a^yt = Recombinant fawn (black with tan patches on the face and underside) has been identified in numerous Tibetan Spaniels and individuals in other breeds, including the Dingo. Its hierarchical position is not yet understood.^[15]^[16]

Allele A^y

Allele a^w^[17]^[18]

Allele a^t

Allele a

Most texts suggest that the dominance hierarchy for the A locus alleles appears to be as follows: A^y > a^w > a^t > 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.^[19]

A^y is incompletely dominant to a^t, so that heterozygous individuals have more black sabling, especially as puppies and A^ya^t can resemble the a^wa^w phenotype. Other genes also affect how much black is in the coat.
a^w is the only allele present in many Nordic spitzes, and is not present in most other breeds.
a^t 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.^[20]

E (extension) locus

Tan point saluki: at/at, E/-

Saluki at/at, Eg/-

The gene at the E locus is the melanocortin 1 receptor (MC1R) - it determine whether an animal expresses a melanistic mask, as well as determining whether an animal can produce eumelanin in its coat. MC1R activity promotes eumelanin synthesis; MC1R inactivity results in phaeomelanin production. A non-functional MC1R would thus result in a coat with no eumelanin (no black).

Any area that contains eumelanin pigment can be affected by genes affecting eumelanin color (i.e. Brown or Dilution).

There are three known, plus two more theorized, alleles that occur at the E locus:

E^m = Mask. A eumelanin mask is added to the face. The distribution of the pigments on the rest of the face and on the body is determined by the agouti locus. Any tan (phaeomelanin) areas on the mask area are replaced with eumelanin (black/etc.) The mask can vary from the muzzle, to the face and ears, to a larger area with shading on the front and sides as in the Belgian Tervuren.
- The mask E^m is unaffected by the greying gene G and will remain dark in a G/- animal while the rest of the dog pales, such as in Kerry Blue Terriers. Some puppies are born with a mask which fades away within a few weeks of birth: these puppies do not have the E^m allele and their temporary mask is due to sabling (A^y).

E^G = Grizzle. A dark overlay covering the top and sides of the body, head and tail, and the outside of the limbs; underparts are pale color. Appearance is that of a modified "tan point" - grizzle requires that the animal be homozygous a^t/a^t at the agouti locus and not possessing K^B.^[21]
- The E^G allele is confirmed only in the Saluki and Afghan Hound, the latter in which it is referred to as "Domino", but also occurs in the Borzoi. Its placement in the dominance hierarchy has not been solidified. Black with fawn-tan points (a^t/a^t E/-) is instead dark-sable with extended clear-tan points (a^t/a^t E^G/-). Brindle affects fawn and sable areas, resulting in black with bridled-tan points (a^t/a^t E/- K^br/-) or brindle with clear-tan points (a^t/a^t E^G/- K^br/-).^[21] E^G is theorized to have no effect on the phenotype of non-at/- nor K^B dogs. This is a single amino acid substitution in the MC1R protein.^[21]
E = Normal extension. Expression of eumelanin and/or phaeomelanin according to the alleles present at the A and K loci
e^h = Cocker sable (if K^B/- and may require a^ta^t, tan with a dark overlay covering the top and sides of the body, head and tail, and the outside of the limbs)
- The e^h sable extension allele has been studied only in English Cocker Spaniels and produces sable in the presence of dominant black K^B and tan point a^t/a^t. Its expression is dependent upon the animal not possessing E^m nor E nor being homozygous for e. e^h is theorized to be on the E locus and to have no effect on k^y/k^y dogs. All cocker spaniels are homozygous for a^t, so it is unknown how the gene may function in the presence of other A-series alleles.
e = Recessive red or clear fawn. Inhibition of eumelanin over entire coat; only pigment is pheomelanin.^[22] Eumelanin can be in nose, eye lids and paw pads but not in the fur. An animal that is homozygous for e will express a red to yellow coat regardless of most alleles at other loci. Eumelanin is inhibited, so there can be no black hairs anywhere, even the whiskers. Pigment on the nose leather can be lost at the middle (Dudley nose). In combination with a/a (phaeomelanin inhibitor), an e/e dog will be white to off-white; in combination with U/U or U/u, an e/e dog will be off-white or cream.^[23]

The dominance hierarchy for the E locus alleles appears to be as follows: E^m > E^G > E > e^h > e.

