Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.
Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:788811827fc345669a1236be5f10233a2021-11-18T06:18:08ZVariation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.1553-73901553-740410.1371/journal.pgen.1002898https://doaj.org/article/788811827fc345669a1236be5f10233a2012-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028339/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.Jennifer S YokoyamaErnest T LamAlison L RuheCarolyn A ErdmanKathryn R RobertsonAubrey A WebbD Colette WilliamsMelanie L ChangMarjo K HytönenHannes LohiSteven P HamiltonMark W NeffPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 9, p e1002898 (2012) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Jennifer S Yokoyama Ernest T Lam Alison L Ruhe Carolyn A Erdman Kathryn R Robertson Aubrey A Webb D Colette Williams Melanie L Chang Marjo K Hytönen Hannes Lohi Steven P Hamilton Mark W Neff Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| description |
Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders. |
| format |
article |
| author |
Jennifer S Yokoyama Ernest T Lam Alison L Ruhe Carolyn A Erdman Kathryn R Robertson Aubrey A Webb D Colette Williams Melanie L Chang Marjo K Hytönen Hannes Lohi Steven P Hamilton Mark W Neff |
| author_facet |
Jennifer S Yokoyama Ernest T Lam Alison L Ruhe Carolyn A Erdman Kathryn R Robertson Aubrey A Webb D Colette Williams Melanie L Chang Marjo K Hytönen Hannes Lohi Steven P Hamilton Mark W Neff |
| author_sort |
Jennifer S Yokoyama |
| title |
Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| title_short |
Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| title_full |
Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| title_fullStr |
Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| title_full_unstemmed |
Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| title_sort |
variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/788811827fc345669a1236be5f10233a |
| work_keys_str_mv |
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