Exploring the Genetics of Canine Hereditary Deafness

Canine hereditary deafness is associated with white pigment, which is controlled by the piebald locus on chromosome 20 and the merle locus on chromosome 10. It is a complex trait and previous studies have failed to identify the mechanism of inheritance or the underlying genetic mutations. Thanks to the dedication and support of several breed clubs and foundations, the AKC Canine Health Foundation has provided funding to study this condition in dogs. (CHF Grant 02172-MOU: Understanding Hereditary Deafness in Dogs and CHF Grant 02387-MOU: Hereditary Deafness in Dogs – Genomic Studies in English Setters Using Full Sibling Pairs) Researchers at Louisiana State University performed a genome-wide association study (GWAS) on DNA samples from 502 Dalmatians, Australian Cattle Dogs, and English Setters to search for genes associated with hereditary deafness.

Results published in PLOS ONE¹ revealed only one genetic mutation that was significantly associated with deafness, and it was only identified when data analysis was limited to bilaterally deaf versus normal Australian Cattle Dogs. Fourteen other mutations were suggestive of association with deafness, but each potential mutation was unique to one of the three breeds studied and none of these mutations were located on the chromosome containing the piebald locus. These findings confirm that congenital pigment-associated deafness in dogs is a complex trait that may be influenced by additional epigenetic and transcriptional factors.

To help in their search for the ‘needle in a haystack,’ the research team turned to artificial intelligence. STRING (which stands for Search Tool for the Retrieval of Interacting Genes/Proteins) is an open access database of protein to protein interactions. The database holds information on the physical and functional interactions of almost 25 million proteins found in five thousand different organisms. Using STRING data, researchers whittled down the list of genes potentially associated with deafness by focusing on the pathways and structures related to hearing or pigment. They identified just over one hundred genes which could be associated with deafness, providing reasonable targets where they can continue the search.²

These studies show that hereditary deafness in dogs, while associated with white pigment, is a very complex trait influenced by multiple factors. The genetic mutations underlying deafness may also be unique to each dog breed, further complicating our quest to understand the mechanisms of this condition.

References:

1. Hayward, J. J., Kelly-Smith, M., Boyko, A. R., Burmeister, L., De Risio, L., Mellersh, C., Freeman, J., & Strain, G. M. (2020). A genome-wide association study of deafness in three canine breeds. PLOS ONE, 15(5), e0232900. 
   https://doi.org/10.1371/journal.pone.0232900
2. Kelly-Smith, M., & Strain, G. M. (2020). STRING Data Mining of GWAS Data in Canine Hereditary Pigment-Associated Deafness. Veterinary and Animal Science, 100118. 
   https://doi.org/10.1016/j.vas.2020.100118