Genetics of Color

APBT genetics OF COLORATION

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Many people often have the misconception that one gene

controls all traits. The goal of this part of the primer is to give the basics

of coat color genetics but more importantly to introduce the concept of how

multiple genes spread throughout the genome can all influence something as

simple seeming as your dogs color.?? For instance that great

angulation on that dog we saw at the show was not attributed to just one gene

but to many genes that interact together.? Here we will use coat color to

show all the interactions that go in to making a dog a flashy blue fawn black

nose with a black mask.

Challenge for this primer: Here is the question for you:?

The most common phenotype color in show APBTs now days seems to be the blue fawn

black nose with black mask.? What is the expressed phenotype and why

genetically is this becoming such a common coloration?

First lets provide a reference table for the Major Loci and

the possible Alleles mapped to these loci.

Remember the canine genome is made up of a bunch 39 pairs

of chromosomes (78 big chunks of DNA).? Well Loci for color are spread out

all over the place on the genome.? Meaning the genes for color are not

located all in the same location within the huge genome of the? dog.

Locus	Symbol	Alleles	Allele symbol
Agouti	A	Solid Black	AS
?	?	Sable	av
?	?	Grey	ag
?	?	Black and Tan	as
Albino	C	Wild Type	C
?	?	chinchilla	cch
?	?	dondo	cd
?	?	cornaz	cb
Brindle (we consider this in our model to be recessive at the Agouti in our model but is mentioned for the sake of many APBT breeders as a separate locus)	Br	Wild Type	Br
?	?	Brindle	br
Brown	B	Wild type	B
?	?	Brown	bb
Dilution	D	Wild type	D
?	?	Maltese	dd
Extension	E	Wild type	E
?	?	Dominant Black (Note: Dominant black is now thought to originate in its own locus - K see below)	eD
?	?	Fawn	ee
Dominant Black/brindle	K	Dominant Black	K
?	?	Brindle	kbr
?	?	not black or brindle	kk
Grey	G	Grey	g
?	?	Wild type	G
White	Wh	Wild type	Wh
?	?	White	wh
Piebald	SS	wild type	S
?	?	irish	si
?	?	piebald	sp
?	?	extreme	sw

The table above shows the major loci responsible for coat

color in the APBT.? The Symbol shows the letter designation used to

references the allele state at that locus.? Capital letters refer to the

dominant state while small case letters refer to the recessive state of the

alleles.? It should be noted that their are other loci not listed in this

table including Pink-Eyed? Dilute-P, Merle-M, Mask-Me?, Intense-INT, Grey-G,

Flecking-F, Ticking-T etc. that can also be involved but for the purpose of our

discussion these should be sufficient to give us insight into how each of these

loci contribute to a final coat color and pattern.? It should also be noted

before we begin, that terminology and the final model and map for coat color in

dogs has not been standardized.? I will present a conglomeration of various

research articles and genetic findings (Little, 1957; Burns and Fraser 1966;

Whitney, 1980; Robinson, 1990; Sponenberg and Rothschild, 2001)

As we stressed above the coat and skin color of the dogs is

determined by many genes that are expressed and interact in various ways.?The

overall process however all depends on one of two pigments being formed and

deposited correctly and in the correct form in skin and hair.? These

pigments are known as melanin.

You ask, why should color be so important to breeders??

Why shouldn't I breed any color I want if I like it.? If I want an all

white dog with blue eyes or a silver-blue with yellow eyes ... it is my choice.?

OK, but just for fun let's read up on genetics anyway??

The answer to why color can be important to some breeders

is simple and complex but consider the following: The entire process of

coloration in dogs starts with embryonic development.? At the early stages,

specific cells that become melanocytes (pigment producing cells) are derived

entirely from the neuronal crest of the embryo.? In other words color is

ultimately of neural origin.??? Yes pigment cells are directly

related to the nervous system.?? ???HEY!!!? Maybe if you have bad

color genetics you might have bad nervous system genetics???? This is a logical

link to why it is so likely that certain colored dogs such as albino, Harlequin,

and Merles are very very prone to neurological problems such as deafness and

blindness and a propensity for other psycho-neuro and immunological problems

The following is conjecture, not theory, but consider for

the sake of arguement: If you wonder why neuronal derived melanocytes might

relate to immune problems the consider that the behavioral, the nervous, and the

immune systems are linked very closely and communicate extensively.? Not to

mention these neuronally derived cells ultimately interact extensively with

epithelial cells which are primary organs involved in many allergic reactions in

the dog (hives, rashes, hotspots etc.).?

