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Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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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
Abstract [en]

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.
Keyword [en]
degenerative myelopathy, amyotrophic lateral sclerosis, ALS, SOD1, SP110
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-298872DOI: 10.1073/pnas.1600084113ISI: 000376784600009PubMedID: 27185954OAI: oai:DiVA.org:uu-298872DiVA: diva2:948294
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2016-07-11Bibliographically approved

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Megquier, KateKozyrev, Sergey V.Murén, EvaLindblad-Toh, Kerstin
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Department of Medical Biochemistry and Microbiology
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