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 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.

• Authors: Katherine L Lucot, Peter J Dickinson, Carrie J Finno, Tamer A Mansour, Anna Letko, Katherine M Minor, James R Mickelson, Cord Drögemüller, C Titus Brown, Danika L Bannasch
• Journal: G3 (Bethesda, Md.) (G3 (Bethesda)) Vol. 8 Issue 8 Pg. 2773-2780 (07 31 2018) ISSN: 2160-1836 [Electronic] England
• PMID: 29945969 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Lucot et al.

Chemical References

• Vesicular Transport Proteins

Topics

• Animals
• Chromosomes (genetics)
• Dog Diseases (genetics, pathology)
• Dogs
• Haplotypes
• Mutation, Missense
• Neuroaxonal Dystrophies (genetics, pathology, veterinary)
• Vesicular Transport Proteins (genetics)