Genetic testing drives a decline in the occurrence of the canine PRA-related RPGRIP1 variant without an increase in...

A variant of the RPGRIP1 gene is a partial causative factor associated with cone-rod dysplasia 1 and progressive retinal atrophy (PRA) in dogs, particularly in purebred miniature dachshunds (DHMs). Although direct-to-consumer genetic testing targeting the RPGRIP1 variant has been actively conducted in Japan, its effect on the DHM population is unknown. Therefore, to address this gap in research, in the present study, we determined the effect of genetic testing by investigating changes in the allele frequency of the RPGRIP1 variant and genetic structures using long-term genetic testing datasets. By assessing the genotypic data of 30,800 DHMs born between 2014 and 2022, we observed a marked decrease in the number of the RPGRIP1 variant homozygous dogs between dogs born in 2019 (11.1%)-when full-scale genetic testing began for puppies-and those born in 2020 (3.4%) (p < 0.001). A subsequent investigation using a single-nucleotide polymorphism array revealed no substantial changes in inbreeding levels (F_ROH) or genome structures among DHM offspring born between 2019 and 2020. These findings suggest a decrease in the allele frequency for several years and that appropriate breeding practices were in effect. Additional analysis of the insurance claim data indicated that the association between RPGRIP1 variant genotype and PRA claim, and PRA was more prevalent in dogs aged 11 years than in younger dogs. RPGRIP1 genetic testing has led to a reduction in the incidence rate of PRA among DHMs with a decline anticipated in the 2030s.