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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
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.
0036-8075
1436-1441
Cirulli, E.T.
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Krueger, B.J.
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Cirulli, E.T., Lasseigne, B.N. and Petrovski, S. et al. (2015) Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science, 347 (6229), 1436-1441. (doi:10.1126/science.aaa3650). (PMID:25700176)

Record type: 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.

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e-pub ahead of print date: 19 February 2015
Published date: 27 March 2015
Organisations: Medical Education

Identifiers

Local EPrints ID: 398182
URI: http://eprints.soton.ac.uk/id/eprint/398182
ISSN: 0036-8075
PURE UUID: 533f90bb-7a5b-4393-af81-7d9ff54d232c
ORCID for K.E. Morrison: ORCID iD orcid.org/0000-0003-0216-5717

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Date deposited: 20 Jul 2016 13:38
Last modified: 17 Dec 2019 01:32

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Contributors

Author: E.T. Cirulli
Author: B.N. Lasseigne
Author: S. Petrovski
Author: P.C. Sapp
Author: P.A. Dion
Author: C.S. Leblond
Author: J. Couthouis
Author: Y.-F. Lu
Author: Q. Wang
Author: B.J. Krueger
Author: Z. Ren
Author: J. Keebler
Author: Y. Han
Author: S.E. Levy
Author: B.E. Boone
Author: J.R. Wimbish
Author: L.L. Waite
Author: A.L. Jones
Author: J.P. Carulli
Author: A.G. Day-Williams
Author: J.F. Staropoli
Author: W.W. Xin
Author: A. Chesi
Author: A.R. Raphael
Author: D. McKenna-Yasek
Author: J. Cady
Author: J. M. B. Vianney de Jong
Author: K. P. Kenna
Author: B. N. Smith
Author: S. Topp
Author: J. Miller
Author: A. Gkazi
Author: A. Al-Chalabi
Author: L.H. van den Berg
Author: J. Veldink
Author: V. Silani
Author: N. Ticozzi
Author: C. E. Shaw
Author: R. H. Baloh
Author: S. Appel
Author: E. Simpson
Author: C. Lagier-Tourenne
Author: S.M. Pulst
Author: S. Gibson
Author: J. Q. Trojanowski
Author: L. Elman
Author: L. McCluskey
Author: M. Grossman
Author: N.A. Shneider
Author: W. K. Chung
Author: J. M. Ravits
Author: J. D. Glass
Author: K. B. Sims
Author: V.M. Van Deerlin
Author: T. Maniatis
Author: S.D. Hayes
Author: A. Ordureau
Author: S. Swarup
Author: J. Landers
Author: F. Baas
Author: A.S. Allen
Author: R.S. Bedlack
Author: J.W. Harper
Author: A.D. Gitler
Author: G. A. Rouleau
Author: R. Brown
Author: M.B. Harms
Author: G.M. Cooper
Author: T. Harris
Author: R.M. Myers
Author: D.B. Goldstein
Author: K.E. Morrison ORCID iD

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