Baranowska Körberg, Izabella
- Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
Sammanfattning
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.
Nyckelord
degenerative myelopathy; amyotrophic lateral sclerosis; ALS; SOD1; SP110
Publicerad i
Proceedings of the National Academy of Sciences
2016, volym: 113, nummer: 22, sidor: E3091-E3100
Utgivare: NATL ACAD SCIENCES
SLU författare
UKÄ forskningsämne
Patobiologi
Publikationens identifierare
- DOI: https://doi.org/10.1073/pnas.1600084113
Permanent länk till denna sida (URI)
https://res.slu.se/id/publ/82840