Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy
2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 22, E3091-E3100 p.Article in journal (Refereed) PublishedText
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 x 10(-5)), and was associated with increased probability of developing DM (P = 4.8 x 10(-6)) and earlier onset of disease (P = 1.7 x 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.
Place, publisher, year, edition, pages
2016. Vol. 113, no 22, E3091-E3100 p.
degenerative myelopathy, amyotrophic lateral sclerosis, ALS, SOD1, SP110
Microbiology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-298872DOI: 10.1073/pnas.1600084113ISI: 000376784600009PubMedID: 27185954OAI: oai:DiVA.org:uu-298872DiVA: diva2:948294