Quick Summary
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Phenotype: The merle pattern is characterized by irregularly shaped patches with diluted pigment while other patches on the coat are fully pigmented in color.
Mode of Inheritance: Incomplete dominance
Alleles: N = Non-merle, ### = Merle allele present, size is provided
Breeds appropriate for testing: Many breeds including but not limited to: American Bully, American Pit Bull Terrier, American Staffordshire Terrier, Australian Shepherd, Beauceron, Bergamasco, Border Collie, Cardigan Welsh Corgi, Catahoula Leopard Dog, Chihuahua, Cockapoo, Cocker Spaniel (American), Collie, Dachshund, Dunker, French Bulldog, Great Dane, Koolie, Mudi, Old English Sheepdog, Pomeranian, Pyrenean Shepherd, Shetland Sheepdog, Crossbred
Explanation of Results:
- Dogs with N/N genotype are not expected to display a merle pattern. They cannot transmit this merle variant to any of their offspring.
- Dogs with N/### or ###/### (### = any number from 200-280) may display a merle pattern. This pattern varies along a continuum. The amount of dilute patches is dependent on which merle allele(s) are present AND if the dog will show black/brown pigment (eumelanin) = NOT e/e at MC1R. In brief, eumelanic dogs with two copies of smaller allele sizes (lower numbers) display little to no merle pattern often referred to as "cryptic merle". Eumelanic dogs with 1 or 2 copies of larger alleles (higher numbers) are expected to display the merle pattern. Eumelanic dogs with one or two copies of the highest numbers (~270-280) display a dramatic dilution/white pattern referred to as harlequin. This is NOT the phenotype resulting from the gene variant identified as Harlequin (H) in the Great Dane. Breeding two dogs that possess any of the merle variants may produce "double merle" offspring (homozygous) which may be prone to health problems. Double merle dogs may have auditory, ophthalmologic, skeletal, and other defects and will transmit a merle variant to all of their offspring.
- Dogs with N/###/### or ###/###/### (### = any number ranging from 200-280) have an additional merle allele likely resulting from the propensity of the repetitive DNA causing the merle phenotype to increase or decrease in size. Each individual cell still only has two copies. However, different cells of the body may have different sizes of alleles. The phenotypic impact of the additional allele cannot be predicted as distribution throughout the body may be variable. Similarly, it is possible for all alleles to be transmitted to offspring but depends on the alleles present in the egg and sperm cells, thus the heritability cannot be predicted.
Results of this test can be submitted to the OFA (Orthopedic Foundation for Animals)
The merle pattern is characterized by irregularly shaped patches with diluted pigment while other patches on the coat are fully pigmented in color (solid). Merle only dilutes eumelanin (black) pigment; dogs with an MC1R e/e genotype do not produce black pigment and thus do not express merle, but can produce merle offspring depending on the genotype of the mate. Merle is governed by a SINE insertion in the PMEL17 or Silver (SILV) gene. SINEs are defined as short interspersed nuclear elements. These are repetitive DNA sequences that can copy and insert into different locations in the genome. The impact of the insertion depends upon the location: they can impact gene expression and function and, if inserted into the germ line cells, can be passed down to future generations.
The presence or absence of the merle SINE insertion determines the possibility of observing the merle phenotype while the length of the end of the SINE insert sequence, which is composed of the nucleotide A (poly-A tail), correlates to the extent of the merle pattern observed. Only one copy of the merle associated variant is necessary to see the effects but the length of the tail directly influences the phenotype.
The length of the poly-A tail can vary by as much as 80 nucleotides. When originally identified, range of sizes were grouped into three categories with 4 results: no SINE insertion= N, short poly-A tail= Mc (cryptic merle aka phantom or ghost and merle phenotype may or not be observed), longer poly-A tail = M (the merle pattern always observed), and an undefined region between long and short where merle pattern prediction was inconsistent. Until September 9, 2020 the VGL reported these as N, Mc, or M.
Further investigations by multiple, independent, researchers have refined the phenotypic correlation with the poly-A tail length. The following figure shows the allelic ranges and nomenclature defined by each research study. The nomenclature differs by study. Many variables likely contributed to the varied ranges and nomenclature some of which is dependent on sample sizes, breeds used, ascertainment bias, etc.
Given the variation that exists in the scientific literature for allele nomenclature the VGL now reports merle alleles based on size instead of by allele designation (please see Figure 1). This allows animal owners to utilize these numbers with the naming scheme they prefer.
