父親に特異的に由来する染色体構造異常発生メカニズム

2011 Fiscal Year Annual Research Report

• Project/Area Number: 21390101
• 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)
• Keywords: 染色体転座 / 切断点 / 回文配列 / パリンドローム / 十字架型DNA / 非B型DNA / 染色体再構成 / 染色体構造異常

Research Abstract

ヒト染色体転座t(11;22)(q23;q11)は、反復性非ロバートソン転座のひとつである。本研究代表者はt(11;22)転座の11番、22番両染色体の切断点にはpalindromic AT rich repeat (PATRR)と呼ばれるAT含量の多い回文配列が存在することを報告し、それが「十字架型」DNAの立体構造をとるためゲノムが不安定になることが本染色体転座の原因であることを提唱している。また、研究代表者は1分子検出感度の転座特異的PCRを用いた実験によって、ヒト精子において新生t(11;22)が検出されるが、その発生頻度は切断点の多型と関連することを報告した。本年度は、その多型アリルの特徴を詳細に解析した。おおまかには、配列が対称性でサイズの大きいものほど転座発生頻度が高いが、まず2次構造予測プログラムを用いると、ヘアピン構造のとりやすさと転座頻度は相関しなかった。次に、それぞれの切断点をプラスミドにクローン化し、環状プラスミドのアガロースゲル電気泳動での移動度のシフトにより、十字架型構造のとりやすさを検討したが、転座頻度とよい相関を示した。また、さらに詳細に解析するために、制限酵素切断後にシフトバンドを定量化したが、よく相関した。各プラスミドの十字架型構造の頻度は原子間力顕微鏡で確認した。以上により、切断点の多型が、十字架型の2次構造のとりやすさに影響を与え、転座頻度を決定していることが示唆された。このデータは、間接的に示しており、非常に重要な知見である(Kato et al. Mol Cytogenet 2011)。

