Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort

Neurobiol Aging. 2016 Mar:39:219.e1-8. doi: 10.1016/j.neurobiolaging.2015.11.030. Epub 2015 Dec 7.

Abstract

We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients.

Keywords: Amyotrophic lateral sclerosis; Genetic screening; Japan; Next-generation sequencer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Asian People
  • C9orf72 Protein
  • Cohort Studies
  • DNA / genetics*
  • Exome / genetics
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Polymerase Chain Reaction / methods
  • Proteins / genetics
  • RNA-Binding Protein FUS / genetics
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, DNA / trends*
  • Superoxide Dismutase-1 / genetics

Substances

  • ALS2 protein, human
  • C9orf72 Protein
  • C9orf72 protein, human
  • FUS protein, human
  • Guanine Nucleotide Exchange Factors
  • Proteins
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • SPG11 protein, human
  • DNA
  • Superoxide Dismutase-1