Equine coat color genetics

Source: Wikipedia, the free encyclopedia.
For less technical information on horse colors generally, see Equine coat color.
Before domestication, horses are thought to have had these coat colors.[1]

Equine coat color genetics determine a

chestnut
.

These three "base" colors can be affected by any number of

wildtype dun gene
, believed to be one of the oldest colors extant in horses and donkeys. The dun gene lightens some areas of the horse's coat, while leaving a darker dorsal stripe, mane, tail, face, and legs. Depending on whether it acts on a bay, black, or chestnut base coat, the dun gene produces the colors known as bay dun, grullo, and red dun.

Another common dilution gene is the cream gene, responsible for palomino, buckskin, and cremello horses. Less common dilutions include pearl, champagne, and silver dapple. Some of these genes also lighten eye color.

Genes that affect the distribution of

gray
gene causes depigmentation of the hair shaft, slowly adding white hairs over the course of several years until the horse's body hair is near or completely white.

Some of these patterns have complex interactions. For example, a single horse may carry both dilution and white patterning genes, or carry genes for more than one spotting pattern. Horses with a gray gene can be born any color and their hair coat will lighten and change with age.

Most wild equids are dun, as were many horses and asses before domestication of the horse. Some were non-dun with primitive markings, and non-dun 1 is one of the oldest coat color mutations, and has been found in remains from 42,700 years ago, along with dun. Non-dun 2, the version of the dun gene that most domestic horses have, is thought to be much more recent, possibly from after domestication.[3] Leopard complex patterns also predate domestication, having been found in horse remains from 20,000 years ago. The mutation responsible for black and grullo also predates domestication.[1] The mutations causing chestnut, sabino 1, and tobiano appeared shortly after horse domestication, roughly 5000 years ago.[4] Silver and cream dilutions appeared at least 2,600 years ago, and pearl appeared at least 1400 years ago.[5] The gray mutation is also post-domestication but thought to be thousands of years old as well.[6]

Fundamental concepts

See also: Introduction to genetics

Terminology

Heritable characteristics are transmitted, encoded, and used through a substance called

recessive, and a trait that has the same effect no matter whether there is one copy or two is called dominant
.

Notation

Often, the dominant

recessive allele by a lowercase letter. For instance, in silver dapple, this is Z for the dominant silver trait and z for the recessive non-silver trait. However, sometimes the alleles are distinguished by which is the "normal" or wild type allele and which is a more recent mutation. In our example z (non-silver) would be wild type and Z would be a mutation. Wild type alleles can be represented as + or n, so Zz, Zz+, Z/+, and Z/n are all valid ways to describe a horse heterozygous for silver. Wild type notation is mainly useful when there is no clear dominant/recessive relationship, such as with cream and frame overo, or when there are many alleles on the same gene, such as with MITF
, which has four known alleles. Using n is also common in the results of genetic tests, where a negative result usually means none of the known mutations were found, but does not rule out undiscovered mutations.

Melanin

Genes affecting coat color generally do so by changing the process of producing

eumelanin, which is brown to black. Melanin is not a protein and therefore there is no gene that changes its structure directly, but there are many proteins involved in the production of melanin or the formation of melanocytes during embryonic development. Mutations that change the structure of proteins with a role in melanin production can result in slightly different variations of melanin.[7]
Some genes do not alter the structure of melanin but instead affect where and whether it is produced.

Extension and agouti

The genes extension and agouti together affect the placement of the two types of pigment, black eumelanin and "red" (coppery brown) pheomelanin.

The extension gene codes for a molecule called the

epistatic to agouti, meaning that if a horse has two e alleles, it will be chestnut no matter what genotype it has at agouti.[10][11]

The

wildtype, allele of agouti is called A, and the non-agouti mutation is called a.[14]

Phenotypes

Extension Agouti Image Description
ee any
Chestnut, or depending on other genes red dun, palomino, cremello, gold champagne
, and others.
EE or Ee aa
silver dapple
, classic champagne, and others.
EE or Ee AA or Aa Bay, or depending on other genes bay dun, buckskin, perlino, silver bay, amber champagne, and others.