Figure 1: Merle Allele Nomenclature Defined by Multiple Scientific Studies. The VGL reports merle as the size of the detected allele. The figure demonstrates the different proposed nomenclature based on the reported allele size.
Dogs with cryptic merle (also called phantom or ghost merle) typically display little to no merle pattern and some may be misclassified as non-merles. The cryptic merle alleles occur in the lower end of the range (typically from 200-255, however, this range and designation varies by study). As the length of the poly-A tail increases, the degree of eumelanin dilution increases to produce the merle pattern with the highest end of the range producing a phenotype that can be completely white (around 280 bp). In dogs with merle, this has been referred to harlequin or merlequin. It is important to note that the merle derived “harlequin” is distinct and caused by a different genetic mechanism from Great Dane Harlequin (H).
The merle poly-A tail is genetically unstable and, although uncommon, parents and offspring may have different sizes and thus different genotypes. Despite claims to the contrary, exhaustive sampling and testing at the VGL has identified heritable expansion and contraction of the merle insert in offspring where parentage testing has been confirmed. Also, in rare cases, the poly-A tail may expand in some cells leading to the appearance of three alleles in one animal. The distribution throughout the body of cells with differing allele sizes depends upon the timing of the origin of the expansion or retraction of the poly-A during development. If early in development, two distinct populations of cells may be present throughout the dog. If later, the appearance of two populations of cells may be restricted to specific tissues.
Blue and partially blue eyes are typically seen with merle, and merle dogs may possess a wide range of auditory and ophthalmologic defects. Dogs with two copies of any of the size variants consistent with merle (alleles other than N) are called double merles and often can have an all white coat accompanied by multiple abnormalities of skeletal, cardiac, and reproductive systems, therefore breeding two merle dogs is discouraged to avoid producing double merle offspring. However, it is important to consider that many double merle dogs with ophthalmic and auditory defects often have a white spotting component and double merles in a breed with low piebald spotting allele frequency such as Catahoula leopard dogs, have fewer noted auditory and ophthalmologic defects.
Because of the complexities of merle inheritance and potential health concerns, DNA testing is recommended to establish the genetic makeup of dogs for the merle gene for those breeds where this color dilution pattern is present.
Species
Breed
| Test Result | Merle |
|---|---|
|
N/N |
No copies of the merle associated SINE insertion. |
|
N/### |
One copy of the merle associated SINE insertion. See attachment (last page) for additional information. |
|
###/### |
Two copies of the merle associated SINE insertion. See attachment (last page) for additional information. |
|
N/###/### |
Two copies of the merle associated SINE insertion and one copy without the insertion. The impact of this may not be resolved. See attachment (last page) for additional information. |
|
###/###/### |
Three copies of the merle associated SINE insertion. The impact of this may not be resolved. See attachment (last page) for additional information. |
### = merle alleles are reported by size (200- 280) so that any of the proposed nomenclature schemes in Figure 1 can be utilized.
Clark, L.A., Wahl, J.M., Rees, C.A., & Murphy, K.E. (2006). 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, 103(5), 1376-1381. doi: 10.1073/pnas.0506940103
Kaelin, C.B., & Barsh, G.S. (2013). Genetics of pigmentation in dogs and cats. Annual Review of Animal Biosciences, 1, 125-156. doi: 10.1146/annurev-animal-031412-103659
Murphy, S. C., Evans, J. M., Tsai, K. L., & Clark, L. A. (2018). Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype. Mobile DNA, 9, 26. PMID: 30123327, PMCID: PMC6091007, doi: 10.1186/s13100-018-0131-6
Langevin, M., Synkova, H., Jancuskova, T., & Pekova, S. (2018). Merle phenotypes in dogs - SILV SINE insertions from Mc to Mh. PloS one, 13(9). PMID: 30235206, PMCID: PMC6147463, doi: 10.1371/journal.pone.0198536
Ballif, B. C., Ramirez, C. J., Carl, C. R., Sundin, K., Krug, M., Zahand, A., Shaffer, L. G., & Flores-Smith, H. (2018). The PMEL Gene and Merle in the Domestic Dog: A Continuum of Insertion Lengths Leads to a Spectrum of Coat Color Variations in Australian Shepherds and Related Breeds. Cytogenetic and Genome Research, 156(1), 22-34. doi: 10.1159/000491408
The Veterinary Genetics Laboratory is licensed by IDEXX Laboratories, Inc. to offer the merle test.
