Every day is a learning day

One of the potential barriers to improving the health of pedigree dogs is breeders’ lack of understanding of genetics. Most breeders are, by now, familiar with DNA tests for genetic mutations for health conditions such as PRA, CLAD, DM and many more (often also with 2 or 3 letter abbreviations!). The principles of recessive mutations with 3 genotypes; Clear, Carrier and Affected and what these mean in terms of clinically healthy or unhealthy dogs is generally known by breeders. This may be less clearly understood by buyers who may still think that Carriers are likely to be a problem and get ill. 

As we move into discussing which combinations of those 3 genotypes can safely be bred together, there are still a range of opinions on whether DNA Affected dogs should be bred from. As long as an affected dog is mated to a clear dog, any puppies will not be affected but will be carriers. In many breeds, where there are small gene pools, it is reasonable to breed with affected dogs (mating only to clears). While it might be argued that not using affected dogs is a quicker way to remove deleterious mutations, it also has the effect of removing all that dog’s genes from the population. Removing dogs from breeding on the basis of one genetic mutation alone is often not in the best interests of the breed.

When it comes to coats and colours, far fewer breeders seem to be educated or to make the effort to understand the genetics. All too often, discussion of colours seems to be based on historical urban myths or worse, on fashion and personal prejudices. It’s such an emotive topic, as we have seen with numerous discussions over many months about Colour Not Recognised (CNR) and Non Breed Standard (NBS) colours.

Emerging science

What I find really fascinating is the rate at which the science underpinning the genetics of coats and colours is developing. Some of the research is being enabled by Citizen Science where dog owners’ contributions help research teams by providing DNA samples and photographs. One such study published last year resulted in an improved understanding of one of the earliest coat colour mutations, designated as ancient red (eA). This genotype is associated with “domino” in Alaskan Malamute and other Spitz breeds, “grizzle” in Chihuahuas and “pied” in Beagles.

Another new paper (2021) explains variations in the PMEL gene which causes dapple (merle) in Dachshunds. A previous study of this gene in Australian Shepherds had correlated the length of an insertion into the PMEL gene with 4 broad phenotype clusters of merle, described as “cryptic”, “atypical”, “classic” and “harlequin”. This new paper reports on a similar study in Dachshunds and identified numerous cases of “hidden” merle in light red dogs. The paper suggests that the frequent identification of cryptic, hidden and mosaic variants of the merle pattern makes DNA testing critical to avoid producing puppies with serious health problems. Double-merles are known to be at risk of deafness, blindness and microphthalmia (small eyes) and are banned from registration by the KC.

Time for cocoa?

Another lesson I learned recently was the existence of a gene associated with the brown (liver/chocolate) colour. Variants of the B locus are the most common cause of the brown coat colour, with 5 known mutations of the TYRP1 gene that explain the majority of dogs with brown coats and noses. One exception has been the brown or chocolate French Bulldog which, when tested, is found to be BB (i.e. not chocolate as normally expressed). Recent research (2020) has identified a mutation on the HPS3 gene associated with brown in FBs and which has been called “cocoa”, for which a DNA test is now available. 2 recessive copies of this mutation (co/co) are required for the dog to be brown/chocolate.

5, not 4, basic coat colour patterns

The most recent paper I have been reading was published by Dannika Bannasch and her colleagues at the University of Bern. Professor Bannasch and one of her collaborators, Prof. Tosso Leeb, have both been winners of the prestigious International Canine Health Awards. The study clarified how coat colours and patterns are genetically controlled but also discovered that the light coat colour in many modern dog breeds is due to a mutation that originated in an extinct species more than 2 million years ago. 

Dogs can make 2 types of pigment; black (eumelanin) and yellow (pheomelanin). Production of these 2 pigments in the right place on a dog’s body results in very different coat colours and patterns. The agouti signalling protein (ASIP) is the main switch for the production of yellow. Without ASIP, black pigment is formed. 

In addition, there are 2 “promoters” which result in ASIP production on (a) the belly and (b) banded hairs. The study identified 2 versions of the ventral promoter and 3 versions of the hair cycle promoter, resulting in 5 possible combinations which cause different coat colour patterns in dogs. Previously, it had been thought that there were only 4 basic patterns.

Image source: https://www.nature.com/articles/s41559-021-01524-x.pdf

Within each of these 5 pattern types, there may be further variation due to other factors such as the position of the boundary between red and black areas, the shade of red (from dark to nearly white) and the presence of a black facial mask or white spotting caused by genes other than ASIP. 

Prof. Bannasch said: ‘While we think about all this variation in coat colour among dogs, some of it happened long before ‘dogs’ were dogs. The genetics turn out to be a lot more interesting because they tell us something about canid evolution.’

Learning from history

While a lot of the science and understanding of the genetics may be new, many breeds have a wealth of historical information on coats, colours and patterns. Much of that is held in Kennel Club registries or breed archives. These should be essential resources to inform any discussion about colours that can or cannot exist legitimately in any breed. I am aware of a study in one breed, looking at dogs from the early part of the last century, which clearly shows that colours that are not currently fashionable were around over 100 years ago. 

The fact that some of these colours are associated with recessive mutations should make it unsurprising that those colours can still crop up and be bred today. There are plenty of examples of breeds where breeders have specifically selected for a particular colour or pattern and that’s not something new. We should be very careful not to forget our breeds’ histories and their genetic origins, and not fall into the trap of altering Breed Standards simply on the basis of what is or isn’t fashionable today. That, of course, applies to conformation as well as to colours!

Remember, prejudice is a great time-saver; it enables you to form opinions without having to gather the facts.