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

2010 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、他の体細胞では検出されないことを報告した。しかし、ヒト卵子は同じ方法で新生転座の発生の有無を調べることができない。そこで、本研究では、十分なインフォームドコンセントの取得後、ヒトt(11;22)均衡型新生転座保因者とその両親のゲノム解析をおこなった。転座切断点周囲の多型解析の結果、新生転座はすべて父親由来であることが判明した。このことから、t(11;22)新生転座はヒト精子形成過程においてのみ発生することがわかった(Ohye et al. 2010)。また、22番染色体の転座切断点には多型があり、健常男子の配列多型と、精子中の新生転座頻度との関係を調べた。その結果、多型は新生転座頻度に影響を及ぼし、回文配列が長くて対称的であるような配列ほど、新生転座発生頻度が高いことが判明した。この結果は、これまでに11番染色体の転座切断点多型で報告してきたデータと一致し、転座切断点のPATRR配列が精子形成時に十字架型の2次構造をとることを間接的に証明した(Tong et al. 2010)。

Research Products

• [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: (In press)
  • Peer Reviewed
• [Journal Article] A rare synaptonemal complex protein 3 gene variant is associated with 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: (In press)
  • 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: (In press)
  • 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: (In press)
  • Peer Reviewed
• [Journal Article] Paternal origin of the de novo constitutional t(11;22)(q23;q11). (2010)
  • Author(s): Ohye T, Inagaki H, Kogo H, Tsutsumi M, Kato T, Tong M, Macville M, Medne L, Zackai EH, Emanuel BS, Kurahashi H.
  • Journal Title: Eur J Hum Genet Volume: 18 Pages: 783-7
  • Peer Reviewed
• [Journal Article] Polymorphisms of the 22q11.2 breakpoint region influence the frequency of de novo constitutional t(11;22)s in sperm. (2010)
  • Author(s): Tong M, Kato T, Yamada K, Inagaki H, Kogo H, Ohye T, Tsutsumi M, Wang J, Emanuel BS, Kurahashi H.
  • Journal Title: Hum Mol Genet Volume: 19 Pages: 2630-7
  • Peer Reviewed
• [Journal Article] A new palindrome -mediated recurrent translocation with 3:1 meiotic non-disjunction : the t(8;22)(q24.13 ; q11.21). (2010)
  • Author(s): Sheridan MB, Kato T, Haldem an-Englert C, Jalali GR, Milunsky JM, Zou Y, Klaes R, Gimelli S, Gemmill RM, Drabkin HA, Hacker AM, Brown J, Tomkins D, Shaikh TH, Kurahashi H, Zackai EH, Emanuel BS.
  • Journal Title: Am J Hum Genet Volume: 87 Pages: 209-18
  • Peer Reviewed
• [Journal Article] The constitutional t(11;22) : implications for a novel mechanism responsible for gross chromosomal rearrangement. (2010)
  • Author(s): Kurahashi H, Inagaki H, Kogo H, Ohye T, Tsutsumi M, Kato T, Tong M, Emanuel BS.
  • Journal Title: Clin Genet Volume: 78 Pages: 299-309
  • Peer Reviewed
• [Journal Article] Screening of genes involved in chromosome segregation during meiosis I : towards the identification of genes responsible for infertility in humans. (2010)
  • Author(s): Kogo H, Kowa-Sugiyama H, Yamada K, Bolor H, Tsutsumi M, Ohye T, Inagaki H, Taniguchi M, Tada T, Kurahashi H.
  • Journal Title: J Hum Genet Volume: 55 Pages: 293-9
  • Peer Reviewed
• [Journal Article] CD9 gene variations are not associated with female infertility in humans. (2010)
  • Author(s): Nishiyama S, Kishi T, Kato T, Suzuki M, Nishizawa H, Pryor-Koishi K, Sawada T, Nishiyama Y, Iwata N, Udagawa Y, Kurahashi H.
  • Journal Title: Gynecol Obstet Invest Volume: 69 Pages: 116-21
  • Peer Reviewed
• [Journal Article] Genetic variation in the indoleamine 2,3-dioxygenase gene in pre-eclampsia. (2010)
  • Author(s): Nishizawa H, Kato T, Ohta S, Nishiyama S, Pryor-Koishi K, Suzuki M, Tsutsumi M, Inagaki H, Kurahashi H, Udagawa Y.
  • Journal Title: Am J Reprod Immunol Volume: 64 Pages: 68-76
  • Peer Reviewed
• [Journal Article] Genetic variation in the indoleamine 2,3-dioxygenase gene in pre-eclampsia (Reply). (2010)
  • Author(s): Nishizawa H, Kurahashi H.
  • Journal Title: Am J Reprod Immunol Volume: 64 Pages: 317
  • Peer Reviewed
• [Journal Article] Polycystic kidney disease in Han : SPRD Cy rats is associated with elevated expression and mislocalization of SamCystin. (2010)
