Article: Coat Colour in the Great Dane

As coat colour is a complex area, I would be doing an injustice to the writer of this article to put it in to my own words. Only left to say that all credit is given to it’s author for their detailed information;


Breed history and current genetics.
By JP Yousha (September 2006)

This article originally appeared in the DANE WORLD: S/O 2006, Vol 15, Issue 5.

INTRODUCTION: Most of our working knowledge in canine coat color genetics in canines is actually taken from research done by C.C. Little more than fifty years ago. Some have actually read his book (now out of print), but most have only read digests of his work offered in other text books, which occasionally provide updates. Many of us have only seen coat color genetics information when presented as commentary, which has been done repeated by a wide variety of derivative sources. Regardless of the source or sources, all this work was predicated on observing statistical phenotype variation. In other words, people bred various dogs and reported the results of the offspring. From these observations various expectations of coat color were predicted; nothing was known at all of the biology of color. This is a time-honored method of discerning various heritable traits, but was simply based on statistics made from personal records. This method is indirect and always somewhat subjective, so errors inevitably crept in and gaps persist in our knowledge.

But in this day and age of dawning molecular medicine and while unraveling the secrets of nucleotides, we can begin to do a bit more. We can begin to actually discuss how color is made and what sort of biologic action a mutation results in. Researchers are now able to ask how a gene is acting to result in a specific color. This article has been written to offer Great Dane breeders a “hands-on” approach to coat color genetics and to acquaint readers with the more recent advances in coat color research, especially as they apply to the Great Dane. We are not “there” yet: we don’t have all the answers today, but we are now on the road to answering completely and accurately all these old and persistent questions of how coat color is inherited. We breeders we need to keep ourselves informed on these advances, so as not be left behind (as well as to fulfill our own breed Code of Ethics which enjoins us all to keep abreast of new information). This article will start with needed terminology and then quickly move into a discussion of the various color genes, outlining known facts and recent advances. Some notes on the tradition and history of color in the Great Dane and a few comments on the relevance of color to a breeding program are offered in conclusion.
So let’s begin with a bit of basic terminology. We must first define a few terms just to put them in place and get them out of the way. A LOCUS is simply the location of a gene; the place it lives on a particular chromosome-its street address if you will. LOCI is the plural. An ALLELE is one of at least two variation of a gene at any given gene location (locus). Essentially you have a wild type allele (the “standard” gene), and any variation is then defined as a mutation. A mutation can be an improvement in some way, a simple variation, or can sometimes be detrimental, but is not necessarily so. Dominant and recessive are old terms, now somewhat antiquated, for whether a gene can express when in a single copy (dominant) or only if two copies were present (recessive). It’s better to say a gene is “unexpressed” rather than “recessive” but it means (roughly) the same thing. Some mutations are “dominant” and many mutations (and more typically in purebred dogs) are “recessive.” Some genes are somewhere in between and are called “incomplete dominants” or “co-dominants.” Simply think of these latter as a case where BOTH genes are expressing simultaneously (vs. where only one or the other is seen as in the dominant and recessive situations). Some genes have a specific effect all on their own, but many are altered by the affects of genes at other locations. A phenotype is the result of their combined action (and various non-heritable conditions as well).

Mutations for pigment produce the variations in coat color that we see, as well as some defects in dogs. Genes named under the old “Little” system typically were identified by what sort of effect the mutation had. The M Locus, for example, was named for the “merle” gene, as here was a dominant mutation that caused a solid coat to appear patched or dappled. The C Locus was named for the “chinchilla” gene, which is a recessive mutation that washes out a rich gold coat to a pale cream color. Under the new system, now emerging, genes are being named in an even more cryptic manner, but the newer names are more accurate and reflect new molecular data. So we shall all have to get used to them I think. The old Extension or “E” locus, for example, is now referred to as MC1R gene. This sounds rather fearsome to most of us already a bit bemused by the “E locus,” but is simply “gene speak” for the actual gene (the melanocortin receptor 1) that has been found to cause the effects we associate with the E Locus. So this is a step forward really, and when you see that these sorts of names that means the actual gene has been found and the action of the gene is known. Knowing this might make it easier to try to remember the new names. This is real progress, as it represents the first time we have real knowledge of the genes involved, and each discovery is quickly producing a DNA test to identify the dogs that carry that mutation. That translates into breeder power, as you will then be able to select the dog you want at the direct, genetic level.

One more quick note on nomenclature: pigment in dogs comes in two basic forms. Eumelanin is the dark pigment that is black, brown (i.e. chocolate) and blue by our breeder terminology. The other pigment is phaeomelanin and this is the bright pigment that produces red, yellow, and cream colors in canine coats. It’s the basic pigment of our fawn. Each type of pigment is affected by different genes. Some genes function to affect the intensity of pigment and so change jet black eumelanin to the flat gunmetal gray Dane people call blue for example. Other genes are “pattern” genes and alter the distribution (not the color) of the pigment; like brindle, which causes striping. Most genes can affect pigment or pattern, but not both, as each gene has its own particular action. (Merle is an exception.) When you have more than one mutation, you can get more than one effect on the same dog. For example, you can have a blue brindle (as opposed to a standard coat of black and gold) from an alteration in basic pigment, or you can have a “brantle” when the normal brindle pattern combines with a mantle pattern. You can multiple effects from multiple genes: for example, a merled blue brindle piebald can result when both pattern and pigment genes are changed from our standard. Note also that “white” genes are actually genes which disable the body’s ability to make pigment, as areas of white actually LACK pigment (i.e. white is not a “third” form of melanin). All white genes in the Great Dane are actually spotting genes. Spotting genes are associated with various defects. More on that later.
A lot of what is needed for breeders to breed color properly has been generally known long before the word gene was even coined, and the lack of precise detail in certain areas of coat color genetics should be responded to with intellectual curiosity, but it should not used as an excuse to do various weird or off-beat breedings. Logically we can now leave this kind of exploration to the geneticists to do at the molecular level; our dogs need no longer be guinea pigs for various test breedings. Nor do newcomers to the breed, please, need to recreate the wheel and so learn for themselves what is otherwise well known by experimenting with odd color pairings. Pockets of these sorts of misadventures do seem chronic problems in this breed so this needs to be said. Note also that this article is intended to provide new information and new avenues of genetic and molecular data to Great Dane breeders and owners, but it is not written as a “breeding guide” nor does it intend to suggest the breed standard is outdated or should be superseded. Plus this candid discussion of non-standard colors does not imply they “should” be bred; quite the contrary.

When thinking of a gene, try to not think of the dog you see so much (i.e. try to forget the phenotype for a moment), and start to think about the biology of the thing-what the gene does to make the color or pattern we see. For each gene there is a specific molecular action taking place. Thinking this way (rather than thinking “there is no blue in my pedigree!”) will help you understand not only the new information on coat color, but help you learn about genetics and how disease and inherited traits in general actually occur. Each functioning gene is preserved DNA code that results in the formation of a protein. Protein literally build bodies. Mutations alter the protein formed, so the change you see are a result of the gene acting differently due to the alterations that occurred to it on a (sub)-molecular level. Isolating this change is the first step to identifying and controlling the gene in question. Traits that are “genetic” (that is heritable) are ultimately under our control given the right tools, so defining a trait as heritable is less dooming an individual to its fate than offering us all a hopeful message that we are going to be able to select just what we want in our dogs. That’s another change we need to make in our mentality about genes: knowing a trait is inherited is GOOD news, even if the trait is a disease or unwanted color! So be glad a trait is inherited, as that means we can ultimately choose to have it or not have it in our dogs. At the end of this article is a set of references for more information on coat color genetics and a fairly extensive bibliography for those who want to read more about this most interesting field of study.

Now on to the specific genes associated with coat color: but please one quick note first. I want to admit that I’ve simply ignored various canine loci postulated (e.g. G Locus) that are not relevant to the Great Dane. My argument for this omission is that this subject is already complicated enough without adding in information that is merely academic to Dane breeders. Anyway the complete list of canine color gene loci is so widely published it’s easily found if needed. However be warned that much of the tradition repeated so widely on coat color in dogs is so outdated and/or so inaccurate, any such source (especially internet layman sources) should be treated with some caution. Check the references I’ve offered first instead.