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.^[24] There are three known alleles that occur at the K locus:

K^B = Dominant black (black)
k^br = Brindle (black stripes added to tan areas)
k^y = 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: K^B > k^br > k^y.

K^B causes a solid eumelanin coat (black, brown, grey or taupe) except when combined with e/e (tan or white), E^h/- (Cocker sable) or E^m/- G/- and appropriate coat type (light eumelanin with dark eumelanin mask)
k^br causes the addition of eumelanin stripes to all tan areas of a dog except when combined with e/e (no effect) or E^G/- a^ta^t non-K^B/- (eumelanin and sabled areas become striped, tan areas remain tan)
k^y is wild-type allowing full expression of other genes.

Interactions of pattern genes

Alleles at the Agouti (A), Extension (E) and Black (K) loci determine colour pattern (eumelanin vs phaeomelanin):

PATTERN GENE INTERACTIONS^[11]		Fawn or Sable A^y/-	Wolf Sable a^w/a^w, *a^w/a^t* or a^w/a	Tan Point a^t/a^t or a^t/a	Rec. Black a/a
Dom. Black K^B/-	Mask E^m/-	black (with mask)*	black (with mask)*	black (with mask)*	black (with mask)*
	wildtype E E/E or E/e	black	black	black	black
	Cocker Sable^† *e^h/e^h* or e^h/e	?	?	cocker sable	?
Brindle K^br/K^br or K^br/k^y	Mask E^m/-	brindle with mask	brindle with mask	black & brindled tan with mask	black (with mask)*
	wildtype E E/E or E/e	brindle	brindle	black & brindled tan	black
	Grizzle^† **E^G/E^G, E^G/E** or E^G/e	?	?	brindle & tan	?
wildtype K k^y/k^y	Mask E^m/-	fawn or sable with mask	wolf sable with mask	black & tan with mask	black (with mask)*
	wildtype E E/E or E/e	fawn or sable	wolf sable	black & tan	black
	Grizzle^† **E^G/E^G, E^G/E** or E^G/e	?	?	grizzle	?
any K -/-	Clear Fawn e/e	tan	tan	tan	white
* Note that the black mask on a black dog is only phenotypically evident in presence of G/- and an appropriate coat type. ^† e^h and E^G are only included in the table where their interactions are known.

Alleles present at the Intensity (I), Urajiro (U), Greying (G) and Albino (C-like) loci determine melanin shade.

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.^[25] 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.^[26]

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.^[27] 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.^[28]

S (spotting) locus

The alleles at the S locus (the microphthalmia-associated transcription factor gene or MITF) determine the degree and distribution of white spotting on an animal's coat.^[29] There is disagreement as to the number of alleles that occur at the S locus, with researchers sometimes postulating a conservative two^[30] or, commonly, four^[31] 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)
s^p = 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)
s^w = Extreme piebald spotting (extremely large areas of white, almost completely white)

S is incomplete dominant (towards co-dominant) to s^p. DNA studies have not yet confirmed the existence of all four alleles, with some research suggesting the existence of at least two alleles (S and s^p)^[29] and other research suggesting the possible existence of a third allele (sⁱ).^[32]

S/s^p heterozygotes usually have some white at birth on the chest and toes, which may be covered by ticking as the puppy grows. Animals of this genotype also commonly display pseudo-Irish spotting; in fact most Irish-spotted dogs are so due to heterozygosity for solid and piebald.
A few breeds (e.g., Boston Terrier) are fixed for Irish spotting and therefore theorized to possess a different allele on the S locus (sⁱ) or an allele on a completely separate gene.
It has been suggested that what appears to be the result of an s^w allele is in fact the result of plus and minus modifiers acting on one of the other alleles.^[29] It is thought that the spotting that occurs in Dalmatians is the result of the interaction of three loci (the S locus, the T locus and F locus) giving them a unique spotting pattern not found in any other breed.^[33]
White spotting also affects skin, causing pink patches.
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 among s^w/s^w dogs (or extreme versions of s^p/s^p if s^w does not exist).