Melanins are simple proteins that are produced by

melanocytes (the neuronally derived pigment cells) and are deposited within skin

and hair cells.? This production of pigments and deposition into epithelial and

hair follicles is actually a complex process with many many steps. The main

point is that because it is a complex process if any step in the process is

altered there is a subsequent alteration in phenotype (coloration or pattern of

coloration).?

There are primarily two types of melanins: Eumelanin and

phaeomelanin.? Eumelanin is the "black" or other derivatives of black such as

blue grey or chocolate brown (liver) depending on various interactions with

other loci.? Phaeomelanin is a slightly different chemical that is generally

reddish brown or yellowish tan.

Melanoyctes are responsible for producing either eumelanin

or phaeomelanin and ultimately depositing these pigments in cells such as

epidermal cells and hair follicles.? Thus, the presence and activity of

melanocytes ultimately controls coloration.? However also consider that

forms of coloration also have hormonal controls that originate from the

pituitary gland.? Only if the melanocytes receive the correct hormonal signals (melanocyte

stimulating hormone) from the pituitary gland (Jackson, 1994) they will produce

eumelanin.? If this hormone signal is not produced they will produce

phaeomelanin.

?Eumelanin and phaeomelanin as the only pigments

controlling color seems like a rather simple system.? However, the actual

control of melanocytes is far more complex and can involve many many genes and

many different alleles found at various positions (loci) within the dog's

genome.? Coloration is in reality under complex cellular and hormonal control

with a multitude of enzymes, hormones, and proteins involved in the final color

and pattern of colors.? Mutations or alternate alleles in these genes can

act to control the differentiation of melanocytes, the migration and

differentiation of the cells or pigments, and also the function or activity of

the proteins involved in production of these pigments.

?The agouti locus (A) (The

place on a chromosome where a specific gene is located, a kind of address for

the gene. The plural is "loci," not "locuses.") listed in table 3-1 contrary to

many online articles does not produce eumelanin or phaeomelanin it actually

produces a protein that counteracts melanocyte stimulating hormone (MSH).? So

where the agouti is active MSH stimulation does not occur so phaeomelanin is

produced.? Thus, in cells that lack an active form of this protein or lack this

gene altogether, as long as the pituitary is producing MSH and this hormone is

efficiently? transported to melanocytes, then eumelanin is produced.

?This raises questions and concerns regarding black as the

dominant color in the APBT.? The main reason for this is based upon differences

in experimental data which suggests that there may be two loci responsible for

black as a color.? For the record MOST of what you will read regarding dominant

black as a color falsely refers to the Agouti locus.? Dominant black is instead

a complete masking of all other Agouti alleles (Table 3-1). ?

?This dominant black completely masks the alleles of the

Agouti but this dominant black can be altered to liver or blue grey when

interacting with other loci.? We will discuss the interactions that produce

these effects below.

NOTE: There are several different forms of dilution in dogs

and each are under separate genetic control.? We will describe most of these

mechanisms that create dilution.

?

The stunning dog to the left has some Irish piebald (see

description of the piebald locus below) but looking at the legs we see what

might be sable or blue coloration and some greying around the muzzle and eyes

(may be effect of localized greying due to the G locus or it may just be an

older dog).? A possible phenotype might be "E K B D G (or g) Ay si".?

As we go through the explanations of these loci you will begin to understand how

each contributes to the final color and pattern.? For now however lets show

a couple more examples.? The handsome dog on the right is a blue with white

with probable greying. The phenotype could be "E K B d G a si".