OUTLINE OF CANINE COAT COLOR GENES (as applies to the Great Dane):

AGOUTI LOCUS: Traditionally thought to begin with a dominant black gene and then followed by various recessive alleles that restricted the expression of black in the dog, (making the dog various patterns of yellow and black), this canine locus has recently fallen in line with a larger mammalian tradition that states the most dominant gene here is a “yellow” gene, which Dane people would call fawn (others call it sable), and moves towards solid black in it’s recessives. So what this means is that “dominant black” has been removed to its own locus & all Great Danes are “fawn” at the agouti locus, i.e. all are homozygous for a^y. Below are proposed alleles currently at this locus.
a^y = Dominant allele that restricts dark pigment distribution; produces fawn/sable.
a^w = agouti “wild-type” allele: gives wolf-grey coloration. Also called a^g.
a^t = tan point allele: gives bicolored animal; dark body with tan points.
a^s = (conjectured) gives dark saddle pattern on tan body.
a^b=recessive black present in some breeds (e.g. GDSs).
In humans this gene is found on the long arm of chromosome 20, and in the dog is located on chromosome 24. This locus is notoriously difficult as to naming how many and what are the order of its alleles. There are details still to be worked out about agouti, however the general molecular action is quite clear and precise: the gene moves slowly and inexorably from a clear yellow dog (our fawn) to a totally black animal; and skin is always black (when left unmodified by other loci). With agouti, a protein called ASIP (agouti signal peptide) interacts with MSH (melanocyte stimulating hormone) to create the various black-n-tan patterns we associated with this gene. And oddly enough agouti has more than one promoter (that’s where a gene starts it’s business of being made), which is why so many dogs colored by this gene have a different color on their backs vs. their bellies: one promoter is producing eumelanin predominately (black pigment), while the other promoter for this same gene is producing phaeomelanin (red/tan pigment). This is how hairs get banded too; two promoters responding differently by “letting through” one pigment preferentially over another. Greg Barsch’s group at Stanford is currently working on (and close to solving) the remaining mysteries of agouti.
For those still shocked by the idea that our black (dominant black) gene isn’t here after all, read the recent molecular evidence that supports this claim: Exclusion of Melanocortin-1 Receptor (Mc1r) and Agouti as Candidates for Dominant Black in Dogs by Kerns JA, Olivier M, Lust G, Barsh GS., (Hered 2003 Jan: 94(1):75-79). The various conundrums here about saddling vs. tan-point really are not pertinent to Danes. The only point here is ALL Danes, be they black, blue, Harlequin, Mantle, fawn, brindle, merle or otherwise, are “fawns” in the sense they are all a^y homozygotes. So there is no need for us to test for this locus; there is also no “recessive fawn gene” here as long thought. There is the rare Dane reported who has a “bas rouge” or “tan point” (think Doberman) pattern, but that’s a rare enough phenomenon in the breed for most of us to safely ignore. A company in Canada called Health Gene (address at the end of this article) offers a test in certain breeds (e.g. Shelties) to distinguish a^y sable (our fawn) from a^t (tan-point) and a^b (a) which is recessive black. So assumably if someone wanted to test a Dane for carrying the tan-point recessive (or even recessive black), it’s possible.

BROWN LOCUS: Brown is the recessive gene that has been romantically called “chocolate” by some Dane breeders and is also called “red” or “liver” in various breeds. The dominant here produces a black dog, the recessive results in a brown dog. Actually it turns out there are at least two recessive brown mutations here, and it’s not obvious from looking at the dogs which has which. Happily you can test for both mutations through Health Gene as they offer a commercial test for the alleles at this locus. This gene is formally called Tyrosinase Related Protein 1, or TYRP1 for short, and is found on canine chromosome 11. Again, this sort of “alphabet soup” name means that the gene and its action are known.
These dogs are, quite literally, bleached in pigment at the molecular level (eumelanin is unprotected from hydrogen peroxide). This diluter gene, like the one that produces Dane blue, works particularly on eumelanin (black) pigment; phaeomelanin (red) pigment is not as obviously affected. All dogs that are brown (or have brown pigment in their patterns) must also have a dominant allele present at the E locus. Brown is a common color in gun dog breeds. Most all these breeds then eschew the blue diluter gene that we in Danes have preserved. It seems that most breeds have decided one, but not both, of these major eumelanin diluters, can be acceptably present in a single breed. Dobermans and Weimaraners are an exception to this rule and accept both D & B dilution mutation.
A brown dilute dog, the “chocolate Dane,” is documented in this breed, but it’s rare. And although this brown isn’t formally connected to any defects, it can be the case that reductions in pigment results in various structures and functions being weakened, and this brown dilute can combine with our blue dilute gene in one dog, creating a “double dilute” individual. When both blue and brown dilutes occur in the same dog, the resulting “double dilute” is what is called “Doberman fawn” and is also the sort of color seen in Weimaraners. In Danes this “double dilute” dog was referred to historically as Drapp-a cafÈ au lait or dull silvery hue results–a sort of flat, pale grayish-tan coat color that has been long recorded in the Great Dane from the combination of various diluter recessives, but a color that still has never found favor in this breed. The term Drapp, by the way, is not a cognate (i.e. is not our “drab”), and is not a standard German word you would find in the usual dictionary, but rather is from old Austrian dialect, and was originally a reference to this muted sandy-gray shade that is typical of leather. (It’s borrowed from the French word for a fabric that looks like leather.) It was a term used in the Austro-Hungarian empire for a particular color, and made its way eventually into the early German Great Dane studbooks to describe what some now call “lilac” Danes. Along with Drapp, “brown” (Braun), “Isabella” (a chinchilla dilute that is like palomino or cream color in horses) and red (Rot) Danes are also mentioned in early breed history records. At least one of these dilutes is likely from the B locus, that is TYRP1; and the occasional “chocolate” colored Dane is still seen in the breed. Older American standards refer to such faults of color as “black-brown” in blacks, and “drab color”-a “dirty yellow color” in fawns, both of which may well be references to various dilute genes.
Pure color bred dogs can carry endlessly for such recessives, and the above illustrates more than one diluter is a part of our breed history if not allowed under the standard for color. we call blue is also a pigment diluter, so it makes sense the breed has discarded this brown dilute, for breeding clarity (knowing what color the dog really is genetically), as well as to avoid potential physical weakness. So brown Danes (or fawns or brindles with brown vs. black markings) are not necessarily the result of cross-color breeding, never mind outright cross-breeding despite claims made they “must be.” It’s worth noting that brown dogs must have brown (not black) noses, eye rims and pads, which is an easy way to distinguish a brown from a black or blue dog. Reduction in eye (iris) color intensity/depth is also noted.
B = Dominant allele that allows for a fully pigmented (black) dog.
b = Recessive that permits the expression of brown (chocolate, liver, red) dilution.
Note: new research indicates there are TWO recessives).
Affects skin/hair color simultaneously.

CHINCHILLA LOCUS: This is the gene that is thought to alter the depth of pigment for phaeomelanin, taking a rich golden coat to pale yellow and ultimately a creamy white. It is found on canine chromosome 21 and results from variations in the production of tyrosinase, an enzyme involved in pigment production. Here the nose and skin can remain very dark and it’s thought that dark pigment, eumelanin, is less affected by the chinchilla locus genes than the bright pigment called phaeomelanin. Traditionally there are at least 3 alleles recognized here and there may be as many as six. There is no record of true (tyrosinase negative) albinos in the domestic dog, but albinonic whites (tyrosinase positive dilutes) are a result of this gene’s mutations. (Think white German Shepherds and white Dobermans.) But other than some recessive here that possibly dilutes the preferred deep golden fawn to a pale, washy shade, this gene has little relevance to the Great Dane.
C = Tyrosinase dominant that allows for a fully pigmented (red/gold) dog.
c^ch = Chinchilla recessive that results in a “washy” pale gold coat.
c^e = extreme dilution = cream-colored coats.
c^a = true albino; total reduction of pigment via the interruption of the tyrosine pathway. The above is taken from such as Little. There is little to no actual molecular work on this done yet, so it’s difficult to say what alleles and actions (other than a general paling of red/yellow pigment) result from this locus.
It’s possible that the faults of “yellow-black” and “brown-black” mentioned in earlier breed standards, i.e. “rusty” black Danes sometimes result from blacks carrying the chinchilla dilute, just as blues with “a tinge of yellow” may have the same diluted recessive gene. Other breeds do claim that their “off” blacks are produced through recessives at this locus.

