title: [Personal genome analysis in amyotrophic lateral sclerosis].
abstract: In amyotrophic lateral sclerosis (ALS), 5% of cases are familial, and most of the remaining cases are sporadic. In familial ALS, many causative genes have been identified during the last 20 years of the golden age of genetics. In particular, the recent discovery of a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) has had a large impact on ALS research, as this mutation is the most frequent cause of familial ALS in Europe and the US. However, the relative rarity of this mutation in Japan and Asia suggests the need to identify further other causative genes of familial ALS. In this regard, the advent of next-generation sequencing technology is expected to accelerate the identification of novel genes. In addition, next-generation sequencing will supersede Sanger sequencing in the molecular diagnosis of familial ALS. A number of genome-wide association studies (GWAS) have been conducted to identify the disease-susceptibility genes of sporadic ALS. In 1,305 Japanese ALS samples, the ZNF512B gene was associated with susceptibility to ALS. This gene has been shown to be one of the prognostic factors in sporadic ALS. Although GWAS that are based on the 'common disease-common variants hypothesis' have successfully revealed many disease-susceptibility genes, including ZNF512B, in sporadic ALS, the odds ratios associated with these risk alleles are generally low. The next challenge in ALS research is to use next-generation sequencing techniques to identify disease-relevant alleles with large effect sizes based on the 'common disease-multiple rare variants hypothesis'.
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Jun
authors.initials: J
authors.lastname: Sone
authors.forename: Naoki
authors.initials: N
authors.lastname: Atsuta
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Koyano
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D030661:Genetic Privacy; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009154:Mutation