Merle allele variations in the Mudi dog breed and their effects on phenotypes

Abstract

A retrotransposon insertion in the SILV gene is associated with a peculiar phenotype of dog, known as a merle. It is characterised by various areas of their coat colour becoming diluted due to a malfunction in the eumelanin-producing pigment cells. Recent studies have shown that the exact size of the short interspersed element (SINE) insertion is in correlation with specific phenotypic attributes, but was not able to absolutely confine dogs to a certain colour pattern. Our study focused on the merle variations occurring in the Mudi breed. Altogether, 123 dog samples from 11 countries were tested and genotyped. The exact length of the merle alleles were determined by automated fluorescent capillary fragment analysis. The most frequent merle genotype in this Mudi sample collection was the ‘classic’ merle (m/M: 61.8%), whereas other variants, such as atypical (m/Ma and m/Ma+: 5.7%), harlequin (m/Mh: 13.8%), double merle (M/M: 0.8%) and mosaic profiles (17.9%) were also observed. The practical significance of testing this mutation is that, phenotypically, not only merle dogs are carriers of this insertion, but also the so-called hidden merle individuals (where the merle phenotype is fully covered by the pheomelanin-dominated colouration) are potentially capable of producing unintentionally homozygous ‘double merle’ progeny with ophthalmologic, viability and auditory impairments.

The PMEL gene and merle (dapple) in the dachshund: cryptic, hidden, and mosaic variants demonstrate the need for genetic testing prior to breeding

“…In general, a single copy merle variant in the cryptic size range will result in a non-merle phenotype, atypical merle variants most commonly result in a "dilute" phenotype, classic merle variants produce traditional merle phenotypes, and harlequin merle variants can result in a range of phenotypes from a patchwork of multiple shades of the same or different colors with or without white to subtle almost non-merle appearances. Furthermore, we and others have also identified numerous cases of mosaicism in dogs of various breeds including cases of gonadal mosaicism (Ballif et al 2018;Murphy et al 2018;Langevin et al 2018;Pelles et al 2019;reviewed in Varga et al 2020). In addition, several cases of merle insertion expansion and contraction have also been observed (Ballif et al 2018;Murphy et al 2018;Langevin et al 2018;Pelles et al 2019;reviewed in Varga et al 2020).…”

“…In recent years, we and other groups have correlated various lengths of the PMEL SINE insertion mutation with variations in the expression of the merle phenotype and established methods for routine genetic testing of merle allele sizes (Ballif et al 2018;Murphy et al 2018;Langevin et al 2018;Pelles et al 2019;reviewed in Varga et al 2020). These studies have demonstrated that, in general, the size of the SINE insertion correlates well with predictable phenotypic expression.…”

Being Merle: The Molecular Genetic Background of the Canine Merle Mutation

“…The fourth main phenotypic category in merle breeds is harlequin, where the original pigmentation appears in the form of scattered dark spots on a white background. There can be differences in this pattern among breeds; for example, the harlequin Mudi tends to have extended white markings at locations not typically shown in the breed (e.g., chest, collar, tip of extremities), whereas there are minimal markings on the body ( Figure 1 D) [ 5 ].…”

“…In our study performed on Mudis, 22 out of 123 merle individuals turned out to be mosaic: 20 with contractions and two with expansions [ 5 ]. This result is in agreement with the biased proportions as described by others, demonstrating the existence of poly(T) expansion at the merle-SINE insertion [ 1 , 2 ].…”

“…Several papers have been published recently regarding the molecular genetics of the merle phenotype ( Figure 1 A–F), including three major articles offering theoretical explanations [ 1 , 2 , 3 ] and two breed-specific papers [ 4 , 5 ]. The aim of our review is to provide a comprehensive analysis of each of these results and hypotheses, as well as compare them with those of previous papers [ 6 , 7 ] which identify the merle mutation at the molecular level.…”