Negative selection on aSOD1mutation limits canine degenerative myelopathy while avoiding inbreeding

Several hundred disease-causing mutations are currently known in domestic dogs. Breeding management is therefore required to minimize their spread. Recently, genetic methods such as direct-to-consumer testing have gained popularity; however, their effects on dog populations are unclear. Here, we aimed to evaluate the influence of genetic testing on the frequency of mutations responsible for canine degenerative myelopathy (DM) and assess the changes in the genetic structure of a Pembroke Welsh corgi population from Japan. Genetic testing of 5,512 dogs for the causative mutation in superoxide dismutase 1 ( SOD1 ) (c.118G>A (p.E40K)) uncovered a recent decrease in frequency, plummeting from 14.5% (95/657) in 2019 to 2.9% (24/820) in 2022. Weir and Cockerham population differentiation ( F ST ) and simulation-based genome-wide single-nucleotide polymorphism (SNP) analysis of 117 selected dogs revealed 143 candidate SNPs for selection. The SNP with the highest F ST value was located in the intron of SOD1 adjacent to the c.118G>A mutation, supporting a strong selection signature on SOD1 . Further genome-wide SNP analyses revealed no obvious changes in inbreeding levels and genetic diversity between the 2019 and 2022 populations. Our study highlights that genetic testing can help inform improved mating choices in breeding programs to reduce the frequency of risk variants and avoid inbreeding. This combined strategy could decrease the genetic risk of canine DM, a fatal disease, within only a few years. Significance statement Genetic breeding methods using direct-to-consumer testing have gained popularity, but their effects on dog populations remain unclear. In this study, the effect of direct-to-consumer genetic testing on SOD1 mutation, the causative element of canine degenerative myelopathy, in a domestic dog population (Pembroke Welsh corgi) from Japan was investigated. Our analyses revealed that since the expansion of genetic testing in 2019, breeders used these tests to artificially select against the SOD1 mutation, considerably decreasing its occurrence in the corgi population within only a few years (2019 versus 2022). Our study makes a substantial contribution to existing literature by providing empirical evidence that direct-to-consumer genetic testing can have rapid influence on pet genetics, noticeable in a span of 2–3 years.