複製ストール依存性・非依存性染色体構造異常の発生機序

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24390085
• Research Institution: Fujita Health University
• Principal Investigator: 倉橋 浩樹 藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 染色体 / 染色体構造異常 / 染色体転座 / パリンドローム配列 / 切断点 / 脆弱部位 / 染色体欠失 / ゲノム不安定性

Outline of Annual Research Achievements

染色体の構造異常の発生メカニズムは、まだよくわかっていない。近年、DNA複製の停止、近傍の別の複製フォークへマイクロホモロジーを介した侵入、引き続いておこる複製の再開、という一連の修復過程が構造異常の発生に関与するという仮説が提唱され、FoSTeSとよばれている。本研究では、ヒトで発生頻度の高い生殖細胞系列の転座t(11;22)をモデルとして、ヒト染色体転座がFoSTeSによって発生しているのかどうかを検証するとともに、そうであればFoSTeSのメカニズムの本態を詳細に解明し、そうでなければFoSTeS以外のどのようなメカニズムで発生しているのかを３年間で検討しようとするものである。本年度は、パリンドローム関連のt(3;8)染色体転座に関して、解析した。家族性の腎癌の家系で生殖細胞系列のt(3;8)転座を同定した。この8番染色体側の切断点は、繰り返す生殖細胞系列のt(8;22)転座の切断点と一致し、ATに富むパリンドローム配列PATRR8の中心部であった。一方、３番染色体側の切断点は染色体脆弱部位FRA3B内にあり、転座により癌抑制遺伝子FHITが分断されていた。FRA3Bは体細胞分裂で不安定性を示し、種々の構造異常の発生源となるが、FRA3Bで生じる染色体欠失の外側に位置し、PATRR8は生殖細胞系列での不安定性には関与するが、体細胞分裂での不安定性は別のメカニズムであることが明らかとなった。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Causes of Carryover

