DNA replication-dependent/independent mechanism of gross chromosomal rearrangement

• Project/Area Number: 24390085
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Fujita Health University
• Principal Investigator: KURAHASHI Hiroki 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: FoSTeS / 染色体構造異常 / DNA複製 / 切断点 / 複製のストール / マイクロホモロジー / パリンドローム / 十字架型DNA / 染色体 / 染色体転座 / パリンドローム配列 / 脆弱部位 / 染色体欠失 / ゲノム不安定性 / 回文配列 / 非B型DNA / 染色体再構成

Outline of Final Research Achievements

We examined the mechanism of palindrome-mediated t(11;22) translocation using plasmid-based assay. Even in the plasmid lacking the replication origin showed translocation when transfected into the human cell line, suggesting that the t(11;22) translocation mechanism is independent of the DNA replication-based mechanism such as FoSTeS. On the other hand, we also examined breakpoints of three non-palindrome gross chromosomal rearrangement. One interstitial deletion and one duplication showed microhomology at the junction, suggesting the rearrangement took place via FoSTeS. In the third deletion case, we identified 11-13 nucleotide sequence at the upstream breakpoint that was repeated four times at the deletion junction. The backward replication slippage or serial replication slippage is the predicted mechanism. These data suggests that the aberrant DNA replication is involved in the generation of a major subset of deletion/duplication.

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, Issue: 5 Pages: 1-8
  • 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 Issue: 1 Pages: 4559-4559
  • DOI: 10.1038/srep04559
  • Peer Reviewed / Open Access
• [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] 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 Issue: 4 Pages: 133-140
  • DOI: 10.1016/j.cancergen.2014.03.004
  • Peer Reviewed / Open Access
• [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 Issue: 4 Pages: 462-466
  • DOI: 10.1111/ped.12437
  • Peer Reviewed / Open Access / 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 Issue: 4 Pages: 545-548
  • DOI: 10.1093/cid/ciu323
  • Peer Reviewed / Open Access
• [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 Issue: 1 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 A
  • Journal Title: Pediatr Pulmonol Volume: 49 Issue: 3
  • 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 Issue: 11 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
  • NAID: 130004443932
  • 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 Issue: 6 Pages: 749-754
  • DOI: 10.1111/ctr.12375
  • Peer Reviewed / Open Access
• [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: in press
  • 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
  • NAID: 130004443932
  • Peer Reviewed
• [Journal Article] Age-related decrease of meiotic cohesins in human oocytes. (2014)
  • Author(s): Tsutsumi M, Fujiwara R, Nishizawa H, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T, Kurahashi H
  • Journal Title: PLoS One Volume: in press
  • 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] MTA3 regulates CGB5 and Snail genes in trophoblast (2013)
  • Author(s): Chen Y, Miyazaki J, Nishizawa H, Kurahashi H, Leach R, Wang K
  • Journal Title: Biochem Biophys Res Commun Volume: (In press) Issue: 4 Pages: 379-384
  • DOI: 10.1016/j.bbrc.2013.02.102
  • Peer Reviewed
• [Journal Article] Decreased expression of apelin in placentas from severe pre-eclampsia patients (2013)
  • Author(s): Inuzuka H, Nishizawa H, Inagaki A, SuzukiM,Ota S,Miyamura H, Miyazaki J, Sekiya T, Kurahashi H, Udagawa Y
  • Journal Title: Hypertens Pregnancy Volume: 32 Issue: 4 Pages: 410-421
  • DOI: 10.3109/10641955.2013.813535
  • Peer Reviewed
• [Journal Article] Definition and refinement of the 7q36.3 duplication region associated with schizophrenia (2013)
  • Author(s): Aleksic B, Kushima I, Ohye T, Ikeda M, Kunimoto S, Nakamura Y, Yoshimi A, Koide T, Iritani S, Kurahashi H, Iwata N, Ozaki N
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 2587-2587
  • DOI: 10.1038/srep02587
  • 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] Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8) deficient patient (2013)
  • Author(s): Tsuge l, Ito K, Ohye T, Kando N, Kondo Y, Nakajima Y, Inuo C, Kurahashi H, Urisu A
  • Journal Title: Pediatric Pulmonology Volume: (In press) (In press)
  • Peer Reviewed
• [Journal Article] HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes (2012)
  • Author(s): Kogo, H., Tsutsumi, M., Ohye, T., Inagaki, H., Abe, T., Kurahashi, H.
