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

G3: Genes, Genomes, Genetics

Carrie J. Finno^1¹  Tamer A. Mansour^1²  Katherine L. Lucot^1³  Peter J. Dickinson^2⁴ 

[1] Department of Clinical Research and Veterinary Public Health, University of Bern, 3001 Bern, Switzerland^3;Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN 55455^4;Departments of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616^1;Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616^2

关键词: autophagy;    canine;    lysosome;    neurodegenerative;    inherited;    genetic;   

DOI  :  10.1534/g3.118.200376

学科分类：生物科学（综合）

来源: Genetics Society of America

【 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.

【 授权许可】

CC BY