Investigation of relationship between inherited arrhythmias and epigenetics

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Hattori Tetsuhisa 国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (80638932)
• Co-Investigator(Kenkyū-buntansha): 大野 聖子 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (20610025)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エピジェネティクス / ロングリードシークエンサー

Outline of Final Research Achievements

Inherited arrhythmia is a disease including congenital long QT syndrome (LQTS), Brugada syndrome (BrS) and so on. In LQTS, pathogenic mutations are detected about 70% of the patients. In contrast, the detection rate of pathogenic mutations in BrS is very low. The one of the reasons is that the disease is not caused by mutations in protein coding regions. Therefore, we started the research focused on the epigenetics. We first planned to perform Chip-seq, however, we introduced a long sequencer, Oxford Nanopore system in 2019 and started to detect genomic structural variant which affect the protein expression. To detect the structural variant, we used the data from targeted gene sequencing obtained by short read sequencer. Comparing the total reads and depth between samples from controls and patients, we could suspect large deletions and duplications in several patients. Then we performed long read sequencing using Nanopore system to detect correct breakpoint.

Free Research Field

循環器病学

Academic Significance and Societal Importance of the Research Achievements

次世代シークエンサーの時代になり、多くの遺伝性疾患について、その原因となる多くの遺伝子および遺伝子変異が同定されるようになってきた。しかし、同定されない遺伝性疾患も残されている。その理由として、いわゆるタンパク翻訳領域以外の異常が隠れていることが考えられている。そこで私たちはロングリードシークエンサーを用いて、タンパク翻訳領域以外の異常について解析を進めている。