Dog Genetic Profile – Merle
Written by Dr. Guy Labbé, DMV
(translation DR)
The merle coat color (sometimes called “dapple”) can come in a variety of possible patterns. The coat is usually randomly spotted, with both darker and faded pigmentation areas. The merle dog’s eyes are often pale or an unusual color. It is an aesthetic trait sometimes sought after in several breeds, including the Australian Shepherd, the Dachshund, the Collie, the Border Collie and the Great Dane. While the merle coat color is accepted in some dog breeds is prohibited in other breeds.
The story of Maddie
Maddie is the offspring of a typical merle father and a mother whose coat is a solid, undiluted color, i.e. non-merle. Early in the life of Maddie, her owner noticed that she was deaf and visual deficits were also diagnosed by her veterinarian thereafter. These issues raised suspicion that Maddie was “double merle”; the owner had therefore done a DNA test for the M Locus (merle), in order to be sure. The DNA test revealed that Maddie has a copy of the merle mutation called “standard merle” and a copy of the mutation called “cryptic merle”; she is “double merle”. Maddie’s mother, having a normal coat and later tested for merle, proved to be a cryptic merle. Thus, the crossing from which Maddie is derived is “Merle X Cryptic Merle”, which explains why Maddie is “double merle”, with the developmental anomalies that are related to this status. This case illustrates the importance of a DNA test for the M Locus (merle) when it involves breeding a merle dog with a dog that appears non-merle, in case the latter is in fact a cryptic merle. It is important to keep in mind that the double merle phenotype exposes the animal to a higher risk of congenital problems.
The Merle Gene Mutation
The “merle” dog is heterozygous (M/N) for a mutation in the PMEL gene (premelanosome protein, also known as SILV). This gene is responsible for the synthesis of a protein that produces melanin. It is because of the mutation of the PMEL gene that changes in the colors and pattern of the coat occur, as well as the absence of pigmentation in the pigmented cells of the eyes, typical of the merle phenotype. At the DNA level, the mutation consists of an insertion of a short interspersed nuclear elements (SINE) sequence of approximately 253 base pairs in intron 10 of the PMEL gene, which is found on the canine chromosome 10.
The Genetics and Pedigree of the Merle Dog
Merle is a dominant genetic factor, that is, only one mutated copy of the merle gene is required to produce an effect on coat color. The possible matings are as follows:
(A) – Normal X Merle. A typical mating is done between a merle dog and a dog that is non-merle, to give birth, in theory, to 50% merle pups (M/N) and 50% puppies that are non-merle (N/N).
(B) – Merle X Merle. A mating between two merle dogs should be strictly avoided, since the litter will have 25% normal pups (N/N), 50% merle puppies (M/N) and 25% double merle puppies (M/M). It is necessary to prevent the birth of double merle dogs because the mutation of the two copies of the merle gene predisposes them to health problems.
(C) – Cryptic Merle X Merle. A cross between a cryptic merle dog (Mc/N) and a typical merle dog presents an additional complication which is the possibility of giving birth to a cryptic double-merle puppy (Mc/M), like Maddie.
Medical Problems of the Double Merle Dog
The PMEL gene is active during embryogenesis, especially in the pre-melanocyte cells of the neural crest. The insertion of a SINE sequence in the PMEL gene is problematic for the pre-melanocyte cells. Melanocytes are normally found in skin and hair, but can also be found in eyes and ears. Disruption of these cells during embryogenesis can lead to problems in pigmentation, thereby causing eye and ear problems.
Dogs with two copies of the PMEL mutation are referred to as “double merle” (M/M) and are at risk of having a multitude of health problems. Usually, there is marked hypopigmentation (white coat and blue eyes) because the double merle dog has difficulty producing pigment. In many cases, the dog is born with hearing loss (25% versus 5% in the typical merle) due to a dysfunction of the pigmented cells in the stria vascularis lining the cochlear duct in the inner ear. Visual impairment (microphthalmia, subluxation of the lens or pupil, deformed pupils, blindness or poor vision) is sometimes also observed. Due to lack of pigment, the animal will also be more sensitive to sunburn and skin cancer.
Cryptic Merle
Some dogs may carry the mutated gene, but do not show a typical merle pattern for coat or eye color; these dogs are described as “Cryptic Merle” (Mc/N). The mutation that results in cryptic merle dogs is caused by the insertion of a SINE sequence that is slightly shorter than the SINE sequence found in the typical merle. Since cryptic merle animals have a normal appearance, a DNA test is required to detect the presence of the cryptic merle gene. A cryptic merle dog (Mc/N), if mated with a typical merle dog (M/N), may unfortunately produce double merle dogs (M/Mc), with a high probability of congenital anomalies. It is therefore not possible to rely on the appearance of the animal to judge whether it is safe to mate with a merle dog.
Preventive Genetic Testing for the Merle Dog
It is important emphasize that a merle dog (M/N) must not be mated with another merle dog. As we have seen in the case of Maddie, a mating between a merle dog and an animal that is not merle in appearance may also be problematic, given the possibility that the “normal” dog is in fact a cryptic merle dog (Mc/N). In these cases, the litter has a high probability of having one or more double merle dogs (M/M). One way to prevent this unwanted scenario is to request a M Locus DNA Test for breeding animals to ensure that the “normal” parent does not carry the mutated gene (cryptic merle) despite its normal appearance.
References:
- Murphy SC, Evans JM, Tsai KL, Clark LAJMD. Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype. 2018;9(1):26. [pubmed/30123327]
- Clark LA, Wahl JM, Rees CA, Murphy KE. Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(5):1376-81. [pubmed/16407134]
- Strain GM, Clark LA, Wahl JM, Turner AE, Murphy KE. Prevalence of deafness in dogs heterozygous or homozygous for the merle allele. Journal of veterinary internal medicine. 2009;23(2):282-6. [pubmed/19192156]
- Ballif BC, Emerson LJ, Ramirez CJ, Carl CR, Sundin K, Flores-Smith H, Shaffer LG. (2021) The PMEL gene and merle (dapple) in the dachshund: cryptic, hidden, and mosaic variants demonstrate the need for genetic testing prior to breeding. Hum Genet. 2021 Aug 9. [pubmed/34370083]
- Merle (dog coat) [Internet]. En.wikipedia.org. 2019 [cited 24 January 2019]. Available from: https://en.wikipedia.org/wiki/Merle_(dog_coat)
- Dog Coat Colour Genetics [Internet]. Doggenetics.co.uk. 2019 [cited 24 January 2019]. Available from: http://www.doggenetics.co.uk/merle.html