Unerwünschte Farbveränderungen

• Color Overlap E-Locus (e/e)

  Extremely rarely, the undesirable allele combination e/e (E locus) appears in Collies and then covers the basic coloration and the nose with a reddish light brown color. The white remains on the collar, legs, etc., so that they are reminiscent of Sable Collies. If it covers Merle, they are also called Hidden Merles.Inheritance is recessive, i.e. the two rare genes must meet in both parents to produce this color. On the other hand, affected alleles can spread completely unnoticed as long as they are covered by a second, unaffected gene and no color changes occur. It is a common color variation in Setters and Retrievers and doesn't cause there any health problems. Some debate wether it has not always been present in Collies as well. Either way, it is considered undesirable today because it overlays everything else.

• Maltese Blue / Maltese Gray (d/d)

  Maltese Blue, also called Maltese Gray, causes a dilution of all colors (eumelanin & pheomelanin). There have been known cases of matings between Classic Blue Merle and Tricolor. While most offsprings are normally colored Tricolor and Classic Blue Merle, there are some whose coats are medium to dark gray, with a tendency to darken as the animals grow. They are somewhat reminiscent of Collies with Atypical Merle. However, in the Maltese Blue, the originally tan markings also lighten to cream. The White on the collar, legs, etc., is normally developed. It should not be confused with GCS (see below).

  Leigh Anne Clark et al. discovered in 2018 that an additional mutation at the D-locus (dilution) is present, with the expression d/d, which leads to this undesirable coloration. Inheritance is recessive, meaning the two rare genes must coincide in both parents to produce this color. On the other hand, affected alleles can spread completely unnoticed as long as they are covered by a second, unaffected gene and no color changes occur. According to Dr. Clark, no health problems are to be expected, which is also consistent with reports from owners (all outside our association). 

• Gray Collie Syndrom (GCS/GCS)

  Maltese Blues should not be confused with Collies affected by Gray Collie Syndrome (GCS), also known as Cyclic Neutropenia, which results in a dramatic decrease in white blood cells (granulocytes) approximately every 11 days. They also have a grayish coat, but usually even lighter, lacking tan markings and lacking full pigmentation on the nasal surface. These dogs are usually in very poor general health, as they are very susceptible to infections. Therefore, they often lag significantly behind their healthy littermates in terms of development. Many do not reach adulthood but die from simple infections. Our breeding regulations prohibit the birth of such dogs. Test: https://labogen.com/en/genetic-diseases-dog/grey-collie-syndrome-canine-cyclic-neutropenia-gcs/ . Further detailed information is available in our breeding program for GCS:

  GCS (Gray/Grey Collie Syndrome or Cyclic Neutropenia-CN): This is a rare genetic disease of blood cell formation in the bone marrow, which leads to a cyclical reduction, especially of neutrophil granulocytes, which are extremely important for the immune system. The latter are the main component of the cellular immune system. Their strong reduction every 11 (10-14) days means that affected dogs are very susceptible to infection. As long as puppies are still being suckled, the antibodies from the mother's milk still seem to have a supportive effect, and the environment is usually relatively germ-free. Until then, the most noticeable feature is the slightly lighter, usually grayish coat color (not caused by Merle), with a nose that does not completely turn black over the course of development, which also remains rosy at first and later grayish. In addition, the tan markings are missing. The greatest risk of symptoms developing is at 8-10 weeks. With few exceptions, a terrible ordeal then begins with infections that become increasingly severe and, sooner or later, life-threatening, initially often caused by the simplest pathogens, that have only little effect on healthy puppies and young dogs. The illnesses are often accompanied by recurring fever, diarrhea, sometimes vomiting, joint pain that soon develops into arthrosis, sometimes accompanied by misalignment. Respiratory infections that develop into serious, life-threatening pneumonia are also typical. The eyes, skin, mouth and teeths are also very susceptible to all kinds of pathogens. Since the entire blood formation is disrupted by the cyclical changes (hence also called cyclic hematopoiesis), anemia can easily develop, possibly accompanied by a blood clotting disorder and symptoms such as nosebleeds and omnipresent additional general weakness. The affected dogs usually die within the first three years of life. Reciprocal bone marrow transplants from sick dogs to healthy ones, which then became ill, and vice versa from healthy dogs to sick dogs that had a chance of recovery, have proven that the cause can clearly be found in the bone marrow. Unfortunately, there is no sufficient developed system for finding suitable bone marrow donors in dogs. There is a similar disease in humans, cyclic neutropenia (CyN). A mutation in exon 20 of the AP3B1 gene has now been identified (https://omia.org/OMIA000248/9615/ ). This primarily causes a deficiency in the enzyme elastase (including agglutination of the precursors that cannot be completed) and, as a result, a disruption in the movement and function of the granulocytes, up to the failure to trigger a final immune response to fight infections. The gene is also the cause of a form of coat dilution, that causes the eponymous gray coloring in affected animals. It can also vary to a beige-yellowish color, depending on the base color and as a new color variant after the rare coat change. The harsh structure is usually also missing. This mutation has now been found in distantly related breeds, and the search is still ongoing in other breeds. These matuations probably occurred very early in the evolutionary history of dogs. In all probability, both parents (carriers) already have limited granulocyte function. We are happy that a suitable genetic test has been developed. Everything suggests that our gene pool is also completely free of carriers and ideally stays that way. When our association was founded, we established the rule that at least one parent in every mating must be genetically free (GCS +/+ or N/N). In the meantime, every breeding candidate must be tested for GCS. This means that the birth of GCS-affected puppies has been and will continue to be completely prevented in our association AC e.V.!

