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Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies
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نویسنده
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yokoyama j.s. ,lam e.t. ,ruhe a.l. ,erdman c.a. ,robertson k.r. ,webb a.a. ,williams d.c. ,chang m.l. ,hytönen m.k. ,lohi h. ,hamilton s.p. ,neff m.w.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 9
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چکیده
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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. © 2012 yokoyama et al.
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آدرس
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department of psychiatry and institute for human genetics,university of california san francisco,san francisco,ca, United States, institute for human genetics,university of california san francisco,san francisco,ca, United States, neurogenomics division,the translational genomics research institute,phoenix,az,united states,veterinary genetics laboratory,university of california davis,davis,ca, United States, department of psychiatry and institute for human genetics,university of california san francisco,san francisco,ca, United States, veterinary genetics laboratory,university of california davis,davis,ca, United States, cullenwebb animal neurology and ophthalmology centre,riverview,nb,canada,department of clinical neuroscience,faculty of medicine,university of calgary,calgary,ab, Canada, school of veterinary medicine,university of california davis,davis,ca, United States, department of anthropology,university of oregon,eugene,or, United States, department of veterinary biosciences and research programs unit,molecular medicine,university of helsinki and folkhälsan research center,helsinki, Finland, department of veterinary biosciences and research programs unit,molecular medicine,university of helsinki and folkhälsan research center,helsinki, Finland, department of psychiatry and institute for human genetics,university of california san francisco,san francisco,ca, United States, neurogenomics division,the translational genomics research institute,phoenix,az,united states,the van andel research institute,grand rapids,mi, United States
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Authors
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