In 2014, a study found that a simple repeat polymorphism in the MITF-M Promoter is a key regulator of white spotting and that white color had been selected for by humans.^[34]^[35]

Theoretical genes for color and pattern

There are at least six 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:^[36]

C (colored) locus

The alleles at the theoretical C locus are thought to 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 are theorised to occur at the C locus:

C = Full color (animal expresses phaeomelanin)
c^ch = Chinchilla (partial inhibition of phaeomelanin resulting in decreased red pigment)
c^e = Extreme dilution (inhibition of phaeomelanin resulting in extremely reduced red pigment)
c^b, c^p = Blue-eyed albino/Platinum (almost total inhibition of phaeomelanin resulting in near albino appearance)
c^a = Albino (complete inhibition of phaeomelanin production, resulting in complete inhibition of melanin production)

The C locus in dogs is not well understood and the theorised alleles are based on those present in other species.^[31] True albinism has not been conclusively shown to exist in dogs. It is thought that an animal that is heterozygous for the C allele with any of the c alleles will express a result somewhere between the two alleles.^[37]

White in Doberman Pinschers and albino-like animals of Asian/Tibetan companion breeds have a phenotype resembling a C locus dilution, but all tested animals have been C/C. The gene responsible is recessive and not at the C locus.^[38]

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

It is thought that F is dominant to f.^[33]

G (progressive greying) locus

The alleles at the theoretical G locus are thought to determine if progressive greying of the animal's coat will occur. Two alleles are theorised to occur at the G locus:

G = Progressive greying (melanin lost from hairs over time)
g = No progressive greying

It is thought that G is dominant to g.

The greying gene affects both eumelanin, and to a lesser extent phaeomelanin. In the presence of E^m/- the eumelanin mask will be unaffected and remain dark. Grey dogs are born fully coloured and develop the greying effect over several months. New hairs are grown fully coloured but their colour fades over time towards white. Greying is most evident in continuous-growing coats (long + wire + curly) as individual hairs remain on the dog long enough for the colour to be lost. In short-haired dogs, hairs are shed out and re-grown before the colour has a chance to change.
Premature greying, in which the face/etc. greys at a young age is not caused by G and has not been proven to be genetic.

I (intensity) locus

The alleles at the theoretical I locus are thought to affect phaeomelanin expression. Two alleles are theorised to occur at the I locus:

I = Intense red, not diluted
i = Not intense red

It is thought 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 darker than i/i animals.

i results in light-coloured phaeomelanin such as gold, yellow, buff and apricot. This gene is the most common cause of lighter tans, and unlike d/d, it allows the skin and eyes to remain dark.

T (ticking) locus

The alleles at the theoretical T locus are thought to determine whether an animal displays small, isolated regions of pigment in otherwise s-spotted white regions. Two alleles are theorised to occur at the T locus:

T = Ticked
t = Not ticked

It is thought that T is dominant to t. Ticking may be caused by several genes rather than just one. Patterns of medium-sized individual spots, smaller individual spots, and tiny spots that completely cover all white areas leaving a roan-like or merle-like appearance (reserving the term large spots for the variation exclusive to the Dalmatian) can each occur separately or in any combination.

The effect of the ticking gene(s) is to add back little coloured spots to areas made white by piebald spotting (-/s) or the limited white markings of S/S animals. It does not affect white areas that were caused by a/a e/e or M/M or M/m H/h. The colour of the tick marks will be as expected or one shade darker. Tick marks are semi-random, so that they vary from one dog to the next and can overlap, but are generally present on the lower legs and heavily present on the nose.

U (urajiro) locus

The alleles at the theoretical U locus are thought to limit phaeomelanin production on the cheeks and underside.^[39] Two alleles are theorised to occur at the U locus:

U = Urajiro
u = Not urajiro

It is thought that U is dominant to u but incomplete with homozygosity required for complete dilution to off-white and heterozygotes displaying a darker cream. The urajiro pattern is expressed in the tan (phaeomelanin) areas of any dog who is not e/e. In e/e dogs, the urajiro gene causes dilution of the entire dog to off-white or cream.

