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Pathologic clarification and development of new medicine for imprinting disorders in terms of hydroxymethylation

Research Project

Project/Area Number 16H05362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research Institution独立行政法人国立病院機構(東京医療センター臨床研究センター)

Principal Investigator

Yamazawa Kazuki  独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 医師 (10338113)

Co-Investigator(Kenkyū-buntansha) 鏡 雅代  国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 室長 (70399484)
松原 圭子  国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (90542952)
Research Collaborator NAKABAYASHI Kazuhiko  
MATSUNAGA Tatsuo  
AKUTSU Hidenori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsエピジェネティクス / メチル化 / インプリンティング / 先天異常症候群 / ゲノムインプリンティング / ヒドロキシメチル化 / ゲノム
Outline of Final Research Achievements

5-hydroxymethyl cytosine (5hmC) has been noted as an intermediate metabolite in DNA demethylation reactions. The purpose of this study is to elucidate how 5hmC is involved in pathogenesis of imprinting disorders caused by methylation defects. We analyzed patient-derived iPS cells for disease model and placenta to clarify the dynamic behavior of 5hmC. The overall 5hmC content in iPS cells was increased compared to the skin fibroblasts. In addition, placenta had a higher content of 5hmC as compared to blood, and in particular, 5hmC was concentrated in the imprinting control regions in placental genome.

Academic Significance and Societal Importance of the Research Achievements

本研究はインプリンティング異常症において5hmCの果たす役割を明らかにすることを目標とする、ヒト臨床検体を用いた世界初の5hmC解析である。不可逆的なゲノム配列の異常とは対照的に、メチル化をはじめとするエピゲノムは可塑性を持ち、治療の標的となる可能性がある。今回得られた知見はpreliminaryなものであるが、今後もサンプルを増やし広範に解析を行うことにより、メチル化・脱メチル化を制御することによるエピゲノム治療法の開発につながることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] A Familial Case of a Whole Germline CDC73 Deletion Discordant for Primary Hyperparathyroidism2019

    • Author(s)
      Hatabu Naomi、Katori Naho、Sato Takeshi、Maeda Naonori、Suzuki Eri、Komiyama Osamu、Tsutsui Hidemitsu、Nagao Toshitaka、Nakauchi-Takahashi Hana、Matsunaga Tatsuo、Ishii Tomohiro、Hasegawa Tomonobu、Yamazawa Kazuki
    • Journal Title

      Hormone Research in Paediatrics

      Volume: 印刷中 Issue: 1 Pages: 1-8

    • DOI

      10.1159/000495800

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology2018

    • Author(s)
      Inoue Takanobu、Yagasaki Hideaki、Nishioka Junko、Nakamura Akie、Matsubara Keiko、Narumi Satoshi、Nakabayashi Kazuhiko、Yamazawa Kazuki、Fuke Tomoko、Oka Akira、Ogata Tsutomu、Fukami Maki、Kagami Masayo
    • Journal Title

      Journal of Medical Genetics

      Volume: 印刷中 Issue: 6 Pages: 413-418

    • DOI

      10.1136/jmedgenet-2018-105463

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-level heteroplasmy for the m.7445A>G mitochondrial DNA mutation can cause progressive sensorineural hearing loss in infancy.2018

    • Author(s)
      Matsushima K, Nakano A, Arimoto Y, Mutai H, Yamazawa K, Murayama K, Matsunaga T.
    • Journal Title

      Intl J Ped Otorhinolaryng

      Volume: 108 Pages: 125-131

    • DOI

      10.1016/j.ijporl.2018.02.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 起立性低血圧症状で発症した自己免疫性自律神経節障害の9歳児例.2018

    • Author(s)
      河津桃子,三春晶嗣,鳥井健一,雨宮あつこ,鈴木絵理,山澤一樹,藤田尚代,込山修,樋口理,中根俊成,小平隆太郎,高橋孝雄.
    • Journal Title

      小児科臨床

      Volume: 71 Pages: 47-53

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Spontaneous intramural duodenal hematoma as the manifestation of Noonan syndrome.2018

    • Author(s)
      Yamazawa K, Yamada Y, Kuroda T, Mutai H, Matsunaga T, Komiyama O, Takahashi T.
    • Journal Title

      Am J Med Genet A

      Volume: 176 Issue: 2 Pages: 496-498

    • DOI

      10.1002/ajmg.a.38556

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 単為生殖とゲノムワイド片親性ダイソミー.2017

    • Author(s)
      山澤一樹
    • Journal Title

      医学のあゆみ

      Volume: 263 Pages: 317-321

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects.2017

    • Author(s)
      Inoue T, Nakamura A, Fuke T, Yamazawa K, Sano S, Matsubara K, Mizuno S, Matsukura Y, Harashima C, Hasegawa T, Nakajima H, Tsumura K, Kizaki Z, Oka A, Ogata T, Fukami M, Kagami M.
    • Journal Title

