Carrier Rate and Mutant Allele Frequency of GM1 Gangliosidosis in Miniature Shiba Inus (Mame Shiba): Population Screening of Breeding Dogs in Japan

SIMPLE SUMMARY: GM1 gangliosidosis, a progressive neurodegenerative lysosomal storage disease, occurs in the Shiba Inu breed due to the GLB1:c.1649delC (p.P550Rfs*50) mutation. Previous surveys performed of the Shiba Inu population in Japan showed that the carrier rate was 1.02–2.94%. Currently, a miniature type of the Shiba Inu called “Mame Shiba”, bred via artificial selection to yield smaller individuals, is becoming more popular than the standard type. A GM1 gangliosidosis mutation survey has yet to be carried out in the Mame Shiba population. Therefore, this study aimed to determine the frequency of the mutant allele and carrier rate of GM1 gangliosidosis in the Mame Shiba breed. We surveyed 1832 adult Mame Shiba Inus used for breeding across 143 Japanese kennels using a genotyping assay. As a result, nine Mame Shiba Inus were found to be carriers, indicating that the carrier rate was 0.49% (corresponding mutant allele frequency = 0.00246). This study demonstrates that there are certain Mame Shiba Inus carrying the mutation for GM1 gangliosidosis and that their breeding should be prevented or controlled. ABSTRACT: GM1 gangliosidosis is a progressive, recessive, autosomal, neurodegenerative, lysosomal storage disorder that affects the brain and multiple systemic organs due to an acid β-galactosidase deficiency encoded by the GLB1 gene. This disease occurs in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan, due to the GLB1:c.1649delC (p.P550Rfs*50) mutation. Previous surveys performed of the Shiba Inu population in Japan found a carrier rate of 1.02–2.94%. Currently, a miniature type of the Shiba Inu called “Mame Shiba”, bred via artificial selection to yield smaller individuals, is becoming more popular than the standard Shiba Inu and it is now one of the most popular breeds in Japan and China. The GM1 gangliosidosis mutation has yet to be surveyed in the Mame Shiba population. This study aimed to determine the frequency of the mutant allele and carrier rate of GM1 gangliosidosis in the Mame Shiba breed. Blood samples were collected from 1832 clinically healthy adult Mame Shiba Inus used for breeding across 143 Japanese kennels. The genotyping was performed using a real-time PCR assay. The survey found nine carriers among the Mame Shibas, indicating that the carrier rate and mutant allele frequency were 0.49% and 0.00246, respectively. This study demonstrated that the mutant allele has already been inherited by the Mame Shiba population. There is a risk of GM1 gangliosidosis occurrence in the Mame Shiba breed if breeders use carriers for mating. Further genotyping surveys are necessary for breeding Mame Shibas to prevent the inheritance of this disease.