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Gene analysis for novel causative mutations in an inherited arrhythmia and functional study for these mutations using zebrafish(Fostering Joint International Research)

Research Project

Project/Area Number 15KK0302
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

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

Principal Investigator

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

Research Collaborator MacRae Calum  ブリガム・アンド・ウィメンズ病院, 循環器内科, 科長兼准教授
Mueller Ferenc  
Sik Attila  
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Keywords遺伝性不整脈 / 次世代シーケンサー / ゼブラフィッシュ / 網羅的遺伝子解析 / 全エクソーム解析 / 細胞電気生理 / 次世代シークエンサー / 循環器・高血圧 / 遺伝子 / 不整脈
Outline of Final Research Achievements

We performed candidate gene analysis or whole exome sequence for inherited arrhythmia including long QT syndrome and Brugada syndrome using a next generation sequencer. We identified many variants of uncertain significance (VUS) as well as many causative mutations. We performed functional studies for these VUS using zebrafish embryo and could show functional abnormality of them.

Academic Significance and Societal Importance of the Research Achievements

次世代シーケンサ-による網羅的遺伝子解析により、従来の方法で見逃されていた数多くの遺伝子変異を見出すことができた。これまで機能解析が困難だった遺伝子に対し、CRISPR/Cas9システムと呼ばれる新しい手法でゼブラフィッシュの遺伝子改変を行い、ゼブラフィッシュ胚の心臓の光学マッピング、活動電位測定、体表面心電図測定といった画期的な方法で数日間以内に遺伝子変異の病的意義を明らかにすることができた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (28 results)

All 2019 2018 2017 2016

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results,  Open Access: 11 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 7 results) Book (1 results)

  • [Int'l Joint Research] ブリガム・アンド・ウィメンズ病院(米国)2016

    • Year and Date
      2016-09-10
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation.2019

    • Author(s)
      Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
    • Journal Title

      Circulation

      Volume: In press Issue: 18 Pages: 2157-2169

    • DOI

      10.1161/circulationaha.118.036761

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients2019

    • Author(s)
      Shimizu Wataru、Makimoto Hisaki、Yamagata Kenichiro、Kamakura Tsukasa、Wada Mitsuru、Miyamoto Koji、Inoue-Yamada Yuko、Okamura Hideo、Ishibashi Kohei、Noda Takashi、Nagase Satoshi、Miyazaki Aya、Sakaguchi Heima、Shiraishi Isao、Makiyama Takeru、Ohno Seiko、Itoh Hideki、et al
    • Journal Title

      JAMA Cardiology

      Volume: in press Issue: 3 Pages: 246-254

    • DOI

      10.1001/jamacardio.2018.4925

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy2019

    • Author(s)
      Hodatsu A, Fujino N, Uyama Y, Tsukamoto O, Imai-Okazaki A, Yamazaki S, Seguchi O, Konno T, Hayashi K, Kawashiri MA, Asano Y, Kitakaze M, Takashima S, Yamagishi M
    • Journal Title

      ESC Heart Fail

      Volume: 6 Issue: 2 Pages: 06-415

    • DOI

      10.1002/ehf2.12410

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous Isolated Superior Mesenteric Artery Dissection Requiring Emergent Surgery2018

    • Author(s)
      Tanaka Y, Tada H, Takeda Y, Iino K, Hayashi K, Takemura H, Yamagishi M, Kawashiri MA.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 18 Pages: 2681-2684

    • DOI

      10.2169/internalmedicine.0641-17

    • NAID

      130007484205

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-09-15
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Author Correction: Heart Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy2018

    • Author(s)
      Nagata Yoji、Yamagishi Masakazu、Konno Tetsuo、Nakanishi Chiaki、Asano Yoshihiro、Ito Shin、Nakajima Yuri、Seguchi Osamu、Fujino Noboru、Kawashiri Masa-aki、Takashima Seiji、Kitakaze Masafumi、Hayashi Kenshi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 7768-7768

    • DOI

      10.1038/s41598-018-26012-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of induced pluripotent stem cells from clinically divergent female monozygotic twins with Danon disease.2018

    • Author(s)
      Yoshida S, Nakanishi C, Okada H, Mori M, Yokawa J, Yoshimuta T, Ohta K, Konno T, Fujino N, Kawashiri MA, Yachie A, Yamagishi M, Hayashi K.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 114 Pages: 234-242

    • DOI

      10.1016/j.yjmcc.2017.11.019

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of B-Type Natriuretic Peptide Level on Risk Stratification of Thromboembolism and Death in Patients With Nonvalvular Atrial Fibrillation ― The Hokuriku-Plus AF Registry ―2018

    • Author(s)
      Hayashi Kenshi、Tsuda Toyonobu、Nomura Akihiro、Fujino Noboru、Nohara Atsushi、Sakata Kenji、Konno Tetsuo、Nakanishi Chiaki、Tada Hayato、Nagata Yoji、Teramoto Ryota、Tanaka Yoshihiro、Kawashiri Masa-aki、Yamagishi Masakazu、on behalf of the Hokuriku-Plus AF Registry Investigators
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 5 Pages: 1271-1278

