Hunting and analysis of novel genes causing Fanconi anemia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H01738
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: Takata Minoru 京都大学, 放射線生物研究センター, 教授 (30281728)
• Co-Investigator(Kenkyū-buntansha): 石合 正道 京都大学, 放射線生物研究センター, 准教授 (90298844) ; 佐藤 浩一 早稲田大学, 理工学術院, 次席研究員(研究院助教) (60708585)
• Co-Investigator(Renkei-kenkyūsha): Hosokawa Hiroshi 京都大学, 情報学研究科, 講師 (90359779) ; Maegawa Shingo 京都大学, 情報学研究科, 助教 (30467401)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ファンコニ貧血 / FA経路 / RFWD3 / ユビキチン化

Outline of Final Research Achievements

We analyzed unclassified FA cases and found that many of them are caused by slicing defects in known FA genes that were not evident in whole exome sequencing. We also identified two siblings that carry biallelic mutations in an important DNA repair factor. In 20 Indian FA cases, we identified frequent specific FANCL mutations, which are very rare in other ethnic groups. We generated novel zebrafish FANCT or FANCD2 model that resulted in 100% male fish. In collaborative efforts with German group, we established mutations in RFWD3 gene encoding a E3 ubiquitin ligase causes FA phenotype and that its targets are critical homologous recombination regulators, RPA and RAD51.

Free Research Field

放射線分子生物学、化学物質影響科学、