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Genetic analysis for inherited arrhythmia and functional study using zebrafish model

Research Project

Project/Area Number 26460670
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionKanazawa University

Principal Investigator

Hayashi Kenshi  金沢大学, 附属病院, 助教 (00422642)

Co-Investigator(Kenkyū-buntansha) 寳達 明彦  金沢大学, 医学系, 協力研究員 (00623662)
藤野 陽  金沢大学, 保健学系, 准教授 (40361993)
清水 渉  日本医科大学, 大学院医学研究科, 大学院教授 (50399606)
Co-Investigator(Renkei-kenkyūsha) SEKINE Akihiro  京都大学, 医学系研究科, 教授 (30425631)
AIBA Takeshi  独立行政法人国立循環器病研究センター, 循環器内科, 医長 (40574348)
Research Collaborator TSUDA Toyonobu  
TANAKA Yoshihiro  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsゼブラフィッシュ / 次世代シークエンス / モルフォリノ / Crispr/Cas9システム / 遺伝子改変ゼブラフィッシュ / 遺伝性不整脈 / 全エクソーム解析 / 次世代シークエンサー / 機能解析
Outline of Final Research Achievements

We performed genetic analysis using next generation sequencing for patients with inherited arrhythmia.We performed electrophysiological study for detected gene mutations in ion channel genes using patch clamp methods. We evaluated mutations in KCNH2 gene using zebrafish embryo. Knockdown or CRISPR-mediated deletions of the human LMNA ortholog, lmna in zebrafish recapitulated the electrophysiological phenotypes of human early-onset bradycardia.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Acknowledgement Compliant: 1 results,  Open Access: 8 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results) Book (3 results) Remarks (2 results)

  • [Int'l Joint Research] Birmingham University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Brigham and women’s hospital(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Dynamical mechanisms of phase-2 early afterdepolarizations in human ventricular myocytes: insights from bifurcation analyses of two mathematical models2017

    • Author(s)
      Kurata Y, Tsumoto K, Hayashi K, Hisatome I, Tanida M, Kuda Y, Shibamoto T
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 312 Issue: 1 Pages: H106-H127

    • DOI

      10.1152/ajpheart.00115.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The genetics of atrial fibrillation.2017

    • Author(s)
      Hayashi K, Tada H, Yamagishi M.
    • Journal Title

      Curr Opin Cardiol.

      Volume: 32 Pages: 10-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Updated Diagnostic Criteria for Long QT Syndrome on Clinical Detection of Diseased Patients: Results from Study of Patients Carrying Gene Mutations.2016

    • Author(s)
      Hayashi K, Konno T, Fujino N, Itoh H, Fujii Y, Imi-Hashida Y, Tada H, Tsuda T, Tanaka Y, Saito T, Ino H, Kawashiri M, Ohta K, Horie M, Yamagishi.M.
    • Journal Title

      JACC Clin Electrophysiol

      Volume: 2 Issue: 3 Pages: 279-287

    • DOI

      10.1016/j.jacep.2016.01.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy.2016

    • Author(s)
      Nomura A, Tada H, Teramoto R, Konno T, Hodatsu A, Won HH, Kathiresan S, Ino H, Fujino N, Yamagishi M, Hayashi K.
    • Journal Title

      J Cardiol.

      Volume: 2 Issue: 2 Pages: 133-9

    • DOI

      10.1016/j.jjcc.2015.09.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lipoprotein(a) in Familial Hypercholesterolemia With Proprotein Convertase Subtilisin/Kexin Type 9 (<i>PCSK9</i>) Gain-of-Function Mutations2016

    • Author(s)
      Tada H, Kawashiri MA, Yoshida T, Teramoto R, Nohara A, Konno T, Inazu A, Mabuchi H, Yamagishi M, Hayashi K.
    • Journal Title

      Circulation Journal

      Volume: 80 Issue: 2 Pages: 512-518

    • DOI

      10.1253/circj.CJ-15-0999

    • NAID

      130005120923

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of Electrocardiographic Voltage to Determine Myocardial Fibrosis in Hypertrophic Cardiomyopathy.2016

    • Author(s)
      Konno T, Nagata Y, Teramoto R, Fujino N, Nomura A, Tada H, Sakata K, Furusho H, Takamura M, Nakamura H, Kawashiri MA, Yamagishi M, Hayashi K.
    • Journal Title

      Am J Cardiol.

