Early onset of adult deafness in the Rhodesian Ridgeback is associated with in-frame deletion in the EPS8L2 gene
Kawakami, Takeshi et al. (2021), Early onset of adult deafness in the Rhodesian Ridgeback is associated with in-frame deletion in the EPS8L2 gene, Dryad, Dataset, https://doi.org/10.5061/dryad.pg4f4qrqt
Domestic dogs exhibit diverse types of both congenital and non-congenital hearing losses. Rhodesian Ridgebacks can suffer from a progressive hearing loss in the early stage of their life, a condition known as early onset of adult deafness (EOAD), where they lose their hearing ability within 1-2 years after birth. In order to investigate the genetic basis of this hereditary hearing disorders, we performed a genome-wide association study (GWAS) by using a sample of 23 affected and 162 control Rhodesian Ridgebacks. We identified a genomic region on canine chromosome 18 (CFA18) that is strongly associated with EOAD, and our subsequent targeted Sanger sequencing analysis identified a 12-bp inframe deletion in EPS8L2 (CFA18:25,868,739-25,868,751 in the UMICH_Zoey_3.1/canFam5 reference genome build). Additional genotyping confirmed a strong association between the 12-bp deletion and EOAD, where all affected dogs were homozygous for the deletion, while none of the control dogs was a deletion homozygote. A segregation pattern of this deletion in a 2-generation nuclear family indicated an autosomal recessive mode of inheritance. Since EPS8L2 plays a critical role in the maintenance and integrity of the inner ear hair cells in humans and other mammals, the inframe deletion found in this study represents a strong candidate causal mutation for EOAD in Rhodesian Ridgebacks. Genetic and clinical similarities between childhood deafness in humans and EOAD in Rhodesian Ridgebacks emphasizes the potential value of this dog breed in translational research in hereditary hearing disorders.
In order to recruit EOAD-affected and normal hearing dogs, we conducted an online survey in 2020 to private dog owners of Rhodesian Ridgebacks who agreed to participate in scientific research. DNA was extracted from buccal swab samples collected by dog owners and extracted by Illumina, Inc. Genotypes of the dogs were collected by using custom Illumina Canine high-density SNP arrays.