Details

Autor(en) / Beteiligte

• Ivansson, Emma L.
• Megquier, Kate
• 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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-05, Vol.113 (22), p.E3091-E3100

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.