      Volume: 117 Issue: 3 Pages: 443-449

    • DOI

      10.1016/j.amjcard.2015.11.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Right ventricular hypertrophy is associated with cardiovascular events in hypertrophic cardiomyopathy: evidence from study with magnetic resonance imaging.2015

    • Author(s)
      Nagata Y, Konno T, Fujino N, Hodatsu A, Nomura A, Hayashi K, Nakamura H, Kawashiri MA, Yamagishi M.
    • Journal Title

      Can J Cardiol.

      Volume: 31 Issue: 6 Pages: 702-708

    • DOI

      10.1016/j.cjca.2014.12.036

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atrial fibrillation: an inherited cardiovascular disease-a commentary on genetics of atrial fibrillation: from families to genomes.2015

    • Author(s)
      Tada H, Kawashiri MA, Yamagishi M, Hayashi K.
    • Journal Title

      J Hum Genet.

      Volume: 61 Issue: 1 Pages: 3-4

    • DOI

      10.1038/jhg.2015.63

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy.2015

    • Author(s)
      Konno T, Hayashi K, Fujino N, Oka R, Nomura A, Nagata Y, Hodatsu A, Sakata K, Furusho H, Takamura M, Nakamura H, Kawashiri MA, Yamagishi M.
    • Journal Title

      J Cardiovasc Electrophysiol.

      Volume: 26 Issue: 10 Pages: 1081-1087

    • DOI

      10.1111/jce.12742

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation.2015

    • Author(s)
      Hayashi K, Konno T, Tada H, Tani S, Liu L, Fujino N, Nohara A, Hodatsu A, Tsuda T, Tanaka Y, Kawashiri MA, Ino H, Makita N, Yamagishi M.
    • Journal Title

      Circ Arrhythm Electrophysiol.

      Volume: 8 Issue: 5 Pages: 1095-1104

    • DOI

      10.1161/circep.114.002519

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High sensitivity of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens in hypertrophic cardiomyopathy.2014

    • Author(s)
      Konno T,Hayashi K,Fujino N,Nagata Y,Hodatsu A,Masuta E,Sakata K,Nakamura H,Kawashiri M,Yamagishi M.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 7 Pages: e101465-e101465

    • DOI

      10.1371/journal.pone.0101465

    • NAID

      120006460361

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founder MYBPC3 mutation: evidence from patients and zebrafish models.2014

    • Author(s)
      Hodatsu A, Konno T, Hayashi K, Funada A, Fujita T, Nagata Y, Fujino N, Kawashiri MA, Yamagishi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 307 Issue: 11 Pages: 1594-604

    • DOI

      10.1152/ajpheart.00637.2013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fragmented QRS Predicts Heart Failure Progression in Patients With Hypertrophic Cardiomyopathy2014

    • Author(s)
      Nomura A, Konno T, Fujita T, Tanaka Y, Nagata Y, Tsuda T, Hodatsu A, Sakata K, Nakamura H, Kawashiri MA, Fujino N, Yamagishi M, Hayashi K.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 1 Pages: 136-143

    • DOI

      10.1253/circj.CJ-14-0822

    • NAID

      130004704014

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Exome Sequencing for Patients with Early-onset Cardiac Conduction Diseases2017

    • Author(s)
      Kenshi Hayashi, Akihiro Nomura, Yoshihiro Asano, Noboru Fujino, Kenji Sakata, Tetsuo Konno, Hayato Tada, Toyonobu Tsuda, Ryota Teramoto, Yoji Nagata, Yoshihiro Tanaka, Masa-aki Kawashiri, Calum MacRae, Seiji Takashima, Masakazu Yamagishi
    • Organizer
      The 81st Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanisms of Fever-induced QT Prolongation in Patients with KCNH2 Mutations in the S5-pore Region: Evidence from Genotypic and Functional Analyses2016

    • Author(s)
      Kenshi Hayashi, Tadashi Nakajima, Yasutaka Kurata, Shoichi Tange, Noboru Fujino, Kenji Sakata, Tetsuo Konno, Toyonobu Tsuda, Yoji Nagata, Ryota Teramoto, Yoshihiro Tanaka, Takekatsu Saito, Masa-aki Kawashiri, Kunio Ohta, Yoshiaki Kaneko, Masahiko Kurabayash, Masakazu Yamagishi
    • Organizer
      AHA 2016
    • Place of Presentation
      New Orleans, LA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Updated Diagnostic Criteria for Long QT Syndrome2016