DILUTION LOCUS: This is the gene that results in the blue Dane. The dominant here is full black coat and the recessive produces that characteristic gunmetal gray color we call blue. As with the brown (TYRP1) locus, with the D locus, skin and hair color are both simultaneously affected. Early data suggests that this gene is another tyrosinase-related gene called TYRP2. TYRP2 is located on canine chromosome 22 and is involved in some form of gray color in the dog. Traditionally the dilution here is called Maltese blue. The color is present at birth (i.e. it’s not a graying gene). Blue dogs have slate-colored noses and lighter eyes than their black littermates. Blue as a pigment is not related to pattern, so any Dane with black pigment, including fawns and brindles, can carry for blue (or chocolate) pigment and produce such non-standard variant (blue-faced fawns, chocolate-striped brindles) when bred to another such carrier. That’s worth remembering. Older breed standards mention such color variations explicitly (e.g. blue striped brindles) as faults, and the English standard is unusual in that it recognizes the blue colored Harlequin.
D = allows for black pigment to form.
d = produces blue/slate/gray dilution.
Affects skin/hair color simultaneously.
There is a phenomenon called “Blue Doberman Syndrome,” (which goes by various other names), that is a form of follicular dysplasia that occurs in some blue dogs. How prevalent this is in Danes is undetermined, and how relevant the blue mutation is to coat quality problems seen in blue Danes is unclear at this time. But it is the case that some blue Danes are reported to have skin and hair coat problems that are much like “Blue Doberman Syndrome.” A study on blue Danes conducted by S. M. Schmutz, Ph.D, resulted in a commercially available test for this mutation (available through Health Gene). In all cases where there is a question of whether the Dane carries for blue can now be definitely resolved by this simple, non-invasive and inexpensive test.

EXTENSION LOCUS: This gene, called MC1R (Melanocortin Receptor 1), restricts the location of dark (eumelanin) pigment. This gene is on canine chromosome 5. There are three known alleles here and two of them are dominant, one is recessive. Recent data has confirmed the presence of masking at the E Locus and all Danes are either E^M (have the dominant masking gene) or E (do not have the masking gene, but carry the other dominant that allows dark pigment to form). The recessive here results in a dog NOT being able to make any dark (eumelanin) pigment and does not appear to exist in the Great Dane breed. At one time it was thought that brindling was found at this locus. This is now known to not be true. Current thinking tends to place brindling at the K locus, as a recessive to the dominant there that produces a solid coat; more on the K locus below. Sheila Schmutz (see references) has in fact recently has offered evidence to place brindling at another locus, see: MC1R Studies in Dogs With Melanistic Mask or Brindle Patterns, S. M. Schmutz, T. G. Berryere, N. M. Ellinwood, J. A. Kerns, and G. S. Barsh, (J Hered 2003 94: 69-73) for more information.

The take home message here for Dane people is that brindles can breed true-they can have two brindle genes and two mask genes simultaneously. However not all Danes have two genes for masking (and not all brindles have two brindle genes). Maskless (white-faced) fawns are still seen in the breed occasionally and especially in fawns from black to black breedings. Brindles and fawns with masks can also throw maskless dogs, as they can be heterozygous for this trait (i.e. have only one gene for mask); so only half their offspring get the mask gene and two such dogs can therefore produce maskless pups. The good news is Health Gene has a gene test for ALL the genes at this locus, including masking. So you can check if you like and find out for sure if you dog has one, none, or two genes for masking. Masking will not show up on blue, black, Harl, Mantle, merle, etc. Danes; only fawn/brindle coats can display masking; but both dominants allow other genes for dark pigment to express. The MC1R gene has three known alleles that are now well defined:
E^m = gives dark mask (superextension) on k recessives; otherwise allows for self.
E = allows for self colored dog; i.e. the actions of alleles of A/K loci are expressed.
e = restricts pigment to red/yellow (no dark pigment can form).
The recessive here is unrecorded in Danes. All Danes are either masked or not, and all masked Danes have one or two genes for masking. Apart from historical records of red (Rot) Danes, and questions of two “fawns” (actually a fawn and a red) producing black puppies, this recessive is not a breed concern and if it did exist at some point, it is now rare to unknown in the breed. But whether it’s for masking or recessive red, if you have questions, test for it: these days it’s that simple.

DOMINANT BLACK LOCUS: This is currently a theoretical locus (i.e. we don’t know where it is or how it does its job), but it is a gene that “has to be” given the new molecular data that is emerging about coat color, as well as the sort of statistical data that has traditionally been used to define coat color. The K locus is where dominant black (once thought to be at the A locus) and brindling (once put at the E locus) are now being placed, and it’s what makes a fawn a fawn, and a brindle a brindle. This new locus is called “K” after the final letter in black, and is casually referred to as “dom black” by some. There are three alleles currently predicated here:
K = dominant black (eumelanin) allele. Gives a solidly dark (black, blue, brown) dog.
k^br = speculative brindle allele.
k= recessive (phaeomelanin) allele. Allows for bright/light pigment to express. Gives us our fawn Danes.

Dominant black was formerly thought to be the dominant allele at agouti and was called A’ (agouti prime) or A^s (agouti solid or self-colored). Now all dogs solidly covered in dark (eumelanin) pigment are referred to as KK or Kk dominants; so all blacks, blues, Harls, Mantles and merles are KK or Kk. All brindles will have at least one k^br (they are k^br homozygotes or k^br/k fawn carriers). All fawns are kk recessive homozygotes. Any dog who is not brindle or fawn and produces either color is a “k recessive carrier.” Many of our black, blue, Harlequin and Mantle (merle, etc.) Danes are “k recessive carriers.” Danes have been very much involved in the development of information on this newly discovered gene, so this information is very breed specific. Expect new details on K to emerge soon. And start thinking of black/blue pigmented (Harl, Mantle, etc. too) Danes as K-dominant dogs and fawns and brindles as “k recessive carriers.” All are a^y agouti homozygotes; that is all have two agouti “fawn” genes despite what most of us were taught. And, again, all solid (self) colored dogs with dark pigment must also have at least one E or E^M allele (i.e. they cannot be homozygotes). DNA tests are not currently available for the K locus, but research is progressing and a commercial test is anticipated. When that arrives we can know for sure every black (or blue or Harl, Mantle, etc.) that is carrying fawn or brindle, and we can also discover which brindles are “true breeding” (homozygotes) as opposed to those who carry for fawn.

SPOTTING LOCUS: This is the traditional location of recessive white spotting patterns that are involved in producing Mantles and piebalds (as opposed to the dominant white spotting genes that produce patterns like merle and Harlequin). There may actually be two or more loci involved in recessive white spotting, however tradition has placed the genes together at the S locus, with four alleles and incomplete dominance postulated to explain the variations seen. And the most recent research suggests this wasn’t a bad guess. There are however multiple genes involved in spotting patterns in mammals, with four well described: KIT, EDNRB, PAX3, and MITF, and it is currently still unknown which exact spotting gene causes the recessive patterning associated with the S locus. However this summer at the Canine and Feline Genetics Conference 2006, recent research was presented by Karlsson that showed MITF to be the recessive spotting gene in Boxers, and it is likely this is the same gene causing similar patterns in other breeds, especially other working breeds like the Great Dane. MITF or Microphthalmia Transcription Factor is a late acting gene in the pigmentation pathway that modifies the expression of genes in the tyrosinase cascade. (Tyrosinase is an enzyme involved in allowing normal pigment as well as producing such mutations as albinism and PKU in human infants.)
Distinct phenotypic effects involving spotting genes are well documented. The traditional four alleles assigned to the S locus that are involved in recessive white spotting in dogs are thought to encompass four typical phenotypes are outlined below.

