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

2018 Fiscal Year Final Research Report

• Project/Area Number: 15KK0302
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kanazawa 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
• Keywords: 遺伝性不整脈 / 次世代シーケンサー / ゼブラフィッシュ

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.

Free Research Field

不整脈

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。