Cavalier King Charles Spaniels Carry More Harmful Genetic Variants Than Other Dog Breeds

The genomic study also identified genetic variants linked to a common heart disease in the breed.

Recent dog breeding practices have loaded Cavalier King Charles Spaniels with disease-causing mutations, including variants associated with the common heart disease, mitral myxomatous valve disease (MMVD). Erik Axelsson of Uppsala University and colleagues published these new findings on September 2nd in the journal PLOS Genetics.

The past 300 years of dog breeding have created an incredible variety of breeds of varying sizes, shapes, and abilities. Unfortunately, this process has also resulted in many breeds being more inbreeding and more likely to inherit genetic diseases. The study’s researchers wanted to know if recent breeding practices have increased the number of disease-causing variants in dogs. They sequenced entire genomes of 20 dogs from eight common breeds such as beagles, German shepherds and golden retrievers. They found that the Cavalier King Charles Spaniel, which experienced the most intensive breeding, carried more damaging genetic variants than the other breeds they studied.

Comparisons of Dachshunds with and without evidence of heart disease were used to identify mutations that may predispose Cavalier King Charles Spaniels to developing MMVD. Photo credit: Måns Engelbrektsson, Swedish Kennel Club, CC-BY 4.0

The researchers also looked for genetic variants in the Cavalier King Charles Spaniel genomes that are associated with MMVD. In this condition, the mitral valve in the heart degenerates, allowing blood to flow back from the left ventricle to the left atrium. They identified two genetic variants linked to the disease that appear to regulate a gene that codes for a common protein in the heart muscle. The results offer a possible explanation for why the Cavalier King Charles Spaniel is prone to developing the disease.

The particularly large number of potentially harmful genes in the genome of Cavalier King Charles Spaniels compared to other dogs is likely due to its breeding history. Records suggest that small spaniel-type dogs have existed for at least 1,000 years and were popular in royal courts across Asia and Europe for several hundred years, including the court of King Charles II (1630-1685). These spaniels experienced several “bottlenecks” in which only a small percentage of the population passed their genes on to the next generation. The shortages may have caused the harmful genes to become more abundant in the Cavalier King Charles Spaniel’s genome before the dog was recognized as a breed in 1945.

Axelsson adds, “We note that recent breeding may have accelerated the accumulation of harmful mutations in certain breeds of dogs. Especially in the Cavalier King Charles Spaniel, one or more of these mutations affect the heart muscle protein NEBL and can predispose this breed to devastating heart diseases. “

Reference: “The Genetic Consequences of Breed Formation – Accumulation of Harmful Genetic Variation and Fixation of Mutations Associated with Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels” by Erik Axelsson, Ingrid Ljungvall, Priyasma Bhoumik, Laura Bas Conn, Eva Muren, Åsa Ohlsson, Lisbeth Høier Olsen, Karolina Engdahl, Ragnvi Hagman, Jeanette Hanson, Dmytro Kryvokhyzha, Mats Pettersson, Olivier Grenet, Jonathan Moggs, Alberto Del Rio-Espinola, Christian Epe, Bruce Taillon, Nilesh Tawari, Shrinivas Mane, Troy Hedhamins,, Philippe Gruet, Jens Häggström and Kerstin Lindblad-Toh, September 2, 2021, PLoS Genetics.
DOI: 10.1371 / journal.pgen.1009726

Funding from Elanco (formerly Novartis Animal Health) to KLT included the generation of WGS data and parts of EA’s salary. Elanco (formerly Novartis Animal Health) influenced the selection of the dog breeds sequenced in this study, participated in the data analysis, and edited and reviewed the manuscript. Two grants from the Agria and SKK Research Foundation, one to IL (19969) and one to RH (P2011-0021), provided funding for the sampling of dogs. EA was funded by a grant from the Swedish Research Council (2016-03826) and a grant from FORMAS (2016-01312), both of which contributed to EA’s salary. KLT is Distinguished Professor at the Swedish Research Council (D0816101). PB’s salary was funded through a Novartis postdoctoral fellowship. With the exception of Elanco (see above), donors played no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.