Homozygous Merle - M^M
Merle - M^m
Non-Merle - m^m
Retrotransposon insertion in SILV is responsible for merle patterning of the
domestic dog
(click HERE to read entire article)
( short interspersed element | pigmentation | linkage disequilibrium )

Leigh Anne Clark *, Jacquelyn M. Wahl *, Christine A. Rees , and Keith E. Murphy *
Departments of *Pathobiology and Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical
Sciences, Texas A&M University, College Station, TX 77843

Edited by Susan R. Wessler, University of Georgia, Athens, GA, and approved November 26, 2005 (received for
review August 11, 2005)

Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted
pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous
for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those
observed for the human auditory-pigmentation disorder Waardenburg syndrome. Mutations in at least five genes
have been identified as causative for Waardenburg syndrome; however, the genetic bases for all cases have not
been determined. Linkage disequilibrium was identified for a microsatellite marker with the merle phenotype in the
Shetland Sheepdog. The marker is located in a region of CFA10 that exhibits conservation of synteny with
HSA12q13. This region of the human genome contains SILV, a gene important in mammalian pigmentation.
Therefore, this gene was evaluated as a candidate for merle patterning. A short interspersed element insertion at
the boundary of intron 10/exon 11 was found, and this insertion segregates with the merle phenotype in multiple
breeds. Another finding was deletions within the oligo(dA)-rich tail of the short interspersed element. Such
deletions permit normal pigmentation. These data show that SILV is responsible for merle patterning and is
associated with impaired function of the auditory and ophthalmologic systems. Although the mutant phenotype of
SILV in the human is unknown, these results make it an intriguing candidate gene for human auditory-pigmentation

The SILV gene causes white in chickens and silver in mice.  

The breeds of dogs that were studied by Keith Murphy's Lab were:
Border Collie
Cardigan Welsh Corgi
Shetland Sheep Dog
Australian Shepherd
Great Dane
American Pit Bull Terrier
Pyrenean Shepherd
Catahoula Leopard Dog
You may see these statements on breeder's websites:

"[Stud dog] has successfully sired four litters including three merle from a solid black Dam,
proving the solid colored Koolies can carry the merle gene and should not be culled as some
farmers have traditionaly done".

Please do not be confused about this statement, as it is not correct.  A genetically solid
(non-merle) colored dog can
not "carry" the merle gene.  
A dog is either a merle, or it isn't.

".... we have been breeding merle to merle for 35 years, we do not produce solids .... and have
not produced any whites in over 6 years"

Unless one of their breeding dogs is a homozygous merle, they are not telling the truth.  
Homozygous merles can be identified by their coloration, or better, their lack of it.  
Genetic Inheritance of the Merle Gene
The merle gene (M) is inherited in an autosomal fashion. In other words, the trait is not
linked to gender and can be passed on from either the mother or the father.
The gene is incompletely dominant, or a gene that has intermediate expression. A
heterozygous dog, carrying only one copy of the merle gene (Mm), expresses the
characteristic diluted coat color pattern. A non-merle dog (mm) is normal in color, while a
homozygous double-merle (MM) is predominantly white. Punnett squares can be
used to determine the expected coat color of offspring when breeding dogs of known
genotype (i.e. coat color genes have been identified). In the example illustrated, a non-merle
dog (mm), indicated in the vertical column, bred to a heterozygous merle (Mm), indicated in
the horizontal column, will give rise to offspring with an expected frequency of 50% merle
(Mm) and 50% non-merle (mm).
Dogs that have merle gene but do not show the characteristic merle phenotype, are known
as cryptic merles. These dogs, genetically, have the merle pattern and could produce merle
offspring.  It is suspected that the DNA sequence of the merle allele in the cryptic is shorter
than the allele expressed in the typical merle dog.

*Health Problems Associated with the Merle Allele
Both heterozygous merle (Mm) and homozygous double merle (MM) dogs may exhibit
auditory and ophthalmic abnormalities including mild to severe deafness, increased
intraocular pressure, ametropia, microphthalmia and colobomas. The double merle genotype
may also be associated with abnormalities of skeletal, cardiac and reproductive systems.*

Genetic Testing for the Merle Gene
with the recent discovery of the merle gene, a genetic test is now available that allows for
the identification of the merle allele. This technology is patent pending (U.S. Serial # 60/708,
589) and available exclusively thru GenMARK, the DNA technology service of VITA-TECH
Laboratories LLC. By testing dogs for this genetic trait, it is possible to:
• allow identification of merle dogs to prevent undesirable merle to merle breeding
• classify harlequin Danes as single or double merle
• identify cryptic merles
For more information, please contact
*Information obtained from GenMark
  • Increased Intraocular pressure:
excessive pressure created in the eye.

