Analysis of chromosome conformation and breakpoints of balanced translocations in human

• Project/Area Number: 24501307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: Fujita Health University
• Principal Investigator: INAGAKI Hidehito 藤田保健衛生大学, 総合医科学研究所, 講師 (70308849)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: DNA secondary structure / Translocation / Chromosome conformation / DNA高次構造 / 染色体転座 / ポジショナルエフェクト / 国際情報交換 / アメリカ

Outline of Final Research Achievements

Chromosomal translocations are mediated by illegitimate joining between distal parts of the different chromosomes. But the mechanism of proximity of these ends remains unknown which should have been repaired precisely. In this study, I used a palindromic sequence that induces frequent (1/20,000) de novo translocation in sperm from healthy men, and analyzed the interaction of these specific sequences that form DNA secondary structures in vivo. I found that the secondary structures were cleaved by two endogenous DNA repair enzymes, that the other DNA secondary structure also influences the chromosome metabolisms. Because of the difficulty of the DNA secondary structure, the chromosome conformation analysis remains a future subject.

Research Products

• [Journal Article] Breakpoint analysis of the recurrent constitutional t(8;22)(q24.13;q11.21) translocation (2014)
  • Author(s): Mishra D, Kato T, Inagaki H, Kosho T, Wakui K, Kido Y, Sakazume S, Taniguchi-Ikeda M, Morisada N, Iijima K, Fukushima Y, Emanuel BS, Kurahashi H
  • Journal Title: Mol Cytogenet Volume: 7 Issue: 1 Pages: 55-55
  • DOI: 10.1186/s13039-014-0055-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Signature of backward replication slippage at the copy number variation junction. (2014)
  • Author(s): Ohye T, Inagaki H, Ozaki M, Ikeda T, Kurahashi H
  • Journal Title: J Hum Genet Volume: in press Issue: 5 Pages: 247-250
  • DOI: 10.1038/jhg.2014.20
  • Peer Reviewed
• [Journal Article] Contribution of fetal genotype of promoter polymorphisms in ANXA5gene to the onset of pre-eclampsia (2013)
  • Author(s): Ota S,Miyamura H, Nishizawa H, Inagaki H, Inagaki A,Inuzuka H, SuzukiM, Miyazaki J, Sekiya T, Udagawa Y, Kurahashi H
  • Journal Title: Placenta Volume: 34 Issue: 12 Pages: 1202-1210
  • DOI: 10.1016/j.placenta.2013.09.010
  • Peer Reviewed
• [Journal Article] Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations (2013)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H
  • Journal Title: Nat Commun Volume: 4 Issue: 1 Pages: 1592-1592
  • DOI: 10.1038/ncomms2595
  • Peer Reviewed
• [Journal Article] Identification of an enhancer region for immune activation in the human GTP cyclohydrolase I gene. (2013)
  • Author(s): Liang Y, Inagaki H, Hao Q, Sakamoto M, Ohye T, Suzuki T, Ichinose H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 442 Issue: 1-2 Pages: 72-78
  • DOI: 10.1016/j.bbrc.2013.11.002
  • Peer Reviewed
• [Presentation] Detection of in vivo G-quadruplex structure of the ANXA5 promoter that contributes to the recurrent pregnancy loss (2014)
  • Author(s): H. Inagaki1, S. Ota1, H. Nishizawa2, H. Miyamura1,2, K. Nakahira3, M. Suzuki1, M. Tsutsumi1, T. Kato1, S. Nishiyama2, Y. Udagawa2, I. Yanagihara3, H. Kurahashi
  • Organizer: The American Society of Human Genetics
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] 生体内でのDNA高次構造形成の探索 (2014)
  • Author(s): 稲垣秀人、加藤武馬、大内雄矢、西澤春紀、倉橋浩樹
  • Organizer: ゲノム支援2014拡大班会議
  • Place of Presentation: 神戸ポートピアホテル (神戸市)
  • Year and Date: 2014-08-20 – 2014-08-21
• [Presentation] Obstetric complication-associated ANXA5 promoter polymorphisms affect gene expression via G-quadruplex structure in vivo (2014)
  • Author(s): H. Inagaki, S. Ota, H. Nishizawa, H. Miyamura, K. Nakahira, M. Suzuki, M. Tsutsumi, T. Kato, S. Nishiyama, Y. Udagawa, I. Yanagihara, H. Kurahashi
  • Organizer: FASEB Summer Reseach Conference
  • Place of Presentation: Itasca (USA)
  • Year and Date: 2014-07-20 – 2014-07-25
• [Presentation] パリンドロームを介した染色体転座の発生メカニズムの解明. (2013)
  • Author(s): 稲垣秀人、加藤武馬、倉橋浩樹.
  • Organizer: 新学術領域「ゲノム支援」２０１３年度 拡大班会議
  • Place of Presentation: 神戸市
• [Presentation] Bisulfite法を用いたプロモータ部位のグアニン四重鎖ＤＮＡ構造の解析. (2013)
  • Author(s): 稲垣秀人、太田小百合、宮村浩徳、大江瑞恵、堤真紀子、加藤武馬、西澤春紀、倉橋浩樹.
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台市
• [Presentation] ゲノム中に存在するDNA高次構造と疾患：習慣流産の例. (2013)
  • Author(s): 稲垣秀人、太田小百合、宮村浩徳、大江瑞恵、堤真紀子、加藤武馬、西澤春紀、倉橋浩樹.
  • Organizer: 第２２回 DNA複製・組換え・修復ワークショップ
  • Place of Presentation: 仙台市
• [Presentation] DNA Quadruplex structure at promoter region analyzed by bisulfite method. (2013)
  • Author(s): 稲垣秀人、太田小百合、宮村浩徳、大江瑞恵、堤真紀子、加藤武馬、西澤春紀、倉橋浩樹.
  • Organizer: 第３６回日本分子生物学会年会
  • Place of Presentation: 神戸市
• [Presentation] Mechanism of recurrent translocation t(11;22) initiated by cruciform conformation of palindromes (2012)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H
  • Organizer: FASEB Science Research Conference
  • Place of Presentation: アメリカ・サクストンズリバー
• [Presentation] Obstetric complication-associated ANXA5 promoter polymorphisms affect gene expression via DNA secondary structures (2012)
  • Author(s): Inagaki H, Ota S, Nishizawa H, Miyamura H, Nakahira K, Suzuki M, Nishiyama S, Udagawa Y, Yanagihara I, Kurahashi H
  • Organizer: American Society of Human Genetics 62nd Annual Meeting
  • Place of Presentation: アメリカ・サンフランシスコ
• [Presentation] 妊娠合併症に関連したANXA5プロモーター多型はDNA高次構造を介して発現量に影響する (2012)
  • Author(s): 稲垣秀人、太田小百合、宮村浩徳、西澤春紀、中平久美子、柳原格、宇田川康博、倉橋浩樹
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡市
• [Remarks] 藤田保健衛生大学 総合医科学研究所 分子遺伝学研究部門
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/
• [Remarks] 分子遺伝学研究部門 トピックス
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/
• [Remarks] 「染色体転座のしくみを解明」 ～がんや不妊・習慣流産の発生機序の解明に期待～
  • URL: http://www.fujita-hu.ac.jp/ICMS/
• [Remarks] 中日新聞
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/np/chunichi130313.jpg
• [Remarks] 朝日新聞
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/np/asahi130313.jpg