  • Journal Title: Genes Cells Volume: 17 Issue: 6 Pages: 439-454
  • DOI: 10.1111/j.1365-2443.2012.01600.x
  • Peer Reviewed
• [Journal Article] HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity (2012)
  • Author(s): Kogo H, Tsutsumi M, Ohye T, Inagaki H, Kiyonari H, Kurahashi H
  • Journal Title: Genes Cells Volume: 17 Issue: 11 Pages: 897-912
  • DOI: 10.1111/gtc.12005
  • Peer Reviewed
• [Journal Article] Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes. (2012)
  • Author(s): Tsutsumi M, Kowa-Sugiyama H, Bolor H, Kogo H, Inagaki H, Ohye T, Yamada K, Taniguchi-Ikeda M, Toda T, Kurahashi H.
  • Journal Title: J Hum Genet Volume: 57 Issue: 8 Pages: 515-522
  • DOI: 10.1038/jhg.2012.61
  • NAID: 10031056588
  • Peer Reviewed
• [Journal Article] Mechanism of complex gross chromosomal rearrangements : A commentary on Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation (2012)
  • Author(s): Kurahashi H, Ohye T, Inagaki H, Kogo H, Tsutsumi M
  • Journal Title: J Hum Genet Volume: 57 Issue: 2 Pages: 81-83
  • DOI: 10.1038/jhg.2011.143
  • NAID: 10030711395
  • Peer Reviewed
• [Journal Article] Molecular basis of maternal age-related increase in oocyte aneuploidy (2012)
  • Author(s): Kurahashi H, Tsutsumi M, Nishiyama S, Kogo H, Inagaki H, Ohye T
  • Journal Title: Congenit Anom (Kyoto) Volume: 52 Issue: 1 Pages: 8-15
  • DOI: 10.1111/j.1741-4520.2011.00350.x
  • Peer Reviewed
• [Journal Article] Failure of homologous synapsis and sex-specific reproduction problems (2012)
  • Author(s): Kurahashi H, Kogo H, Tsutsumi M, Inagaki H, Ohye T
  • Journal Title: Front Genet Volume: 3 Pages: 112-112
  • DOI: 10.3389/fgene.2012.00112
  • Peer Reviewed
• [Journal Article] Chromosomal translocations and palindromic AT-rich repeats (2012)
  • Author(s): Kato T, Kurahashi H, Emanuel BS
  • Journal Title: Curr Opin Genet Dev Volume: 22 Issue: 3 Pages: 221-228
  • DOI: 10.1016/j.gde.2012.02.004
  • Peer Reviewed
• [Journal Article] Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia (2012)
  • Author(s): Inagaki A, Nishizavva H, Ota S, Suzuki M, Inuzuka H, Miyamura H, Sekiya T, Kurahashi H, Udagawa Y
  • Journal Title: Placenta Volume: 33 Pages: 919-926
  • Peer Reviewed
• [Journal Article] Serum neutrophil gelatinase-associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death (2012)
  • Author(s): Kusaka M, Iwamatsu F, Kuroyanagi Y, Nakaya M, Ichino M, Marubashi S, Nagano H, Shiroki R, Kurahashi H, Hoshinaga K
  • Journal Title: J Urol Volume: 187 Issue: 6 Pages: 2261-2267
  • DOI: 10.1016/j.juro.2012.01.033
  • Peer Reviewed
• [Journal Article] A Functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan (2012)
  • Author(s): Ahmed WA, Tsutsumi M, Nakata S, Mori T, Nishimura Y, Fujisawa T, Kato I, Nakashima M, Kurahashi H, Suzuki K
  • Journal Title: Laryngoscope Volume: 122 Issue: 4 Pages: 925-929
  • DOI: 10.1002/lary.23179
  • Peer Reviewed
• [Journal Article] Global Gene ExpressionProfiling in PPAR-γ Agonist-TreatedKidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease. (2012)
  • Author(s): Yoshihara D, Kugita M, Yamaguchi T, Aukema HM, Kurahashi H, Morita M, Hiki Y, Calvet JP, Wallace DP, Toyohara T, Abe T, Nagao S.