Miscolours in dog breeds

Miscolours occur quite rarely in dog breeds, because genetic carriers of the recessive alleles causing fur colours that don't correspond to the breed standard are very rare in the gene pool of a breed and there is an extremely low probability that one carrier will be mated with another. In case two carriers have offspring, according to the law of segregation an average of 25% of the puppies are homozygous and express the off-colour in the phenotype, 50% become carriers and 25% are homozygous for the standard colour. Usually off-coloured individuals are excluded from breeding, but that doesn't stop the inheritance of the recessive allele from carriers mated with standard-coloured dogs to new carriers.

In the breed Boxer large white markings in heterzygous carriers with genotype S sⁱ or S s^w belong to the standard colours, therefore extreme white Boxers are born regularly, some of them with health problems.^[40] The cream-white colour of the Shiba Inu is not caused by any spotting gene but by strong dilution of pheomelanin. Melanocytes are present in the whole skin and in the embryonic tissue for the auditory organs and eyes, therefore this colour is not associated with any health issues.^[41] Recessive genes can be a remnant of the gene pool of the breeds from which the current breed was bred in the past.

Punnett square: Inheritance with one carrier of a recessive gene
Litter of a Boxer Genotype S sⁱ mated with another sⁱ carrier.
Punnett square: Inheritance with two genetic carriers
Shiba Inu: According to the AKC cream-white is a non-standard colour^[42] but is accepted by the British Kennel Club.^[43]
For normal Yorkshire Terriers Piebald spotting s^p s^p is not allowed. Tricolor Yorkies became a separate breed.
For the Beagle tricolor Genotype s^p s^p is the first colour in the breed standard.^[44]

The occurrence of a dominant coat colour gene not belonging to the standard colours is a suspicion for crossbreeding with another breed. For example the dilute gen D in the suddenly appeared variety "silver coloured" Labrador Retriever might probably come from a Weimaraner.^[45] The same applies for Dobermann Pinschers suffering from Blue dog syndrome.^[46]^[47]^[48]

Genetic testing and phenotype prediction

In recent years genetic testing for the alleles of some genes has become available.^[49] Software is also available to assist breeders in determining the likely outcome of matings.^[50]

Characteristics linked to coat colour

The genes responsible for the determination of coat colour also affect other melanin-dependent development, including skin colour, eye colour, eyesight, eye formation and hearing. In most cases, eye colour is directly related to coat colour, but blue eyes in the Siberian Husky and related breeds, and copper eyes in some herding dogs are not known to be related to coat colour.

The development of coat colour, skin colour, iris colour, pigmentation in back of eye and melanin-containing cellular elements of the auditory system occur independently, as does development of each element on the left vs right side of the animal. This means that in semi-random genes (M merle, s spotting and T ticking), the expression of each element is independent. For example, skin spots on a piebald-spotted dog will not match up with the spots in the dog's coat; and a merle dog with one blue eye can just as likely have better eyesight in its blue eye than in its brown eye.

Loci for coat colour, type and length

All known genes are on separate chromosomes, and therefore no gene linkage has yet been described among coat genes. However, they do share chromosomes with other major conformational genes, and in at least one case, breeding records have shown an indication of genes passed on together.

Gene	Chromosome (in Dogs) ^[51]^[11]	Symbol	Locus Name	Description	Share Chr^[52]^[53]
ASIP	24	A^y, a^w, a^t, a	Agouti	Sable, wolf-sable, tan point, recessive black; a^s disproven
TYRP1	11	B, b^s, b^d, b^c	Brown	Black, 3 x chocolate / liver
SLC45A2	4	C	Colour	No alleles known; possible tyrosinase gene^[54]	STC2, GHR(1) & GHR(2) size
MLPH	25	D, d	Dilution	Black/chocolate, blue/isabella
MC1R	5	E^m, E^g, E, e^h, e	Extension	Black mask, grizzle, normal extension, cocker-sable, recessive fawn
PSMB7	9	H, h	Harlequin	Harlequin, non-harlequin
DEFB103	16	K^B, K^br, k^y	blacK	Dominant black, brindle, agouti-enabler
FgF5	32	L, l	Longcoat	Short coat, long coat
PMEL	10	M, m	Merle	Double merle, merle, non-merle	HMGA2 size
KRT71	27	R, r	cuRlycoat	Straight coat, curly coat
MITF	20	S, sⁱ, s^p	Spotting	Solid, Irish spotting, piebald spotting; s^w not proven to exist
RSPO2	13	W, w	Wirecoat	Wire coat, non-wire coat
MC5R	1	n/a	Shedding	Single coat/minimal shedding, double coat/regular shedding	C189G bobtail
FOXI3	17	n/a	Hairless	Hairless, coated
SGK3	29	n/a	AHT	Coated, AHT-hairless
n/a	18	n/a	Ridgeback	Ridgeback, non-ridgeback
--	3	-	-	No coat genes yet identified here.	IGF1R size
--	7	-	-	No coat genes yet identified here.	SMAD2 size
--	15	-	-	No coat genes yet identified here.	IGF1 size