  • Ametropia: vision impairment due to a
refractive error such that images fail to
focus upon the retina.

  • Microphthalmia: a smaller than normal
eye due to a defect occurring early in
development. Affected dogs may have
prominent third eyelids. Other eye defects
are common in animals with this condition,
including defects of the cornea, anterior
chamber, lens and retina.

  • Coloboma:  a defect in ocular tissue; a
cleft or missing portion of components of
the eye, most commonly affecting the iris.
Coat colour in dogs: identification of the Merle locus in
the Australian shepherd breed
Benoit Hédan,1 Sébastien Corre,1 Christophe Hitte,1 Stéphane Dréano,1 Thierry Vilboux,1 Thomas Derrien,1
Bernard Denis,2 Francis Galibert,1 Marie-Dominique Galibert,1 and Catherine André1
1UMR 6061 CNRS, Génétique et Développement, Faculté de Médecine, Université de Rennes1, 35043 RENNES
Cédex, France.
25 avenue Foch 54200 Toul, France.
Corresponding author.
Benoit Hédan: benoit.hedan@univ-rennes1.fr; Sébastien Corre: sebastien.corre@univ-rennes1.fr; Christophe Hitte:
christophe.hitte@univ-rennes1.fr; Stéphane Dréano: stephane.dreano@univ-rennes1.fr; Thierry Vilboux:
thierry.vilboux@univ-rennes1.fr; Thomas Derrien: thomas.derrien@univ-rennes1.fr; Bernard Denis:
denis.brj@wanadoo.fr; Francis Galibert: francis.galibert@univ-rennes1.fr; Marie-Dominique Galibert:
marie-dominique.galibert-anne@univ-rennes1.fr; Catherine André: catherine.andre@univ-rennes1.fr
Received November 11, 2005; Accepted February 27, 2006.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Coat colours in mammals depend on skin and hair pigment synthesis. Melanocytes
manufacture two types of melanin: the black/brown photo-protective eumelanin pigment, and
the red-yellow cytotoxic phaeomelanin pigment. Several paracrine factors secreted primarily
by surrounding keratinocytes are involved in the melanogenic pathway by stimulating the
switch between phaeomelanin and eumelanin [1]. In this pathway, microphthalmia
transcription factor (MITF) plays a central role by regulating the expression of the TYR
(Tyrosinase), TRP-1 (Tyrosine Related Protein) and DCT (Dopachrome Tautomerase)
genes that encode enzymes involved in pigment manufacture [2,3].

Coat colour is highly polymorphic in dogs. In 1957, Little described, after observing the
possible phenotypes, more than 20 loci affecting coat colours [4,5]. Until recently, only a few
genes were recognised as involved in pigmentation. However, more and more genes, alleles
and new interactions are being discovered: variants of melanocortine 1 receptor gene
(MC1R), (locus previously called extension E) [6-8], variants of Agouti, the antagonist ligand
of MC1R [9,10], variants of tyrosinase-related protein 1 (TYRP1) [11] and variants of
melanophillin [12]. Three mutations responsible for the brown coat colour versus black coat
colour were described in TYRP1 in several dog breeds including the Australian Shepherd
dog [11]. Genomic tools are now fully available in canine genetics: dense radiation hybrid
maps with 1500 polymorphic microsatellite markers and anchored BAC markers [13,14], a
radiation hybrid map comprising 10,000 canine gene-based markers [15], and a whole
sequence assembly of the canine genome, build 2.1 [16]. Altogether, the dog appears to be
a good model for understanding better the genetics of pigmentation in mammals and for
isolating new genes, new variants and interactions between alleles of different loci.

We are interested in the merle phenotype because of its involvement in coat colour and
developmental impairments. The merle phenotype is a dominant trait, with heterozygous
dogs presenting a coat colour in which eumelanic regions are incompletely and irregularly
diluted, leaving intensely pigmented patches. Merle is found throughout the body except on
the pheomelanic regions of the black and tan coat colour (Figure 1A, 1B). These dogs often
have heterochromia iridis or blue eyes and often have a lack of retinal pigment visible on the
fundus. Homozygous merle dogs display a more severe phenotype. The dogs are usually
very pale, sometimes completely white and present developmental defects with an
incomplete penetrance, microphthalmia and hearing loss (Figure 1C, 1D). In merle European
lineages, microphthalmia and/or hearing loss are not frequently observed as breeders avoid
mating merle dogs to avoid these developmental defects. However, several veterinary
studies on the "merle syndrome", reported retinal defects [17], microphthalmia and coloboma
[18]. The non-survival or degeneration of melanocytes in the cochlea have been suggested
to explain hearing loss [19].
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