Sable-Ay as a dominant allele at Agouti if no other locus

interacts to change this.? Sable (seal) is interesting and typically represented

by eumelanic tips on the hairs but the body of the hair is phaeomelanic.? Most

sable colors are very dark and can be mistaken for black.? However the

extremities are often partially or entirely phaeomelanic.? It is said that

in the APBT it is now extremely rare to find a true dominant black genotype (not

phenotype).

?

Though called as black this picture indicates what is

probably a nice dark sable/seal dog with only a little Irish allele interaction of

the piebald locus (see below).? A possible phenotype would be "E k B D g Ay

si"

Agouti and tan point is an Agouti allele represented

typically by a body that is eumelanic and phaeomelanic regions over each eye,

the muzzle, chest, belly, and lower legs.? This coloring is typical of hounds

and German breeds such as the Rottweiler and Doberman Pincher.? There are

several lines of APBT known for this coloring.

?

This is a typical black and tan APBT.? The probable

phenotype might be "E k B D g at m S"

?

Another color that should not be confused with "BLACK" is

the "no pattern" phenotype or "recessive black" at Agouti allele (aa).?

This is an entirely eumalenic state that is very rare among the APBT especially

because of the interaction of other loci.? This is not to be confused with

"dominant black K" which is found at a separate locus.

?

The Extension-E locus is a gene that produces an MSH

receptor protein.? The action of this protein when MSH binds to it is to

switch melanocytes from phaeomelanin production to eumelanin production.?

This is DOMINANT BLACK.? Again we see that the interaction of loci with

each other can be dramatic.? While so many references mistakenly identify

the Agouti locus as that which controls dominant black it is indeed the

interaction of the Extension locus with the Agouti locus that causes complete

eumelanin expression.? This goes even further because the Extension locus

by lack of action causes phaeomelanic production.? The extension locus has

several alleles, wild type allows for expression of the agouti locus, and the

fawn allele results in entirely phaeomelanic coat with dark skin and eyes.?

Fawn varies from very dark to cream colored, but consistently lacks eumelanic

hairs.? Another allele thought to originate at Extension is the mask

allele which as the name indicates causes a eumelanic mask over the muzzle.?

Brindle is another allele that is often thought to be localized at the

Extension locus.? This is typically a colorization pattern consisting of

vertical stripes of eumelanin superimposed over phaeomelanin.

This very dramatic dog has piebald irish, brindle black

over brown.? A possible expressed genotype might be "kbr B C E D aw si".

Dominant Black

(K) is completely eumelanic.?

It is probably an interaction with the Extension and the Agouti loci as

described below.? Consider the dominant Agouti allele, which results in

phaeomelanic expression, while a recessive agouti allele results in eumelanic

expression.? (Many online articles accidentally assign dominant expression

at Agouti to eumelanic production and many even go so far as to list dominant

black as an allele of agouti.)? Actual data suggest that Dominant Black is

probably at a separate locus though some evidence points to its localization at

the Extension locus.? The main point is that it is not at the Agouti locus.

Dominance at the Extension locus definitely causes

eumelanic production.? Dominant black is one of the most common alleles in

some breeds of dog but not necessarily in the APBT, yet also consider that it is

nearly invariably present in fawn (light brown) dogs.? It is only certain

to be lacking in dogs that express intermediate Agouti alleles because these are

unable to mask its presence.? As indicated some research demonstrates a

dominant black at Extension (Newton et al., 2000) but the common thought is that

it is localized at it's own locus K.? Together however these data, Suggest

that multiple genetic mechanisms in dogs may result in a black that masks the

Agouti locus.

The Dominant Black Locus

K is not a fully accepted determinant as

of yet (hard to let go of the past) and is more often associated with the

Extension.? However the Dominant black locus is becoming more popular

especially in light of the canine genome project and increasingly stringent

experimental data.? Consider the 3 alleles in decreasing dominance: K which

would be a black phenotype, k_br which would exhibit brindling, k

which would be normal phenotype describe the Dominant Black Locus. Remember

however that Dominant black (K) is epistatic to whatever is found at the Agouti

locus, however it in turn is overridden by ee at the E locus.?

