Investigation of disease-causing variants of Long QT syndrome using whole exome sequencing

• Project/Area Number: 16K19068
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: National Center for Geriatrics and Gerontology (2017); Tokyo Medical and Dental University (2016)
• Principal Investigator: SHIGEMIZU Daichi 国立研究開発法人国立長寿医療研究センター, メディカルゲノムセンター, ユニット長 (70617464)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 中間サイズインデル / 次世代シークエンサー / エクソーム解析 / QT延長症候群 / エクソーム家系解析 / long indel / 遺伝学 / ゲノム / 循環器 / 遺伝子

Outline of Final Research Achievements

I developed a new method that detects InterMediate-Size indels using a combination of soft-clipped fragments realignment and de novo assembly of unmapped reads (IMSindel). I suggest that this methodology will contribute to the discovery of intermediate-size indels associated with long QT syndrome as well as the other diseases.

Research Products

• [Journal Article] IMSindel: An accurate intermediate-size indel detection tool incorporating de novo assembly and gapped global-local alignment with split read analysis (2018)
  • Author(s): Shigemizu Daichi、Miya Fuyuki、Akiyama Shintaro、Okuda Shujiro、Boroevich Keith A、Fujimoto Akihiro、Nakagawa Hidewaki、Ozaki Kouichi、Niida Shumpei、Kanemura Yonehiro、Okamoto Nobuhiko、Saitoh Shinji、Kato Mitsuhiro、Yamasaki Mami、Matsunaga Tatsuo、Mutai Hideki、Kosaki Kenjiro、Tsunoda Tatsuhiko
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5608-5608
  • DOI: 10.1038/s41598-018-23978-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 次世代シークエンサーを用いた臨床研究の実際 (2017)
  • Author(s): 重水 大智
  • Organizer: 科研費基盤研究S ＆ 第8回生物統計ネットワークシンポジウム 統計科学が切り拓く個別化医療：方法論・実践のフロンティア
  • Place of Presentation: アクロス福岡（福岡県福岡市）
  • Year and Date: 2017-03-27
  • Invited
• [Presentation] Development and assessment of a pathogenic mutations search method for subjects where exome has previously failed. (2017)
  • Author(s): Miya, F., Shigemizu, D., Kanemura, Y., Saitoh, S., Okamoto, N., Kato, M., Yamasaki, M., Matsunaga, T., Mutai, H., and Kosaki, K.
  • Organizer: The Japan Society of Human Genetics
• [Presentation] An accurate intermediate-size indel detection tool for discovery of mutations associated with human disease. (2017)
  • Author(s): Shigemizu, D., Miya, F., Akiyama, S., Okuda, S., Boroevich, KA., Fujimoto, A., Nakagawa, H., Ozaki, K., Niida, S., Kanemura, Y., Okamoto, N., Saitoh, S., Kato, M., Yamasaki, M., Matsunaga, T., Mutai, H., Kosaki, K., and Tsunoda, T.
  • Organizer: The Japan Society of Human Genetics
• [Presentation] Exome sequencing analyses for late-onset Alzheimer's disease in Japanese (2017)
  • Author(s): Asanomi, Y., Shigemizu, D., Nagata, Y., Mitsumori, R., Mori, T., Niida, S., and Ozaki, K.
  • Organizer: The Japan Society of Human Genetics
• [Presentation] Genome wide association study for late-onset Alzheimer's Disease in a Japanese population. (2017)
  • Author(s): Mitsumori, R., Asanomi, Y., Shigemizu, D., Nagata, Y., Mori, T., Akiyama, S., Niida, S., and Ozaki, K.
  • Organizer: The Japan Society of Human Genetics
• [Presentation] Development of an accurate intermediate-size indel detection tool for discovery of mutations associated with human disease. (2017)
  • Author(s): Shigemizu, D., Miya, F., Akiyama, S., Okuda, S., Boroevich, KA., Fujimoto, A., Nakagawa, H., Ozaki, K., Niida, S., Kanemura, Y., Okamoto, N., Saitoh, S., Kato, M., Yamasaki, M., Matsunaga, T., Mutai, H., Kosaki, K., and Tsunoda, T.
  • Organizer: 第6回生命医薬情報学連合大会 (IIBMP2017)
• [Presentation] IMSindel: An accurate intermediate-size indel detection tool incorporating de novo assembly and gapped global-local alignment into spit reads. (2017)
  • Author(s): Shigemizu, D., Miya, F., Akiyama, S., Okuda, S., Boroevich, KA., Fujimoto, A., Nakagawa, H., and Tsunoda, T.
  • Organizer: The American Society of Human Genetics
  • Int'l Joint Research
• [Presentation] Identification of novel long QT syndrome-associated mutations by targeted sequencing analyses. (2017)
  • Author(s): Watanabe, R., Ohno, S., Aiba, T., Ishikawa, Nakano, Y., Aizawa, Y., Hayashi, K., Murakoshi, N., Nakajima, T., Yagihara, N., Shigemizu, D., et al
  • Organizer: European Human Genetics Conference
• [Presentation] 既存のexome解析では疾患原因変異同定が困難な検体の原因変異探索手法の開発. (2017)
  • Author(s): 宮 冬樹, 重水 大智, 齋藤 伸治, 須藤 章, 中川 英刀, 奥田 修二郎, 岡本 伸彦, 加藤 光広, 山崎 麻美, Keith A. Boroevich, 金村 米博, 小崎 健次郎, 角田達彦
  • Organizer: NGS現場の会第５回研究会
• [Presentation] 疾患原因となる遺伝子変異同定のためのエクソーム解析の現在 (2016)
  • Author(s): 重水 大智
  • Organizer: 科研費基盤研究Aシンポジウム (I)複雑な生命現象を読み解くための大規模データ解析とモデリング
  • Place of Presentation: 久留米シティプラザ（福岡県久留米市）
  • Year and Date: 2016-11-07
  • Invited
• [Presentation] Development of a long indel detection method using the realignment of the misaligned reads (2016)
  • Author(s): Shigemizu, D., Miya, F., Fujimoto, A., Boroevich, KA., Okuda, S., and Tsunoda, T
  • Organizer: The American Society of Human Genetics
  • Place of Presentation: Vancouver Convention Centre (Canada, Vancouver)
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Performance comparison of four commercial human whole-exome capture platforms (2016)
  • Author(s): Shigemizu, D., Momozawa, Y., Abe, T., Morizono, T., Boroevich, KA., Takata, S., Ashikawa, K., Kubo, M., and Tsunoda, T.
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: Kyoto International Conference Center (Kyoto, Kyoto)
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] 疾患原因遺伝子同定のためのエクソーム解析の現在 (2016)
  • Author(s): 重水 大智
  • Organizer: 第２回バイオインフォマティクスアゴラ
  • Place of Presentation: 東京工業大学（東京都目黒区大岡山）
  • Invited
• [Book] 細胞 (2017)
  • Author(s): 重水 大智
  • Total Pages: 4
  • Publisher: ニューサイエンス社
• [Book] アンチ・エイジング医学 (2017)
  • Author(s): 重水 大智
  • Total Pages: 5
  • Publisher: メディカルレビュー社
• [Book] BIO Clinica (2017)
  • Author(s): 重水 大智
  • Total Pages: 4
  • Publisher: 北隆館