Research Products

• [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 Pages: 8-15
  • DOI: 10.1111/j.1741-4520.2011.00350.x
  • 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 Pages: 81-83
  • DOI: 10.1038/jhg.2011.143
• [Journal Article] Characterization of a novel mouse gene encoding an SYCP3-like protein that re-localizes from the XY body to the nucleolus during prophase of male meiosis I (2011)
  • Author(s): Tsutsumi M, Kogo H, Kowa-Sugiyama H, Inagaki H, Ohye T, Kurahashi H
  • Journal Title: Biol Reprod Volume: 85 Pages: 165-171
  • DOI: 10.1095/biolreprod.110.087270
  • Peer Reviewed
• [Journal Article] Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy (2011)
  • Author(s): Taniguchi-Ikeda M, Kobayashi K, Kanagawa M, Yu CC, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, DiMauro S, Kaji R, Yokota T, Takeda S, Toda T
  • Journal Title: Nature Volume: 478 Pages: 127-131
  • DOI: 10.1038/nature10456
  • Peer Reviewed
• [Journal Article] A rare synaptonemal complex protein 3 gene variant in unexplained female infertility (2011)
  • Author(s): Nishiyama S, Kishi T, Kato T, Suzuki M, Bolor H, Udagawa Y, Kurahashi H
  • Journal Title: Mol Hum Reprod Volume: 17 Pages: 266-271
  • DOI: 10.1093/molehr/gaq098
  • Peer Reviewed
• [Journal Article] Polymorphism in annexin A5 gene promoter in Japanese women with recurrent pregnancy loss (2011)
  • Author(s): Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Markoff A, Yanagihara I, Udagawa Y, Kurahashi H
  • Journal Title: Mol Hum Reprod Volume: 17 Pages: 447-452
  • DOI: 10.1093/molehr/gar008
  • Peer Reviewed
• [Journal Article] DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation (2011)
  • Author(s): Kato T, Inagaki H, Tong M, Kogo H, Ohye T, Yamada K, Tsutsumi M, Emanuel BS, Kurahashi H
  • Journal Title: Mol Cytogenet Volume: 4 Pages: 18
  • DOI: 10.1186/1755-8166-4-18
  • Peer Reviewed
• [Journal Article] Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction (2011)
  • Author(s): Nishizawa H, Ota S, Suzuki M, Kato T, Sekiya T, Kurahashi H, Udagawa Y
  • Journal Title: Reprod Biol Endocrinol Volume: 9 Pages: 107
  • DOI: 10.1186/1477-7827-9-107
  • Peer Reviewed
• [Journal Article] Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients (2011)
  • Author(s): Nishizawa H, Suzuki M, Pryor-Koishi K, Sekiya T, Tada S, Kurahashi H, Udagawa Y
  • Journal Title: Syst Biol Reprod Med Volume: 57 Pages: 174-178
  • DOI: 10.3109/19396368.2011.587590
  • Peer Reviewed
• [Journal Article] Global gene expression profiling in early-stage polycystic kidney disease in the Han : SPRD Cy rat identifies a role for RXR signaling (2011)
  • Author(s): Kugita M, Nishii K, Morita M, Yoshihara D, Kowa-Sugiyama H, Yamada K, Yamaguchi T, Wallace DP, Calvet JP, Kurahashi H, Nagao S
  • Journal Title: Am J Physiol Renal Physiol Volume: 300 Pages: F177-188
  • DOI: 10.1152/ajprenal.00470.2010
  • Peer Reviewed
• [Journal Article] PPAR-{gamma} agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease (2011)
  • Author(s): Yoshihara D, Kurahashi H, Morita M, Kugita M, Hiki Y, Aukema HM, Yamaguchi T, Calvet JP, Wallace DP, Nagao S
  • Journal Title: Am J Physiol Renal Physiol Volume: 300 Pages: F465-474
  • DOI: 10.1152/ajprenal.00460.2010
  • Peer Reviewed
• [Journal Article] Lack of Association between Orexin Receptor Genes Polymorphisms and Obstructive Sleep Apnea Syndrome in Japanese (2011)
  • Author(s): Ahmed WA, Mori T, Nishimura Y, Kitanaka T, Kato T, Bhardwaj KA, Kurahashi H, Suzuki K
  • Journal Title: Sleep Biol Rhythms Volume: 9 Pages: 73-77
  • Peer Reviewed
• [Journal Article] Chromosomal translocations and palindromic AT-rich repeats
  • Author(s): Kato T, Kurahashi H, Emanuel BS
  • Journal Title: Curr Opin Genet Dev. Volume: (In press)
  • Peer Reviewed
• [Journal Article] HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes
  • Author(s): Kogo H, Tsutsumi M, Ohye T, Inagaki H, Abe T, Kurahashi H
  • Journal Title: Genes Cells Volume: (In press)
  • Peer Reviewed
• [Journal Article] A Functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan
  • 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: (In press)
  • 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
  • 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: (In press)
  • Peer Reviewed
• [Presentation] Global gene expression profiling in kidneys of PPAR-gamma agonist-treated PCK rats, an orthologous model of human ARPKD (2011)
  • Author(s): Yoshihara D, Kugita M, Kurahashi H, Morita M, Hiki Y, Yamaguchi T, Aukema HM, Wallace DP, Calvet JP, Toyohara T, Abe T, Nagao S
  • Organizer: American Society of Nephrology 44th Annual Meetine & Scientific Exposition
  • Place of Presentation: Philadelphia, PA USA
  • Year and Date: 20111100
• [Presentation] Mechanism of recurrent translocation t(11;22) initiated by cruciform conformation of palindromic sequences (2011)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H
  • Organizer: The 12th International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20111011-20111015
• [Presentation] Identification of a recombination hotspot sequence at the breakpoint region of the 22q11 deletion using a yeast model (2011)
  • Author(s): Ohye T, Inagaki H, Kogo H, Tsutsumi M, Emanuel BS, Kurahashi H
  • Organizer: The 12th International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20111011-20111015
• [Presentation] HORMAD1-deficiency causes azoospermia in males and pregnancy loss in females (2011)
  • Author(s): Kogo H, Tsutsumi M, Ohye T, Inagaki H, Kurahashi H
  • Organizer: The 12th International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20111011-20111015
• [Presentation] Identification of a novel palindrome mediated translocation associated with the t(3;8) of hereditary renal cancer (2011)
  • Author(s): Kato T, Sheridan MB, Hacker AM, Inagaki H, Glover TW, Plon SE, Drabkin HA, Gemmill RM, Kurahashi H, Emanuel BS
  • Organizer: The 12th International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20111011-20111015
• [Presentation] Mutation in the SYCP3 gene identified in a woman with recurrent pregnancy loss affect the synaptonemal complex conformation at meiotic prophase I (2011)
  • Author(s): Tsutsumi M, Kogo H, Inagaki H, Ohye T, Kurahashi H
  • Organizer: The 12th International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20111011-20111015
• [Presentation] HORMAD1-dependent synapsis checkpoint in mammalian meiosis (2011)
  • Author(s): Kogo H, Tsutsumi M, Ohye T, Inagaki H, Kurahashi H
  • Organizer: 2011 FASEB Summer Research Conferences, Genetic Recombination & Genome Rearrangements
  • Place of Presentation: Steamboat Spring, USA
  • Year and Date: 20110724-20110729
• [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss (2011)
  • Author(s): Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Markoff A, Yanagihara I, Udagawa Y, Kurahashi H
  • Organizer: 27th Annual Meeting of ESHRE-Stockholm 2011
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20110703-20110706
• [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss (2011)
  • Author(s): Kurahashi H, Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Negi R, Markoff A, Yanagihara I, Udagawa, Y
  • Organizer: European Society of Human Genetics Conference 2011
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 20110528-20110531
• [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss (2011)
  • Author(s): Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama s, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Markoff A, Yanagihara I, Udagawa Y, Kurahashi H
  • Organizer: 59th Annual Clinical Meeting, ACOG
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20110430-20110504
• [Presentation] PPAR-gamma agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease (2011)
  • Author(s): Yoshihara D, Kurahashi H, Morita M, Kugita M, Hiki Y, Aukema HM, Yamaguchi T, Calvet JP, Wallace DP, Nagao S
  • Organizer: World Congress of Nephrology 2011
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20110400
• [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/