Exome sequencing to identify de novo mutations in sporadic ALS trios

View/ Open
Author
Chesi, Alessandra
Staahl, Brett T.
Jovicic, Ana
Couthouis, Julien
Fasolino, Maria
Raphael, Alya R.
Yamazaki, Tomohiro
Elias, Laura
Polak, Meraida
Kelly, Crystal
Williams, Kelly L.
Fifita, Jennifer A.
Maragakis, Nicholas J.
Nicholson, Garth A.
King, Oliver D.
Crabtree, Gerald R.
Blair, Ian P.
Glass, Jonathan D.
Gitler, Aaron D.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nn.3412Metadata
Show full item recordCitation
Chesi, A., B. T. Staahl, A. Jovicic, J. Couthouis, M. Fasolino, A. R. Raphael, T. Yamazaki, et al. 2013. “Exome sequencing to identify de novo mutations in sporadic ALS trios.” Nature neuroscience 16 (7): 10.1038/nn.3412. doi:10.1038/nn.3412. http://dx.doi.org/10.1038/nn.3412.Abstract
ALS is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic risk factors, here we assess the role of de novo mutations in ALS by sequencing the exomes of 47 ALS patients and both of their unaffected parents (n=141 exomes). We found that amino acid-altering de novo mutations are enriched in genes encoding chromatin regulators, including the neuronal chromatin remodeling complex component SS18L1/CREST. CREST mutations inhibit activity-dependent neurite outgrowth in primary neurons, and CREST associates with the ALS protein FUS. These findings expand our understanding of the ALS genetic landscape and provide a resource for future studies into the pathogenic mechanisms contributing to sporadic ALS.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709464/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879598
Collections
- HMS Scholarly Articles [18278]
Contact administrator regarding this item (to report mistakes or request changes)