• Fever Coat

  Despite the brightening effect, fever coat has nothing to do with merle. A (usually harmless) infection during pregnancy can be a trigger. Excessive stress has also not been ruled out as a potential trigger. The key point seems to be when the puppies begin developing the pigments for their coat color. If a disruption occurs here, the head (sometimes extending to the shoulders and forelegs) is a normal strong colored, while the rest of the body's coat is more or less brightened. Often, it is only a slight shade. This effect is only temporary. During the next coat change (at the latest, with the adult coat), the pigment will reappear with its normal color.

Merle

• (Classic) Merle (m/M)

  In its classic and probably best-known form, the Merle gene in (Classic) Merles (m/M) causes a brightening of the Tricolors black color to a light silver-blue (dark steel gray is undesirable). This is why they are also called Blue Merles. Due to its incomplete penetrance, areas of the original color (here black) always remain, in form of small or large patches, that often appear torn. Because only eumelanin appears to be affected, the pheomelanin of the reddish-brown tan markings is normally unaffected by such changes. In the Blue Merle, the brightened coat (sometimes it darkens a bit) with the dark spots remains for life. In the Sable Merles, on the other hand, which developed from the brightening of sable-colored coat, the darker sable mottling is usually only visible in very young puppies. Later, the spots usually disappear, so that an adult Sable Merle can often no longer be easily distinguished from a Sable without a Merle factor. They are then also called Hidden Merles, as well as the other variants where Merle is not or hardly visible (see below). Sable Merles that originate from Pure Sables are often very similar to Gold Sables when fully grown, although the color can often appear faded. Sable Merles that originate from Dark Sables can also be quite light, but they can also develop a fairly strong, often almost reddish-brown color. Very rarely, Classic Merles can have one or more lighter spots that tend towards White. This has nothing to do with the Harlequin/Fawnequin variant (see below), even if it looks that way at first glance. Such spots are called Dilute Spots. 

• Cryptic Merle (m/Mc, m/Mc+)

  Cryptic Merles have the m/Mc or m/Mc+ gene variant. In terms of their phenotype, they look like normal Sables or Tricolors. Even if the gene section already shows an extension here, it is not long enough to produce pigment brightening anywhere. This is how the dogs grow up with their original intended coloring. There are reports here and there that the puppies may be a touch lighter at their hair-ends shortly after birth, but this is no longer visible some time later. The genetic change is so small that, based on current knowledge, one could theoretically even breed Cryptic Merles with the m/Mc, m/Mc+ and m/Ma variants without puppies being born with health problems. By the m/Mc variant (without a plus sign) even m/Ma+, m/M is added. In practice, however, it remains forbidden as long as the legislature fundamentally prohibits the mating of Merles, because he does not differentiate between the different Merle variants.

• Atypical Merle (m/Ma, m/Ma+)

  Atypical Merles have the m/Ma or m/Ma+ gene variant. While by the m/Ma variant a slight brightening of the base color is possible at the best, comes by the second variant m/Ma+ a slight Merle pattern usually through. The Tricolore's fur becomes silver-greyish, a faded merle pattern may or may not be visible. Sable can appear a little paler and no pattern will be visible here by adults. Atypical Merle can be seen as a kind of transitional form from Cryptic Merle to Classic Merle. The extended gene section is not as short as in the Cryptic Merle, but also not as long as in the Classic Merle. Similar to the Cryptic Merle, according to current knowledge, no damage to the health of the resulting offspring is to be expected from a theoretical mating of m/Ma with the variants m/Mc, m/Mc+ and m/Ma. With the m/Ma+ variant, mating with m/Mc would theoretically be possible. But in practice both remain prohibited, according to the requirements of the legislature.