  • Journal Title: PPAR Res Volume: 2012 Pages: 695898-695898
  • DOI: 10.1155/2012/695898
  • 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
• [Presentation] Towards the identification of novel palindrome-mediated translocations (2013)
  • Author(s): Kurahashi H, Inagaki H, Ohye T, Tsutsumi M, Kato T, Okamoto N
  • Organizer: European Human Genetics Conference 2013
  • Place of Presentation: Paris, France
• [Presentation] HORMAD2 phosphorylation may be involved in the initiation of meiotic silencing of unsynapsed chromatin (2013)
  • Author(s): Kogo H, Tsutsumi M, Iizuka-Kogo A, Kurahashi H, Matsuzaki T
  • Organizer: EMBO Conference Meiosis
  • Place of Presentation: Dresden, Germany
• [Presentation] Age-related decrease of meiotic cohesins in human oocytes (2013)
  • Author(s): Tsutsumi M, Fujiwara R, Nishizawa H, Kogo H, Inagaki H, Ohye T, Kato T, Kurahashi H
  • Organizer: ASHG 2013
  • Place of Presentation: Boston, USA
• [Presentation] Disease-causing candidate genes in the patients with congenital vertebral anomalies (2013)
  • Author(s): Nakamura Y, Kikugawa S, Seki S, Takahata M, Terai H, Akaoka Y, Matsubara M, Fujioka F, Inagaki H, Kurahashi H, Kobayashi T, Kato H
  • Organizer: ASHG 2013
  • Place of Presentation: Boston, USA
• [Presentation] Polymorphisms in the ANXA5gene promoter in Japanese women with pre-eclampsia (2012)
  • Author(s): Kurahashi H, Miyamura H, Nishizavva H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Udagawa Y
  • Organizer: European Society of Human Genetics Conference 2012
  • Place of Presentation: Nurnberg, Germany
• [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, Kurahashi H
  • Organizer: FASEB SRC : "Dynamic DNA structures in biology"
  • Place of Presentation: Saxtons River, USA
• [Presentation] Polymorphisms in the ANXA5gene promoter in Japanese women with preeclampsia (2012)
  • Author(s): Miyamura H, Nishizavva H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kurahashi H, Udagawa Y
  • Organizer: The XX FIGO World Congress
  • Place of Presentation: Rome, Italy
• [Presentation] Pathogenic exon-trapping by SVA retrotransposon and rescue in Faukuyama muscular dystrophy (2012)
  • Author(s): Taniguchi M, Kobayashi K, Kanagawa M, Yu CC, Oda T, Kuga A, Kurahashi H, Akmen H0, DiMauro S, Yokota T, Takeda S, Toda T
  • Organizer: ASHG 2012, annual meeting
  • Place of Presentation: San Francisco, USA
• [Book] Clinical Genomics: Practical Applications in Adult Patient Care (2014)
  • Author(s): Nisizawa H, Kurahashi H
  • Total Pages: 928
  • Publisher: McGraw-Hill Professional
• [Book] Clinical Genomics (2014)
  • Author(s): Michael Murray, Mark Babyatski, Monica Giovanni
  • Publisher: McGraw Hill
• [Book] Brenner's Encyclopedia of Genetics (2013)
  • Author(s): Stanley Maloy, Kelly Hughes
  • Publisher: Elsevier
• [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/
• [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/research_category/res05/index.html
• [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・総合医科学研究所
  • URL: http://www.fujita-hu.ac.jp/ICMS/
• [Remarks] 分子遺伝学研究部門
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/