This series of genes goes from solid to white: the more heavily pigmented dogs can produce whiter dogs and not the other way around (a fact worth remembering). And there can be heterozgyotes: intermediate hybrids in pattern with one more dominant and one more recessive gene that produce an intermediate phenotype that is deceptive as to breeding capacity. For example you can have two show-marked Mantles that look nearly identical, but one has two “Irish” genes and will breed consistently, always producing more dogs with this same correct pattern, while the other Mantle has a piebald gene and a solid gene (that combined to make him “look” like a Mantle), and so (as a hybrid) will produce more mismarked get than the “true” Irish Mantle dog. (Again think of the white, check and solid Boxers produced by two flashy parents.) Piebald Danes have also deliberately been bred to mismarked blacks to produce “pseudo-Irish” Danes-dogs with the show marked pattern of Mantles that do not carry the needed genetics to produce Mantles; the same has been tried with Harlequin partners as well. None of this can benefit the breed in the long run, for all it’s a short cut some breeders have taken for themselves. It is important to remember that the genes involved in spotting can be associated with various defects, and the piebald genes are associated with sensorial deafness in many breeds. Recall we said earlier that white is actually a lack of pigment. Pigment is structural, not merely decorative, and pigment cells have other duties at times. A loss of pigment can have effects beyond changes in coat color, and the severe loss of pigmentation that produces a largely white dog often also disables or damages other normal functions of skin, hair coat, sensory and even other organ function. The search is on to map these various spotted phenotypes to various genes known to produced spotting.
S = allows for self-colored dog: no more than 10% body white confined to the toes and chest even when full extension of white is even present.
s^i = “Irish pattern”: produces an extension of white from 10% to 30% in a symmetrical pattern involving some or all of the following areas: feet/lower legs/belly/chest/tail tip/collar/muzzle and blaze. Commonly produces what North American Dane breeders refer to as “mismarked blacks” (the traditional black, or “harl black” found in the breed), as well as the “Boston” or Mantle Dane–i.e. “tuxedo” white trim on a solidly pigmented dog. Recessive to S, this locus demonstrates incomplete dominance, so intermediate types appear in heterozygoes. Range therefore overlaps with both the S=self and s^p=piebald alleles, especially in heterozygotes.
s^p = “Piebald pattern”: produces a wide range of variation in color percentage and location of pigmented areas with notable asymmetry. Total white in the coat ranges from 20% to 80%: seen are individuals with a full collar, blaze, white legs, belly & tail tip to individuals with only head and tail root color, and “split heads” and other asymmetrical markings are typical of piebaldism. S is incompletely dominant when combined with s^p, producing dogs who typically appear as “irish” (Boston or Mantle) in their markings and were called by Little “pseudo-Irish” dogs because they cannot breed the Mantle pattern they appear to be. (This phenomenon is apparently what occurs in so many Boxers and is why they have white and “check” and even solid colored puppies from “flashy” parents). The typical piebald is a parti-colored dog such as seen in the beagle, pointer, Cocker and Brittany.
s^w = “Extreme-white piebald” where color is restricted to no more than 10-15% total area: if pigment is present it is confined to the head & tail root. Color-headed dogs (e.g. harl-heads) would be a^w homozygotes. Another incompletely dominant allele described as combining with S or si to produce dogs that appear to be “normal” piebalds or even Mantles-dogs who do not breed as they appear. This gene is also associated with sensorial deafness in a wide range of dog breeds.

MERLE LOCUS: This is the notorious gene that produces the dappled coat and is a pleiotrophic gene, meaning it routinely disables sensory organs, gut and reproductive capabilities, as well as changing coat color and so can result in various congenital and developmental defects. This gene is related (in effects) to other such dominant white spotting loci found in mammals (e.g. von Waardenburg’s Syndrome, Lethal White Overo Syndrome). Recent work at Texas A&M University’s (TAMU) Canine Genetics Laboratory, under the leadership of Keith Murphy, resulted in the startling discovery that the canine merle gene is PMEL17-a pigment gene (SILV retrotransposon) associated in rats with silvering that had been overlooked in canine coat color research.
M = merling/dappling/patching with increase in white/mid-tone (diluted pigment) areas. Present only in the Harlequin family: All Harlequin, all merles and all whites have this gene. No Mantles, “harl blacks” or piebalds carry merle.
m = non-merling allele (the only gene nearly ALL dogs and most all Danes have).

Merle in dogs produces a characteristic increase in white areas and areas of reduced pigment, with patches of mid-tone and full pigment when the dog is a heterozygote. In other words a gray dog with black spots emerges where a black dog once stood–this is our typical merle. Having one copy of the gene makes it obvious the dog is a merle bearing animal usually. The merle gene produces coats called dapple, leopard, or blue and red merles in other breeds, and has been shown to be necessary to produce the Harlequin variant that is traditional and prized in the Great Dane breed. Merle does not express well without eumelanin (dark pigment), which means that fawns can be genetic merles and not appear different from other fawns, for example, so there are problems in some cases of “cryptic” merles occurring if merles are bred into colors like fawn. This matters as “double merles” (our whites) are normally plagued with congenital defects.
Breeding merles therefore is typically restricted to coat colors (unlike fawn) where the pattern clearly shows up. Note that merle is unique in that it is considered both a pigment AND pattern locus-as a gene it affects both at once. And it’s worth repeating that pigment is not merely decorative; pigment has structural and protective functions, and pigment cells have other duties beyond color. The predominance of white is a gross lack of pigment. Dysfunction of pigment and pigment cells can have far reaching effects: not all colors and patterns are therefore born equal. And homozygous merle puppies, if they survive at all, are going to typically suffer with various congenital defects from having two doses of this fascinating, but somewhat deadly, gene. Note that the heterozygote, be in the normal merle or our prized Harlequin, does not usually suffer from defect. In fact an argument for the value of merle, when present in a single copy, can be made from a Darwinian standpoint, as a dappled coat might provide superior protection in a wild or feral dog scenario. But there is no question that two doses of the merle gene is harmful.
All Great Danes identified as Harlequins must have at least one merle gene, and some of the lighter marked Harlequins apparently are actually genetic whites, or “double merles,” not “true” Harlequins (i.e. they are homozygous for merle, so are actually genetic whites). Since there is now a commercially available test for merle, it would be advisable to test all mostly white animals in Harlequin litters, including “lightly marked Harlequins” for just how many merle genes each puppy actually has. It’s a simple, non-invasive and inexpensive test. See the reference section below for how to contact GenMark (the company that offers testing for merleÖand soon the harl gene too).

Any Harlequin color family litter that does not have at least one Mantle/black parent is capable of producing homozygous or “double” merles, called whites by most Dane breeders, and “white merles” or “double merles” in other breeds. These “double merle” individuals are at high at risk for merle-related defects. Most breed clubs react to this fact by banning the breeding of merle to merle, and restricting merle breeding to eumelanin dogs, or simply banning merle entirely. Merle is a required component of our Harlequin pattern, so we have to consider our options. CERFing all merle-bearing Danes (at least those to be used for breeding) wouldn’t be a bad idea, as that would go a long way to answering exactly what combination of genes produces the syndrome of eye defects called merle ocular dysgenesis. BAER testing predominately white dogs in any breed is the only way to ascertain which dogs are partially deaf. We are far behind other breeds and even our European counterparts in employing BAER testing. And since the typical rate of “uni’s” (partially deaf dogs) in breeds that have undergone BAER testing is often more than twice that of the dogs obviously deaf, we are likely missing out on properly identifying a large number of white Danes with some hearing loss by not BAER testing the puppies that are predominately white. You cannot tell by looking which ones have a partial hearing loss, but this trait can still be passed on to offspring. There is now a commercially available test for merle from GenMark, that came out of the research at TAMU’s Canine Genetics Lab, so at the very least it would be advisable to use this test to know for sure how many merle genes these mostly white animals (including “lightly marked” Harlequins) actually have. Breeding a genetic white or a genetic piebald when misidentified as a Harlequin is clearly something the conscientious breeder would strive to avoid. Without testing claims to the contrary are largely empty.

In the homozygote (”double”) merle, white in the coat typically predominates and sensory defects are normally found, but the dog is NOT usually all white and not necessarily obviously deaf or blind. So without careful testing and/or much experience, many whites get misidentified. Fetal death rate for MM dogs is reported by some to be as high as 50% and surviving pups generally do suffer from some form of sensory and other anomalies, with hearing and sight defects most common. Most Danes identified as “merlikins” appear to be genetic “whites” (i.e. homozygous MM “double” or white merles). They just have enough pigment to have been given a separate name based on appearance. This doesn’t happen in many other breeds, as it’s recognized a “white merle” can be 50% pigmented (with merle markings). Genetic whites (double merles) sometimes (not always) carry an additional Harl gene, and in that case have found their way into Harlequin pedigrees as the parents of even Champion Harlequins via our practice of “white to black” breedings, where “harl blacks” and Mantle Danes are deliberately bred to double merle whites so the percentage of spotted offspring can be maximized. So the breeding of whites and “merlikins” continues in the pursuit of more Harlequins. Other Danes identified as “merlikins” are actually genetic merle piebalds (hhMms^p/s^p) that have also been misidentified: they carry only one merle gene, no harl genes, but two piebald genes. However, lumped in with genetic whites (MM) they are sometimes bred as Harlequins or whites, and so treated as valuable bloodstock having these desirable dominants, when actually these dogs are mostly white from unwanted (S locus) recessives. The one thing a “merlikin” cannot be is what it was traditionally thought to be: a Harlequin dog that just has grey (instead of black) pigment predominating. Merle is the only phenotype in the Harlequin color family that, by definition, does NOT carry the Harlequin gene. Merlikins are either whites or piebalds-never a form of Harlequin. (More on the Harlequin gene and its research below).
Merle is a complex phenomenon and still incompletely understood. The subject of “cryptic” merles (dogs that produce merle but don’t appear to be merles) is still being investigated, as is the “flip side” of that coin, the germinal reversion of merle that produces a non-merle dog where all get should be merle (i.e. black to white breedings). And it’s well known, but still left unexplained, how there is such a wild variation in coat patterning resulting from this one gene, although this phenomenon is typical of spotting patterns in mammals. Merling has quite a bit of natural variation in all aspects of its phenotype, but is still the only known canine coat color gene definitely and directly associated with physical disability. Ideally all merles would be properly identified as heterozygotes or homozygotes and also then BAER and CERF tested (especially by those advocating their breeding) to ascertain the extent of their sensory deficits. This would also help provide appropriate clinical data on effects of this gene. But this logical step has unfortunately been left undone. In summary, merle is the only canine coat color gene absolutely associated with defined defects so it must be treated knowledgeably and with due caution by breeders.