  • Author(s): Nagao S, Morita M, Kugita M, Yoshihara D, Yamaguchi T, Kurahashi H, Calvet JP, Wallace DP.
  • Journal Title: Am J Physiol Renal Physiol Volume: 299 Pages: F1078-86
  • Peer Reviewed
• [Journal Article] Urinary neutrophil gelatinase-associated lipocalin is a potential non-invasive marker for renal scarring in patients with vesicoureteral reflux. (2010)
  • Author(s): Ichino M, Kusaka M, Kuroyanagi Y, Mori T, Morooka M, Sasaki H, Shiroki R, Shishido S, Kurahashi H, Hoshinaga K.
  • Journal Title: J Urol Volume: 183 Pages: 2001-7
  • Peer Reviewed
• [Journal Article] Serum tissue inhibitor of metalloproteinases 1 (TIMP-1) predicts organ recovery from delayed graft function after kidney transplantation from donors after cardiac death. (2010)
  • Author(s): Kusaka M, Kuroyanagi Y, Ichino M, Sasaki H, Maruyama T, Hayakawa K, Shiroki R, Sugitani A, Kurahashi H, Hoshinaga K.
  • Journal Title: Cell Transplant Volume: 19 Pages: 723-9
  • Peer Reviewed
• [Journal Article] Correlation of axillary osmidrosis to a SNP in the ABCC11 gene determined by the smart-amplification process (SMAP). (2010)
  • Author(s): Inoue Y, Mori T, Sakurai A, Mitani Y, Toyoda Y, Ishikawa T, Hayashizaki Y, Yoshimura Y, Kurahashi H, Sakai Y.
  • Journal Title: J Plast Reconstr Aesthet Surg Volume: 63 Pages: 1369-74
  • Peer Reviewed
• [Journal Article] Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure. (2010)
  • Author(s): Ohtsuki M, Morimoto S, Izawa H, Ismail TF, Ishibashi-Ueda H, Kato Y, Horii T, Isomura T, Suma H, Nomura M, Hishida H, Kurahashi H, Ozaki Y.
  • Journal Title: Int J Cardiol Volume: 145 Pages: 333-4
  • Peer Reviewed
• [Presentation] GEN1 resolves cruciform-forming palindromic DNA leading to a recurrent translocation in humans. (2011)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H.
  • Organizer: Keystone Symposia : Functional Consequences of Structural Variation in the Genome
  • Place of Presentation: Steamboat Springs, Colorado, USA
  • Year and Date: 20110108-20110113
• [Presentation] Mutation of the SYCP3 gene in women with recurrent pregnancy loss. (2010)
  • Author(s): Kurahashi H, Tsutsumi M, Egusa H, Nishiyama S, Suzuki M, Kogo H, Inagaki H, Ohye T.
  • Organizer: International Symposium on Epigenome Network, Development and Reprogramming of Germ Cells.
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20101122-20101124
• [Presentation] GEN1 resolves cruciform-forming palindromic DNA leading to a recurrent translocation in humans. (2010)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H.
  • Organizer: The American Society of Human Genetics 60th Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20101102-20101106
• [Presentation] GEN1 resolves cruciform-forming palindromic DNA leading to a recurrent translocation in humans. (2010)
  • Author(s): Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H.
  • Organizer: The 7th 3R Symposium
  • Place of Presentation: Toyama, Japan
  • Year and Date: 20101026-20101030
• [Presentation] Palindrome-mediated chromosomal translocation in humans. (2010)
  • Author(s): Kurahashi H.
  • Organizer: FASEB Summer Research Conferences. Biological Impact of Alternatively Structured DNA.
  • Place of Presentation: Steamboat Springs, Colorado, USA(招待講演)
  • Year and Date: 20100705-20100710
• [Presentation] Paternal origin of the de novo constitutional t(11;22) (q23;q11). (2010)
  • Author(s): Ohye T, Inagaki H, Kogo H, Tsutsumi M, Kato T, Tong M, Macville MVE, Medne L, Zackai EH, Emanuel BS, Kurahashi H.
  • Organizer: European Society of Human Genetics Conference 2010.
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 20100612-20100615