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- Title
A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs.
- Authors
Lucot, Katherine L.; Dickinson, Peter J.; Finno, Carrie J.; Mansour, Tamer A.; Letko, Anna; Minor, Katherine M.; Mickelson, James R.; Drögemüller, Cord; Brown, C. Titus; Bannasch, Danika L.
- 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.
- Subjects
MISSENSE mutation; CHROMOSOMES; HOMOZYGOSITY
- Publication
G3: Genes | Genomes | Genetics, 2018, Vol 8, Issue 8, p2773
- ISSN
2160-1836
- Publication type
Article
- DOI
10.1534/g3.118.200376