    • Author(s)
      Kenshi Hayashi, Tetsuo Konno, Noboru Fujino, Hideki Itoh, Yusuke Fujii, Yoko Imi-Hashida, Hayato Tada, Toyonobu Tsuda, Yoshihiro Tanaka, Takekatsu Saito, Hidekazu Ino, Masa-aki Kawashiri, Kunio Ohta, Minoru Horie, Masakazu Yamagishi.
    • Organizer
      APHRS 2016
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-10-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Role of Common and Rare Genetic Variants Implicated in Susceptibility to Atrial Fibrillation2016

    • Author(s)
      Kenshi Hayashi, Hayato Tada, and Masakazu Yamagishi
    • Organizer
      APHRS 2016
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-10-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hypertrophic Cardiomyopathy.2015

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Tetsuo Konno, Kenji Sakata, Takashi Fujita, Akihiko Hodatsu, Akihiro Nomura, Toyonobu Tsuda, Yoji Nagata, Yoshihiro Tanaka, Masa-aki Kawashiri, Masakazu Yamagishi.
    • Organizer
      2015 8TH APHRS SCIENTIFIC SESSIONS
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of Fever-induced QT Prolongation in Patients with KCNH2 Mutations in the S5-pore Region.2015

    • Author(s)
      Kenshi Hayashi, Tadashi Nakajima, Shoichi Tange, Noboru Fujino, Kenji Sakata, Tetsuo Konno, Toyonobu Tsuda, Yoshihiro Tanaka, Takekatsu Saito, Masa-aki Kawashiri, Kunio Ohta, Yoshiaki Kaneko, Masahiko Kurabayashi, Masakazu Yamagishi.
    • Organizer
      ESC CONGRESS 2015
    • Place of Presentation
      London, UK
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of common and rare genetic variants implicated in susceptibility to atrial fibrillation.2015

    • Author(s)
      Kenshi Hayashi, Hayato Tada, Masakazu Yamagishi.
    • Organizer
      2015 Annual Convention & Scientific Session of the Taiwan Society of Cardiology.
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Prognostic Significance of Sarcomere Gene Mutations and Myocardial Fibrosis in Hypertrophic Cardiomyopathy.2014

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Tetsuo Konno, Kenji Sakata, Takashi Fujita, Akihiko Hodatsu, Akihiro Nomura, Toyonobu Tsuda, Yoji Nagata, Yoshihiro Tanaka, Masa-aki Kawashiri, Masakazu Yamagishi.
    • Organizer
      7th Asia-Pacific Heart Rhythm Society Scientific Session
    • Place of Presentation
      New Delhi, India
    • Year and Date
      2014-10-31
    • Related Report
      2014 Research-status Report
  • [Presentation] Functional Characterization of Rare Variants Associated with Lone Atrial Fibrillation.2014

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Tetsuo Konno, Akihiko Hodatsu, Toyonobu Tsuda, Yoshihiro Tanaka, Masa-aki Kawashiri, Hidekazu Ino, and Masakazu Yamagishi.
    • Organizer
      ESC CONGRESS 2014
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2014-09-02
    • Related Report
      2014 Research-status Report
  • [Book] 循環器ジャーナル2017

    • Author(s)
      林 研至 山岸正和
    • Total Pages
      216
    • Publisher
      医学書院
    • Related Report
      2016 Annual Research Report
  • [Book] 遺伝性不整脈症候群2015

    • Author(s)
      林 研至 今野哲雄 川尻剛照 藤野陽 山岸正和
    • Total Pages
      4
    • Publisher
      南江堂
    • Related Report
      2015 Research-status Report
  • [Book] 不整脈症候群2015

    • Author(s)
      林 研至、山岸正和
    • Total Pages
      4
    • Publisher
      南江堂
    • Related Report
      2014 Research-status Report
  • [Remarks] 金沢大学循環器病態内科学ホームページ

    • URL

      http://intmed2.w3.kanazawa-u.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 金沢大学大学院医学系研究科循環医科学専攻臓器機能制御学

    • URL

      http://intmed2.w3.kanazawa-u.ac.jp/

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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