CONFUSING?????

OK LETS LOOK AT THE POSSIBLE Interactions of E, K, and A

Consider the main interaction is at the E.? The dual recessive (ee) at

the E locus, will result in a phaeomelanin based (reddish, yellow) coat.??

However, if the dog is heterozygous or homozygous dominant at the E locus (i.e.

it is Ee or EE), and if it is KK at the K locus its

coat will be entirely eumelanin based (dominant black); but if it is recessive

k_brk_br or k_brk at the K

locus it will be brindled with the color of the phaeomelanin in part of the

brindling in turn affected by the Agouti alleles present; but if it is kk

at the K locus, Agouti-A will determined distribution of

phaeomelanin and eumelanin.? In other words Agouti only controls color if

there is a dominant Ee or EE and a homozygous recessive kk.

Brown Locus-B Another interesting locus is the

Brown.? This is actually an allele which expresses a protein that

reduces the activity of another protein (catalase) that protects eumelanin.?

The result is that eumelanic cells become brown.? Due to the action of the

protein encoded at the Brown locus, the melanocytes produced are even

structurally different from normal melanocytes.? Because catalase protects

eumelanin during production the reduction in it's activity by the protein

encoded in the brown locus allows hydrogen peroxide to break eumelanin down.?

The wild type Brown locus allows normal expression of eumelanin while the

recessive allele results in a brown (broken down) melanin.? This results in

the color typically referred to as chocolate or liver.

Red-R as a locus has been proposed by laukner (1998)

as a recessive allele condition that results in phaeomelanic coat with no

eumelanic hairs.? This is similar to the action of the recessive Extension

allele.

Dilution-D is a locus of particular interest to the

APBT these days.? This locus causes clumping of pigment in hair shafts.?

It is basically a faulty transport or solubility protein.? The wild type

allows for full color expression while the recessive allele causes lack of color

in the extremities of the hair follicle.? In example, Black becomes

blue-grey, liver becomes light fawn.? Other dilution alleles or locus

include the pink eyed dilute (a lilac color from black or yellowish from liver).

The intense locus which has a dominant effect of causing reduction in the

intensity of phaeomelanic areas.? Thus phaeomelanic areas become cream with

the dominant version of this allele, the recessive version causes no effect.

Merle-M locus is more of an interesting occurrence.?

The merle mutation is due to a transposable element (kinda like a genetic virus

but not contagious except by transfer of to the gametes).? merle is also a

particularly dangerous, because in the homozygous state dogs are often hearing

and visual impaired to various degrees.? It can often be challenging to

diagnose even a 50% decrease in hearing or vision in a dog that has grown up

with this impairment.? It is only in the very severe cases that most people

can see the effects of homozygous recessive mm occurrence of the merle locus.

White-Wh is typically either the lack of pigment or

melanocytes in skin or hair follicles.? White coat color can result from white

spotting (overly piebald LOL) or dilution. This is basically a very big

issue with the APBT.? The UKC standard for instance discourages more than

80% white.? White can occur in combinations ranging from Flashy to piebald

to all white.? White-Wh is also a locus.? However, white is

often classified along with the Piebald locus described below as a locus called

White spotting.??? In the APBT it is assumed that white is

associated with a recessive gene especially when it is also associated with

normally colored eyes.? There is also some evidence though controversial

among owners of white dogs that this condition is also associated with skin, eye

and ear defects.? Again, it should be pointed out that, as with the Albino

locus discussed below, only severe impairments in vision and hearing are readily

notable without professional clinical diagnosis.? Granted, there are also

instances where no such defects are evident even with high quality clinical

testing.?

This lack of pigment resulting in white dogs can arise from

failure of melanoblasts to differentiate from neural cells during embryogenesis,

failure to migrate to skin regions, or death of the melanocytes after they do

migrate (Searle, 1968).? Another mechanism for producing white is based upon

dilution of pigment or if the melanocytes are prevented form producing enough

pigment.? White can occur by combining a dilution factor with the fawn loci.?

