Prevalence of congenital hereditary sensorineural deafness in Australian Cattle Dogs and associations with coat characteristics and sex.

BACKGROUND: Congenital hereditary sensorineural deafness (CHSD) occurs in many dog breeds, including Australian Cattle Dogs. In some breeds, CHSD is associated with a lack of cochlear melanocytes in the stria vascularis, certain coat characteristics, and potentially, abnormalities in neuroepithelial pigment production. This study investigates phenotypic markers for CHSD in 899 Australian Cattle Dogs. RESULTS: Auditory function was tested in 899 Australian Cattle Dogs in family groups using brainstem auditory evoked response testing. Coat colour and patterns, facial and body markings, gender and parental hearing status were recorded.Deafness prevalence among all 899 dogs was 10.8% with 7.5% unilaterally deaf, and 3.3% bilaterally deaf, and amongst pups from completely tested litters (n = 696) was 11.1%, with 7.5% unilaterally deaf, and 3.6% bilaterally deaf.Univariable and multivariable analyses revealed a negative association between deafness and bilateral facial masks (odds ratio 0.2; P ≤ 0.001). Using multivariable logistic animal modelling, the risk of deafness was lower in dogs with pigmented body spots (odds ratio 0.4; P = 0.050).No significant associations were found between deafness and coat colour.Within unilaterally deaf dogs with unilateral facial masks, no association was observed between the side of deafness and side of mask. The side of unilateral deafness was not significantly clustered amongst unilaterally deaf dogs from the same litter. Females were at increased risk of deafness (odds ratio from a logistic animal model 1.9; P = 0.034) after adjusting for any confounding by mask type and pigmented body spots. CONCLUSIONS: Australian Cattle Dogs suffer from CHSD, and this disease is more common in dogs with mask-free faces, and in those without pigmented body patches. In unilaterally deaf dogs with unilateral masks, the lack of observed association between side of deafness and side of mask suggests that if CHSD is due to defects in molecular pigment pathways, the molecular control of embryonic melanoblast migration from ectoderm to skin differs from control of migration from ectoderm to cochlea. In Australian Cattle Dogs, CHSD may be more common in females.

A Missense Mutation in the KLF7 Gene Is a Potential Candidate Variant for Congenital Deafness in Australian Stumpy Tail Cattle Dogs.

Congenital deafness is prevalent among modern dog breeds, including Australian Stumpy Tail Cattle Dogs (ASCD). However, in ASCD, no causative gene has been identified so far. Therefore, we performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. For GWAS, 3 bilateral deaf ASCDs, 43 herding dogs, and one unaffected ASCD were used, resulting in 13 significantly associated loci on 6 chromosomes, i.e., CFA3, 8, 17, 23, 28, and 37. CFA37 harbored a region with the most significant association (-log10(9.54 × 10-21) = 20.02) as well as 7 of the 13 associated loci. For whole genome sequencing, the same three affected ASCDs and one unaffected ASCD were used. The WGS data were compared with 722 canine controls and filtered for protein coding and non-synonymous variants, resulting in four missense variants present only in the affected dogs. Using effect prediction tools, two variants remained with predicted deleterious effects within the Heart development protein with EGF like domains 1 (HEG1) gene (NC_006615.3: g.28028412G>C; XP_022269716.1: p.His531Asp) and Kruppel-like factor 7 (KLF7) gene (NC_006619.3: g.15562684G>A; XP_022270984.1: p.Leu173Phe). Due to its function as a regulator in heart and vessel formation and cardiovascular development, HEG1 was excluded as a candidate gene. On the other hand, KLF7 plays a crucial role in the nervous system, is expressed in the otic placode, and is reported to be involved in inner ear development. 55 additional ASCD samples (28 deaf and 27 normal hearing dogs) were genotyped for the KLF7 variant, and the variant remained significantly associated with deafness in ASCD (p = 0.014). Furthermore, 24 dogs with heterozygous or homozygous mutations were detected, including 18 deaf dogs. The penetrance was calculated to be 0.75, which is in agreement with previous reports. In conclusion, KLF7 is a promising candidate gene causative for ASCD deafness.

Guided bone augmentation around a titanium bone-anchored hearing aid implant in canine calvarium: an initial comparison of two barrier membranes.

