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Development of mutagenesis to the mitochondrial DNA using artificial restriction enzyme and application to definitive diagnosis.

Research Project

Project/Area Number 25670261
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionSaitama Medical University

Principal Investigator

YATSUKA YUKIKO  埼玉医科大学, 医学部, 助手 (20458524)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsミトコンドリアDNA / 遺伝子診断・治療 / 人工制限酵素 / 遺伝子工学
Outline of Final Research Achievements

We performed whole mitochondrial DNA (mtDNA) sequence analysis in patients with mitochondrial respiratory chain disorder, and identified several plausible causative mutations. Here, we tried to produce mutant cell lines harboring the variants of unknown significance (VUSs) from normal cells using artificial nucleases in the aim for establishing a new method for definitive diagnosis for VUSs.
We applied TALENs (Transcription activator-like effector nucleases) system, and engineered so that they localize to mitochondria and recognize the specific target sequence on mtDNA. Actually, the engineered mitochondria-targeted TALENs correctly recognized one-base -difference in the specific target sequence, and cut the proper site.
Although we’ve not achieved producing mutant cell lines from normal cells, our TALEN system cut the specific mtDNA site. This system can control the heteroplasmy rate inside the mitochondria, and will pave the way for establishing a new method for definitive diagnosis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results) Remarks (7 results)

  • [Journal Article] A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain deficiency.2016

    • Author(s)
      Kohda M, Mizuno Y, Hirata T, Yatsuka Y, Yamashita, Okuda A, Borna NN, Banshoya K, Ohnuma K, Suzuki T, Nagao A, Maehata H, Matsuda F, Higasa K, Nagasaki M, Yasuda J, Yamamoto M, Fushimi T, Shimura M, Kaiho-Ichimoto K, Harashima H, Yamazaki T, Mori M, Murayama K, Ohtake A, Okazaki Y.
    • Journal Title

      PLoS Genetics:

      Volume: 12(1) Issue: 1 Pages: e1005679-e1005679

    • DOI

      10.1371/journal.pgen.1005679

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Myocerebrohepatopathy spectrum disorder due to POLG mutations: A clinicopathological report.2014

    • Author(s)
      Montassir H, Maegaki Y, Murayama K, Yamazaki T, Kohda M, Ohtake A, Iwasa H, Yatsuka Y, Okazaki Y, Sugiura C, Nagata I, Toyoshima M, Saito Y, Itoh M, Nishino I, Ohno K.
    • Journal Title

      Brain & development

      Volume: S0387-7604(14) Issue: 7 Pages: 261-267

    • DOI

      10.1016/j.braindev.2014.10.013

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain complex deficiencies.2015

    • Author(s)
      Masakzu Kohda, Yoshimi Tokuzawa, Yoshihito Kishita, Hiromi Nyuzuki, Yosuke Mizuno, Tomoko Hirata, Yukiko Yatsuka, et al.
    • Organizer
      第15回日本ミトコンドリア学会年会
    • Place of Presentation
      福井県国際交流会館(福井県福井市)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 全エキソーム解析で病因を同定したミトコンドリア呼吸鎖異常症の出生前遺伝子診断2015

    • Author(s)
      山崎太郎、原嶋宏子、伏見拓矢、志村 優、八塚由紀子、木下善仁、神田将和、岡崎康司、村山 圭、大竹 明
    • Organizer
      第13回 アジア先天代謝異常症シンポジウム
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア呼吸鎖複合体異常症のゲノム解析と新規原因遺伝子の発見2015

    • Author(s)
      神田 将和、徳澤 佳美、木下 善仁、森山 陽介、水野 洋介、平田 智子、八塚 由紀子、菅原 泉、仲地 豊、加藤 英政、田丸 俊輔、入月 浩美、Nurun Nahar Borna、原嶋 宏子、山崎 太郎、森雅人、村山 圭、大竹 明、岡崎 康司
    • Organizer
      日本人類遺伝学会 第60回大会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-10-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] Large-scale comprehensive identification and analysis of causative genes in mitochondrial respiratory chain disorder2014

    • Author(s)
      Y Kishita, Y Tokuzawa, M Kohda, Y Moriyama, Y Yamashita-Sugahara, S Tamaru, H Tochigi, Y Mizuno, N Uehara, Y Nakachi, Y Yatsuka, H Nyuzuki, S Suzuki, NN Borna, T Hirata, N Matoba, H Kato, A Okuda, M Mori, M Ajima, H Harashima, T Yamazaki, K Murayama, A Ohtake, Y Okazaki
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] A comprehensive genomic analysis of 144 patients with mitochondrial respiratory chain deficiencies.2014

    • Author(s)
      Masakazu Kohda, Yoshimi Tokuzawa, Yoshihito Kishita, Yzumi Yamashita-Sugahara, Yosuke Mizuno, Yutaka Nakachi, Tomoko Hirata, Yukiko Kanesaki-Yatsuka, Hiroko Harashima, Taro Yamazaki, Masato Mori, Kei Murayama, Hidemasa Kato, Akira Ohtake, Yasushi Okazaki
    • Organizer
      日本人類遺伝学会第59回大会
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] A comprehensive genomic analysis for mitochondrial respiratory chain disorder.2014

    • Author(s)
      M. Kohda, Y. Tokuzawa, Y. Kishita, Y. Yamashita-Sugahara, Y. Mizuno, Y. Nakachi, Y. Moriyama, T. Hirata, Y. Kanesaki-Yatsuka, H. Harashima, M. Ajima, T. Yamazaki, M. Mori, K. Murayama, H. Kato, A. Ohtake, Y. Okazaki
    • Organizer
      アメリカ人類遺伝学会(ASHG2014)
    • Place of Presentation
      サンディエゴ(米カリフォルニア)
    • Year and Date
      2014-10-18 – 2014-10-22
    • Related Report
      2014 Research-status Report
  • [Remarks] MO Bank

    • URL

      http://mo-bank.com/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 文部科学省 革新的細胞解析研究プログラム(セルイノベーション)先導研究 課題A

    • URL

      http://www.cell-innovation.org/html/program/theme_010_okazaki.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 埼玉医科大学ゲノム医学研究センター

    • URL

      http://www.saitama-med.ac.jp/genome/

    • Related Report
      2014 Research-status Report
  • [Remarks] 埼玉医科大学ゲノム医学研究センター(ゲノム科学部門)

    • URL

      http://www.saitama-med.ac.jp/genome/Div05_FGSM/index.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 文部科学省 革新的細胞解析研究プログラム(セルイノベーション)先導研究 課題A

    • URL

      http://www.cell-innovation.org/html/program/theme_010_okazaki.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 埼玉医科大学ゲノム医学研究センター

    • URL

      http://www.saitama-med.ac.jp/genome/

    • Related Report
      2013 Research-status Report
  • [Remarks] 埼玉医科大学ゲノム医学研究センター(ゲノム科学部門)

    • URL

      http://www.saitama-med.ac.jp/genome/Div05_FGSM/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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