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, C. Titus Brown, Danika L. Bannasch

Research output: Contribution to journalArticlepeer-review

11 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

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