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

2014 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 – 2016-03-31
• Keywords: エクソーム / パーキンソン病 / 孤発性神経疾患 / 神経内科学 / 人類遺伝学 / 神経遺伝

Outline of Annual Research Achievements

申請者らは、主要な神経難病 パーキンソン病（PD）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 Genetics 2009）。本申請ではこの研究を格段に進展、さらなるPD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PDの全エクソン塩基配列を解読。全エクソン家系解析・全エクソン関連解析を行い、孤発性PDのRare variantリスクを発見する。本年度はさらに患者検体の解読をすすめ、患者群におおい、一塩基の変化を抽出することができた。

Current Status of Research Progress

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

Reason

計画通り進んでいるため

Strategy for Future Research Activity

家族歴のあるパーキンソン病患者の全エクソン解読を行い、塩基配列を決定。孤発性のデータと合わせて、パーキンソン病遺伝子をさらに発見する。

Causes of Carryover

検体の準備日程との関係で、実験試薬の使用量が減ったため。

Expenditure Plan for Carryover Budget

今後の検体準備に伴い、実験を遂行するので、それに使用する。

Research Products

• [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] 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 / Open Access / Acknowledgement Compliant
• [Journal Article] Novel calmodulin mutations associated with congenital arrhythmia susceptibility (2014)
  • Author(s): Makita N, Yagihara N, Crotti L, Johnson CN, Beckmann BM, Roh MS, Shigemizu D, Lichtner P, Ishikawa T, Aiba T, Homfray T, Behr ER, Klug D, Denjoy I, Mastantuono E, Theisen D, Tsunoda T,Satake W, Toda T, Nakagawa H, (16名省略), Watanabe H, Chazin WJ, George AL Jr.
  • Journal Title: Circ Cardiovasc Genet Volume: 7 Pages: 466-474
  • DOI: 10.1161/CIRCGENETICS.113.000459
  • Peer Reviewed / Open Access
• [Journal Article] A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child (2014)
  • Author(s): Saida K, Inaba Y, Hirano M, Satake W, Toda T, Suzuki Y, Sudo A, Noda S, Hidaka Y, Hirabayashi K, Imai H, Kurokawa T, Koike K.
  • Journal Title: Brain Dev Volume: 36 Pages: 721-724
  • DOI: 10.1016/j.braindev.2013.10.013
  • Peer Reviewed / Open Access
• [Presentation] 孤発性パーキンソン病のエクソーム関連解析と第2期SNP-GWAS (2014)
  • Author(s): 佐竹渉、重水大智、鈴木穣 、山本健、富山弘幸、高橋篤、村田美穂、服部信孝、田中敏博 、角田達彦 、久保充明、辻省次、松本直通 、菅野純夫、戸田 達史
  • Organizer: 日本人類伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Risk genes and genome research of sporadic Parkinson’s disease (2014)
  • Author(s): Satake W, Toda T
  • Organizer: The 20th International Congress of Personalized Medicine
  • Place of Presentation: Tokyo
  • Year and Date: 2014-11-15 – 2014-11-15
  • Invited
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Shigemizu D, Suzuki Y, Yamamoto K, Tomiyama H, Yamamoto M, Murata M, Hattori N, Tsunoda T, Kubo M, Tsuji S, Nakamura Y, Sugano S, Toda T.
  • Organizer: American Society of Human Genetics Annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Exome Association Study and 2nd SNP-GWAS of Japanese Parkinson’s disease (2014)
  • Author(s): Satake W, Hasegawa K, Murata M, Hattori N, Toda T.
  • Organizer: Genetic Epidemiology of Parkinson's disease Annual meeting
  • Place of Presentation: Vancouver
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Exome sequencing of Parkinson's disease in order to identify genetic variants with high disease-risk (2014)
  • Author(s): Satake W, Ando Y, Tomiyama H, Kashihara K, Mochizuki H, Murayama S, Takeda A, Hasegawa K, Tsuji S, Yamamoto M, Murata M, Hattori N, Toda T.
  • Organizer: The MDS 18th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Stockholm
  • Year and Date: 2014-06-08 – 2014-06-12
• [Presentation] パーキンソン病感受性遺伝子α-synuiclein SNPとnoncoding RNA (2014)
  • Author(s): 水田依久子、佐竹渉、村山繁雄、金川基、小林千浩、高藤和輝、永森収志、山本光利、服部信孝、村田美穂、金井好克、水野敏樹、中川正法、戸田達史
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24