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


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.

SUBMITTER: Ivansson EL 

PROVIDER: S-EPMC4896683 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Ivansson Emma L EL   Megquier Kate K   Kozyrev Sergey V SV   Murén Eva E   Körberg Izabella Baranowska IB   Swofford Ross R   Koltookian Michele M   Tonomura Noriko N   Zeng Rong R   Kolicheski Ana L AL   Hansen Liz L   Katz Martin L ML   Johnson Gayle C GC   Johnson Gary S GS   Coates Joan R JR   Lindblad-Toh Kerstin K  

Proceedings of the National Academy of Sciences of the United States of America 20160516 22


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 analy  ...[more]

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