Extension

Extension is found on equine chromosome 3 as part of a linkage group with

roan, tobiano, and the KIT gene.[15] Extension is also sometimes called "red factor" and can be identified through DNA testing.[10] Horses with the genotype E/E are sometimes called "homozygous black", however depending on the agouti genotype there is no guarantee that any offspring can be black coated
, only that no offspring will be "red".

A study that compared horse genotypes to their coat color phenotypes did find a statistically significant connection that suggested that lighter bay shades were heterozygous for the Extension mutation (E/e) and darker bay shades were homozygous.[13]

Mutations that break protein function generally lead to

recessively inherited lighter or redder coat colors in various mammals, while mutations that cause MC1R to be constantly active result in dominantly inherited black coats.[16][17]
In horses, both known mutations break the protein and therefore result in red coats.

Various

blond hair, fair skin, and susceptibility to sunburnt skin and melanoma.[8] Polymorphisms of MC1R also lead to light or red coats in mice,[18] cattle,[19] and dogs,[20] among others. The Extension locus was first suggested to have a role in horse coat color determination in 1974 by Stefan Adalsteinsson.[21] Researchers at Uppsala University, Sweden, identified a missense mutation in the MC1R gene that resulted in a loss-of-function of the MC1R protein. Without the ability to produce a functional MC1R protein, eumelanin production could not be initiated in the melanocyte, resulting in coats devoid of true black pigment. Since horses with only one copy of the defective gene were normal, the mutation was labeled e.[9]

Extension alleles

There are three known alleles of extension, the wildtype E, and two recessive alleles e and ea which cause chestnut color.[10] The E allele can also be called E+ or EE, and the e allele may also be called Ee.

Of the two known mutations, the first to be discovered was e, and is a change of a single

polypeptide. Visually there is no difference between the two.[22][23]

Agouti

In many species, successive pulses of ASIP block contact between α-MSH and MC1R, resulting in alternating production of eumelanin and pheomelanin; hairs are banded light and dark as a result. In other species, ASIP is regulated such that it only occurs in certain parts of the body. The light undersides of most mammals are due to the carefully controlled action of ASIP. In mice, two mutations on Agouti are responsible for yellow coats and marked obesity, with other health defects. Additionally, the Agouti locus is the site of mutations in several species that result in black-and-tan pigmentations.[24][25]

One genetics testing lab began offering a test for another allele At,[26] thought to be responsible for seal brown, but it was later found to be inaccurate and is no longer offered.

Dun

The flat, earthy tone of the coat and vivid dorsal stripe are indicative of the D allele. Primitive markings are seldom visible on horses without the dominant, wildtype dun allele (D).
See also: Primitive markings and Dun gene

Dun is one of several genes that control the saturation or intensity of pigment in the coat. Dun is unique in that it is simple dominant, affects eumelanin and pheomelanin equally, and does not affect the eyes or skin.[27] Horses with the dominant D allele (D/D or D/d genotype) exhibit hypomelanism of the body coat, while d/d horses have otherwise intense, saturated coat colors. The mane, tail, head, legs, and primitive markings are not diluted. Zygosity for Dun can be determined with a DNA test.[27]

The Dun locus is TBX3 on equine chromosome 8.[3][28] The molecular cause behind the dun coat colors is not entirely understood, but the dilution effect comes from the placement of pigment in only part of the hair. The associated coat colors were assigned to the Dun locus in 1974 by Stefan Adalsteinsson, separate from Cream, with the presence of dun dilution indicated by the dominant D allele.[21] The dominant D allele is relatively rare compared to the alternative d allele, and for this reason, the dominant allele is often treated as a mutation. However, the pervasive coat color among wild equids is dun, and researchers from Darwin to modern day consider dun to be the wildtype state.[29][30]

An older non-dun mutation was found in 2015 and named non-dun 1. It creates primitive markings but does not dilute the base color, and is co-dominant with the more common non-dun 2 but recessive to dun.[3]

Dun phenotypes

  • D/D (+/+, D+/D+) wildtype, homozygous dominant. Visually, the horse may be bay dun, grullo, red dun, palomino dun, amber dun, gray, and so on. Such a horse will always pass on the D allele and will therefore always have dun offspring.
  • D/d (+/d, D+/Dd) wildtype, heterozygous. Visually indistinguishable from the homozygous D horse.
  • d/d (Dd/Dd) non-dun, homozygous recessive. The entire coat, barring the influence of other alleles, is a rich, saturated color. The
    gray, palomino
    , and so on.

