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

Autor:	Ivansson EL; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142; emma.ivansson@ki.se kersli@broadinstitute.org., Megquier K; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;, Kozyrev SV; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden;, Murén E; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden;, Körberg IB; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden;, Swofford R; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;, Koltookian M; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;, Tonomura N; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142; Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA 01536;, Zeng R; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211;, Kolicheski AL; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211;, Hansen L; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211;, Katz ML; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO 65201;, Johnson GC; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211;, Johnson GS; Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211;, Coates JR; Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211., Lindblad-Toh K; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142; emma.ivansson@ki.se kersli@broadinstitute.org.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 May 31; Vol. 113 (22), pp. E3091-100. Date of Electronic Publication: 2016 May 16.
DOI:	10.1073/pnas.1600084113
Abstrakt:	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.
Databáze:	MEDLINE
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