26年度が最終年度であるため、記入しない。

Expenditure Plan for Carryover Budget

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Age-related decrease of meiotic cohesins in human oocyte (2014)
  • Author(s): Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T, Kurahashi H
  • Journal Title: PLoS One Volume: 9, Pages: e96710
  • DOI: 10.1371/journal.pone.0096710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dual roles for the telomeric repeats in chromosomally integrated human herpesvirus-6 (2014)
  • Author(s): Ohye T, Inagaki H, Ihira M, Higashimoto Y, Kato K, Oikawa J, Yagasaki H, Niizuma T, Takahashi Y, Kojima S, Yoshikawa T, Kurahashi H
  • Journal Title: Sci Rep Volume: 4 Pages: 4559
  • DOI: 10.1038/srep04559
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Pages: 55
  • DOI: 10.1186/s13039-014-0055-x
  • Peer Reviewed / 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: 59 Pages: 247-250
  • DOI: 10.1038/jhg.2014.20
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Analysis of the t(3;8) of hereditary renal cell carcinoma: A palindrome mediated translocation (2014)
  • Author(s): Kato T, Franconi CP, Sheridan MB, Hacker AM, Inagakai H, Glover TW, Arlt MF, Drabkin HA, Gemmill RM, Kurahashi H, Emanuel BS
  • Journal Title: Cancer Genet Volume: 207 Pages: 133-140
  • DOI: 10.1016/j.cancergen.2014.03.004
  • Peer Reviewed
• [Journal Article] Prevalence of Emanuel syndrome: theoretical frequency and surveillance result (2014)
  • Author(s): Ohye T, Inagaki H, Kato T, Tsutsumi M, Kurahashi H
  • Journal Title: Pediatr Int Volume: 56 Pages: 462-466
  • DOI: 10.1111/ped.12437
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency (2014)
  • Author(s): Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, Kurahashi H, Yoshikawa T, Katano H, Inoue N, Imai K, Takagi M, Morio T, Mizutani S
  • Journal Title: Clin Infect Dis Volume: 59 Pages: 545-548
  • DOI: 10.1093/cid/ciu323
  • Peer Reviewed
• [Journal Article] An immunocompetent child with chromosomally integrated human herpesvirus 6B accidentally identified during the care of Mycoplasma pneumoniae infection (2014)
  • Author(s): Oikawa J, Tanaka J, Yoshikawa T, Morita Y, Hishiki H, Ishiwada N, Ohye T, Kurahashi H, Kohno Y
  • Journal Title: J Infect Chemother Volume: 20 Pages: 65-67
  • DOI: 10.1016/j.jiac.2013.07.004
  • Peer Reviewed
• [Journal Article] Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8) deficient patient (2014)
  • Author(s): Tsuge I, Ito K, Ohye T, Kando N, Kondo Y, Nakajima Y, Inuo C, Kurahashi H, Urisu
  • Journal Title: Pediatr Pulmonol Volume: 49 Pages: E52-E55
  • DOI: 10.1002/ppul.22814
  • Peer Reviewed
• [Journal Article] Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case (2014)
  • Author(s): Hibi Y, Ohye T, Ogawa K, Shimizu Y, Shibata M, Kagawa C, Mizuno Y, Uchino S, Kosugi S, Kurahashi H, Iwase K
  • Journal Title: Surg Today Volume: 44 Pages: 2195-2200
  • DOI: 10.1007/s00595-013-0826-8
  • Peer Reviewed
• [Journal Article] A MEN2A family with two asymptomatic carriers affected by unilateral renal agenesis (2014)
  • Author(s): Hibi Y, Ohye T, Ogawa K, Shimizu Y, Shibata M, Kagawa C, Mizuno Y, Kurahashi H, Iwase K
  • Journal Title: Endocr J Volume: 61 Pages: 19-23
  • Peer Reviewed
• [Journal Article] Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death (2014)
  • Author(s): Kawai A, Kusaka M, Kitagawa F, Ishii J, Fukami N, Maruyama T, Sasaki H, Shiroki R, Kurahashi H, Hoshinaga K
  • Journal Title: Clin Transplant Volume: 28 Pages: 749-754
  • DOI: 10.1111/ctr.12375
  • Peer Reviewed
• [Presentation] Detection of in vivo G-quadruplex structure of the ANXA5 promoter that contributes to the recurrent pregnancy loss (2014)
  • Author(s): Inagaki H, Ota S, Miyamura H, Tsutsumi M, Kato T, Nishizawa H, Yanagihara I, Kurahashi H. Detection of in vivo G-quadruplex structure of the ANXA5 promoter that contributes to the recurrent pregnancy loss
  • Organizer: ASHG 2014
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Two cases of lissencephaly with marked hydrocephalus caused by TUBA1A mutation (2014)
  • Author(s): Ishihara N, Yokoi S, Yamamoto H, Natsume J, Tsutsumi M, Ohye T, Kato M, Saito S, Kurahashi H
  • Organizer: ASHG 2014
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] EFNB1 mutation found in patients with craniofrontonasal syndrome in a Japanese family (2014)
  • Author(s): Kato H, Okumoto T, Yoshimura Y, Taguchi Y, Sugimoto M, Inagaki H, Kurahashi H
  • Organizer: The 10th Asian Pacific Craniofacial Association Conference
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2014-10-03 – 2014-10-05
• [Presentation] Cytogenetic analysis of monopronucleated (1PN) zygotes after intracytoplasmic sperm injection and conventional in-vitro fertilization (2014)
  • Author(s): Nishiyama S, Kato T, Kani C, Miyazaki J, Nishizawa H, Ochi M, Fujii T, Kurahashi H
  • Organizer: International Society for Mild Approaches in Assisted Reproduction
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Obstetric complication-associated ANXA5 promoter polymorphisms affect gene expression via G-quadruplex structure in vivo (2014)
  • Author(s): Inagaki H, Ota S, Nishizawa H, Miyamura H, Nakahira K, Suzuki M, Tsutsumi M, Kato T, Nishiyama S, Udagawa Y, Yanagihara I, Kurahashi H
  • Organizer: FASEB SRC, Dynamic DNA Structures in Biology
  • Place of Presentation: Itasca, Illinois
  • Year and Date: 2014-07-20 – 2014-07-25
• [Presentation] Age-related decrease of meiotic cohesins in human oocyte (2014)
  • Author(s): Kurahashi H, Tsutsumi M, Fujiwara R, Nishizawa H, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T
  • Organizer: Eshre 2014
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-06-29 – 2014-07-02
• [Book] Clinical Genomics: Practical Applications in Adult Patient Care (2014)
  • Author(s): Nisizawa H, Kurahashi H
  • Total Pages: 928
  • Publisher: McGraw-Hill Professional
• [Remarks] 藤田保健衛生大学・総合医科学研究所
  • URL: http://www.fujita-hu.ac.jp/ICMS/
• [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] 藤田保健衛生大学・疾患遺伝子網羅的解析センター
  • URL: http://www.fujita-hu.ac.jp/~gtac/
• [Remarks] t(11;22)
  • URL: http://www.fujita-hu.ac.jp/~genome/11&22/