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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
| File | Description | Size | Format | |
|---|---|---|---|---|
 Science_2015.pdf | Accepted version | 460.63 kB | Adobe PDF | View/Open |
| Science_2015_SI.pdf | Supporting information | 687.96 kB | Adobe PDF | View/Open |
| Science_2015_Tables.pdf | Supporting information | 92.27 kB | Adobe PDF | View/Open |
| Title: | Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. |
| Authors: | Cirulli, ET Lasseigne, BN Petrovski, S Sapp, PC Dion, PA Leblond, CS Couthouis, J Lu, YF Wang, Q Krueger, BJ Ren, Z Keebler, J Han, Y Levy, SE Boone, BE Wimbish, JR Waite, LL Jones, AL Carulli, JP Day-Williams, AG Staropoli, JF Xin, WW Chesi, A Raphael, AR McKenna-Yasek, D Cady, J Vianney de Jong, JM Kenna, KP Smith, BN Topp, S Miller, J Gkazi, A FALS Sequencing Consortium, Al-Chalabi, A van den Berg, LH Veldink, J Silani, V Ticozzi, N Shaw, CE Baloh, RH Appel, S Simpson, E Lagier-Tourenne, C Pulst, SM Gibson, S Trojanowski, JQ Elman, L McCluskey, L Grossman, M Shneider, NA Chung, WK Ravits, JM Glass, JD Sims, KB Van Deerlin, VM Maniatis, T Hayes, SD Ordureau, A Swarup, S Landers, J Baas, F Allen, AS Bedlack, RS Harper, JW Gitler, AD Rouleau, GA Brown, R Harms, MB Cooper, GM Harris, T Myers, RM Goldstein, DB |
| Item Type: | Journal Article |
| Abstract: | Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention. |
| Issue Date: | 27-Mar-2015 |
| URI: | http://hdl.handle.net/10044/1/19593 |
| DOI: | http://dx.doi.org/10.1126/science.aaa3650 |
| Journal / Book Title: | Science |
| Copyright Statement: | © the Authors 2015. Published by the American Association for the Advancement of Science. |
| Appears in Collections: | Department of Medicine (up to 2019) |