A Missense Mutation in the Vacuolar Protein Sorting 11 ( VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs
Abstract Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized pathologically by axonal spheroids primarily targeting sensory axon terminals. A genome-wide association study of seven Rottweilers affe...
Published in: | G3 Genes|Genomes|Genetics |
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Main Authors: | , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Oxford University Press (OUP)
2018
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Subjects: | |
Online Access: | http://dx.doi.org/10.1534/g3.118.200376 http://academic.oup.com/g3journal/article-pdf/8/8/2773/37126070/g3journal2773.pdf |
Summary: | Abstract Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized pathologically by axonal spheroids primarily targeting sensory axon terminals. A genome-wide association study of seven Rottweilers affected with NAD and 42 controls revealed a significantly associated region on canine chromosome 5 (CFA 5). Homozygosity within the associated region narrowed the critical interval to a 4.46 Mb haplotype (CFA5:11.28 Mb – 15.75 Mb; CanFam3.1) that associated with the phenotype. Whole-genome sequencing of two histopathologically confirmed canine NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T > C; p.H835R) that was associated with the phenotype. These findings present the opportunity for an antemortem test for confirming NAD in Rottweilers where the allele frequency was estimated at 2.3%. VPS11 mutations have been associated with a degenerative leukoencephalopathy in humans, and VSP11 should additionally be included as a candidate gene for unexplained cases of human NAD. |
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