Abstract

In 2006, Mellersh et al. reported a mutation in the RPGRIP1 gene corresponding to progressive retinal atrophy (PRA, known as cord1 in the breed) a genetic disease leading to blindness in Miniature Longhaired Dachshunds (MLHDs). Since then, a DNA test has been commercially available worldwide.

As Mellersh's study involved only MLHDs from an inbred research colony, we examined MLHDs from the pet population to study the PRA phenotype and the effect of the mutation in RPGRIP1 in a genetically heterogeneous background.

To investigate the phenotypic variation in a shared environment, 18 related MLHDs including six PRA cases from the same kennel were ophthalmologically examined and DNA tested for the mutation in RPGRIP1. To study the correlation between the clinical phenotype and the RPGRIP1 mutation genotype, 59 sporadic PRA cases and 200 controls with no apparent clinical signs were also examined.

Among sporadic PRA cases from the MLHD pet population, the age of onset varied from four months to 15 years old. MLHDs from the same kennel also showed highly variable onset and rate of progression. Screening for the mutation in RPGRIP1 in 259 MLHDs identified substantial phenotype-genotype discordance: 16% of controls were homozygous for the insertion (RPGRIP1-/-) while 20% of PRA cases were not homozygous for it.

Conclusions

Among PRA cases of the MLHD pet population, extensive phenotypic variation was seen. Also, in a substantial portion of MLHDs, the RPGRIP1 genotype did not correlate with the expected clinical phenotype and additional/alternative factors are required to account for the discordance.

Advice to Breeders

Although the mutation in RPGRIP1 does not fully correlate with the clinical phenotype, it is advised to avoid breeding that could produce dogs that are homozygous for the mutation (RPGRIP1 -/-). At the same time, given the high frequency of the mutation allele in the control dogs, it is not recommended to try to immediately exclude all animals with the mutation (incl. carriers) from the breeding population. This is to conserve genetic diversity in the breed, and to avoid possible rise of other genetic disorders and disease susceptibility.

To practice these points, breeders should choose at least one of the sire or dam that is homozygous for the wild type allele (RPGRIP1+/+).