Elucidation of the pathogenicity of novel gene mutations detected through comprehensive genetic analysis in familial ALS

Research Project

Project/Area Number	17H06526
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Neurology
Research Institution	Tohoku University
Principal Investigator	Nishiyama Ayumi 東北大学, 大学病院, 医員 (50805413)
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	遺伝子 / 神経変性疾患
Outline of Final Research Achievements	The purpose of this research is to reveal the pathogenicity of gene mutations detected in familial amyotrophic lateral sclerosis (ALS) and the underlying mechanism of selective motor neuron degeneration. We performed comprehensive genetic analysis using next-generation sequencer in a consecutive series of 134 Japanese familial ALS pedigrees. We identified known mutations in approximately half of all cases. In the remaining genetically unidentified cases, we have found novel candidate mutations and perform validation of their significance.
Academic Significance and Societal Importance of the Research Achievements	1991年より有数規模の日本人・家族性ALSサンプルを収集し、続々と追加試料を得て研究対象を集積している。また、次世代シークエンサーとバイオインフォマティクス技術を駆使して、多検体を効率的に解析する体制を確立している。本研究は、単なる遺伝子解析にとどまらず、創薬に活用できるALS細胞モデル作出にもつながり、新しい変性機構の解明によって、広く神経変性疾患の病態解明と治療法開発に波及効果をもち得る。