A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs

作者:Lucot Katherine L; Dickinson Peter J; Finno Carrie J; Mansour Tamer A; Letko Anna; Minor Katherine M; Mickelson James R; Droegemueller Cord; Brown C Titus; Bannasch Danika L*
来源:Genes Genomes Genetics, 2018, 8(8): 2773-2780.
DOI:10.1534/g3.118.200376

摘要

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.

  • 出版日期2018-8