This preprint is under consideration at Human Genetics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Hannes Lohi
Helsingin Yliopisto Laaketieteellinen tiedekunta
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1087-5532
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This work is licensed under a CC BY 4.0 License. Read Full License
Hearing loss is a common sensory deficit both in humans and dogs. In canines the genetic basis is largely unknown, as genetic variants have only been identified for a syndromic form of hearing impairment. We observed a congenital or early-onset sensorineural hearing loss in a Rottweiler litter. Assuming an autosomal recessive inheritance, we used a combined approach of homozygosity mapping and genome sequencing to dissect the genetic background of the disorder. We identified a fully segregating missense variant in LOXHD1, a gene that is known to be essential for cochlear hair cell function and associated with nonsyndromic hearing loss in humans and mice. The canine LOXHD1 variant was specific to the Rottweiler breed in our study cohorts of pure-bred dogs. However, it also was present in mixed-breed dogs, of which the majority showed Rottweiler ancestry. Low allele frequencies in these populations, 2.6 % and 0.04 %, respectively, indicate a rare variant. To summarize, our study describes the first genetic variant for canine nonsyndromic hearing loss, which is clinically and genetically similar to human LOXHD1-related hearing disorder, and therefore, provides a new large animal model for hearing loss. Equally important, the affected breed will benefit from a genetic test to eradicate the hearing disorder from the population.
Keywords
dog, hearing, hearing loss, deafness, Rottweiler, stereocilia, PLAT
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- OnlineResource1.xlsx
The number of genomes and exomes from different breeds used as control variant data set in filtering.
- OnlineResource2ROH.xlsx
Coordinates of 22 ROH shared by and specific to three affected dogs.
- OnlineResource3filteringSNVindel.xlsx
Results of SNV and indel filtering with two affected dogs against 537 unaffected controls.
- OnlineResource4filteringSV.xlsx
Results of SV filtering with one WGS case against 290 unaffected controls.
- OnlineResource5filteringMEI.xlsx
Results of MEI filtering with one WGS case against 290 unaffected controls.
- OnlineResource6clustal.pdf
Multiple alignment of 99 Eutherian LOXHD1 orthologs flanking the canine p.(G1914A) variant site.
- OnlineResource7.xlsx
Results of the LOXHD1 variant screening in a commercial genetic testing panel in 28116 dogs from 374 breeds.
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This preprint is under consideration at Human Genetics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Hannes Lohi
Helsingin Yliopisto Laaketieteellinen tiedekunta
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1087-5532
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 16 Mar, 2021
No community comments so far
Editorial decision: Minor revisions
On 08 Apr, 2021
Reviewers invited
Invitations sent on 03 Mar, 2021
Review #? received
Received 03 Mar, 2021
Editor assigned
On 03 Mar, 2021
First submitted
On 01 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Hearing loss is a common sensory deficit both in humans and dogs. In canines the genetic basis is largely unknown, as genetic variants have only been identified for a syndromic form of hearing impairment. We observed a congenital or early-onset sensorineural hearing loss in a Rottweiler litter. Assuming an autosomal recessive inheritance, we used a combined approach of homozygosity mapping and genome sequencing to dissect the genetic background of the disorder. We identified a fully segregating missense variant in LOXHD1, a gene that is known to be essential for cochlear hair cell function and associated with nonsyndromic hearing loss in humans and mice. The canine LOXHD1 variant was specific to the Rottweiler breed in our study cohorts of pure-bred dogs. However, it also was present in mixed-breed dogs, of which the majority showed Rottweiler ancestry. Low allele frequencies in these populations, 2.6 % and 0.04 %, respectively, indicate a rare variant. To summarize, our study describes the first genetic variant for canine nonsyndromic hearing loss, which is clinically and genetically similar to human LOXHD1-related hearing disorder, and therefore, provides a new large animal model for hearing loss. Equally important, the affected breed will benefit from a genetic test to eradicate the hearing disorder from the population.
Figure 1
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