• Harlequin / Fawnequin / Minimal Merle (m/Mh)

  At first glance, Harlequins (Harlekins) resemble classic Blue Merles, and Fawnequins (Fawnekins) resemble classic Sable Merles, depending on the intensity of their characteristics. Often, the brightened areas (such as the silver-blue of the Blue Merle) are even brighter. Furthermore, the desired fine spottings in the base color (Tricolor in the Blue Merle and Sable in the Sable Merle) is usually less pronounced and more likely to be found in patches. These are then also called Herding Merles. Very large patches are also called Tweed. Many are found more at the edges and less within the lightened areas. This is also referred to as a "loud Merle pattern." In Fawnequins, the color can deviate from the expected natural Sable color, sometimes appearing faded, ranging from a light gold tone to a reddish brown tone, the latter especially when a Tricolor allele is present. Particularly striking are the often newly added, more or less extensive white areas without pigmentation. These are usually the first obvious indication of Harlequins or Fawnequins. They are not caused by a white factor. The tan markings are usually normal, although sometimes somewhat paler. Since Harlequins/Fawnequins have the same genetic status as Minimal Merles (m/Mh), these can also arise from them (see below)! These color variations are not to be confused with the Harlequin of Great Danes, which have an additional genetic mutation at the so-called H locus.

  Essentially, Harlequins and Fawnequins, as well as the other Merle carrier variants (m/M...), are, according to current knowledge, completely normal, healthy dogs. Accordingly, the changes associated with Merle relate solely to pigment brightening or loss, and not to other illnesses or behavioral effects. Pigment loss and the formation of white areas can only occur in the m/Mh breed due to Merle. This, too, has no harmful effects. Only in the quite unlikely event that the inner ear or the inner eye also suffers pigment loss, is there a risk that puppies could be born with varying degrees of hearing or vision impairment. Because Collies are specifically bred for a colored head, the risk of health impairments is extremely low, in contrast to Dalmatians (hearing) and completely white breeds based on pigment loss, such as White American Bulldogs. To ensure this remains the case, Collies with m/Mh may not be bred with those with a high proportion of white, such as a white factor or a blaze extending high on the forehead, and of course, not with other Merles, as required by law. In my many years of breeding Collies and researching Collies, I have yet to encounter a Collie with the genetic status m/Mh that has any hearing or vision impairments. If anyone ever finds such a case, please let me know so I can correct this.

  Minimal Merles, also called Phantom Merles, often look like normal Sables or Tricolors (phenotype) at first glance. If you look more closely, you will often find one or sometimes several small, sometimes tiny spots where the dog has a normal, classic merle color, especially at the edges. Sometimes you will just find a colored dot in the eye. Sometimes nothing is visible at all if the changes are too small or hidden by long fur or color overlaps. This includes White, for example. The Collie does not even need to have a white factor for this to happen; the pronounced collar (Irish Pattern) or white on the legs is enough. If the Merle would be located exactly in this area, (we remember, it is often found in the edges), then it would be covered by White. The same would happen with very rare and undesirable phenomena, such as the e/e at the E locus and the d/d at the D locus (see below). All of these are also called Hidden Merles because the merle is not visible (hidden).

  It was a great surprise when it was discovered some years ago that the allele variant of Minimal Merles (m/Mh) corresponds to that of Harlequins/Fawnequins! It was previously thought that they belonged to the Cryptic Merles, a transitional form to Classic Merles, with the first possible visible Merle areas. Due to the actual allele variant, Minimal Merles should not be bred with other Merles, even if the law were relaxed. It was previously thought that the genetic expression of Harlequins/Fawnequins & Minimal Merles was very rare. Today it is assumed that it was probably the first mutation that led to the later expression of the Merle variants known to us. Because here we have the longest A-tail appendage. Changes generally lead primarily to further shortening, which explains the other Merle variants. As Minimal Merles, this genetic variant managed to spread unnoticed due to the hidden appearance. Often, owners of Minimal Merles aren't even aware they have a Merle. They are often astonished when such a dog suddenly produces Harlequin or Fawnequin offspring, due to the same genetic status (m/Mh). Undetected Merle also increases the risk of Double Merles being born with health problems due to unknowingness (see below) after a wrong mating. Only a genetic test for Merle, cleverly using the currently common allele itemisation, can shed light on the mystery, as our breeding regulations require for every breeding dog: https://laboklin.com/en/products/genetics/coat-colour-coat-structure-coat-length/dog/m-locus-merle-alleles-mh-m-ma-ma-mc-mc-m-and-mosaics/ .

• Mosaic Merle (m/…/...)