      Clin Epigenetics

      Volume: 9 Issue: 1 Pages: 52-52

    • DOI

      10.1186/s13148-017-0350-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells2016

    • Author(s)
      Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S, Hashimoto H, Egashira T, Tanimoto Y, Mizuno S, Tanaka S, Okuno H, Yamazawa K, Watanabe H, Oda M, Kaneda R, Matsuzaki Y, Nagai T, Okano H, Yagami K, Tanaka M, Fukuda K.
    • Journal Title

      Stem Cell Reports

      Volume: 6 Issue: 6 Pages: 825-833

    • DOI

      10.1016/j.stemcr.2016.04.015

    • NAID

      120007135348

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Multi-gene testingでBRCA2遺伝子の病的バリアントおよびCHEK2遺伝子の意義不明バリアントを認めた兄妹例2019

    • Author(s)
      山澤一樹、井上沙聡、安齋純子、安達将隆、松永達雄
    • Organizer
      第25回日本家族性腫瘍学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HBOCリスクが高い患者を拾い上げるための当院での取り組み2019

    • Author(s)
      井上沙聡、安斎純子、植木有紗、安達将隆、山澤一樹、笹岡綾子、三善友莉、岩田侑子、山下博、松井哲、松永達雄
    • Organizer
      第7回HBOCコンソーシアム学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SMAD4遺伝子に病的バリアントを同定した若年性ポリポーシス/遺伝性出血性末梢血管拡張症症候群家系2018

    • Author(s)
      山澤一樹、安達将隆、國富晴子、増田健太、石田文孝、三須久美子、小崎健次郎、浜本康夫、後藤修、矢作直久、牛尼美年子、吉田輝彦、菅野康吉
    • Organizer
      第24回日本家族性腫瘍学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SMAD4遺伝子に病的バリアントを同定した若年性ポリポーシス/遺伝性出血性末梢血管拡張症症候群家系2018

    • Author(s)
      山澤一樹、安達将隆、國富晴子、増田健太、石田文孝、三須久美子、小崎健次郎、浜本康夫、後藤修、矢作直久、牛尼美年子、吉田輝彦、菅野康吉
    • Organizer
      第24回日本家族性腫瘍学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 臨床的観点からみたジェネティクスとエピジェネティクス2018

    • Author(s)
      山澤一樹
    • Organizer
      第3回三重NICUフォローアップ検討会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 東京医療センター・臨床遺伝センターの歩み2018

    • Author(s)
      山澤一樹
    • Organizer
      Ophthalmic Genetics Meeting 2018
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] CDC73遺伝子の生殖細胞系列における全欠失および体細胞系列における病的バリアントを同定した原発性副甲状腺機能亢進症の男児例.2018

    • Author(s)
      山澤一樹,籏生なおみ,香取奈穂,前田直則,鈴木絵理,込山修,筒井英光,長尾俊孝,佐藤武志,石井智弘,長谷川奉延.
    • Organizer
      第40回日本小児遺伝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Germline whole-gene deletion and somatic nonsense variant of the CDC73 gene in a boy with primary hyperparathyroidism.2017

    • Author(s)
      Hatabu N, Katori N, Maeda N, Suzuki E, Komiyama O, Tsutsui H, Nagao T, Sato T, Ishii T, Hasegawa T, Yamazawa K.
    • Organizer
      日本人類遺伝学会第62回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メチル化異常に起因する小児先天異常症候群においてヒドロキシメチル化が果たす役割の解明.2017

    • Author(s)
      山澤一樹
    • Organizer
      第51回日本小児内分泌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CDC73遺伝子全領域を含む3.4 Mbの欠失を認めた副甲状腺腺腫の15歳男児例.2017

    • Author(s)
      山澤一樹, 前田直則, 籏生なおみ, 香取奈穂, 鈴木絵理, 込山修, 佐藤武志, 石井智弘, 長谷川奉延, 筒井英光, 長尾俊孝.
    • Organizer
      第23回日本家族性腫瘍学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 非典型的表現型により未診断のまま重篤な出血エピソードを繰り返したヌーナン症候群の一例.2017

    • Author(s)
      山澤一樹, 込山修, 高橋孝雄.
    • Organizer
      第120回日本小児科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 2回の重篤な出血のエピソードを認め、エクソーム解析によって診断されたヌーナン症候群の一例2016

    • Author(s)
      山澤一樹, 山田洋平, 務台英樹, 松永達雄, 込山修, 高橋孝雄
    • Organizer
      第39回日本小児遺伝学会学術集会
    • Place of Presentation
      慶應義塾大学三田キャンパス(東京都港区)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions2016

    • Author(s)
      Yamazawa K, Matsubara K, Kagami M, Nakabayashi K, Hata K, Fukami M, Ogata T
    • Organizer
      International Congress of Human Genetics 2016 Annual Meeting
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2022-06-10  

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