This webpage is part of a series on Dog Coat Color Genetics and was last updated on June 7, 2009 by Sheila Schmutz
The first gene that causes at least some spotting patterns in dogs was identified and published in 2007. Furthermore potential mutations causing some forms of spotting have been identified in this gene.This gene is MITF, microphthalmia associated transcription factor. MITF is a critical gene in the pigmentation pathway.
MITF has been shown to cause spotting of the piebald or random type in crossbreds by Rothschild and colleagues. It also caused the Landseer pattern in Newfoundlands. However the causative mutation was not identified in their study.
Another study presented by Karlsson on behalf of the Broad Institute and the Univerisity in Uppsala, Sweden focussed primarily on Boxers. They have shown that MITF is the gene causing the solid, flashy, and virtually white forms in Boxers and Bull Terriers. They suggest that two mutations in the promoter region of the MITF form that works in the pigmenation pathway (MITF-M) are necessary for white in these breeds. One of these is called a SINE (short interspersed nucleotide element) and the other is a string of repeated alleles that varies in length in different spotted dogs, which they call a "Length Polymorphism or LP". Their data suggest that the LP is found to be longer in breeds with white markings than in dogs with no white.
Although Charles Little (1957) suggested that most spotting patterns other than merle and Harlequin were caused by four alleles of the S locus, this does not fit that well with new DNA studies.
Ojvind Winge (1950) was a contemporary of Little but is rarely quoted. In his book, Winge does not attempt to assign multiple alleles to the Spotting locus but simply suggests that a recessive allele controls "white-mottling" in dogs and when it is homozygous, the dog has a considerable amount of white. When it is absent he suggests the white markings are either not present or minimal, usually on the feet, tail tip and chest. This diagram above appears in his book, but was adapted from a publication by G. M. Allen in 1914. Winge suggests that this one gene for the presenece or absence of white mottling, might explain most or all of the dogs in this diagram.
There may be other genes, besides MITF, involved in spotting, but further research is needed to determine this. Little suggested these were plus and minus modifiers. Winge is more vague about this. Pape (1990) also suggested modifiers when he postulated the genetics of white markings in Newfoundlands. Further research will be needed to determine which other genes, if any are involved.
Piebald Spotting
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A few dog breeds contain dogs that are solid colored and those that are spotted. Little (1957) suggested that solid colored is dominant to spotted, as did all other authors. I would define the type of spotting in the Landseer or the Holstein cow as piebald. Likewise, Dauceur the Brittany Spaniel at the left and the Spinone at the right are both dogs with piebald spotting. Piebald spotting is a pattern of spots which occur randomly anywhere on the body, including the torso. They are not of consistent size or location therefore. Dogs that have piebald spotting (sp) can have very few colored spots or very many. In cattle and pigs, some spotting patterns have been shown to be caused by the KIT gene. Although the spotting pattern of a Landseer Newfoundland looks somewhat like the spotting pattern of Holstein dairy cows, this pattern was NOT caused by the KIT gene, based on a recent study we completed. This form of spotting appears to be inherited as an autosomal recessive of some allele of MITF. Therefore Landseer Newfoundlands are s/s according to the nomenclature of Winge or sp/sp according to the nomenclature of Little. Their genotype is SINE/SINE at MITF. Testing for carriers of piebald spotting in several breeds is now available at HealthGene. |
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Little and others have suggested that there is also an allele, sw, which is the most recessive in the S series that causes "extreme white spotting". There is thus far no evidence of such an allele in MITF although Stacey, and other Papillon, may be examples of this phenotype. All such dogs studied also were homozygous for the SINE at MITF. Note that the head remains deeply pigmented. This breed is not thought to have much problem with deafness, probably because it remains pigmented in the critical regions. Stacey is black-and-tan with a great deal of white. However, is she so much more white than Dauceur, the Brittany above? The "demarcation" between a dog with few piebald spots and a dog that is "extreme white" spotted is not that clearcut. Therefore it is not that surprising that they both have the same genotype at MITF. |
Boxer Markings: Co-dominant Inheritance
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"Irish spotting" was a term coined by Doncaster in 1905, according to Little, to describe a spotting pattern in wild rats from Ireland as an alternative pattern to "hooded". Doncaster suggested that this "hooded" phenotype occurred in the heterozytogte, whereas the homozygotes were solid or piebald. He found this in Norway rats and also in some wild rats in Ireland and it is believed that is why it came to be known as "Irish spotting" in rats. In Boxers one homozygote has virtually no white markings and the other homozygote is virtually all white. The heterozygote is the "flashy" Boser with white muzzle and blaze, white collar and undersides. This fits a co-dominant inheritance pattern. Little referred to this as "pseduo-Irish" markings even though the inheritance pattern fit the rat model better. However he seems to contradict himself later in his chapter on spotting (p. 87) and suggests that S, si, and sp all exist in Boxers. Karlsson et al. have studied Boxers extensively and described two muations which occurred in all white Boxers (see more above) and also in white Bull Terriers. Another simultaneous study by Leegwater et al. map Boxer spotting to MITF. Previously Van Hagen and others studied this trait as a discrete co-dominant trait and thereby excluded both KIT and EDNRB, under this hypothesis. |
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White Undersides or Irish Pattern
Little discusses the "pseudo-Irish Spotting" phenotype in the flashy Boxer and then raises the perplexing pattern he refers to as "Irish spotting", in dogs such as Basenji. He also suggests that plus and minus modifiers are likely. He says the si causes this pattern and that is is recessive to the S allele for solid, but dominant to the allele causing piebald spotting (sp).