BACKGROUND: The placement of a bone-anchored hearing aid (BAHA) implant in young children may be hampered by the presence of thin, poor-quality calvarial bone. The use of extraskeletal guided skull bone augmentation around the titanium implant is one potential solution. PURPOSE: To compare the effectiveness of a collagen membrane BioSISt (Cook Biotech Inc., Lafayette, IN, USA) and a PGA/PLA barrier membrane, Osseoquest (W.L. Gore & Associates, Flagstaff, AZ, USA) in promoting extraskeletal bone formation, when combined with cancellous bone graft, around a titanium implant in the canine calvarium. The quality and quantity of bone tissue was compared. MATERIALS AND METHODS: A 4-mm titanium BAHA implant was placed in the cranial parietal bone of 11 dogs. The implant protruded from the bone surface by a measured distance. Two groups, each of three dogs, received an implant, cancellous bone graft, and either a BioSISt or Osseoquest membrane. Three dogs received implant and bone graft (positive controls), and two received an implant only (negative controls). Samples were retrieved at 3, 6, and 9 months after placement. Undecalcified histologic and histomorphometric assessments were made of the augmented bone thickness, and bone gain factors were calculated for each sample group. RESULTS: The process of osseointegration of the implants was ongoing and increased over time. Bone generation occurred with both test membranes and the early trabecular bone that formed, matured, and remodelled to compact bone at 9 months. BioSISt membrane samples showed superior quality and quantity of augmented bone compared with Osseoquest samples that exhibited thinner bone with persistent inflammation. Quantitatively, the BioSISt samples showed statistically greater new bone contact and bone area than both the positive and negative controls, whereas Osseoquest samples did not. The bone gain factor was statistically greater for BioSiSt samples when compared to the positive and negative controls whereas the Osseoquest samples were not. CONCLUSIONS: In this study, the collagen BioSISt membrane promoted bone formation of superior quality and quantity compared with the polyglycolic/polylactic acid-based Osseoquest membrane and positive and negative controls over 9 months. Further investigation of the use of the collagen BioSISt membrane for cranial bone augmentation is warranted.

Congenital sensorineural deafness in Australian stumpy-tail cattle dogs is an autosomal recessive trait that maps to CFA10.

BACKGROUND: Congenital sensorineural deafness is an inherited condition found in many dog breeds, including Australian Stumpy-tail Cattle Dogs (ASCD). This deafness is evident in young pups and may affect one ear (unilateral) or both ears (bilateral). The genetic locus/loci involved is unknown for all dog breeds. The aims of this study were to determine incidence, inheritance mechanism, and possible association of congenital sensorineural deafness with coat colour in ASCD and to identify the genetic locus underpinning this disease. METHODOLOGY/PRINCIPAL FINDINGS: A total of 315 ASCD were tested for sensorineural deafness using the brain stem auditory evoked response (BAER) test. Disease penetrance was estimated directly, using the ratio of unilaterally to bilaterally deaf dogs, and segregation analysis was performed using Mendel. A complete genome screen was undertaken using 325 microsatellites spread throughout the genome, on a pedigree of 50 BAER tested ASCD in which deafness was segregating. Fifty-six dogs (17.8%) were deaf, with 17 bilaterally and 39 unilaterally deaf. Unilaterally deaf dogs showed no significant left/right bias (p = 0.19) and no significant difference was observed in frequencies between the sexes (p = 0.18). Penetrance of deafness was estimated as 0.72. Testing the association of red/blue coat colour and deafness without accounting for pedigree structure showed that red dogs were 1.8 times more likely to be deaf (p = 0.045). The within family association between red/blue coat colour and deafness was strongly significant (p = 0.00036), with red coat colour segregating more frequently with deafness (COR = 0.48). The relationship between deafness and coat speckling approached significance (p = 0.07), with the lack of statistical significance possibly due to only four families co-segregating for both deafness and speckling. The deafness phenotype was mapped to CFA10 (maximum linkage peak on CFA10 -log10 p-value = 3.64), as was both coat colour and speckling. Fine mapping was then performed on 45 of these 50 dogs and a further 48 dogs (n = 93). Sequencing candidate gene Sox10 in 6 hearing ASCD, 2 unilaterally deaf ASCD and 2 bilaterally deaf ASCD did not reveal any disease-associated mutations. CONCLUSIONS: Deafness in ASCD is an incompletely penetrant autosomal recessive inherited disease that maps to CFA10.