Cream

Main article: Cream gene

Cream is another one of the genes that control the saturation or dilution of pigment in the coat. Cream differs from Dun in that it affects the coat, skin, and eyes, and unlike Dun, is dosage dependent rather than simple dominant. Furthermore, the effects on eumelanin and pheomelanin are not equal. Horses with the homozygous recessive genotype (C/C) are not affected by cream. Heterozygotes (CCr/C) have one cream allele and one wildtype non-cream allele. Such horses, sometimes called "single-dilutes", exhibit dilution red pigment in the coat, eyes, and skin to yellow or gold, while eumelanin is largely unaffected. Homozygotes (CCr/CCr) have two cream alleles, and are sometimes called "double-dilutes." Homozygous creams exhibit strong dilution of both red and black pigment in the coat, eyes, and skin to ivory or cream. The skin is rosy-pink and the eyes are pale blue. Cream is now identifiable by DNA test.[31]

See also:
SLC45A2

The Cream locus is occupied by the

medaka, though the specific action is not known.[32]

single nucleotide polymorphism in Exon 2 resulting in an aspartic acid-to-asparagine substitution (N153D), was located and described in 2003 by a research team in France.[32]

Cream phenotypes

  • C/C homozygous wildtype. Visually, the horse may be any color other than the cream dilute shades of palomino, buckskin, smoky black, cremello, perlino, smoky cream, and so on.
  • CCr/C heterozygous. The colors most commonly associated with this genotype are palomino, buckskin, and smoky black, though the phenotype may vary depending on other factors. Any pheomelanin in the coat is diluted to yellow or gold, and the eyes and skin are often slightly lighter than unaffected horses.
  • CCr/CCr homozygous. The colors most commonly associated with this genotype are cremello, perlino, and smoky cream. Regardless, the coat will be cream- or ivory-colored, and the skin a rosy-pink. The eyes are pale blue.

Champagne

Main article: Champagne gene

Champagne is a gene that controls the saturation or dilution of pigment in the coat. Unlike Cream, Champagne is not strongly dosage-dependent, and affects both types of pigment equally.[36] Champagne differs from Dun in that it affects the color of the coat, skin, and eyes, and in that the unaffected condition is the wildtype. Horses with the dominant CH allele (CH/CH or CH/ch genotype) exhibit hypomelanism of the body coat, such that phaeomelanin is diluted to gold and eumelanin is diluted to tan. Affected horses are born with blue eyes which darken to amber, green, or light brown, and bright pink skin which acquires darker freckling with maturity.[36] The difference in phenotype between the homozygous (CH/CH) and heterozygous (CH/ch) horse may be subtle, in that the coat of the homozygote may be a shade lighter, with less mottling.[36] Horses with the homozygous recessive genotype (ch/ch) are not affected by champagne. Champagne is now identifiable by DNA test.[31][37]

See also:
SLC36A1

The Champagne locus is occupied by the

single nucleotide polymorphism responsible for the champagne phenotype is a missense mutation in exon 2, in which a C is replaced with a G, such that a threonine is replaced with arginine.[36]
This mutation was identified and described by an American research team in 2008.

Champagne phenotypes

  • ch/ch (N/N) wildtype, homozygous recessive. Visually, the horse may be any color other than the champagne shades.
  • CH/ch (CH/N) heterozygous. The colors most commonly associated with this genotype are gold champagne, amber champagne, and classic champagne, though the exact phenotype depends on a variety of factors. At birth, the skin is bright pink and the eyes bright blue, darkening to freckled and light brown or green, respectively, with age. Both red and black pigment in the hair are also diluted.
  • CH/CH homozygous champagne. Homozygotes, which will never produce non-champagne offspring, are indistinguishable from heterozygotes except that their freckling may be sparser, and their coats a shade lighter.

