A genome-wide association study of deafness in three canine breeds.

Jessica J. Hayward,Maria Kelly-Smith,Adam R. Boyko,George M. Strain,Luisa De Risio,Cathryn Mellersh,Louise Burmeister,Julia Freeman,Carlos E. Ambrósio

doi:10.1371/journal.pone.0232900

Jessica J. Hayward, Maria Kelly-Smith + Show 7 more

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https://doi.org/10.1371/journal.pone.0232900

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Abstract

Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs.

Highlights

The most common form of deafness in dogs is hereditary, congenital, and associated with white pigmentation [1,2,3]
principal component analysis (PCA) showed a genetic difference between the North American and UK populations of Dalmatians and Australian cattle dogs (Fig 1)
There are different phenotype patterns for the two geographic regions–North American samples are predominantly controls (50% of samples) and unilaterally deaf (40% of samples), while the UK samples are predominantly bilaterally deaf (60% of samples) and controls (36% of samples) (Fig 1A). Due to this different distribution of cases and controls in genetically distinct populations, Dalmatian dogs were separated into North American and UK samples for analyses

Summary

Introduction

The most common form of deafness in dogs is hereditary, congenital, and associated with white pigmentation [1,2,3]. The most associated genetic locus in dogs is piebald [4].

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