Characterizing an ancient gene variant influencing coat color in modern dogs using citizen science and dog DNA samples

Citizen science has facilitated a large genotype screening of pet dogs in order to understand the effect of one of the earliest mutations captured by canine domestication. Dr Heidi Anderson, author of the new study published in Canine Medicine and Genetics, takes us through the findings on the genetic background of coat color.

The impact of an ancient gene variant on coat colors in modern dog breeds has been characterized by a team of researchers at Wisdom Health Genetics. The findings, which were supported by citizen science, are published in Canine Medicine and Genetics.

What do the coat colors of prehistoric and modern dogs have in common? The most recent connection is a newly characterized genetic variant: ancient red. The ancient red variant (R301C) was first identified in 10,000-year-old dog DNA samples and is thought to be one of the earliest mutations captured by dog domestication.

The breed characteristic dark and light markings in the Alaskan Klee Kai caused by the ancient red variant. © Sara Lampi

Our research team conducted a large genotype screening effort of thousands of DNA samples submitted for commercial genetic panel testing to determine the frequency and distribution of an ancient gene variant—the R301C variant located in the Melanocortin 1 Receptor gene (MC1R)—in today’s dog population. The study found the R301C variant retained in 35 breeds, with a frequency of 1.5% across the researched population. Hound breeds, like the Drever and English Foxhound, and Spitz breeds, like the Alaskan Malamute, Alaskan Klee Kai, and Siberian Husky, most commonly showed the ancient R301C variant at the MC1R gene.

The MC1R gene is important because it determines a dog’s coat color by producing a key signaling molecule on melanocytes, including enzymes responsible for the synthesis of eumelanin (dark) pigment. If the MC1R function is lost, only pheomelanin (light) pigment can be produced. Five MC1R function altering variants are associated with the dark mask, grizzle, and recessive red coat color phenotypes in dogs, and as we discovered, there is a sixth variant R301C of MC1R that also widely impacts coat color.

Understanding the far-reaching impact of a prehistoric variant

To characterize the impact of the ancient R301C variant on a dog’s coat color phenotype, we obtained a combination of genotypes for other known coat color variants in the Canine Beta-Defensin 103 (CBD103) and Agouti Signaling Protein (ASIP). We then compared the coat color genotype combinations to the dog’s appearance or phenotype thanks to owners turned citizen scientists who submitted photos of their dogs.

Since there are various genes at play in determining dogs’ coat color we first searched for any coat color impact that R301C would have within one breed, Tamaskan Dog. We found a significant association between the ancient R301C variant to a coat color patterning referred to as “domino”, a phenotype encompassing striking facial markings with a receded eumelanin line forming a widow’s peak in the forehead.The domino patterning is common in Alaskan Malamute, Alaskan Klee Kai, Finnish Lapphund, and Siberian Husky, and now our findings strongly suggest that we have a genetic cause for this phenotype.

The phenotypic analysis across breeds and individuals also reveals that the R301C variant, designated ancient red (eA), does not only result in domino patterning. It also results in various phenotypes of more pheomelanin (yellow-red) and less eumelanin (black-brown) pigmentation.

Our findings propose that the R301C variant is a partial loss-of-function variant not previously described in dogs; it will allow us to learn more about the relationship between MC1R, CBD103, and ASIP, the main genes contributing to coat colors in dogs. The reduced MC1R variant: ancient red (eA) prevents the expression of solid black coat color, having the reverse effect on CDB103 and ASIP gene interaction.

Impact of Citizen Science

The ancient red variant in the American Foxhound results in reddish-yellow coat color. © Jenni Hyytiäinen

Citizen science played a crucial role in this study; the photos of dogs helped us understand which genes underlie different coat color phenotypes. Without such inputs from the owners who provided photos of their dogs, the discovery of the ancient red variant would not be possible.

Thanks to a robust DNA database—with millions of dogs tested worldwide—the research team behind the Wisdom Panel™ dog DNA test is able to analyze large sample sizes to find these genetic connection points across time and space.

Citizen science further enhances the potential of these studies, making it especially exciting for the field of companion animal genetics; pet owners’ contributions can not only help research teams like ours make new discoveries but also help make the world better for their pets.

Heidi Anderson

Heidi Anderson Ph.D. is a Senior R&D Manager at Wisdom Health Genetics currently heading the genetic discoveries in felines and developing pet DNA testing for molecular diagnostics. She received her Ph.D. in genetics from the University of Helsinki, Finland, and completed her postdoctoral training at Brigham & Women’s Hospital at Harvard Medical School.
Heidi Anderson

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