Researchers discover rare novel genetic defect causing hearing loss in Rottweilers providing a new large animal model for human hearing disorders
Wisdom Health Genetics, the world leader in pet genetics and maker of the WISDOM PANEL™ dog DNA test, announced today the publication in Human Genetics of a landmark study conducted in partnership with the University of Helsinki.
The study—Missense variant in LOXHD1 is associated with canine nonsyndromic hearing loss—describes the first identified genetic variant for canine nonsyndromic hearing loss, a common deficiency in humans and dogs.
Researchers utilized homozygosity mapping and genome sequencing to identify a rare variant in LOXHD1, a gene associated with nonsyndromic hearing loss in both humans and mice.
The finding was confirmed by a screening of more than 800,000 dogs, which found the LOXHD1 variant to be the most likely cause of hearing loss in some identified purebred Rottweilers and mixed-breed dogs, the majority of which have Rottweiler ancestry.
“Congenital and adult-onset hearing loss conditions have been reported in dogs across many breeds, but their genetic background still remains mostly uncharacterized,” said Jonas Donner, Ph.D., Discovery Manager at Wisdom Health Genetics. “In addition to becoming one of the largest published canine genotyping efforts to date, this study is an important step toward a deeper understanding of the molecular genetics behind hearing loss and the population management of LOXHD1-related hearing loss through genetic testing.”
Found in the Rottweiler breed, nonsyndromic hearing loss is both clinically and genetically similar to LOXHD1-related hearing disorders in humans. Thus, this discovery provides a new large animal model for hearing loss.
Nonsyndromic hearing loss has been linked to more than one hundred genetic variants to date. However, future research is needed to understand the biology of this type of hearing loss and the related genes and variants.
“We are grateful to the more than 1000 Banfield™ Pet Hospital clinicians who diligently and consistently recorded their observations in medical records during 2019-2021—without that collective effort this work would not have been possible,” said Rebecca Chodroff Foran, Ph.D., R&D Director at Wisdom Health Genetics. “This study in particular shows the value of large-scale sampling efforts integrating clinical data and genotyping: not only does it elucidate the underlying genetics of canine disease, it also sets the groundwork for the development of a targeted genetic test to manage LOXHD1-related hearing disorders in the canine population.”
This study demonstrates the value of genetic research in helping pet parents worldwide to provide the best care to their pets and furthers Kinship Partners’ commitment to setting ever-higher standards in pet care. The discovery of this specific genetic variant will allow research teams to develop a targeted genetic test to manage nonsyndromic hearing loss, empowering pet parents to make better, more educated health decisions for their pet.
About the nonsyndromic hearing loss study:
- Researchers from University of Helsinki and Wisdom Health Genetics conducted a study of nonsyndromic hearing loss, discovering a rare genetic variant in LOXHD1 associated with an autosomal recessive congenital nonsyndromic hearing loss in Rottweilers—the first of its kind related to nonsyndromic hearing loss.
- Though the exact mechanism by which the LOXHD1 variant causes hearing loss remains unknown, the gene is essential for cochlear hair cell function and is also associated with nonsyndromic hearing loss in humans and mice.
- The researchers made this discovery using a combination of homozygosity mapping and genome sequencing, and obtained confirmation for its relevance through screening more than 800,000 dogs from DNA samples obtained at Banfield™ Pet Hospitals. The rare LOXHD1 variant was found in both purebred Rottweilers and mixed-breed dogs with Rottweiler ancestry at low allele frequencies.
- The characterized nonsyndromic form of hearing loss in dogs is clinically and genetically similar to the condition in humans, and therefore, provides a large animal model for its study. Likewise, Rottweilers will benefit from the development of a genetic test to manage this LOXHD1-related hearing disorder in the population.