Alleles and effects

Locus Alleles Effect of combined pairs of alleles
MC1R
(Extension) 		E
e
ea 		EE, Ee, or Eea: Horse forms
chestnut
; it has black pigment in skin, but red pigment in hair.
ASIP

(Agouti) 		A
a 		Agouti: Restricts
eumelanin, or black pigment, to "points," allowing red coat color to show on body. No visible effect on red horses, as there is no black pigment to restrict.
AA or Aa horse is bay, black hair shows only in points pattern (usually mane
, tail, legs, sometimes tips of ears).
aa: If horse has E allele, then horse will be uniformly black.
MATP
(Cream, Pearl)[5] 		Cr
prl
C, Prl, or n 		Cr/Cr: Horse is a double dilute cream (cremello, perlino, or smoky cream) and will have creamy off-white hair with pale eyes and skin.
Cr/n: Horse is a single dilute cream (palomino, buckskin, or smoky black/black carrying cream) with red pigment diluted to gold.
prl/prl: Horse is pearl. Red is lightened to an apricot color, and skin coloration is pale.
Cr/prl: Horse is a pseudo-double cream with pale skin and eyes.
n/n: Horse has normal, undiluted, coloration.
TBX3
(Dun) 		D
nd1
nd2 or d 		D/D, D/nd1, or D/nd2:
Wildtype dilution
. Horse shows a diluted body color to pinkish-red, yellow-red, yellow or mouse gray and has dark points called primitive markings including dorsal stripe, shoulder stripe and leg barring.
nd1/nd1: Horse is very slightly diluted and primitive markings are darker.
nd1/nd2: Horse is not diluted and has faint primitive markings.
nd2/nd2: Horse has undiluted coat color with no primitive markings.
SLC36A1
(Champagne) 		Ch
n 		Champagne: A dominant dilution gene that creates freckled skin, amber or green-ish eyes, and gives a bronze cast to hair. The skin surrounding the eye must be pink with freckles in adulthood.
Ch/Ch or Ch/n: Champagne dilution evident (See Genetic Formulas Chart below.)
chch: No champagne dilution [38]
PMEL or SILV
(Silver dapple) 		Z
n 		Z/Z or Z/n: Silver dapple - Dilutes eumelanin (black pigment). Converts black to brown with white/silvery mane and tail or results in silver coloring.
n/n: No silver.
MFSD12[39]
(Mushroom) 		Mu
mu 		Mu/Mu or Mu/mu: Mushroom - Dilutes red pigment to a sepia shade.
mu/mu: No mushroom effect.
Gray
) 		G
g 		G/G or G/n:
Gray
The greying process is progressive and unique to the horse.
n/n: No grey.
EDNRB
(Frame Overo/Lethal white syndrome
) 		OLW or Fr
n 		OLW/n: Frame Overo pattern -
colon
and the inability to defecate, which leads to death or humane euthanization within days of birth.
Inversion starting about 100k bp downstream of
KIT[40]
(Tobiano
) 		TO
n 		TO/TO or TO/n: Tobiano, a form of pinto patterning. Produces regular and distinct ovals or rounded patterns of white and color with a somewhat vertical orientation. White extends across the back, down the legs, and often over the shoulder and crest. A white tail head is also very common.
n/n: No tobiano pattern present.
KIT or CD117
(White, Sabino
) 		W1
W2
...
W27
SB1
n 		Complicated. See
white from birth. There may be some patches of color, which may fade to white as the horse grows older. When this is caused by SB1 it may be referred to as "maximum sabino".
SB1/n - Classic sabino has assorted pinto or roan-like markings. Recognized by abundant white on the legs, belly spots or body spots that can be flecked or roaned, chin spots, or white on the face extending past the eyes. Sabino is registered as overo by some registries, but is not frame overo and does not cause overo lethal white syndrome.
n/n: No sabino.
Note: The above applies when W is one of W1, W2, W3, W4, W9, W10, W11, W13, W14, W17, W23, W24, or W25. See white
for a description of the other W alleles.
Near or at
KIT[42]
(Roan
) 		RN
n 		RN/RN or RN/n: roan pattern of white hair mixed in with base color. Head and lower legs remain dark. Inverted “V”s are present just above the knees. It used to be thought that roan was homozygous lethal, but since then living homozygous roan horses have been found.[43][44]
n/n: No roan.
TRPM1
(Leopard complex) 		LP
n
Leopard spotting gene. Produces coat spotting patterns, mottling over otherwise dark skin, striped hooves and often white sclera
. Can also produce varnish roan.
LP/LP: Fewspot or snowcap horse.
LP/n: Leopard or blanket horse.
n: No leopard complex.
RFWD3
(Pattern 1) 		PATN1
n 		PATN1/PATN1 or PATN1/n: Combined with the leopard complex, produces a leopard/fewspot or near-leopard/near-fewspot horse. It has no visible effect on n/n (for LP) horses.
n/n: Horse is solid or varnish roan, unless it has (an)other (as yet undiscovered) PATN gene(s).
MITF
(Splashed white, macchiato) 		SW1
SW3
macchiato
n 		SW1/SW1: Classic splashed white.
SW1/n: White markings on head and legs.
SW3/SW3: May be embryonic lethal.[45]
SW3/n: Splashed white.
Macchiato/n: The macchiato allele has been found in a single stallion named Apache, who had a white pattern in similar places as for splashed white, a dilution, deafness, and reduced fertility. It is likely that this mutation will not be passed on.[46]
n/n: No splashed white or macchiato.[47]
PAX3
(Splashed white) 		SW2
SW4
n 		SW2/SW2: Previously thought to be lethal, but SW2/SW2 horses have since been identified. However it often causes short tongue and/or infertility.[45]
SW2/n: Splashed white, but usually not as loud as a classic splash.
SW4/SW4: Might be lethal.
SW4/n: Splashed white or broad blaze.
n/n: No splashed white.[47]

