Submitted by:
Sheila M. Schmutz and Tom G Berryere, University of Saskatchewan, Saskatoon Canada
Coat color has been of considerable interest to
dog breeders for many years. In 1957, C.C. Little provided a comprehensive hypothesis
with many genes and alleles to explain most of the colors and patterns in dogs, based on breeding records. For the past few years we have studied genes involved in the pigmentation pathway at the DNA level (http://skyway.usask.ca/~schmutz/dogcolors.html). Many
of Little’s predictions have held true but some have not.
We found DNA polymorphisms in several genes in the
pigmentation pathway. We used these polymorphisms or markers to map genes name
EDNRB and DCT to chromosome number 22, KITLG to chromosome number 11.
These markers have also been used in family studies to follow whether the same variant of the marker always was inherited
with a particular coat color, pattern, or associated health problem.
We have identified multiple mutations in some genes
such as TYRP1 that cause brown color, none of which have ill effects on health.
Whereas other coat color genes have multiple effects, including some on health.
For example merle, which when homozygous, usually causes deafness and sometimes also serious eye problems. We have conducted a family study using Australian Shepherds and have excluded several genes as the cause
of merle: EDNRB, KITLG, MITF, ASIP, TYR, PAX3. We are currently
studying Harlequin and merle in Great Danes using the polymorphisms in these same genes.
Family and data collection are still ongoing but results thus far are more optimistic.
(Harlequin Great Danes are thought to be HhMm, or heterozygous at both the Harl and merle causing genes and so finding
which gene causes the Harlequin pattern may also lead us to find the gene that causes merle.
It was suggested that “albino” Dobermans
may have a mutation in tyrosinase, since that is the cause of many types of albinism in humans and mice. However, in a recently completed study, the entire coding sequence of TYR was normal in such Dobermans
(GenBankAY336053) and also in blue and Isabella Doberman Pinschers. These results
suggest that the P gene may be the cause of albinism. We did find that
these same Isabella and red Dobermans were both homozygous for the TYRP1 proline deletion mutation indicating both
are actually brown in base color.
Black Hair Follicular Dysplasia is a disorder that has occurred
in my own kennel in Large Munsterlanders. Areas of the coat that are normally
black in color are grey at birth and then these weak hairs break and fall out. The
underlying darkly pigmented skin is also wrinkled and sometimes pimply. Using
this litter we have shown that neither MC1R, DCT, TYRP1, KITLG, nor TYR are the genes causing this disease. Colleagues at the University of Pennsylvania plan to continue studies of this disease and samples were also sent to other collaborators in Germany.
Currently, we are also studying MITF in microphthalmicied
multipe forms of this gene in the dog (GenBank AY2400952). Alternate start codons
and some differential splicing of exon 1 and 6 result in different forms in different tissues.
Thereby a mutation in exon 1 may lead to an effect on the eye and not on coat color, whereas a mutation in exon 7 could
affect both tissues.
We have recently identified the mutation in MC1R
that causes melanistic mask. At amino acid 264, methionine is replaced by valine. Some dogs with melanistic mask have premature graying of the muzzle but this does
not seem to be correlated with whether they are homozygous or heterozygous for mask.
Some coat patterns such as Harlequin, merle and Irish spotting can make it impossible to see the mask. Likewise, dogs that are black or brown or blue do not show their mask against their similar body color. This further confirms that dogs in breeds where mask is part of the standard such
as Bullmastiffs and Boxers, the reddish coat colors are due to the agouti alleles and not an ee genotype at MC1R.
In the course of this same study we were able to
show conclusively that brindle is not caused by an MC1R allele, as Little had predicted. Several dog owners had found that the prediction of an Ebr allele did not fit their breeding
data either.
We thank the many dog owners who have contributed
DNA samples from their dogs or complete litters to our study. In addition, we
are particularly grateful to C.A. Sharp (Australian Shepherds), J.P. Yousha (Great Danes), and Ione Smith (Doberman Pinschers)
who coordinated collection of groups of animals in particular breeds for family studies.
Key to Gene Abbreviations:
Gene Abbreviation Gene
Name C.C.
Little's Locus
ASIP agouti
signaling protein A
locus
TYRP1 tryrosinase related protein 1 B
locus
TYR tyrosinase C
locus?
MC1R melanocortin
1 receptor
E locus
DCT dopachrome tautomerase
EDNRB endothelin receptor B
KITLG KIT ligand
MITF microphthalmia transcription factor
PAX3 paired
box 3 protein
AWS Partners’
recommended resources:
Genetics of Coat Color in the Dog
http://www.people.fas.harvard.edu/~brown/dogs/genetics/color-genetics.htm
Genetics of Coat Color in Dogs
http://sask.usask.ca/~schmutz/dogcolors.html
Vet Gen’s New ChromaGene: DNA Test for Coat
Color in Labrador Retrievers
http://www.vetgen.com/color.html
Vet Gen’s New ChromaGene: DNA Test for Coat
Color in Cocker Spaniels
http://www.vetgen.com/cockcolor.html
Canine Color Genetics
http://bowlingsite.mcf.com/Genetics/ColorGen.html
Interaction of Major Coat Color Gene Functions in
Mice as Studied by Chemical Analysis of Eumelanin and Pheomelanin
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11277491
Coat Color Genes: The International Federation of
Pigment Cell Societies
http://www.cbc.umn.edu/ifpcs/micemut.htm
Genetics of Colors in the English Cocker Spaniel
http://www.stirling-ecs.org/general/color_genes.html
