Development of biological dosimetry after the irradiation.

• Project/Area Number: 25550033
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nagasaki University
• Principal Investigator: YOSHIURA Koh-ichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
• Research Collaborator: HAYASHIDA Chisa
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 放射線 / 変異 / 生物学的測定法 / DNA変異 / dUTP / DNAポリメラーゼ

Outline of Final Research Achievements

The aim of this research is to develop the biological dosimetry by measuring genome alterations after radiation exposure. Firstly, we developed the method for library construction from a tiny amount of DNA. DNA was amplified by using phi29 DNA polymerase with dUTP. After the amplification, 5’-end was converted to phosphate and 3’-end was to hydroxy group afer uracil DNA glycosylation and other enzymatic reactions. DNA library for sequencing was constructed from those DNA fragments for next generation sequencer. But we have not reached the step for measuring the DNA mutations after one-cell radiation exposure and for the development of biological dosimetry.

Research Products

• [Journal Article] Genome-wide association study of HPV-associated cervical cancer in Japanese women. (2014)
  • Author(s): Miura K, Mishima H, Kinoshita A, Hayashida C, Abe S, Tokunaga K, Masuzaki H, Yoshiura KI.
  • Journal Title: Journal of Medical Virology Volume: 86 (7) Pages: 1153-1158
  • DOI: doi: 10.1002/jmv.23943.
  • Peer Reviewed
• [Journal Article] Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis. (2014)
  • Author(s): Kaname T, Ki CS, Niikawa N, Baillie GS, Day JP, Yamamura KI, Ohta T, Nishimura G, Mastuura N, Kim OH, Sohn YB, Kim HW, Cho SY, Ko AR, Lee JY, Kim HW, Ryu SH, Rhee H, Yang KS, Joo K, Lee J, Kim CH, Cho KH, Kim D, Yanagi K, Naritomi K, Yoshiura KI, Kondoh T, Nii E, Tonoki H, Houslay MD, Jin DK.
  • Journal Title: Cellular Signaling Volume: 26 (11) Pages: 2446-2459
  • DOI: doi: 10.1016/j.cellsig.2014.07.025.
  • Peer Reviewed
• [Journal Article] De novo SOX11 mutations cause Coffin-Siris syndrome. (2014)
  • Author(s): Tsurusaki Y, Koshimizu E, Ohashi H, Phadke S, Kou I, Shiina M, Suzuki T, Okamoto N, Imamura S, Yamashita M, Watanabe S, Yoshiura K, Kodera H, Miyatake S, Nakashima M, Saitsu H, Ogata K, Ikegawa S, Miyake N, Matsumoto N.
  • Journal Title: Nature Communications Volume: 5 Pages: 4011
  • DOI: doi: 10.1038/ncomms5011.
  • Peer Reviewed
• [Journal Article] Circulating levels of maternal plasma cell-free pregnancy-associated placenta-specific microRNAs are associated with placental weight. (2014)
  • Author(s): Miura K, Morisaki S, Abe S, Higashijima A, Hasegawa Y, Miura S, Tateishi S, Mishima H, Yoshiura K, Masuzaki H.
  • Journal Title: placenta Volume: 35 (10) Pages: 848-851
  • DOI: doi: 10.1016/j.placenta.2014.06.002.
  • Peer Reviewed
• [Journal Article] ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion. (2014)
  • Author(s): Matsumoto H, Tsuchiya T, Yoshiura K, Hayashi T, Hidaka S, Nanashima A, Nagayasu T.
  • Journal Title: Acta Histochemica et Cytochemica Volume: 47 (3) Pages: 85-89
