Molecular biological analysis of genome wide paternal uniparental disomy

• Project/Area Number: 25461648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Saga University
• Principal Investigator: Ohtsuka Yasufumi 佐賀大学, 医学部, 助教 (50448479)
• Co-Investigator(Renkei-kenkyūsha): Soejima Hidenobu 佐賀大学, 医学部分子遺伝学エピジェネティクス分野, 教授 (30304885) ; Yoshiura Koh-ichiro 原爆後障害医療研究所, 教授 (00304931)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Beckwith-Wiedemann症候群 / 片親性ダイソミー / ゲノムワイド父性ダイソミー / エクソーム解析 / メチル化解析 / 父性ダイソミー / 次世代シークエンサー / エピジェネティック / 全ゲノム父性ダイソミー / インプリント疾患 / Beckwith-Wiedemann 症候群

Outline of Final Research Achievements

In uniparental disomy (pUPD) of the 11 chromosome with Beckwith-Wiedemann syndrome, we identified seven cases of genome wide uniparental paternal disomy (GWPUPD). GWPUPD was complicated for tumorigenesis, mental retardation and congenital heart disease. We whole exome analysis and performed methylation analysis about GWPUPD 4 cases. We detected many mutations of autosomal recessive gene, and cystinuria developed in one subject. In addition, methylation abnormality was detected to multiple imprinting locus including 11p15.5. We revealed that GWpUPD influenced both autosomal recessive genes and multiple imprinting genes.

Research Products

• [Journal Article] Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11. (2016)
  • Author(s): Ohtsuka Y, Higashimoto K, Oka T, Yatsuki H, Jozaki K, Maeda T, Kawahara K, Hamasaki Y, Matsuo M, Nishioka K, Joh K, Mukai T, Soejima H.
  • Journal Title: Hum Mol Genet. Volume: 25 Issue: 7 Pages: 1406-19
  • DOI: 10.1093/hmg/ddw023
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome. (2014)
  • Author(s): Ohtsuka Y, Higashimoto K, Sasaki K, Jozaki K, Yoshinaga H, Okamoto N, Takama Y, Kubota A, Nakayama M, Yatsuki H, Nishioka K, Joh K, Mukai T, Yoshiura KI, Soejima H.
  • Journal Title: Clin Genet. Volume: 8 Issue: 3 Pages: 1-1
  • DOI: 10.1111/cge.12496
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions (DMRs) to aberrant methylation in Beckwith-Wiedemann syndrome with epimutations (2014)
  • Author(s): Maeda T, Higashimoto K, Jozaki K, Hitomi H, Nakabayashi K, Makita Y, Tonoki H, Okamoto N, Takada F, Ohashi H, Migita M, Kosaki R, Matsubara K, Ogata T, Matsuo M, Hamasaki Y, Ohtsuka Y, Nishioka K, Joh K, Mukai T, Hata K, Soejima H
  • Journal Title: Genet Med Volume: 16(12) Issue: 12 Pages: 903-912
  • DOI: 10.1038/gim.2014.46
  • Peer Reviewed / Open Access
• [Journal Article] Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY. (2014)
  • Author(s): Nozu K, Iijima K, Ohtsuka Y, Fu XJ, Kaito H, Nakanishi K, Vorechovsky I
  • Journal Title: Mol Genet Genomic Med Volume: 2 Issue: 5 Pages: 451-451
  • DOI: 10.1002/mgg3.89
  • Peer Reviewed / Open Access
• [Journal Article] A novel de novo point mutation of OCT-binding site in the IGF2/H19-imprinting control region in a patient with Beckwith-Wiedemann syndrome. (2013)
  • Author(s): Higashimoto K, Jozaki K, Kosho T, Matsubara K, Sato T, Yamada D, Yatsuki H, Maeda T, Ohtsuka Y, Nishioka K, Joh K, Koseki H, Ogata T, SoejimaH*
  • Journal Title: Clin Genet Volume: in press Issue: 6 Pages: 539-544
  • DOI: 10.1111/cge.12318
  • Peer Reviewed / Open Access
• [Journal Article] Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome. (2013)
  • Author(s): Higashimoto K, Maeda T, Okada J, Ohtsuka Y, Sasaki K, Hirose A, Nomiyama M, Takayanagi T, Fukuzawa R, Yatsuki H, Koide K, Nishioka K, Joh K, Watanabe Y, Yoshiura K, Soejima H.
  • Journal Title: Eur J Hum Genet. Volume: 21（11） Pages: 1316-1319
  • Peer Reviewed
• [Journal Article] 抗CFH抗体陽性およびCFHR1遺伝子欠失を伴うDEAP-HUSの1例 (2013)
  • Author(s): 岡 政史, 大塚 泰史, 稲田 由紀子, 佐藤 忠司, 吉田 瑶子, 藤村 吉博, Fan Xinping, 宮田 敏行, 濱崎 雄平．
  • Journal Title: 本小児腎臓病学会雑誌 Volume: 26（2） Pages: 285-291
  • NAID: 130004495423
  • Peer Reviewed
• [Presentation] Beckwith-Wiedemann症候群の原因となる片親性父性ダイソミーの切断点領域の解析． (2015)
  • Author(s): 大塚泰史、岡岳彦、川原弘三、八木ひとみ、東元健、副島英伸．
  • Organizer: 第60回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-14
• [Presentation] 小児腎臓医からみた成人腎Fabry病スクリーニング． (2014)
  • Author(s): 大塚泰史
  • Organizer: 日本小児腎臓病学会
  • Place of Presentation: 秋田
  • Year and Date: 2014-06-05 – 2014-06-07
• [Presentation] Treatment of cisplatin overdose in pediatric case. (2013)
  • Author(s): Yasufumi Ohtsuka, Masafumi Oka, Junya Eto, Masanori Nishi, Yuhei Hamasaki.
  • Organizer: 16th congress of the International Pediatric Nephrology Association.
  • Place of Presentation: 中華人民共和国（上海）
• [Presentation] シスチン尿症を伴うゲノムワイド父性片親性ダイソミー症例の遺伝子解析. (2013)
  • Author(s): 大塚泰史、佐々木健作、城崎幸介、東元健、岡本伸彦、高間 勇一、窪田 昭男、松本富美中山 雅弘、吉浦孝一郎、副島英伸.
  • Organizer: 第48回日本小児腎臓病学会学術集会
  • Place of Presentation: 日本、徳島
• [Presentation] シスチン尿症を伴うゲノムワイド父性片親性ダイソミー症例の遺伝子解析. (2013)
  • Author(s): 大塚泰史、佐々木健作、城崎幸介、東元健、岡本伸彦、高間 勇一、窪田 昭男、松本富美、中山 雅弘、吉浦孝一郎、副島英伸.
  • Organizer: 第58回日本人類遺伝学会.
  • Place of Presentation: 日本、宮城
• [Book] 小児特発性ネフローゼ症候群 診療ガイドライン2013. (2013)
  • Author(s): 一般社団法人日本小児腎臓病学会、大塚泰史（作成委員：一般療法担当）
  • Total Pages: 77
  • Publisher: 診断と治療社