Notable color combinations

Phenotype Potential Genotype
Extension
Agouti
Dun
Champagne
Silver
Cream/Pearl
Bay E/- A/- d/d ch/ch z/z n/n or n/prl
Chestnut e/e -/- d/d ch/ch -/- n/n or n/prl
Black E/- a/a d/d ch/ch z/z n/n or n/prl
Bay dun E/- A/- D/- ch/ch z/z n/n or n/prl
Red dun e/e -/- D/- ch/ch -/- n/n or n/prl
Grullo (Blue dun) E/- a/a D/- ch/ch z/z n/n or n/prl
Amber champagne E/- A/- d/d Ch/- z/z n/n or n/prl
Gold champagne e/e -/- d/d Ch/- -/- n/n or n/prl
Classic champagne E/- a/a d/d Ch/- z/z n/n or n/prl
Silver bay E/- A/- d/d ch/ch Z/- n/n or n/prl
Silver black E/- a/a d/d ch/ch Z/- n/n or n/prl
Buckskin E/- A/- d/d ch/ch z/z Cr/n
Perlino E/- A/- d/d ch/ch z/z Cr/Cr
Palomino e/e -/- d/d ch/ch -/- Cr/n
Cremello e/e -/- d/d ch/ch -/- Cr/Cr
Bay pearl E/- A/- d/d ch/ch z/z prl/prl
Bay pseudo-double pearl E/- A/- d/d ch/ch z/z Cr/prl
Apricot (Chestnut pearl) e/e -/- d/d ch/ch -/- prl/prl
Chestnut pseudo-double pearl e/e -/- d/d ch/ch -/- Cr/prl
Black pearl E/- a/a d/d ch/ch z/z prl/prl
Black pseudo-double pearl E/- a/a d/d ch/ch z/z Cr/prl
Dunskin E/- A/- D/- ch/ch z/z Cr/n
Dunalino e/e -/- D/- ch/ch -/- Cr/n
Silver buckskin E/- A/- d/d ch/ch Z/- Cr/n
Silver smoky E/- a/a d/d ch/ch Z/- Cr/n
Gold cream e/e -/- d/d Ch/- -/- Cr/n
Amber cream E/- A/- d/d Ch/- z/z Cr/n
Classic cream E/- a/a d/d Ch/- z/z Cr/n

See also

References

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