  • DOI: doi: 10.1267/ahc.13040.
  • Peer Reviewed
• [Journal Article] Malfunction of the ERCC1/XPF endonuclease results in diverse clinical manifestations and causes three nucleotide excision-repair-deficient disorders, Cockayne Syndrome, xeroderma pigmentosum and Fanconi Anemia. (2013)
  • Author(s): Kashiyama K, Nakazawa Y, Pilz D, Guo C, Shimada M, Sasaki K, Fawcett H, Wing J, Lewin S, Carr L, Yoshiura K, Utani A, Hirano A, Yamashita S, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Takahashi Y, Nagayama Y, Mitsutake N, Lehmann AR, and Ogi T.
  • Journal Title: American Journal of Human Genetics Volume: 92(5) Pages: 807-819
  • DOI: 10.1016/j.ajhg.2013.04.007
  • Peer Reviewed
• [Journal Article] Initial viral load in cases of single human papillomavirus 16 or 52 persistent infection is associated with progression of later cytopathological findings in the uterine cervix. (2013)
  • Author(s): Hamaguchi D, Miura K, Abe S, Kinoshita A, Miura S, Yamasaki K, Yoshiura KI, Masuzaki H.
  • Journal Title: Journal of Medical Virology Volume: 85(12) Pages: 2093-2100
  • DOI: 10.1002/jmv.23709
  • Peer Reviewed
• [Journal Article] 遺伝性疾患におけるエクソーム解析の有用性と近将来 (2013)
  • Author(s): 吉浦孝一郎
  • Journal Title: 医学のあゆみ Volume: 245(5) Pages: 363-368
• [Presentation] 家族性肺がんにおける新規責任遺伝子の同定 (2014)
  • Author(s): 朝重耕一，渡辺聡，三嶋博之，木下晃，松本桂太郎，及川将弘，宮崎拓郎，土谷智史，山崎直哉，福島喜代康，永安 武，吉浦孝一郎
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] 多発性歯牙腫合併症例を含むSATB2遺伝子変異症候群の新規変異の同定 (2014)
  • Author(s): 三嶋博之，菊入 崇，三古谷 忠，木下晃，吉浦孝一郎
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] Panic障害多発家系例に対するExome解析 (2014)
  • Author(s): 森本芳郎，小野慎治，森 貴俊，黒滝直弘，吉浦孝一郎，小澤寛樹
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] ddPCRを用い他McCune-Albright症候群のGNASモザイク変異検出の試み (2014)
  • Author(s): 渡辺 聡，伊達木 澄人，中富明子，木下 晃，朝重耕一，木下英一，三嶋博之，森内浩幸，吉浦孝一郎
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] 単一遺伝子病の遺伝子診断 (2014)
  • Author(s): 吉浦孝一郎
  • Organizer: 第9回九州遺伝子診断研究会
  • Place of Presentation: 崎大学医学部良順会館（長崎）
  • Year and Date: 2014-09-27 – 2014-09-27
  • Invited
• [Presentation] 次世代シーケンサーで何が出来るのか (2014)
  • Author(s): 吉浦孝一郎
  • Organizer: 第23回日本組織適合性学会大会
  • Place of Presentation: 長崎大学医学部良順会館（長崎）
  • Year and Date: 2014-09-14 – 2014-09-15
  • Invited
• [Presentation] 「予防的乳房切除の今後」 特別企画1－1 遺伝子診断が医療にもたらすもの (2014)
  • Author(s): 吉浦孝一郎
  • Organizer: 第57回日本形成外科学会総会・学術集会
  • Place of Presentation: 長崎ブリックホール（長崎）
  • Year and Date: 2014-04-09 – 2014-04-11
  • Invited
• [Presentation] 「小児血液・主要研究における全エキソーム解析の可能性」 次世代シーケンサーを用いた疾患解析法～総論 (2014)
  • Author(s): 吉浦孝一郎
  • Organizer: 第18回小児血液セミナー
  • Place of Presentation: ANAクラウンプラザホテル福岡（福岡市）
  • Year and Date: 2014-04-05
  • Invited
• [Presentation] Ion AmpliSeqTM Custom Panel を用いたKabuki症候群の変異解析 (2013)
  • Author(s): 渡辺 聡，三嶋博之，朝重耕一，木下晃，吉浦孝一郎
  • Organizer: 第58回日本人類遺伝学会
  • Place of Presentation: 江陽グランドホテル，仙台
  • Year and Date: 20131120-20131123
• [Presentation] 地域蓄積・収集した稀少難病の遺伝子原因究明と遺伝性疾患診断システムの構築 (2013)
  • Author(s): 吉浦孝一郎
  • Organizer: 公開シンポジウム－次世代遺伝子解析装置を用いた難病の原因究明，治療法開発研究プロジェクトの成果－
  • Place of Presentation: 都市センターホテル，東京
  • Year and Date: 20130713-20130713