Genome-wide Analyses Identify KIF5A as a Novel ALS Gene - Archive ouverte HAL Access content directly
Journal Articles Neuron Year : 2018

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

, , , (1) , (1) , , (2) , , , , , (3) , , , (4) , , , , , , , , (5) , , , , (6) , , , , , , , , , , , , , , , , , , , , , , , , , , , (5) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , (7) , , , , , , , (8) , , , , , , , , , , , , , (9, 10) , (9) , , , , , , , , , , , , (11) , , , , , , , , , , , , (12) , , , , , , , , , (13) , (14) , , , , , , , , (15) , , , , , , , , , , , , (16) , , , , , , (6) , (17, 18) , (17, 18) , , , (1) , , , (19, 20) , , (21) , , , , , , , (22) , , , (23) , , , , , , , , (24) , , , , , , , , (25) , , (26) , , , , , , , (27) , , ,
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
Franco Taroni
  • Function : Author
Antonia Ratti
  • Function : Author
Cinzia Gellera
  • Function : Author
Pietro Fratta
  • Function : Author
Christian Lunetta
  • Function : Author
Albert C. Ludolph
  • Function : Author
Peter M. Andersen
  • Function : Author
Jochen H. Weishaupt
  • Function : Author
John Q. Trojanowski
  • Function : Author
Vivianna M. van Deerlin
  • Function : Author
Leonard H. van Den Berg
  • Function : Author
Jan H. Veldink
  • Function : Author
Matthew B. Harms
  • Function : Author
Jonathan D. Glass
  • Function : Author
David J. Stone
  • Function : Author
Pentti Tienari
  • Function : Author
Vincenzo Silani
  • Function : Author
Christopher E. Shaw
  • Function : Author
Bryan J. Traynor
  • Function : Author
John E. Landers
  • Function : Author
Kevin P. Kenna
  • Function : Author
Alan E. Renton
  • Function : Author
Nicola Ticozzi
  • Function : Author
Faraz Faghri
  • Function : Author
Ruth Chia
  • Function : Author
Janice A. Dominov
  • Function : Author
Brendan J. Kenna
  • Function : Author
Mike A. Nalls
  • Function : Author
Pamela Keagle
  • Function : Author
Alberto M. Rivera
  • Function : Author
Wouter Van Rheenen
  • Function : Author
Natalie A. Murphy
  • Function : Author
Joke J. F. A. Van Vugt
  • Function : Author
Joshua T. Geiger
  • Function : Author
Rick A. van Der Spek
  • Function : Author
Hannah A. Pliner
  • Function : Author
Null Shankaracharya
  • Function : Author
Bradley N. Smith
  • Function : Author
Giuseppe Marangi
  • Function : Author
Simon D. Topp
  • Function : Author
Yevgeniya Abramzon
  • Function : Author
Athina Soragia Gkazi
  • Function : Author
John D. Eicher
  • Function : Author
Aoife Kenna
  • Function : Author
Italsgen Consortium
  • Function : Author
Gabriele Mora
  • Function : Author
Letizia Mazzini
  • Function : Author
Nilo Riva
  • Function : Author
Jessica Mandrioli
  • Function : Author
Claudia Caponnetto
  • Function : Author
Stefania Battistini
  • Function : Author
Paolo Volanti
  • Function : Author
Vincenzo La Bella
  • Function : Author
Francesca L. Conforti
  • Function : Author
Giuseppe Borghero
  • Function : Author
Sonia Messina
  • Function : Author
Isabella L. Simone
  • Function : Author
Francesca Trojsi
Fabrizio Salvi
  • Function : Author
Francesco O. Logullo
  • Function : Author
Sandra d'Alfonso
  • Function : Author
Lucia Corrado
  • Function : Author
Margherita Capasso
  • Function : Author
Luigi Ferrucci
  • Function : Author
Sitharthan Kamalakaran
  • Function : Author
David B. Goldstein
  • Function : Author
Als Sequencing Consortium
  • Function : Author
Aaron D. Gitler
  • Function : Author
Tim Harris
  • Function : Author
Richard M. Myers
  • Function : Author
Nygc Als Consortium
  • Function : Author
Hemali Phatnani
  • Function : Author
Rajeeva Lochan Musunuri
  • Function : Author
Uday Shankar Evani
  • Function : Author
Michael C. Zody
  • Function : Author
Answer Als Foundation
  • Function : Author
Julia Kaye
  • Function : Author
Steven Finkbeiner
  • Function : Author
Stacia K. Wyman
  • Function : Author
Alex Lenail
  • Function : Author
Ernest Fraenkel
  • Function : Author
Clive N. Svendsen
  • Function : Author
Leslie M. Thompson
  • Function : Author
Jennifer E. van Eyk
  • Function : Author
James D. Berry
  • Function : Author
Timothy M. Miller