HARLEQUIN LOCUS: This is the proposed dominant white/spotting locus that produces the Harlequin pattern when the M allele is present: it takes the mid-range (gray) pigment away, leaving a white base coat and full pigmented black patches. The Harlequin, as our own Neil O’Sullivan so eloquently put it is “a double heterozygote” () which must have one copy of the harl gene and one copy of the merle gene to be a true Harlequin. The Harlequin gene is seen in its full effect on Harlequin Great Danes of course, but it can be carried “sight unseen” by the blacks and Mantles from Harlequin breeding, as these dogs lack the merle gene (so harl cannot express). Merles by definition cannot carry the harl gene and therefore cannot alone produce Harlequins-they need to be bred to an “H-factored” partner who is the parent actually responsible for producing Harlequin. Harlequins would be MmHh and merle Mmhh. Blacks (including Mantles) and white could carry the “H factor” unseen, and in fact black/Mantle Danes might carry two such desirable genes. But now all blacks, and likely not too many whites, will have this gene and so be able to aid in the production of Harlequin puppies.
And, again, true “merlikins” are impossible, although various “porcelains” such as fawnikins–dogs with the Harl gene for pattern, but not the proper genes for black coat to produce the Harlequin phenotype–do occur in the breed. And more importantly, the best breeding partners to Harlequins, the Mantle sort of black-n-white dog, can carry the Harl gene selectively, and thereby raise the percentage of Harlequin (vs. merle) puppies in a litter. Sponnenberg and O’Sullivan published evidence of this phenomenon (2:1 Harl: merle puppy ratio) some time back, so this trait has been noted by the careful observer, and I’d include in that many of our breeders as well as researchers of course. Sponnenberg conjectured the harl gene to be lethal in all iterations when homozygotic while simply producing only a change in base coat in the heterozygote. However it’s perfectly feasible that problems do not arise except in the presence of the merle gene, as it appears that “harl factoring” is inert otherwise, and the harl gene alone has not been shown to cause defect. Neil O’Sullivan and Jane Chopson both have written on the “Sponenberg Hypothesis” so no more time need be spent on it here.

When the ongoing research at TAMU (again under Keith Murphy’s leadership) to find the Harlequin gene is successful, we will be able to test our Mantles, for example, and declare some of them as “harl factored” (or even “double harl factored”) and declare them preferable breeding partners as to the production of Harlequin puppies. The current research for the Harlequin gene being undertaken by TAMU is being sponsored by the Charitable Trust with the support of the GDCA and many of its affiliates as well as has been made possible by the many donations made by individual Great Dane breeders and owners.
One final note on spotting phenotypes as with Harlequins, Mantles, and merles: spotting patterns are always, and in all ways, somewhat unstable. In our breed this has two obvious consequences. The first is that since pigment tends to increase in individual dogs over time: dogs get darker, slowly, as they grow up. This means that blazes on newborn Mantles will narrow and narrow blazes may well disappear. It also means that areas of white are likely to see “freckling” occur as the dog ages, which is to say that skin pigment will tend to increase and even new “spots” will appear as pigmented hairs may sprout in these formerly white areas. This is not what is traditionally thought of as ticking, despite it so often being called that. Ticking is a dominant gene phenomenon seen in various gun dogs (e.g. GSPs) where the dog is born white and the spots appear in the first few weeks of life. Ticking and roaning are thought to result from genes on canine chromosome 15 (e.g. KITLG, MGF) and are unrelated to the “freckles” we see in our Harlequins and Mantles.

H = Harlequin gene. Combined with the Merle gene, produces the Harlequin coat pattern. Present in all Harlequins and some whites. May lay “dormant” in black/Mantle dogs.
h = recessive allele present in all normal (heterozygote) merles and most all Danes.
The other thing to note is that since spotting patterns are inherently unstable they are also somewhat erratic, so are not wholly predicable in pigment placement or amount. Even cloned calves that are black and white do not have the exact same pattern of white. Basic pattern (solid vs. Mantle vs. piebald or Harlequins within or outside the standard) CAN be predicted, but exact amounts and specific locations of color cannot. Which is why the standard itself makes a good outline of what is suitable for breeding as a general rule: dogs who are disqualified under the standard are typically poor breeding candidates as they will (sooner or laterÖif not in this litter, then down the generations) produce more mismarks than the dogs that meet the breed standard. And conversely any and all dogs within the loose confines of the standard as to color, despite personal taste and even ring prejudice, are equally good candidates for breeding consideration as it is unlikely indeed that the small variations seen among correctly marked dogs are really relevant gene categories (i.e. such variations are not inherited, but unique to the individual dog). In other words spotted Danes who fit the standard (i.e. show-marked Mantles and Harlequins) will produce the highest percentage of correctly marked dogs over time and multiple generations, and disqualifying mismarks are therefore to be avoided in breeding programs whenever possible.

CONCLUSIONS: Danes have several traditional coat color (and patterns) as we all know. How exactly that set of breed colors is defined has only alerted in small detail from country to country and century to century. So essentially the standard colors accepted in the breed today have been the same in broad outline as long as the breed has been a breed. In fact longer, as what was defined in the first standard was what was typical for the breed (or proto-breed if you prefer) in the mid-19th century and even further back in history. The colors we ended up with, as well as the guidelines to breeding them, are simply a way to keep and manage our traditional color families and still celebrate the breed’s traditional variety. So coat colors really should be treated in a less moralistic and more pragmatic way. Danes come in several traditional colors and yet this is not a “color immaterial” breed. So how do we effectively then manage this array? Logically you do this by sorting the colors into color families. You cluster up the colors that, when bred to each other, are most likely to produce acceptable breed colors, and you encourage all to restrict their breeding to these better choices. You also eliminate from the breed those colors (and patterns) that can confuse the issue by their being misidentified, or which will otherwise cause some of the more traditional colors to be interfered with or even lost. This is arguably just how we ended up with what we have, as this translates into three basic color families and about six acceptable colors.

And that’s in fact, if you look, actually how it’s always been managed the world over, time out of mind? Presumably this is why standards for the breed, here and everywhere, have always fundamentally allowed and disallowed the same basic colors and patterns. You can look at the struggles in the early German stud books and see that certain colors and patterns were more difficult to manage, caused more problems (in health and otherwise), and ended in confusion for so many of the breeders involved. Hence the concentration on ONE dilute, blue, which has been a Dane color since the advent of the breed. Add brown dilution (so-called chocolate) and not only do you get another gene able to hide away unseen, but the combination of dilution genes brings out what was called Drapp, which as a double dilute arguably has some health issues involved with it, and ends anyway in a bunch of dilutions that may be hard to identify on certain coats, so is a practical problem for breeders to manage. Chinchilla dilution, or cream, is also not desirable and likely for the same reasons. There is lots of evidence that dilutions bring with them problems when too concentrated as pigment is structural, not just decorative. So there is a certain limit to its loss; go beyond that and health problems rise. Plus, add in so many variations, and you heighten the problem of confusing the color as to what a dog looks like (phenotype) vs. what it is genetically (genotype) and end up losing control of your breeding program in this aspect. So one good strategy that our breed standard simply reflects is that you “keep it simple” when it comes to dilutes, and you honor our breed tradition by choosing to keep blue.