These dogs maintain skin coloration resulting in a very pale, but not starkly

white dog.? Yet another cause of all white dogs is attributed to EXTENSIVE

PIEBALD coloring which is not uncommon among the APBT.? This is generally a

white dog with dark colored lips, nose, eye rims and dark eyes.? The

mention of piebald with the white locus is because these two loci are often

considered as one.

Piebald-S is through a complex mechanism and

recessive genotype can results in a completely white coat.?? Piebald

is a locus that acts at the stages of actual melanocytes differentiation during

embryonic development.? The recessive alleles at the piebald locus

ultimately results in white regions where there would typically have been

pigmentation.? With piebald the dominant genotype is non-spotted and dogs

typically lack any white except maybe on the feet.? Another allele is known

as the irish pattern which is typically associated with varying white

particularly on chest, socks, and head (a blaze) for instance.? Thus the

irish pattern is the very showy flash dog show folks love so much.? Beyond

the moderate to exaggerated irish pattern is the piebald and extreme piebald.?

Piebald is a very severe Irish pattern that may be the entire leg rather than

just socks, the fully white neck and chest region and large facial blazing.?

Extreme piebald extends this to cover the entire body as indicated above in the

white discussion.

Albino is a locus that codes for tyrosinase which is

essential for melanogenesis (the formation of melanocytes).? Recessive

alleles at this locus result in production of faulty tyrosinase such that

melanocytes are present but are incapable of full levels of melanogenesis

resulting in pale colors.? There are other alleles here that also result in

blue eyes (Dondo and cornaz).

EXAMPLES

Based upon all of this information on genetic interaction

of the various alleles, particularly A, E, and K, lets take a stab at predicting

the phenotypes of various dogs (Capital letter will represent dominant and small

case recessive at the corresponding locus).? We did the photo examples

above already and these can be reviewed now that all of the major locus have

been defined. We will not guess at the actual genotype of the animal but if a

recessive gene is indicated then we can assume that the genotype is homozygous

recessive.? We will not include a R locus in our model but we will consider

the K locus.

Example 1

This dog is a black brindle over fawn or red with white

chest and feet and the appearance of a masking (can really tell with the

resolution). The probably phenotype is "C E kbr B D g Ay Se m si t"

Example2

This is a brownish-red bitch with a black nose, some white

on the chest and a black mask.? The probable phenotypic pattern is "C E k B

D g Ay(probably) Se (Se is the mask locus) Si t m"

Example 3

This dog is a handsome red-red nose:? There is no

brindling, piebald, dilution etc. though the heterozygous genotypic state is not

of course phenotypic LOL.? The genotype would probably be something like

"k b D g C E Ay m S t"

Example 4

This cute female was described by the owner "who sent in

the picture" as a coco-fawn red nose.? We see immediately that there is a

recessive in the piebald locus because of the amount of whitening to the head,

chest and neck, the lightening of the coat from red suggests a dilution effect.?

The genotype is probably something like "C E k b d g Ay S t"

Example 5

Finally lets do a hard one ;-)

This handsome boy was described by the owner as "smut?".??

This is actually a tri-colored dog. OK we can see obvious piebald, black nose,

brown, and what looks like saddleing combined with blue-grey? and dilution.?

Lets try this as the probable phenotype "E k B d g as Se m sp (saddling at the

Agouti locus)? t"

?

OK LAST THING!!? WHAT WOULD WE GET WITH ALL DOMINANT

OR ALL RECESSIVE PHENOTYPES?

ALL DOMINANT: C E K B D G Ay Se S M T= BLACK DOG HIDING

merle AND OTHER NOT SO FUN THINGS

ALL RECESSIVE: OK LETS JUST SAY IT IS ALL WHITE HIDING NOT

SO FUN THINGS LOL

THE POINT OF THESE LAST COMMENTS ARE THAT PERSONALLY I'LL

TAKE A MIXTURE OF DOMINANT AND RECESSIVE COLOR GENES IN MY DOGS ;-)