Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Show full item record



Permalink

http://hdl.handle.net/10138/301252

Citation

ITALSGEN Consortium , Genomic Translation ALS Care GTAC , ALS Sequencing Consortium , NYGC ALS Consortium , Answer ALS Fdn , Clinical Res ALS Related Disorders , SLAGEN Consortium , French ALS Consortium & Project MinE ALS Sequencing Consor 2018 , ' Genome-wide Analyses Identify KIF5A as a Novel ALS Gene ' , Neuron , vol. 97 , no. 6 , pp. 1268-+ . https://doi.org/10.1016/j.neuron.2018.02.027

Title: Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
Author: ITALSGEN Consortium; Genomic Translation ALS Care GTAC; ALS Sequencing Consortium; NYGC ALS Consortium; Answer ALS Fdn; Clinical Res ALS Related Disorders; SLAGEN Consortium; French ALS Consortium; Project MinE ALS Sequencing Consor
Date: 2018-03-21
Language: eng
Number of pages: 21
Belongs to series: Neuron
ISSN: 0896-6273
URI: http://hdl.handle.net/10138/301252
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.
Subject: AMYOTROPHIC-LATERAL-SCLEROSIS
KINESIN HEAVY-CHAIN
DNA-DAMAGE
AXONAL-TRANSPORT
HEXANUCLEOTIDE REPEAT
TARGETED DISRUPTION
GENOTYPE IMPUTATION
MOTOR-NEURONS
FAMILIAL ALS
MUTATIONS
3112 Neurosciences
3124 Neurology and psychiatry
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S089662731830148X_main.pdf 2.247Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record