Essentially the same arguments apply to all the odd by-products of Harlequin breeding. Harlequin is the traditional breed color that can be faithfully recorded as far back as Egypt. It is arguably also a color only preserved in the Great Dane so we have a trust and legacy to canines in keeping this color alive. It’s also part of the hunting heritage of the breed. So there are lots of reasons to concentrate on its preservation. Dogs which are black, or black with white trim, have always been a by-product of Harlequin breeding, and breeding such “harl black” Danes to Harlequins has always been a preferred breeding as it avoids the production of so-called white Danes which are typically defective as they are actually double merles (MM white merles). Harl to Harl breeding would be the fall-back position as it uses dogs that preserve the traditional spotting pattern, maximizes the number of show marks, and minimizes the production of merles. And despite all sorts of declarations about merles as breeding stock, it’s not the case that history records them as a breed success, so there is actually every reason to exclude them. Merle is a rather tangled complication can simply be avoided by eliminating them from the standard, which should eliminate them largely from breeding consideration. This is, in fact, how the merle has always been treated in the Dane. And it’s not without reason surely, that in all but a dozen breeds worldwide, the merle pattern is banned outright. Nor is it any coincidence in the few breeds where merle is allowed its breeding is highly restricted. A passion for merles won’t change those facts: this is the only gene known in dogs to have health consequences directly related to the gene expression. Their breeding by definition has to be managed responsibly and restricted to the least lethal combinations.

The same goes for the piebald, also called Plattenhund, which is traditionally disqualifying in Danes and likely has been discarded for the same practical reasons. Piebald in its extreme form is associated with deafness and as a recessive it is insidious and difficult to rid a breeding program (or breed!) of once introduced. If you are already dealing with one gene with health consequences (merle) and already have a favored spotted black-n-white pattern (Harlequin), as we do in Danes, then why add to your problems by adding in another pattern that means: (a) you have more phenotypes leading to health defects and (b) you are introducing a color/pattern which make identifying each dog’s genetics more difficult (i.e. piebalds get confused with white merles and even Harlequins). Piebaldism results in the loss of the Harlequin and Mantle patterns (i.e. the loss of show marked puppies), and offers the chance for an increase in the number and severity of sensory-defective puppies. So eliminating piebald and merle phenotypes simplifies things in what is already a complicated color family in the Dane. That way it’s easier to find and keep Harlequins; the color is then as stabilized as biology allows. And for both merle and piebald, again, an increase in white at some point has consequences of it’s own from simple loss of pigment; look at any of the dozens of breeds struggling with piebald deafness to see that well illustrated. So piebald and merle traditionally got excluded in the Dane. This way you keep your Harlequin as a treasured and unique breed trait, and concentrate on its breeding using its black (with white trim) brethren who then help cut down on defective whites while they make for the correct Harlequin pattern in their offspring. Agree or not you can at least follow the logic of this argument that is part and parcel of breed history. And it makes logical and practical sense.

Making the decision to limit a breed to certain color/patterns which are part of its main heritage, and eliminate “variations,” “exotics,” and colors/patterns long associated with high-risk situations is simply good common sense? Even giving beginners a warning about the more complex color families and a guide for what is traditional for each color family (i.e. a “code”) may be useful at times. The point of all this I would think is rather less moralistic than practical: this way you can generally put color away as the minor issue it is and concentrate on the main business of getting good type, stable structure, and good heritable patterns for health and temperament in your dogs. After all, the whole point of color is to get it right in your breeding stock (i.e. breed within the standard) and to forget about it otherwise surely? Ultimately it’s just “paint”? So it’s a practical consideration to the serious breeder, but should not be the focus of a breeding program. Naturally some good working knowledge of how color genes interact is required to handle these issues appropriately, and that is often woefully lacking in many who engage in these complex breedings…and conversations about color as well. But far too much time still and all is spent on issues of color, and too often the practical considerations are lost in an emotional furor of finger pointing and moral declaration. We need to refocus our efforts here on producing correct and healthy puppies, and learn how color genes work for and against us.

A final word about mismarks: breeds have traits that identify them as breeds. Just as Golden Retrievers are not black, and St. Bernards are not white, Great Danes come in recognizable colors and always have. It’s a breed trait like any other and you have to believe that breed traits matter if you think preserving the purebred dog matters. That said most mismarks in the Great Dane are the result of two carriers producing a recessive color trait. For all that mismarks are typically undesirable as breeding stock, they are not normally undesirable as Danes, as they are simply healthy animals who are of a non-standard color. (There are some exceptions to this involving spotting genes, but that has already been discussed.) Parents of such mismarks also are not per se less desirable or less well bred, as any number of very noble and superior animals with a “color pure” heritage have produced mismarks.

It’s not the case necessarily that mismarks result from careless breeding, although careless breedings produce a lot of dogs who do not fit the standard, in color as in other traits. (So such a litter’s poor color is merely the tip of a very ugly iceberg.) The more dominant the color and pattern a dog has, the more recessives that can hide there; black pigment can hide any number of dilutes and solid coats can hide any number of patterns. So this notion that mismarks are some sort of “sin” is an idea that we need to outgrow, as is the idea that pedigrees can really be “color pure,” or that a gene can be somehow “diluted” over time and so be lost if the trait isn’t seen in a few generations. None of this is true. Here we really need to grow up in our ideas about color. Let’s treat color as a practical consideration, not a set of ethical considerations, and understand that color families help us preserve breed tradition, but understand the limits of what “color codes” can do, and know also that mismarks do occur to the best of us. Naturally this is not meant to be interpreted as a license to breed indiscriminately, but to help encourage people to share accurate pedigree information. Moral outrage about mismarks (along with ignorance of the possibilities of color) has more than once led in this breed to dogs not being properly identified and properly registered. Ideally all traits carried down or even suspected ought to be recorded in the pedigrees and discussed with the relevant parties for breed betterment. That cannot be accomplished in an atmosphere of secrecy and fear.

For most mismarks found in our litters, be it piebald or blue brindle, maskless fawns or some disqualifying dilute, the take-home message is “it takes two to tango:” i.e. both parents are carriers. Carriers can remain unseen for 3 generations or 30. So a blue fawn pup from two standard fawn parents or a fawn pup from a Harlequin breeding can happen without mixed color pedigrees or bad breeders being the issue. It’s simply a matter of recessives carried along–sight unseen. And since many of the diseases that plague purebred dogs come from recessives this way, here is a thing to learn from color and apply elsewhere to better our breeding through more perspicacious selection. Which would be a good point to note about color genetics: they are relatively simple to comprehend and control compared to the more important issues of type, structure, health and temperament. Color genes are a good place to start when wanting to understand overall the practical genetics involved in breeding dogs. The important point is don’t hide them and don’t gossip about others who are honest about them (disease or color genes for that matter). Just record them honestly and then let’s get on to the issues that really need to engage the our attention in the pursuit of better individual Danes and breed preservation.
The last paragraph is largely my opinion, obviously, and is written partially as a plea to those interested in breeding to please focus on more important traits and turn their attention to eradicating real defects of structure and temperament, while selecting for correct type and against serious disease. These issues, not issues of color, ought to engage most of a breeder’s time. For all color is interesting and color faults obvious to even the most rank beginner, it is ultimately just paint and a good dog has to be built beneath that paint job, whatever color it ends up to be. There is much new information being learned about the action of genes and cells and how their produce all sorts of traits, including color traits. We are more and more going to be able to actually test our dogs for various colors and patterns they may carry and select directly the genes we want to breed. This will make color (and disease) something we can control. So surely we ought to learn about color genes, keep up on new data and new techniques and use these new tools to help us breed to the standard. But let’s not let color issues become the focus of our breeding programs? We’ve much more to engage us in preserving the Great Dane breed for posterity. For more information on color genes and coat color genetics, see the resources and references below. I hope this article has helped everyone feel more comfortable with both genetics and color! Take care! jpY

HEALTH GENE: Offers DNA-based technology including gene tests for coat color in dogs: blue, brown, masking in Danes, also agouti & extension. Website is:
GENMARK: Offers DNA-based technology including gene tests for coat color in dogs: merle (and soon harl) gene(s). Website is:
CANINE GENETICS LABORATORY, TAMU (Keith Murphy, Ph.D): Main researcher for current coat color work (involving spotting genes & associated health issues). Website is:
S. M. Schmutz, Ph.D. A current researcher on coat color in dogs who has worked extensively with coat color in the Great Dane. She has a tutorial and informational website: GENETICS OF COAT COLOR IN DOGS:
JP Yousha. Author of various articles on health and color issues in dogs, research liaison for coat color research in the Great Dane. Former Chairman, Health and Welfare Committee & member of Color Research Committee, GDCA. Current member (new) Health & Research committee. Email: Phone (CT): 432-684-8940. Links page for color-related articles: GDCA Health & Research main page (links to color gene studies):