There are size genes on all 39 chromosomes, 17 classified as "major" genes.^[55] 7 of those are identified as being of key importance and each results in ~2x difference in body weight.^[56] IGF1 (Insulin-like growth factor 1), SMAD2 (Mothers against decapentaplegic homolog 2), STC2 (Stanniocalcin-2) and GHR(1) (Growth hormone receptor one) are dose-dependent with compact dwarfs vs leaner large dogs and heterozygotes of intermediate size and shape. IGF1R (Insulin-like growth factor 1 receptor) and HMGA2 (High-mobility group AT-hook 2) are incomplete dominant with delicate dwarfs vs compact large dogs and heterozygotes closer to the homozygous dwarfed phenotypes. GHR(2) (Growth hormone receptor two) is completely dominant, homozygous and heterozygous dwarfs equally small, larger dogs with a broader flatter skull and larger muzzle.^[57] It is believed that the PMEL/SILV merle gene is linked to the HMGA2 size gene, meaning that alleles are most often inherited together, accounting for size differences in merle vs non-merle litter mates, such as in the Chihuahua (merles usually larger) and Shetland Sheepdog (merles frequently smaller).

pictures here

B/_ D/_

B/_ d/d

b/b D/_

b/b d/d

bodyshot

Lorem ipsum dolor sit amet, sed ne illud apeirian, ex sea alienum accumsan. Eam ut malorum feugiat. Ut elitr atomorum maiestatis ius. Mel eu tritani discere adversarium.

An vide nemore pro, sit suscipit invenire ei. Vis cu possim intellegat liberavisse, nam eu delenit corpora vituperata, et unum offendit duo. An delenit scaevola has, qui et esse ullamcorper. Id facer consequuntur est, eu stet natum iusto qui. Etiam accusata his ne, no aperiri molestie duo. Est quot nulla ut, iudico legendos efficiendi has et, quis persius virtute vis ut. Nam no dicam molestie concludaturque.

Ut vidisse aliquam detraxit est. Eam omnis atqui at, duo ad summo quaeque corpora, fastidii quaerendum sit an. Sea ea solum ignota. Has ex discere accusata nominati. Offendit consetetur accommodare his id, corpora invenire at vim. Eu vim aperiri gubergren.

Putant principes per no. Mundi scripta nominavi id sea, lorem tollit reformidans eu nam. Ut vivendo perpetua per. Possim torquatos assueverit in qui, id fabellas facilisis ullamcorper his. Ad quis facilisi contentiones pri. Ei nam eius habeo apeirian, fabulas periculis sententiae ex vix, ne sit repudiandae neglegentur.

Mea eu timeam conclusionemque, vim cu case sensibus maiestatis, utinam mucius fabellas et sit. Ne quo wisi habemus. Regione habemus necessitatibus ei mea, ubique perpetua constituto sit ut, sed graeci facilisis et. Meis ignota vix ei. Eum ei intellegat repudiandae, clita impetus appareat est ne.

Lorem ipsum dolor sit amet, sed ne illud apeirian, ex sea alienum accumsan. Eam ut malorum feugiat. Ut elitr atomorum maiestatis ius. Mel eu tritani discere adversarium.

An vide nemore pro, sit suscipit invenire ei. Vis cu possim intellegat liberavisse, nam eu delenit corpora vituperata, et unum offendit duo. An delenit scaevola has, qui et esse ullamcorper. Id facer consequuntur est, eu stet natum iusto qui. Etiam accusata his ne, no aperiri molestie duo. Est quot nulla ut, iudico legendos efficiendi has et, quis persius virtute vis ut. Nam no dicam molestie concludaturque.

B/_ D/_

B/_ d/d

b/b D/_

b/b d/d