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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.

Publication ,  Journal Article
Cirulli, ET; Lasseigne, BN; Petrovski, S; Sapp, PC; Dion, PA; Leblond, CS; Couthouis, J; Lu, Y-F; Wang, Q; Krueger, BJ; Ren, Z; Keebler, J ...
Published in: Science
March 27, 2015

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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Published In

Science

DOI

EISSN

1095-9203

Publication Date

March 27, 2015

Volume

347

Issue

6229

Start / End Page

1436 / 1441

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factor TFIIIA
  • Sequestosome-1 Protein
  • Sequence Analysis, DNA
  • Risk
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Middle Aged
  • Membrane Transport Proteins
  • Male
 

Citation

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Cirulli, E. T., Lasseigne, B. N., Petrovski, S., Sapp, P. C., Dion, P. A., Leblond, C. S., … Goldstein, D. B. (2015). Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science, 347(6229), 1436–1441. https://doi.org/10.1126/science.aaa3650
Cirulli, Elizabeth T., Brittany N. Lasseigne, Slavé Petrovski, Peter C. Sapp, Patrick A. Dion, Claire S. Leblond, Julien Couthouis, et al. “Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.Science 347, no. 6229 (March 27, 2015): 1436–41. https://doi.org/10.1126/science.aaa3650.
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 Mar 27;347(6229):1436–41.
Cirulli, Elizabeth T., et al. “Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.Science, vol. 347, no. 6229, Mar. 2015, pp. 1436–41. Pubmed, doi:10.1126/science.aaa3650.
Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, Couthouis J, Lu Y-F, 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 JMB, 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. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015 Mar 27;347(6229):1436–1441.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

March 27, 2015

Volume

347

Issue

6229

Start / End Page

1436 / 1441

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factor TFIIIA
  • Sequestosome-1 Protein
  • Sequence Analysis, DNA
  • Risk
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Middle Aged
  • Membrane Transport Proteins
  • Male