パーキンソン病および認知機能関連分子とパーソナルゲノム解析

2014 Fiscal Year Annual Research Report

• Project Area: Personal genome-based initiatives toward understanding bran diseases
• Project/Area Number: 22129006
• Research Institution: Kobe University
• Principal Investigator: 戸田 達史 神戸大学, 医学研究科, 教授 (30262025)
• Co-Investigator(Kenkyū-buntansha): 小林 千浩 神戸大学, 医学研究科, 准教授 (90324780)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: パーソナルゲノム / パーキンソン病 / 認知機能 / 多型 / 次世代シークエンサー

Outline of Annual Research Achievements

孤発性パーキンソン病遺伝子を同定するため、エクソンに存在すると推定される、Rareながら強いPDゲノム因子を発見するため、次世代シークエンサーによる全エクソン配列解読し、患者・対照関連解析をおこなった（エクソーム関連解析）。主成分分析において患者対照間の集団構造化をみとめなかった。まず先述の4つの孤発性PD遺伝子のエクソン配列を関連解析（PD 625例とcontrol 961例）したところ、LRRK2領域に、中等度の強さのリスクとなる2つのアミノ酸置換を伴うSNVを検出した（P=~10-4）。LRRK2以外の3つの遺伝子座には、アミノ酸置換を伴う強いPDリスクを検出しなかった。全遺伝子全エクソン配列の関連解析による孤発性PDのゲノム因子発見へつなげる。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

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, ShimizuS, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, ShinomiyaN.
  • Journal Title: Ann Clin Transl Neurol Volume: 2 Pages: 302–306
  • DOI: 10.1002/acn3.167.
  • Peer Reviewed / Open Access
• [Journal Article] Fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression. (2015)
  • Author(s): Ohtsuka Y, Kanagawa M, Yu CC, Ito C, Chiyo T, Kobayashi K, Okada T, Takeda S’I, Toda T.
  • Journal Title: Sci Rep Volume: 5 Pages: 8316
  • DOI: 10.1038/srep08316.
  • Peer Reviewed / Open Access
• [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, Yuanzhe L, Ogaki K, Ando M, Yoshinon 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] TRPV2 is critical for the maintenance of cardiac structure and function in mice. (2014)
  • Author(s): Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K, Kanagawa M, Sudo A, Toda T, Katanosaka K, Mohri S, Naruse K.
  • Journal Title: Nat Comm Volume: 5 Pages: 3932
  • DOI: 10.1038/ncomms4932.
  • Peer Reviewed / Open Access
• [Journal Article] Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy. (2014)
  • Author(s): Suzuki A, Nagasaka H, Ochi Y, Kobayashi K, Nakamura H, Nakatani D, S Yamaguchi, Yamaki S, Wada A, Shirata Y, Hui SP, Toda T, Kuroda H, Chiba H, Hirano K.
  • Journal Title: Mol Genet Metab Rep Volume: 1 Pages: 249-253
  • DOI: 10.1016/j.ymgmr.2014.05.001.
  • Peer Reviewed / Open Access
• [Journal Article] Disease-associated marked hyperalphalipoproteinemia. (2014)
  • Author(s): Hirano K, Nagasaka H, Kobayashi K, Yamaguchi S, Suzuki A, Toda T, Doyu M.
  • Journal Title: Mol Genet Metab Rep Volume: 1 Pages: 264-268
  • DOI: 10.1016/j.ymgmr.2014.06.001.
  • Peer Reviewed / Open Access
• [Journal Article] The role of Pak-interacting exchange factor-β phosphorylation at serines 340 and 583 by PKCγ in dopamine release. (2014)
  • Author(s): Shirafuji T, Ueyama T, Yoshino K, Takahashi H, Adachi N, Ago Y, Koda K, Nashida T, Hiramatsu N, Matsuda T, Toda T, Sakai N, Saito N.
  • Journal Title: J Neurosci Volume: 34 Pages: 9268-9280
  • DOI: 10.1523/JNEUROSCI.4278-13.2014.
  • Peer Reviewed / Open Access
• [Journal Article] Association of the ASCO classification with the executive function subscores of the Montreal Cognitive Assessment in patients with post-ischemic stroke. (2014)
  • Author(s): Washida K, IharaM, Tachibana H, Sekiguchi K, Kowa H, Kanda F, Toda T.
  • Journal Title: J Stroke Cerebrovasc Dis Volume: 23 Pages: 2250-2255
  • DOI: 10.1016/j.jstrokecerebrovasdis.2014.04.009.
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of LARGE suppresses muscle regeneration via down-regulation of insulin-like growth factor 1 and aggravates muscular dystrophy in mice. (2014)
  • Author(s): Saito F, Kanagawa M, Ikeda M, Hagiwara H, Masaki T, Ohkuma H, Katanosaka Y, Shimizu T, Sonoo M, Toda T, Matsumura K.
  • Journal Title: Hum Mol Genet Volume: 23 Pages: 4543-4558
  • DOI: 10.1093/hmg/ddu168.
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of dysferlin deficiency to skeletal muscle pathology in asymptomatic and severe dystroglycanopathy models: generation of a new model for fukuyama congenital muscular dystrophy. (2014)
  • Author(s): Kanagawa M, Lu Z, Ito C, Matsuda C, Miyake K, Toda T.
  • Journal Title: Plos ONE Volume: 9 Pages: e106721
  • DOI: 10.1371/journal.pone.0106721. eCollection 2014.
  • Peer Reviewed / Open Access
• [Journal Article] Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. (2014)
  • Author(s): Nagata E, Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki H, Mizuno S, Watanabe S, Yoshiura KI, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura G, Toda T, et al.
  • Journal Title: Orphanet J Rare Dis Volume: 9 Pages: 125
  • DOI: 10.1186/s13023-014-0125-5.
  • Peer Reviewed / Open Access
• [Journal Article] ゴーシェ病の多様性 (2014)
  • Author(s): 戸田達史
  • Journal Title: Medical Science Digest Volume: 40 Pages: 562-563
• [Presentation] EXOME SEQUENCING AND 2ND SNP-GWAS OF PD. (2015)
  • Author(s): Toda T, Satake W, Hattori N, Murata M.
  • Organizer: The 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders.
  • Place of Presentation: Nice, France
  • Year and Date: 2015-03-18 – 2015-03-22
• [Presentation] Exome sequencing and 2nd SNP-GWAS of Japanese Parkinson’s disease. (2014)
  • Author(s): Toda T, Satake W, Yamamoto M, Murata M, Hattori N, Sugano S.
  • Organizer: 4th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress.
  • Place of Presentation: Pattaya, Thailand
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] 神経・筋疾患の分子メカニズム、遺伝子治療、分子標的治療 / Molecular pathogenesis, genetic counseling, and molecular targeting therapy for neurological and muscular diseases. (2014)
  • Author(s): 戸田達史
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-19 – 2014-11-22
  • 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 2014.
  • Place of Presentation: San Diego U.S.A.
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] 神経難病の治療と研究の現状と展望 (2014)
  • Author(s): 戸田 達史
  • Organizer: 第38回日本遺伝カウンセリング学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-26 – 2014-06-29
  • Invited
• [Presentation] パーキンソン病のリスク遺伝子 (2014)
  • Author(s): 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
  • Invited
• [Remarks] 神戸大学大学院 医学研究科 生理学・細胞生物学講座 分子脳科学分野
  • URL: http://www.med.kobe-u.ac.jp/clgene/