  • Function : Author
Stephen J. Kolb
  • Function : Author
Merit Cudkowicz
  • Function : Author
Emily Baxi
  • Function : Author
Clinical Research In Als
  • Function : Author
Michael Benatar
  • Function : Author
Gang Wu
Joanne Wuu
  • Function : Author
Slagen Consortium
  • Function : Author
Giuseppe Lauria
  • Function : Author
Federico Verde
  • Function : Author
Isabella Fogh
  • Function : Author
Cinzia Tiloca
  • Function : Author
Giacomo P. Comi
  • Function : Author
Gianni Sorarù
  • Function : Author
Cristina Cereda
  • Function : Author
French Als Consortium
  • Function : Author
Hannu Laaksovirta
  • Function : Author
Liisa Myllykangas
  • Function : Author
Lilja Jansson
  • Function : Author
Miko Valori
  • Function : Author
John Ealing
  • Function : Author
Hisham Hamdalla
  • Function : Author
Sara Rollinson
  • Function : Author
Stuart Pickering-Brown
  • Function : Author
Richard W. Orrell
  • Function : Author
Katie C. Sidle
  • Function : Author
Andrea Malaspina
  • Function : Author
Andrew B. Singleton
  • Function : Author
Janel O. Johnson
  • Function : Author
Sampath Arepalli
  • Function : Author
Peter C. Sapp
  • Function : Author
Diane Mckenna-Yasek
  • Function : Author
Meraida Polak
  • Function : Author
Seneshaw Asress
  • Function : Author
Safa Al-Sarraj
  • Function : Author
Andrew King
  • Function : Author
  • PersonId : 864624
Caroline Vance
  • Function : Author
Jacqueline De Belleroche
  • Function : Author
Frank Baas
  • Function : Author
Anneloor L. M. A. ten Asbroek
  • Function : Author
José Luis Muñoz-Blanco
  • Function : Author
Dena G. Hernandez
  • Function : Author
Jinhui Ding
  • Function : Author
Sonja W. Scholz
  • Function : Author
Mary Kay Floeter
  • Function : Author
Roy H. Campbell
  • Function : Author
Francesco Landi
  • Function : Author
Robert Bowser
  • Function : Author
Stefan M. Pulst
  • Function : Author
John M. Ravits
  • Function : Author
Daniel J. L. Macgowan
  • Function : Author
Janine Kirby
  • Function : Author
Erik P. Pioro
  • Function : Author
Roger Pamphlett
  • Function : Author
Glenn Gerhard
  • Function : Author
Travis L. Dunckley
  • Function : Author
Christopher B. Brady
  • Function : Author
Neil W. Kowall
  • Function : Author
Juan C. Troncoso
  • Function : Author
Terry D. Heiman-Patterson
  • Function : Author
Freya Kamel
  • Function : Author
Robert H. Baloh
  • Function : Author
Tim M. Strom
  • Function : Author
Aleksey Shatunov
  • Function : Author
Mamede De Carvalho
  • Function : Author
Maarten Kooyman
  • Function : Author
Bas Middelkoop
  • Function : Author
Matthieu Moisse
  • Function : Author
Russell L. Mclaughlin
  • Function : Author
Michael A. van Es
  • Function : Author
Kevin B. Boylan
  • Function : Author
Marka van Blitterswijk
  • Function : Author
Karen E. Morrison
  • Function : Author
A. Nazli Basak
  • Function : Author
Jesús S. Mora
  • Function : Author
Vivian E. Drory
  • Function : Author
Pamela J. Shaw
  • Function : Author
Martin R. Turner
  • Function : Author
Kevin Talbot
  • Function : Author
Orla Hardiman
Kelly L. Williams
  • Function : Author
Jennifer A. Fifita
  • Function : Author
Garth A. Nicholson
  • Function : Author
Ian P. Blair
  • Function : Author
Guy A. Rouleau
  • Function : Author
Jesús Esteban-Pérez
  • Function : Author
Alberto Garc'Ia-Redondo
  • Function : Author
Lorne Zinman
  • Function : Author
Lyle W. Ostrow
  • Function : Author
Nicholas J. Maragakis
  • Function : Author
Jeffrey D. Rothstein
  • Function : Author
Zachary Simmons
  • Function : Author
Johnathan Cooper-Knock
  • Function : Author
Stephen A. Goutman
  • Function : Author
Eva L. Feldman
  • Function : Author
Summer B. Gibson
  • Function : Author

Abstract

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Dates and versions

hal-02345947 , version 1 (04-11-2019)

Identifiers

Cite

Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip van Damme, Wim Robberecht, et al.. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron, 2018, 97 (6), pp.1268--1283.e6. ⟨10.1016/j.neuron.2018.02.027⟩. ⟨hal-02345947⟩
124 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More