{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T21:13:41Z","timestamp":1757452421786,"version":"3.40.5"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Embark Veterinary, Inc. and the participants"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Domestic dogs exhibit diverse types of both congenital and non-congenital hearing losses. Rhodesian Ridgebacks can suffer from a progressive hearing loss in the early stage of their life, a condition known as early onset adult deafness (EOAD), where they lose their hearing ability within 1\u20132 years after birth. In order to investigate the genetic basis of this hereditary hearing disorder, we performed a genome-wide association study (GWAS) by using a sample of 23 affected and 162 control Rhodesian Ridgebacks. We identified a genomic region on canine chromosome 18 (CFA18) that is strongly associated with EOAD, and our subsequent targeted Sanger sequencing analysis identified a 12-bp inframe deletion in<jats:italic>EPS8L2<\/jats:italic>(CFA18:25,868,739\u201325,868,751 in the UMICH_Zoey_3.1\/canFam5 reference genome build). Additional genotyping confirmed a strong association between the 12-bp deletion and EOAD, where all affected dogs were homozygous for the deletion, while none of the control dogs was a deletion homozygote. A segregation pattern of this deletion in a 2-generation nuclear family indicated an autosomal recessive mode of inheritance. Since<jats:italic>EPS8L2<\/jats:italic>plays a critical role in the maintenance and integrity of the inner ear hair cells in humans and other mammals, the inframe deletion found in this study represents a strong candidate causal mutation for EOAD in Rhodesian Ridgebacks. Genetic and clinical similarities between childhood deafness in humans and EOAD in Rhodesian Ridgebacks emphasizes the potential value of this dog breed in translational research in hereditary hearing disorders.<\/jats:p>","DOI":"10.1371\/journal.pone.0264365","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T17:48:56Z","timestamp":1649267336000},"page":"e0264365","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Early onset adult deafness in the Rhodesian Ridgeback dog is associated with an in-frame deletion in the EPS8L2 gene"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-6852","authenticated-orcid":true,"given":"Takeshi","family":"Kawakami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-2299","authenticated-orcid":true,"given":"Vandana","family":"Raghavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison L.","family":"Ruhe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan K.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ausra","family":"Milano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam R.","family":"Boyko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"pone.0264365.ref001","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1001\/archinte.168.14.1522","article-title":"Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999\u20132004","volume":"168","author":"Y Agrawal","year":"2008","journal-title":"Arch Intern Med"},{"key":"pone.0264365.ref002","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"GBD 2015 Disease and Injury Incidence and Prevalence Collaborators","year":"2016","journal-title":"Lancet"},{"key":"pone.0264365.ref003","doi-asserted-by":"crossref","first-page":"a033217","DOI":"10.1101\/cshperspect.a033217","article-title":"Age-related hearing loss","volume":"9","author":"MR Bowl","year":"2019","journal-title":"Cold Spring Harb Perspect Med"},{"key":"pone.0264365.ref004","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3109\/14992027.2014.989548","article-title":"Performance and characteristics of the Newborn Hearing Screening Programme in England: The first seven years","volume":"54","author":"SA Wood","year":"2015","journal-title":"Int J Audiol"},{"key":"pone.0264365.ref005","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1177\/0194599816640485","article-title":"Quality of life in children with hearing impairment: systematic review and meta-analysis","volume":"155","author":"L Roland","year":"2016","journal-title":"Otolaryngol Head Neck Surg"},{"key":"pone.0264365.ref006","doi-asserted-by":"crossref","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","article-title":"Congenital hearing loss","volume":"3","author":"AMH Korver","year":"2017","journal-title":"Nat Rev Dis Primer"},{"key":"pone.0264365.ref007","article-title":"AudioGene: predicting hearing loss genotypes from phenotypes to guide genetic screening","volume":"34","author":"KR Taylor","year":"2013","journal-title":"Hum Mutat"},{"key":"pone.0264365.ref008","unstructured":"Van Camp G, Smith R. 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