” Ackan, A. and W. Wegner. 1983. Veranderungen an Sehbahn und Sehzentren beim Merle-Syndrom des Hundes. Zeitschrift Fur Veruchstierkunde. 25(2): 91-9.
” Ackerman, Lowell, DVM. 1996. Dr. Ackerman’s Book of Great Danes. Neptune City, NJ: T.F.H. Publications, Inc.
” Beerman F, Orlow SJ & Lamoreux ML. 2004. The Tyr (albino) locus of the laboratory mouse. Mammalian Genome 15:749-758.
” Bianchi E, Dondi M, & Poncelet L. 2006. N3 potentials in response to high intensity auditory stimuli in animals with suspected cochleo-saccular deafness. The Veterinary Journal (in press; available on line).
” Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, & Goossens M. 2000. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Human Molecular Genetics 9:1907-1917.
” Branis M, Burda H. 1985. Inner ear structure in the deaf and normally hearing Dalmatian dog. Journal of Comparative Pathology 95:295-299.
“Breen M, Jouquand S, Renier C, Mellersh CS, Hitte C, Holmes NG, Cheron A, Suter N, Vignaux F, Bristow AE, Priat C, McCann E, Andre C, Boundy S, Gitsham P, Thomas R, Bridge WL, Spriggs HF, Ryder EJ, Curson A, Sampson J, Ostrander EA, Binns MM, Galibert F. 2001. Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes. Genome Research 11:1784-1795.
” Brenig B, Pfeiffer I, Jaggy A, Kathmann I, Balzari M, Gaillard C, Dolf G. 2003. Analysis of the 5′ region of the canine PAX3 gene and exclusion as a candidate for Dalmatian deafness. Animal Genetics 34:47-50.
” Burns, M. and Fraser, M.N. 1966. Genetics of the Dog: The basis of successful breeding. Edinburgh: Oliver & Boyd.
” Carroll-Draper, Nancy. 1981. The Great Dane: Dogdom’s Apollo. New York: Howell Book House.
” Cattanach, B. (1999). The ‘dalmatian dilemma’: white coat colour and deafness. J. of Small Animal Practice 40: 193-+.
” Clark LA, Wahl JM, Rees CA, & Murphy KE. 2006. Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog. Proceedings of the National Academy of Sciences, 103(5):1376-81.
” Clark, Ross D., DVM, and Joan R. Stainer. 1994. Medical and Genetic Aspects of Purebred Dogs. St. Simon Island, GA: Forum Publishing.
” Chopson, J. 1992. Inheritance of Great Dane Coat Color. GDCA Color Committee.
” Coppens AG, Resibois A, & Poncelet L. 2000. Bilateral deafness in a Maltese terrier and a Great Pyrenean puppy: inner ear morphology. Journal of Comparative Pathology 122:223-228.
” Coppens AG, Kiss R, Heizmann CW, Schafer BW, & Poncelet L. 2001. Immunolocalization of the calcium binding S100A1, S100A5 and S100A6 proteins in the dog cochlea during postnatal development. Brain Research Developmental Brain Reseach 28;126:191-9.
” Coppens AG, Salmon I, Heizmann CW, Kiss R, & Poncelet L. 2003. Postnatal maturation of the dog stria vascularis - an immunohistochemical study. Anatomical Record Part A 270A:82-92.
” Coppens AG, Steinberg SA, & Poncelet L. 2003. Inner ear morphology in a bilaterally deaf Dogo Argentino pup. Journal of Comparative Pathology 128:67-70.
” Coppens AG, Salmon I, Heizmann CW, & Poncelet L. 2004. Dark-cell areas in the dog vestibular endorgans: an immunohistochemical study. Histology and Histopathology 19:1227-1235.
” Cordaux R & Batzer MA. 2006. Teaching an old dog new tricks: SINEs of canine genomic diversity. Proceedings of the National Academy of Sciences, 9 January 2006, 103(5):1157-8.
” Daush, D., Wegner, W., Michaelis, M. and I. Reetz. 1977. Opthalmologische Befunde in einer Merlezucht. DTW (Deustche Teirarztliche Wochenschrift). 84(12):468-75.
” Daush, D., Wegner W., Michaelis, W. and I. Reetz. 1978. Augenveranderungen beim Merlesyndrom des Hundes. Albrecht v Graff Archiv fur Klin. u. Exp. Opthal. 206(2):135-50.
” Evans, Jill. The Time Traveler. 2002 Self-published: Salt Springs Island, BC CA.
” Flach, M., Dausch, D., and W. Wegner. 1980. Floureszenzangiographie bei Teckeln. Weitere Befunde zum Merlesyndrom des Hundes. 8(3):375-83.
” Gelatt, K.N., Powell, N.G., and K. Huston. 1981. Inheritance of micropthalmia with colomboma in the Australian shepherd dog. Am. J. Vet. Res. 42(10): 1686-90.
” Green, B.K. 1974. The Color of Horses. Flagstaff, AZ: Northland Press.
” Greibrokk, T. 1994. Hereditary Deafness in the Dalmatian-Relationship to Eye and Coat Color. JAAHA 30: 170-176.
” Hayes, H.M., Wilson, G.P., Fenner, W.R. & Wyman, M. 1981. Canine congenital deafness: epidemiologic study of 272 cases. Journal of the American Animal Hospital Association 17:473-476.
” Hoskins, J.D. 1990. Veterinary Pediatrics: Dogs and Cats from Birth to Six Months. Philadelphia, PA: W. B. Saunders Company.
” Johnson, Di. 1994. Great Danes Today. New York: McMillian.
” Juraschko K. 2000. Populationsgenetische Untersuchung der kongenitalen Taubheit beim Dalmatiner (Genetic analysis of congenital deafness in Dalmatians). Doctoral thesis, Tierarztliche Hochschule Hannover, Hanover, Germany.
” Karlsson EK, Hillbertz NS, Wade CM, ANdersson G, von Euler H, Hedhammar ≈, Zody MC, Biagi T, Lai J, Anderson N, Liu G, Jones K, Andersson L, Lindblad-Toh K. 2006. Two-stage association mapping in dogs identifies coat color locus. Third International Conference on Advances in Canine and Feline Genomics, Davis, CA, Aug, 2006. To be published in a future issue of the Journal of Heredity.
” Kerns JA, Newton J, Berryere TG, Rubin EM, Cheng J-F, Schmutz SM & Barsh GS. 2004. Characterization of the dog Agouti gene and a nonagouti mutation in German Shepherd Dogs. Mammalian Genome 15:798-808.
” Kerns, J.A., M. Olivier, G. Lust, & G. S. Barsh. 2003. Exclusion of Melanocortin-1 Receptor (Mc1r) and Agouti as candidates for dominant black in dogs. J. of Hered. 94:75-79.
Kim JH, Kang KI, Sohn HJ, Woo GH, Jean YH, & EK Hwang. 2005. Color-dilution alopecia in dogs. J. Vet Sci Sep: 6(3):259-61.
” Klein, E., Steinberg, S.A., Weiss, S.R.B., Matthews, D.M., and T.W. Uhde. 1988. The relationship between genetic deafness and fear- related behaviors in nervous pointer dogs. Physiology and Behavior 43: 307-312.
” Klinckmann, G., Koniszewski, G. and Wegner, W. 1986. Light-microscope investigations on the retinae of dogs carrying the Merle factor. J. Vet. Med. A. 33:674-88.
” Klinckmann G., Koniszewski, G., and W. Wegner. 1987. Lichtmikroskopische Untersuchungen an den Corneae von Merle-Dachshunden. DTW (Deutsche Tierarztliche Wochenschrifte). 94(6): 338-41.
” Klinckmann G., and W. Wegner. 1987. Tonometrien bei Merlehunden. DTW (Deutsche Tierarztliche Wochenschrifte). 94(6): 337-8.
1935. Dominant dilution and other color factors in Collie dogs. J. Hered. 26: 424-30.
” Krempler, A., Breen, M. and Brenig, B. 2000. Assignment of the canine paired-box 3 (PAX3) gene to chromosome 37q16->q17 by in situ hybridization. Cytogenet. Cell Genet. 90 (1-2), 66-67.
” Langebaek, R. 1986. Variations of hair coat and skin texture in blue dogs. Nord Vet Med: Nov-Dec:: 38 (6): 383-7.
” Laukner, A. 1998. [Coat color in dogs. 2: Clinical significance] Tierarztl Prax Ausg K Kleintiere: Feb;26(1):49-54.
” Little, Clarence C. 1957. The Inheritane of Coat Color in Dogs. New York: Howell Publishing.
” Metallinos, D and Rine, J. 2000. Exclusion of EDNRB and KIT as the basis for white spotting in Border Collies. Genome Biology (a web based only journal) online article