  Mosaic Merle is a type of mixed form of various Merle alleles. Variations in the Merle alleles are relatively unstable. During embryonic development, which is characterized by numerous cell divisions until the final individual develops, minor variations can occur. Rarely, the A-tail becomes longer. It seems to be quite common for something to break off there, resulting in the A-tail shortening. This can lead to a proliferation of a different Merle variant alongside the original variant. Genetic testing then reveals three or more alleles in different cells instead of two alleles. Typically, the original variant remains the most prevalent, and is then referred to as a major allele. Added variants are referred to as minor alleles; to make them easier to identify, they are placed in square brackets. If, for example, a Classic Merle (m/M) has a shortening in the Merle allele, the Merle allele (M) changes into an Atypical Merle allele (Ma), and the result would be: m/[Ma]/M. Rarely, there is another additional shortening, for example a Cryptic Merle allele (Mc), in which would be also added, also in square brackets, m/[Mc]/[Ma]/M. If there is a plus sign somewhere, it will of course be added. If there is an extension of the original Classic Merle allele, an (Mh) allele is also possible, also in square brackets. Shortening and lengthening can also occur at the same time. Sometimes the respective number of base pairs (bp) is also added, e.g. in parentheses.

  Even if three or more alleles are named in mosaicism, this does not mean that they are all found in one cell. It remains a double set of chromosomes (diploid), with two alleles in each body cell, just in a different composition. Thus, in the examples mentioned, in addition to the original M/m variant, cells with m/Ma, m/Mc, or m/Mh can also be found. To avoid unnecessary complications, the result is summarized by listing the named alleles one after the other, placing the minor alleles in square brackets. During the formation of eggs and sperm, the chromosome set in each cell is halved as usual (haploid), thus resulting in sex cells (gametes) with all possible variants. In these examples, in addition to cells with an "m" or "M", one would also find cells with "Ma" and/or "Mc," or possibly also with an "Mh." For male dogs, it may also make sense to submit a semen sample for testing instead of a cheek swab. So Mosaic Merles are completely normal, healthy dogs. The same rules apply to mating as before, namely that they should only be mated with Merle-free dogs. This also complies with legal requirements.

• Double Merle (M/M)

  Double Merles are also called "White Tigers" because they like to have large areas of White, including areas of the head. This makes it easy to distinguish them from the White Collies, which always must have a colored head, this is why they are also called Color Headed White (CHW). The White coloring of White Collies is not due to Merle (see above)!

  Affected Double Merles not only exhibit pigment loss (leucism) in their coat, but can also exhibit it in their skin, inner ear, and eyes. Where the skin is affected, it appears rosier. If the nose is affected, it also turns pink, as do affected lips and eyelid margins, which are then all more sensitive to UV light when exposed to sunlight. In the inner ear, the lack of melanocytes disrupts the development of the normally well-perfused vascular layer (stria vascularis) on the outside of the cochlea. This prevents the sensory hair cells normally present there, which in healthy dogs receive and transmit sounds like antennas. Depending on the severity, this can lead to inner ear hearing loss or deafness. Affected eyes often turn an unnaturally light blue (significantly lighter than the blue found in Blue Merles) with a dark pupil sometimes. Normally, the eye is protected from excessive light and glare by the pigment deposited in the iris. A loss of pigment there can lead to light sensitivity. The iris can become so light that it becomes transparent, making the eye appear pink, allowing one to see directly through it to the blood vessels of the retina at the back of the eye. Lack of pigment in the choroid causes (like the vascular layer in the inner ear) to become significantly thinner. According to Olivia Schatz (Schwab & Haas 2018, University of Graz), angiogenesis (the formation of new blood vessels from existing ones) appears to be significantly reduced. Affected eyes and ears are often surrounded by white fur.

  The problem of the missing pigment-producing melanocytes (leucism) probably lies in a disruption in the transmission of their precursor cells (pluripotent melanoblasts) from the embryonic neural crest, along the nerve sheaths to the target location, such as the eye and inner ear. (In albinism, on the other hand, the melanocytes are present, but there is a dysfunction that prevents them from producing melanin.) In both cases, a lack of melanin can lead to more or less severe visual impairment. In addition, affected Double Merles often have eye deformities in form of microphthalmia. Then the eye is too small or not developed at all. Depending on the severity, this can lead to functional restrictions and even complete loss of vision. 

  It is therefore essential to avoid mating two Merles (even across breeds) if this could result in puppies with limitations or a complete lack of hearing and vision. It is all the more important to know the Merle Status of each dog so that its responsible owners can take early influence to avoid matings that are harmful to the health of their offspring (whether planned or not). Special attention is also paid to the Hidden Merles (especially Minimal Merles & Sable Merles (see above)), dogs whose Merle factor cannot be easily seen. Responsibly managed breeding clubs, like ours, ensure that breeding dogs are tested for Merle (a newer test with allele breakdown) before mating, as well as for all other common testable genetic abnormalities, such as those that can occur in MDR1, DM, PRA, GCS, etc. This allows matings to be chosen appropriately without producing affected puppies. Buyers are also informed accordingly. Test: https://laboklin.com/en/products/genetics/coat-colour-coat-structure-coat-length/dog/m-locus-merle-alleles-mh-m-ma-ma-mc-mc-m-and-mosaics/

White & White Factor

Sable & Tricolor