Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy

Author:

Ivansson Emma L.,Megquier KateORCID,Kozyrev Sergey V.,Murén Eva,Körberg Izabella Baranowska,Swofford Ross,Koltookian Michele,Tonomura Noriko,Zeng Rong,Kolicheski Ana L.,Hansen Liz,Katz Martin L.,Johnson Gayle C.,Johnson Gary S.,Coates Joan R.,Lindblad-Toh Kerstin

Abstract

Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10−5), and was associated with increased probability of developing DM (P = 4.8 × 10−6) and earlier onset of disease (P = 1.7 × 10−5). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds.

Funder

American Kennel Club Canine Health Foundation

ALS Association

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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