” O’Sullivan, Neil. (1988-89) “Harlequin colour in the Great Dane dog.” Genetica. 78(3):215-8.
” Padgett, George A., DVM. (1998) “Control of Canine Genetic Diseases.” New
York: Howell Publishing.
” Phillip U, Hanamm H, Mecklenburg L, Mishino S, Mignot E, Gunzel-Apel AR, Schutx SM & T Leeb 2005. Polymorphism within the canine MLPH gene are associated with dilute coat color in dogs. BMC Genet. Jun 16;6:34.
” Rak SG, Drogemuller C, Leeb T, Quignon P, Andre C, Scott A, Breen M, & Distl O. 2003. Chromosomal assignment of 20 candidate genes for canine congenital sensorineural deafness by FISH and RH mapping. Animal Cytogenetics and Comparative Mapping 101:130-135.
” Rak SG & Distl O. 2005. Congenital sensorineural deafness in dogs: A molecular genetic approach toward unravelling the responsible genes. The Veterinary Journal 169:188-196.
” Rawitz, B. 1896. Gehˆrorgan und Gehirn eines Weissen Hundes mit blauen Augen (Hearing and deafness in white dogs with blue eyes). Morphol. Arbeiten. 6, 545-553.
” Reetz, I., Stecker M., and W. Wegner. 1977. Audiometrische befunde in einer Merlezucht. [Audiometric findings in dachshonds (merle gene carriers)]. DTW (Deustche Teirarztliche Wochenschrift). 84(7):273-7.
” Robinson, R. 1982. Genetics for dog breeders. Oxford: Pergamon Press.
” Schaible, R.H. and Brumbaugh, J.A. 1976. Electron microscopy of pigment cells in variegated and nonvariegated piebald spotted dogs. Pigment Cell. 3: 191-220.
” Schmutz, S. M., T. G. Berryere, and C. A. Sharp. 2003. KITLG mapping to CFA15 and exclusion as a candidate gene for merle. Animal Genetics 34: 75-76.
” Schmutz, S. M., T. G. Berryere, N. M. Ellinwood, J. A. Kerns, and G. S. Barsh, MC1R Studies in Dogs With Melanistic Mask or Brindle Patterns. J Hered 2003 94: 69-73.
” Schmutz, S. M., T. G. Berryere, and A. D. Goldfinch. 2002. TYRP1 and MC1r genotypes and their effects on coat color in dogs. Mammalian Genome 13:380-387.
” Schmutz S.M., Moker J.S, Yuzbasiyan-Gurkan V., Zemke D., Sampson J., Lingaas F., Susana Dunner S., and G Dolf. 2001. DCT and EDNRB map to DogMap Linkage Group L07. Animal Genetics 32:321.
” Sorsby, A. 1970. Ophthalmic Genetics. London: Butterworths.
” Sorsby, A. and Davey, J.B. 1954. Ocular associations of dappling (or merling) in the coat color of dogs. 1. Clinical and genetical data. J. Gene. 52: 425-40.
” Sponenberg DP, Rothschild MF 2001. Genetics of coat colour and hair texture. In The Genetics of the Dog, eds. A. Ruvinsky, J. Sampson, pp. 61-85. Wallingford, Oxon, UK: CABI Publishing.
” Sponenberg, D.P. 1984. Germinal reversion of the merle allele in Australian shepherd dogs. J. Hered. 75:78.
“Sponenberg, D.P. 1985. Inheritance of the harlequin color in Great Dane dogs. J. Hered. 76:224-5.
“Sponenberg, D. P. and A. T. Bowling 1985. Heritable syndrome of skeletal defects in a family of Australian shepherd dogs. J. Hered. 76(5): 393-4.
“Sponenberg, D.P. and Lamoreux, M.L. 1985. Inheritance of tweed, a modification of merle, in Australian shepherd dogs. J. Hered. 76(4):303-4.
” Steel KP, Kros CJ. 2001. A genetic approach to understanding auditory function. Nature Genetics 27:143-9.
” Steel, K.P., and C. Barkway.1989. Another role for melanocytes: their importance for normal stria vascularis development in the inner ear. Development 107: 453-463.
” Strain GM. 2004. Deafness prevalence and pigmentation and gender associations in dog breeds at risk. Veterinary Journal 167(1):23-32. Strain GM. 1992. Deafness in dogs and cats. Proceedings of the 10th American College of Veterinary Internal Medicine Forum 10, 275-278.
” Strain GM. 1996. Aetiology, prevalence, and diagnosis of deafness in dogs and cats. British Veterinary Journal 152:17.
” Strain GM. 1991. Congenital deafness in dogs and cats. Compendium on Continuing Education for the Practicing Veterinarian 13:245.
” Tsai KL, Guyon T, & Murphy KE. 2003. Identification of isoforms and RH mapping of canine KIT. Cytogenetic and Genome Research 102:261-263.
” van Hagen MAE, van der Kolk J, Barendse MAM, Imholz S, Leegwater PAJ, Knol BW, & van Oost BA. 2004. Analysis of the inheritance of white spotting and the evaluation of KIT and EDNRB as spotting loci in Dutch boxer dogs. Journal of Heredity 95(6): 526-531.
” Watanabe K-I, Takeda R, Yasumoto K-I, Udono T, Saito H, Ikeda K, Takasaka T, Takahashi K, Kobayashi T, Tahibana M, & Shibahara S. 2002. Identification of a distal enhancer for the melanocyte-specific promoter of the MITF gene. Pigment Cell Research 15:201-211.
” Wegner, W., and A. Akcan. 1980. Auswirkungen der Merlefactors auf die Area optica beim Hund. DTW (Deutsche Teirarztliche Wochenschrift). 87(9):342.
Willis, Malcolm B. 1989. Genetics of the Dog. New York: Howell Publishing.
” Wood JLN, Lakhani KH. 1997. Prevalence and prevention of deafness in the Dalmatian - Assessing the effect of parental hearing status and gender using ordinary logistic and generalized random litter effect models. Veterinary Journal 154:121-33.
” Wood, JLN, Lakhani, KH, & Henley, WE. 2004. An epidemiological approach to prevention and control of three common heritable diseases in canine pedigree breeds in the United Kingdom. The Veterinary Journal 168:14-27.
” Yousha, JP. Black, blue and fawn: Color gene interaction in solid colored Danes. Online publication: August 2006. Online article.
” Yousha, JP. Control of Canine Genetic Disease. 2005. Dane World Nov-Dec: Vol 11, Issue 6, pp.97-99. GDCA publication: November 2005. Online article.
” Yousha, JP & Neil OSullivan. 2005. Deafness and color-related eye defects in white Great Danes. GDCA publication: August 2005. Online article.
? Yousha, JP. 2005. The Piebald Dane: Pinto, Parti-colored, Check: the color-headed or white-factored Dane. (Der Plattenhund). Nemetskiy Dog February 2005 issue. (The Russian National Great Dane magazine). Translated into Russian by Dmitry P. Tishin, M.D., Ph.D. Online article. (in English).
” Yousha, JP. Coat Color Genetics in the Toy Poodle: an adaptation and update., 2004. Aiken no tomo. July Issue: Seibundo Publishing, Tokyo. Translated into Japanese by Sachika Takeda.
” Yousha, JP. 2004. Color Genes in the Great Dane: New Data on whats up in coat color genetics. Danes Unlimited April; Vol 1, No. 2, pp.13-25.
” Yousha, JP. 1997. Mantledane Genetics: How to get & keep Boston-patterned dogs. Great Dane Reporter: M/A
” Yousha, JP. 1996. A Summary of Theories Concerning the Harlequin Variant in the Great Dane. Great Dane Reporter: M/A.
” Zemke D, Cao Y, Yuzbasiyan-Gurkan V. 1999. Hereditary hearing loss in dogs: models for sensorineural deafness. Hereditary Deafness Newsletter 16:34 ( hereditary/newsletters/ index.shtml).
” Zemke, D. and V. Yuzbasiyan-Gurkan. 1999. A single nucleotide polymorphism and a (GA)n microsatellite in intron 6 of the canine endothelin receptor B (EDNRB) gene. Anim. Genet. 30:390.

WordPress database error: [Table 'wf-3b48-454151.wp_comments' doesn't exist]
SELECT * FROM wp_comments WHERE comment_post_ID = '139' AND comment_approved = '1' ORDER BY comment_date

Say your words