A missense mutation in the vacuolar protein sorting 11 (VPS11) gene is associated with neuroaxonal dystrophy in rottweiler dogs

Katherine L. Lucot, Peter J Dickinson, Carrie J Finno, Tamer A. Mansour, Anna Letko, Katherine M. Minor, James R. Mickelson, Cord Drögemüller, Charles Brown, Danika L Bannasch

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2773-2780
Number of pages8
JournalG3: Genes, Genomes, Genetics
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Neuroaxonal Dystrophies
Protein Transport
Missense Mutation
Dogs
Genes
Canidae
Phenotype
Leukoencephalopathies
Chromosomes, Human, Pair 5
Genome-Wide Association Study
Presynaptic Terminals
Gene Frequency
Haplotypes
Young Adult
Genome
Mutation

Keywords

  • Autophagy
  • Canine
  • Genetic
  • Inherited
  • Lysosome
  • Neurodegenerative

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

A missense mutation in the vacuolar protein sorting 11 (VPS11) gene is associated with neuroaxonal dystrophy in rottweiler dogs. / Lucot, Katherine L.; Dickinson, Peter J; Finno, Carrie J; Mansour, Tamer A.; Letko, Anna; Minor, Katherine M.; Mickelson, James R.; Drögemüller, Cord; Brown, Charles; Bannasch, Danika L.

In: G3: Genes, Genomes, Genetics, Vol. 8, No. 8, 01.08.2018, p. 2773-2780.

Research output: Contribution to journalArticle

Lucot, Katherine L. ; Dickinson, Peter J ; Finno, Carrie J ; Mansour, Tamer A. ; Letko, Anna ; Minor, Katherine M. ; Mickelson, James R. ; Drögemüller, Cord ; Brown, Charles ; Bannasch, Danika L. / A missense mutation in the vacuolar protein sorting 11 (VPS11) gene is associated with neuroaxonal dystrophy in rottweiler dogs. In: G3: Genes, Genomes, Genetics. 2018 ; Vol. 8, No. 8. pp. 2773-2780.
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