    • DOI

      10.1253/circj.CJ-17-1085

    • NAID

      130006725972

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.2017

    • Author(s)
      Shimojima M, Yuasa S, Motoda C, Yozu G, Nagai T, Ito S, Lachmann M, Kashimura S, Takei M, Kusumoto D, Kunitomi A, Hayashiji N, Seki T, Tohyama S, Hashimoto H, Kodaira M, Egashira T, Hayashi K, Nakanishi C, Sakata K, Yamagishi M, Fukuda K.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 44312-44312

    • DOI

      10.1038/srep44312

    • NAID

      120006325351

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genotype-phenotype correlation of SCN5A mutation for clinical and electrocardiographic characteristics of probands with Brugada syndrome: Japanese Multicenter Registry.2017

    • Author(s)
      Yamagata K, Horie M, et al.
    • Journal Title

      Circulation

      Volume: 印刷中 Issue: 23 Pages: 0-0

    • DOI

      10.1161/circulationaha.117.027983

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ventricular Fibrillation Associated With Dynamic Changes in J-Point Elevation in a Patient With Silent Thyroiditis.2017

    • Author(s)
      Karashima S, Tsuda T, Wakabayashi Y, Kometani M, Demura M, Ichise T, Kawashiri MA, Takeda Y, Hayashi K, Yoneda T.
    • Journal Title

      J Endocr Soc.

      Volume: 2 Issue: 2 Pages: 135-139

    • DOI

      10.1210/js.2017-00276

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy.2017

    • Author(s)
      Nagata Y, Yamagishi M, Konno T, Nakanishi C, Asano Y, Ito S, Nakajima Y, Seguchi O, Fujino N, Kawashiri MA, Takashima S, Kitakaze M, Hayashi K.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 17417-17417

    • DOI

      10.1038/s41598-017-17572-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Journal Article] The genetics underlying acquired long QT syndrome: impact for genetic screening.2016

    • Author(s)
      Itoh H, Crotti L, Aiba T, Spazzolini C, Denjoy I, Fressart V, Hayashi K, Nakajima T, Ohno S, Makiyama T, Wu J, Hasegawa K, Mastantuono E, Dagradi F, Pedrazzini M, Yamagishi M, Berthet M, Murakami Y, Shimizu W, Guicheney P, Schwartz PJ, Horie M.
    • Journal Title

      European Heart Journal

      Volume: 37 (18) Issue: 18 Pages: 1456-1464

    • DOI

      10.1093/eurheartj/ehv695

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed
  • [Presentation] Cardiac Events during Competitive Sports and Daily Activities in Children and Adolescents with Long QT Syndrome2019

    • Author(s)
      Kenshi Hayashi, Kunio Ohta, Takekatsu Saito, Noboru Fujino, Yasuhiro Todo, Kenji Sakata, Hayato Tada, Akihiro Nomura, Toyonobu Tsuda, Yoshihiro Tanaka, Masakazu Yamagishi, Masa-aki Kawashiri
    • Organizer
      JCS2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] EXOME SEQUENCING AND FUNCTIONAL ANALYSIS FOR PATIENTS WITH EARLY ONSET CARDIAC CONDUCTION-SYSTEM DISEASES2018

    • Author(s)
      Kenshi Hayashi, Akihiro Nomura, Yoshihiro Asano, Manu Beerens, Yasutaka Kurata, Noboru Fujino, Hayato Tada, Calum A MacRae, Seiji Takashima, Masakazu Yamagishi
    • Organizer
      INTERNATIONAL ACADEMY OF CARDIOLOGY ANNUAL SCIENTIFIC SESSIONS 2018 23rd WORLD CONGRESS ON HEART DISEASE
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] J Wave for Predicting Cardiac Events in Hypertrophic Cardiomyopathy2018

    • Author(s)
      Kenshi Hayashi, Toyonobu Tsuda, Akihiro Nomura, Noboru Fujino, Masakazu Yamagishi
    • Organizer
      11th Asia Pacific Heart Rhythm Society Scientific Session
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Predictors for Exacerbating Kidney Function in Patients with Nonvalvular Atrial Fibrillation: The Hokuriku-plus AF Registry2018

    • Author(s)
      Kenshi Hayashi, Toyonobu Tsuda, Akihiro Nomura, Noboru Fujino, Atsushi Nohara, Kenji Sakata, Chiaki Nakanishi, Hayato Tada, Yoshihiro Tanaka, Masa-aki Kawashiri, and Masakazu Yamagishi
    • Organizer
      AHA Scientific sessions 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [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
      Kanazawa
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Exome Sequencing for Patients with Early-onset Cardiac Conduction Diseases2017

    • Author(s)
      Kenshi Hayashi
    • Organizer
      The 81st Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2017 Research-status Report
  • [Presentation] CRISPR-mediated insertions or deletions of the human LMNA homolog in zebrafish as a model of early-onset cardiac conduction disease2017

    • Author(s)
      Kenshi Hayashi
    • Organizer
      The 64th Annual Meeting of the Japanese Heart Rhythm Society
    • Related Report
      2017 Research-status Report
  • [Presentation] CRISPR-mediated insertions or deletions of the human LMNA homolog in zebrafish as a model of early-onset cardiac conduction disease2017

    • Author(s)
      Kenshi Hayashi
    • Organizer
      AHA 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [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
      AHA2016
    • Place of Presentation
      New Orleans, LA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status 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 Research-status 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 Research-status Report
    • Int'l Joint Research
  • [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 Research-status Report

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Published: 2016-10-04   Modified: 2020-03-30  

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