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Border Collie markings or white undersides do not seem to be the same pattern as "Flashy markings" in the Boxer, even though the white is located on simlar parts of the body. Although the markings of the Boston Terrrier at the left closely resemble the heterozygous Boxer's markings, they are not inherited as a heterozygous pattern and hence may not be caused by the same gene (MITF) or at least not by the same mutation. All Boston Terriers are considered to have Irish spotting. Karlsson et al. (2007) have reported that Basenji and Bernese Mountain Dogs have a long LP mutation in the MITF gene, but no SINE mutation. Dogs with other types of white markings also were reported with this long LP but with a SINE too. Topper, the Great Dane at the right, shows these characteric markings also, but in this breed the pattern is called "mantle". Dogs with this mantle pattern with homozygous for the SINE in some breeds and heterozygous in others. |
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A study some years ago, which was an offshoot of the California study of dog behaviors, involved crossing a black Newfoundland dam with a small white chest spot to a Black and white Border Collie with white undersides. A litter was produced with all pups having only a white chest spot. Two of these were crossed and the resulting litter had some pups with white undersides and some not. The authors conclude that neither EDNRB nor KIT is the gene responsible for this pattern. It would have been fantastic if these authors had also studied MITF in this group of dogs. |
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Because melanocytes migrate down from the spinal column during embryogenesis (see the page about this), not all animals complete this process by birth or thereafter. In dogs, it is therefore not uncommon to see white toes on an otherwise black or red dog. This is probably more a random event than the result of a specific allele. Another common "white spot" on dogs occurs on the chest. This must again be a site where melanocytoe migration occurs very late in fetal development and a cold or other developmental delay prevents the completion of melanocyte migration. It may be that the rate of melanocyte migration is itself inherited. In some dogs, such as the Gordon Setter at the left, a white chest spot occurs. Some standards mention this as a fault. This is likely simply incomplete pigment migration in the particular individual, and not an inherited trait. Such small amounts of white on the chest or on the toes, do not seem to be caused by mutations in MITF. |
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Dalmatians are born white and the spots develop after birth. Karlsson et al. found that these dogs appeared to inherit the same SINE mutation as the white Boxers, in homozygous form, but a different LP mutation, causing them to be white. So what causes Dalmatian black spots on this white background? Some authors, such as Little (1957) and Sponenberg and Rothschild, suggest that Dalmatian spots are caused by the same gene as ticking. The Dalmatian above illustrates the typical pattern. When comparing the Dalmatian to the ticked hunting dogs above, there is some similarity but also considerable difference. Sponenburg and Rothschild further say that an additional gene for flecking, with the Dalmatian carrying the recessive genotype for "nonflecked", makes the Dalmatian spots distinct on a white background. They distinguish this as a separate gene from roan. Dalmatian spots can be black or liver brown. This difference is caused by recessive mutations in the B locus gene TYRP1, discussed on the page about brown. |
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Ticking is considered by Little (1957) to be tiny spots of color on a white background. It is also called "belton" in some breeds such as English Setters. Ticking is considered to be dominant to its absence, which is called Plating in some breeds, such as the Large Munsterlander. Plating is used because large plates of color still occur on these dogs, but very few small ticks appear. A side effect of the recessive plating genotype is that the pads have pink areas into adulthood. The pup below is pleased to demonstrate pink on the pads! Little stated that ticking does not occur at birth but develops during the first few weeks. The gene causing ticking versus its absence is not yet known but at least one group is actively studying it. Ticked dogs also typically have roan areas. Roan was inherited as a heterozygous genotype at the MGF locus in cattle but plated and ticked dogs have identical MGF sequence. Little (1957) suggested that roan could be caused by a separate gene. It might be said that merle dogs also have roan areas. |
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The Large Munsterlander family above shows that the amount of ticking and/or roan varies amongst the offspring in a continuous distribution. All have a few large black patches but some are much darker than others. The dam, on the top right, is slightly darker than the sire on the left. It would be difficult to categorize these dogs into only 2 discrete categories. Are 8 offspring becoming darker from left to right because of more ticking or more roan or both? Such a continuum does not lead one to think of simple single gene inheritance. However it is likely that the presence or absence of ticking may be caused by such a mechanism, and these dogs all would therefore have the allele for ticking.
Photo by Randi Kerlinger
The litter of Great Dane pups above, from a black dam and Harlequin sire, shows a wide range of spotting patterns. Spotting patterns could include merle which is discussed on a separate page. Harlequin is another special spotting pattern than seems to occur only in Great Danes, discussed below. Harlequin spotting was reported to be caused by an interaction of the gene causing merle and some other gene by Little and later by Sponenberg and his collaborators. In a small DNA study to find the gene causing Harlequin, we had excluded EDNRB and MITF.
Recently the gene causing merle, PMEL17, has been discovered by Keith Murphy's group. This will now aid in the search for the Harlequin gene. They have shown that Great Danes that were Harlequin had either one or two copies of the merle mutation.
In 2008, this same group published a study mapping the gene for Harlequin to dog chromosome 9. The gene has not yet been identified and so the mutation is not yet known either of course.
Studies of genes which may be related to spotting in dogs