The role of hydroxymethylation in congenital anomaly syndromes caused by aberrant methylation

• Project/Area Number: 25713040
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• 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) (2015); Keio University
• 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)
• Research Collaborator: OGATA Tsutomu ; KAGAMI Masayo ; MATSUBARA Keiko ; NAKABAYASHI Kazuhiko ; FERGUSON-SMITH Anne C.
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2014: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2013: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: ゲノムインプリンティング / エピジェネティクス / メチル化 / 先天異常症候群

Outline of Final Research Achievements

5-hydroxymethylcytosine (5hmC), converted from 5-methylcytosine (5mC) by TET enzymes, is an intermediate of the demethylation pathway. We applied the newly developed oxidative BS (oxBS) treatment to detect 5hmC in blood samples from Kagami-Ogata syndrome (KOS) patients. As a result, it was found that 5hmC was not a major component in abnormally hypermethylated IG-DMR or at a global level, at least in blood from KOS patients. As the brain sample contained large amounts of 5hmC, the neural tissues of KOS patients are promising candidates for analysis in elucidating the role of 5hmC in the neurodevelopmental context.

Research Products

• [Int'l Joint Research] University of Cambridge/Babraham Institute(英国)
• [Journal Article] ゲノム時代の到来と遺伝リテラシー (2016)
  • Author(s): 山澤一樹
  • Journal Title: 国立医療学会誌 Volume: 70 Pages: 106-109
  • Peer Reviewed
• [Journal Article] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions. (2015)
  • Author(s): Matsubara K, Kagami M, Nakabayashi K, Hata K, Fukami M, Ogata T, Yamazawa K.
  • Journal Title: Clin Epigenetics Volume: 28;7(1) Issue: 1 Pages: 90-90
  • DOI: 10.1186/s13148-015-0124-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression (2015)
  • Author(s): Ruslan Strogantsev, Felix Krueger, Kazuki Yamazawa, Hui Shi, Poppy Gould, Megan Goldman-Roberts, Kirsten McEwen, Bowen Sun, Roger Pedersen, Anne C. Ferguson-Smith
  • Journal Title: Genome Biology Volume: 16 Issue: 1 Pages: 112-112
  • DOI: 10.1186/s13059-015-0672-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 今月の用語 次世代シークエンサー (2015)
  • Author(s): 山澤一樹
  • Journal Title: 国立医療学会誌 Volume: 69 Pages: 383-383
  • Peer Reviewed
• [Journal Article] In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism (2014)
  • Author(s): Elizabeth J. Radford, Mitsuteru Ito, Hui Shi, Jennifer A. Corish, Kazuki Yamazawa, Elvira Isganaitis, Stefanie Seisenberger, Timothy A. Hore, Wolf Reik, Serap Erkek, Antoine H. F. M. Peters, Mary-Elizabeth Patti, Anne C. Ferguson-Smith
  • Journal Title: Science Volume: 345 Issue: 6198
  • DOI: 10.1126/science.1255903
  • Peer Reviewed
• [Journal Article] A pediatric case of antibiotic-associated hemorrhagic colitis caused by Klebsiella Oxytoca (2014)
  • Author(s): Mamiko Yamada, Kazuki Yamazawa, Shinichiro Sekiguchi, Masayoshi Shinjoh, Kentaro Tomita, Toshiki Takenouchi, Takao Takahashi
  • Journal Title: Global Pediatric Health Volume: 1
  • DOI: 10.1177/2333794x14550525
  • Peer Reviewed / Open Access
• [Presentation] インプリンティング調節領域の高メチル化に起因したKagami-Ogata症候群におけるヒドロキシメチル化の探索 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、中林一彦、秦健一郎、深見真紀、緒方勤
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-15
• [Presentation] Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions (2015)
  • Author(s): Kazuki Yamazawa, Keiko Matsubara, Masayo Kagami, Kazuhiko Nakabayashi, Kenichiro Hata, Maki Fukami, Tsutomu Ogata
  • Organizer: ASHG 2015 Annual Meeting
  • Place of Presentation: Baltimore Convention Center (Baltimore, MD, USA)
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] IG-DMRの高メチル化に起因するKagami-Ogata症候群におけるヒドロキシメチル化の探索 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、中林一彦、深見真紀、緒方勤
  • Organizer: 第49回日本小児内分泌学会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-10-09
• [Presentation] メチル化異常に起因するKagami-Ogata症候群においてヒドロキシメチル化の果たす役割の解明 (2015)
  • Author(s): 山澤一樹、松原圭子、鏡雅代、深見真紀、中林一彦、緒方勤
  • Organizer: 第38回小児遺伝学会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2015-07-25
• [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 (2015)
  • Author(s): 山澤一樹
  • Organizer: 第118回日本小児科学会
  • Place of Presentation: 大阪国際会議場（大阪市）
  • Year and Date: 2015-04-18
• [Presentation] メチル化異常に起因するヒトインプリンティング異常症においてヒドロキシメチル化の果たす役割の解明 (2014)
  • Author(s): 山澤一樹、鏡雅代、松原圭子、中村明枝、深見真紀
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] Allele-specific distribution of 5-hydroxymethylcytosine at imprinting control regions (2014)
  • Author(s): Kazuki Yamazawa, Anne C Ferguson-Smith
  • Organizer: The 64th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Diego（アメリカ合衆国）
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] メチル化異常に起因するヒトインプリンティング異常症においてヒドロキシメチル化の果たす役割の解明 (2014)
  • Author(s): 山澤一樹、鏡雅代、松原圭子、中村明枝、深見真紀
  • Organizer: 第48回日本小児内分泌学会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Allele-specific distribution of 5-hydroxymethylcytosine at differentially methylated imprinting control regions (2013)
  • Author(s): Kazuki Yamazawa, Mitsuteru Ito, Anne Ferguson-Smith
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場（兵庫県）
• [Presentation] ゲノムインプリンティングと先天異常症候群
  • Author(s): 山澤一樹
  • Organizer: TTT meeting
  • Place of Presentation: 明治安田生命ビル（東京都）
  • Invited