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

9 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'A missense mutation in the vacuolar protein sorting 11 (VPS11) gene is associated with neuroaxonal dystrophy in rottweiler dogs'. Together they form a unique fingerprint.

  • Cite this