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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Elizabeth T. Cirulli, Brittany N. Lasseigne, Slavé Petrovski, Peter C. Sapp, Patrick A. Dion, Claire S. Leblond, Julien Couthouis, Yifan Lu, Quanli Wang, Brian J. Krueger, Zhong Ren, Jonathan Keebler, Yujun Han, Shawn Levy, Braden Boone

Science · 2015 · ▲ 980 citations

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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.

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Provenance

Source: OpenAlex
DOI: 10.1126/science.aaa3650
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Fetched: 2026-06-06 MST

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APA

Cirulli, E.T., Lasseigne, B.N., Petrovski, S., Sapp, P.C., Dion, P.A., Leblond, C.S., Couthouis, J., Lu, Y., Wang, Q., Krueger, B.J., Ren, Z., Keebler, J., Han, Y., Levy, S., Boone, B., Wimbish, J.R., Waite, L.L., Jones, A.L., Carulli, J.P., & Williams, K.L. (2015). Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. <em>Science</em>. https://doi.org/10.1126/science.aaa3650

Vancouver

Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015. doi:10.1126/science.aaa3650.

BibTeX

@unpublished{elizabeth2015Exomes, title = {Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways}, author = {Elizabeth T. Cirulli and Brittany N. Lasseigne and Slavé Petrovski and Peter C. Sapp and Patrick A. Dion and Claire S. Leblond and Julien Couthouis and Yifan Lu and Quanli Wang and Brian J. Krueger and Zhong Ren and Jonathan Keebler and Yujun Han and Shawn Levy and Braden Boone and Jack R. Wimbish and Lindsay L. Waite and Angela L. Jones and John P. Carulli and Kelly L. Williams and John F. Staropoli and Winnie Xin and Alessandra Chesi and Alya R. Raphael and Diane McKenna‐Yasek}, journal = {Science}, year = {2015}, doi = {10.1126/science.aaa3650}, }