次世代シーケンサーを用いた新規パーキンソン病原因遺伝子の単離

2017 Fiscal Year Research-status Report

• Project/Area Number: 16K09678
• Research Institution: Juntendo University
• Principal Investigator: 西岡 健弥 順天堂大学, 医学部, 准教授 (40348933)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 遺伝子 / パーキンソン病 / 次世代シーケンサー

Outline of Annual Research Achievements

常染色体優性遺伝形式を呈する家族性パーキンソン病にて同一家系内に濃厚な集積を認める一家系に注目した。既知の遺伝子であるSNCA, LRRK2, PINK1, DJ1が無いことを確認した上で、次世代シーケンサーを用いた解析を施行している。この家系は同一家系内に４名おり、３名についてDNAを回収した。次世代シーケンサーによる解析後、CLC Genomic workbenchを用いて、11万程度のSNPsやindelを同定し、この中からnon-synonymous exonic variants、frequency < 0.01、heterozygous variantsの条件で絞り込みをかけた。これにより病的遺伝子変異が疑われる46遺伝子を同定した。その後46の変異についてすべてSanger sequnecingを施行し、実際に存在することを確認した。現在、当院のDNA bankに保管されている常染色体優性遺伝形式を呈するproband 50名の遺伝子に対して、ion PGM(Thermo Fisher Scientific)によるhigh through put解析を行いスクリーニグを施行した。現在はそのデータの解析中である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

上記の内容で研究を進めている。現在のところ比較的順調に推移している。

Strategy for Future Research Activity

原因遺伝子を同定した後は、細胞培養実験や動物モデルにて解析を行い、病的なものかどうかの確認、細胞内での発現動向、コードする蛋白質の機能解析を行っていく。

Research Products

• [Int'l Joint Research] University of British Columbia(Canada)
  • Country Name: Canada
  • Counterpart Institution: University of British Columbia
• [Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy. (2018)
  • Author(s): Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
  • Journal Title: Journal of Neural Transmission Volume: 125 Pages: 937-958
  • DOI: 10.1007/s00702-018-1885-1
  • Peer Reviewed
• [Journal Article] Genetic analysis of TMEM230 in Japanese patients with familial Parkinson's disease. (2018)
  • Author(s): Conedera SA, Li Y, Funayama M, Yoshino H, Nishioka K, Hattori N.
  • Journal Title: Parkinsonism and related disorders Volume: 48 Pages: 107-108
  • DOI: 10.1016/j.parkreldis.2017.12.020.
  • Peer Reviewed
• [Journal Article] Association between abnormal nocturnal blood pressure profile and dementia in Parkinson's disease. (2018)
  • Author(s): Tanaka R, Shimo Y, Yamashiro K, Ogawa T, Nishioka K, Oyama G, Umemura A, Hattori N.
  • Journal Title: Parkinsonism and Related Disorders Volume: 46 Pages: 24-29
  • DOI: 10.1016/j.parkreldis.2017.10.014.
  • Peer Reviewed
• [Journal Article] Marked reduction in striatal dopamine transporter uptake during the early stage of motor symptoms in patients with the MAPT N279K mutation (2018)
  • Author(s): Takeshige H, Nakayama S, Nishioka K, Li Y, Motoi Y, Hattori N.
  • Journal Title: Internal Medicine Volume: in press Pages: in press
  • DOI: in press
  • Peer Reviewed
• [Journal Article] DNAJC12 and dopa-responsive nonprogressive parkinsonism. (2017)
  • Author(s): Straniero L, Guella I, Cilia R, Parkkinen L, Rimoldi V, Young A, Asselta R, Sold, G, Sossi V, Stoessl AJ, Priori A, Nishioka K, Hattori N, Follett J, Rajput A, Blau N, Pezzoli G, Farrer MJ, Goldwurm S, Rajput AH, Duga S.
  • Journal Title: Annals of Neurology Volume: 82 Pages: 640-646
  • DOI: 10.1002/ana.25048.
  • Peer Reviewed
• [Journal Article] Homozygous alpha-synuclein p.A53V in familial Parkinson's disease. (2017)
  • Author(s): Yoshino H, Hirano M, Stoessl AJ, Imamichi Y, Ikeda A, Li Y, Funayama M, Yamada I, Nakamura Y, Sossi V, Farrer MJ, Nishioka K, Hattori N.
  • Journal Title: Neurobiology of Aging Volume: 57 Pages: :248.e7-248.e12
  • DOI: 10.1016/j.neurobiolaging.2017.05.022.
  • Peer Reviewed
• [Journal Article] A novel mutation of CHCHD2 p.R8H in a sporadic case of Parkinson's disease. (2017)
  • Author(s): Ikeda A, Matsushima T, Daida K, Nakajima S, Conedera S, Li Y, Yoshino H, Oyama G, Funayama M, Nishioka K, Hattori N.
  • Journal Title: Parkinsonism and Related Diosorders Volume: 34 Pages: 66-68
  • DOI: 10.1016/j.parkreldis.2016.10.018
  • Peer Reviewed
• [Journal Article] CSF1R Mutation p.G589R and the Distribution Pattern of Brain Calcification. (2017)
  • Author(s): Daida K, Nishioka K, Li Y, Nakajima S, Tanaka R, Hattori N.
  • Journal Title: Internal Medicine Volume: 15 Pages: 2507-2512
  • DOI: 10.2169/internalmedicine.8462-16.
  • Peer Reviewed
• [Presentation] HOMOZYGOUS ALPHA-SYNUCLEIN A53V IN FAMILIAL PARKINSON'S DISEASE (2017)
  • Author(s): Kenya Nishioka, Makito Hirano, A. Jon Stoessl, Hiroyo Yoshino, Yoko Imamichi, Aya Ikeda, Yuanzhe Li, Manabu Funayama, Ikuko Yamada, Yusaku Nakamura, Vesna Sossi, Matthew J. Farrer, Nobutaka Hattori.
  • Organizer: The XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] The correlation of CHCHD2 mutations and alpha-synculein in the brain pathology and fly models (2017)
  • Author(s): Kenya Nishioka, Aya Ikeda, Masashi Takanashi, Hiroyo Yoshino, Yuanzhe Li, Manabu Funayama, Yuzuru Imai, Nobutaka Hattori.
  • Organizer: Genetic Epidemiology of Parkinson’s disease
  • Int'l Joint Research
• [Presentation] Missense mutations and multiplications of alpha-synuclein in familial Parkinson’s disease; genotype-phenotype correlation (2017)
  • Author(s): Kenya Nishioka, Hiroyo Yoshino, Yuanzhe Li, Manabu Funayama, Tara Candido, A. Jon Stoessl, Matthew J Farrer, Nobutaka Hattori.
  • Organizer: The American Society of Human Genetics
  • Int'l Joint Research
• [Book] Parkinson病のゲノム医療 (2017)
  • Author(s): 西岡健弥 李元哲 吉野浩代 服部信孝
  • Total Pages: ｀６
  • Publisher: 科学評論社
  • ISBN: 0386-9709
• [Remarks] 順天堂大学 研究者情報ベース
  • URL: https://www.juntendo.ac.jp/graduate/kenkyudb/maintenance.html?MID=1762