統合ゲノム解析によるパーキンソン病の遺伝子同定と個別化医療開発

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25713015
• Research Institution: Kobe University
• Principal Investigator: 佐竹 渉 神戸大学, 医学(系)研究科(研究院), 助教 (50467594)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: パーキンソン病

Outline of Annual Research Achievements

申請者らは、主要な神経難病であるパーキンソン病のゲノムワイド関連解析を行い、本症を引き起こす4つの遺伝子リスクを同定、世界に先駆けて発表した(Satake W et al, Nature Genet 2009)。本申請ではこの研究を格段に進展、さらなるパーキンソン病遺伝子発見のため、次世代シークエンサーのゲノム解読能を本症に応用する。特にエクソンに存在する、疾患への効果サイズの大きいrare variantリスクに焦点をあて、孤発性パーキンソン病の全エクソン塩基配列を解読。全エクソン関連解析をこない、孤発性パーキンソン病のrare variantリスクを発見する。
パーキンソン病1400例の全エクソーム解読を行い、非患者群データと比較、関連検定を行うことにより、疾患効果サイズの大きい、パーキンソン病リスクの候補variantを同定できた。

Current Status of Research Progress

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

Reason

当初の予定どおり進んでいるため。

Strategy for Future Research Activity

追加実験を行い、結果をまとめて成果発表をする。

Causes of Carryover

追加実験の必要が生じたため。またそれら結果をまとめて成果発表をするため。

Expenditure Plan for Carryover Budget

遺伝学的、分子生物学的解析を行い、成果発表を行う。

Research Products

• [Journal Article] A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency. (2016)
  • Author(s): Nakagawa T, Taniguchi-Ikeda M, Murakami Y, Nakamura S, Motooka D, Emoto T, Satake W, Nishiyama M, Toyoshima D, Morisada N, Takada S, Tairaku S, Okamoto N, Morioka I, Kurahashi H, Toda T, Kinoshita T, Iijima K.
  • Journal Title: Am J Med Genet A. Volume: 170A Pages: 183-188
  • DOI: 10.1002/ajmg.a.37397.
  • Peer Reviewed
• [Journal Article] ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout. (2015)
  • Author(s): Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y, Nakayama A, Shimizu S, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, Shinomiya N.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Pages: 302-306
  • DOI: 10.1002/acn3.167
  • Peer Reviewed
• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy. (2015)
  • Author(s): Mitsui J, Matsukawa T,,(51名略), Satake W, (14名略),, Tsuji S.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Pages: 417-426
  • DOI: 10.1002/acn3.185.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. (2015)
  • Author(s): Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Li Y, Ogaki K, Ando M, Yoshino H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
  • Journal Title: Lancet Neurol Volume: 14 Pages: 274-282
  • DOI: 10.1016/S1474-4422(14)70266-2.
  • Peer Reviewed
• [Journal Article] The First Nationwide Survey and Genetic Analyses of Bardet-Biedl Syndrome in Japan. (2015)
  • Author(s): Hirano M, Satake W, Ihara K, Tsuge I, Kondo S, Saida K, Betsui H, Okubo K, Sakamoto H, Ueno S, Ikuno Y, Ishihara R, Iwahashi H, Ohishi M, Mano T, Yamashita T, Suzuki Y, Nakamura Y, Kusunoki S, Toda T.
  • Journal Title: PLoS One Volume: 10 Pages: e0136317
  • DOI: 10.1371/journal.pone.0136317.
  • Peer Reviewed / Open Access
• [Journal Article] Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes. (2015)
  • Author(s): Shigemizu D, Aiba T, Nakagawa H, Ozaki K, Miya F, Satake W, Toda T, Miyamoto Y, Fujimoto A, Suzuki Y, Kubo M, Tsunoda T, Shimizu W, Tanaka T.
  • Journal Title: PLoS One Volume: 10 Pages: e0130329
  • DOI: 10.1371/journal.pone.0130329
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy. (2015)
  • Author(s): Oda T, Xiong H, Kobayashi K, Wang S, Satake W, Jiao H, Yang Y, Cha PC, Hayashi YK, Nishino I, Suzuki Y, Sugano S, Wu X, Toda T.
  • Journal Title: Hum Genome Var Volume: 16 Pages: 15022
  • DOI: 10.1038/hgv.2015.22
  • Peer Reviewed / Int'l Joint Research
• [Presentation] パーキンソン病のゲノム解析研究 (2016)
  • Author(s): 佐竹渉
  • Organizer: ニューロサイエンスネットワーク
  • Place of Presentation: 神戸
  • Year and Date: 2016-03-18 – 2016-03-18
• [Presentation] Genomic study and subsequent in silico drug discovery for Parkinson’s disease (2016)
  • Author(s): Satake W, Uenaka T, Cha PC, Okada Y, Kashihara K, Murayama S, Hasegawa K, Mochizuki H, Takeda A, Yamamoto M, Murata M, Hattori N, Toda T
  • Organizer: 5th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress
  • Place of Presentation: Manila
  • Year and Date: 2016-03-11 – 2016-03-13
  • Int'l Joint Research
• [Presentation] Next step of GWAS and Exome study for Parkinson’s disease (2015)
  • Author(s): Satake W, Takeda A, Mochizuki H, Hasegawa K, Yamamoto M, Murata M, Hattori N, Toda T
  • Organizer: 10th Annual Meeting Genetic Epidemiology of Parkinson's disease
  • Place of Presentation: Tokyo
  • Year and Date: 2015-10-01 – 2015-10-02
  • Int'l Joint Research / Invited
• [Presentation] Genome-wide association study (GWAS) in neurodegenerative disorders (2015)
  • Author(s): Satake W
  • Organizer: International Parkinson and Movement Disorder Society Basic Summer School
  • Place of Presentation: Tokyo
  • Year and Date: 2015-08-06 – 2015-08-08
  • Int'l Joint Research / Invited
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson's disease (2015)
  • Author(s): Satake W, Ando Y, Suzuki M, Tomiyama H, Nagai Y, Kashihara K, Murayama S, Mochizuki H, Nakashima K, Hasegawa K, Takeda A, Wada K, Tsuji S, Yamamoto M, Murata M, Hattori N, and Toda T.
  • Organizer: 19th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: San Diego
  • Year and Date: 2015-06-14 – 2015-06-18
  • Int'l Joint Research
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Parkinson's disease (2015)
  • Author(s): Satake W， Ando Y， Suzuki M， Tomiyama H， Nagai Y， Murayama S， Mochizuki H， Nakashima K， Obata F， Hasegawa K， Takeda A， Wada K， Tsuji S， Yamamoto M， Murata M， Hattori N， Toda T
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20 – 2015-05-23
• [Presentation] Exome Association study and SNP-GWAS of Parkinson’s disease (2015)
  • Author(s): Satake W, Suzuki Y, Shigemizu D, Cha PC, Tsuji S, Tsunoda T, Kubo M, Sugano S, Matsumoto N, Toda T
  • Organizer: The 11th International workshop on Advanced Genomics; 国際ゲノム会議
  • Place of Presentation: Tokyo
  • Year and Date: 2015-05-20 – 2015-05-22
  • Int'l Joint Research / Invited