Centers & Labs

RIKEN BioResource Center

Mutagenesis and Genomics Team

Team Leader: Yoichi Gondo (Ph.D.)
Yoichi  Gondo(Ph.D.)

Efficient mutagenesis technologies and mutation detection systems are indispensable to develop biological resources. The genome-wide mutation discovery is also a key for the quality control of archived bioresources. The Mutagenesis and Genomics Team will develop a high-throughput and high-resolution mutation discovery system in particular to detect unknown newly-arisen mutations in the whole genome of higher eukaryotes. At the same time, we will develop useful mutagenesis infrastructures and technologies and indeed provide useful bioresources such as model mice for human diseases to the research community. We, for instance, used a potent mutagen, ethylnitrosourea (ENU) to induce point mutations in the mouse genome. Then the mutation discovery system allows us to detect randomly induced single-base-substitutions in any target genes. Contrary to ordinary genetics, it is called "reverse genetics" or "gene-driven mutagenesis", which provides mutant mouse lines to understand the biological function of the gene and genome. Mutant mice carrying mutations in candidate genes for human diseases are subjected to study the mechanism of the diseases. In particular, so-called "next-generation sequencing technology" is currently being developed at the astonishing pace and scale. We integrate such state-of-arts technologies to the ultra-throughput detection system of mutations and polymorphisms for the development of human disease models as well as the quality control of our bioresources. The integrated system is now enable to establish new model mice encompassing the gene-to-gene interaction(s). The feasibility to establish polygenic model mice has already been shown by the comprehensive discovery of all the coding mutations by the next-generation sequencers with the whole mouse coding-exon enrichment system.

Main Research Field

Biological Sciences

Related Research Fields

Complex systems

Keywords

  • mutagenesis
  • Functional genomics
  • Next-generation sequencing
  • Disease model
  • Gene-to-gene interaction

Selected Publications

  1. Gondo Y, Makino S, Fukumura R:
    "Forward and Reverse Genetics to Model Human Diseases in the Mouse." in Animal Model for the Study of Human Disease, 2nd Ed. (Ed. By Conn PM),pp.727-752 (2017)
  2. Bi L, Qing T, Zhu J, Wen Z, Yu Y, Fukumura R, Zheng Y, Gondo Y, Shi L:
    "tA Comprehensive Mouse Transcriptomic BodyMap across 17 Tissues by RNA-seq."
    Scientific Reports 7:4200 (2017) doi: 10.1038/s41598-017-04520-z.
  3. Makino S, Fukumura R, Gondo Y:
    "Illegitimate translation causes unexpected gene expression from on-target out-of-frame alleles created by CRISPR-Cas9."
    Scientific Reports 6:39608 (2016) doi: 10.1038/srep39608.
  4. Makino S, Zhulyn O, Mo R, Puviindran V, Zhang X, Murata T, Fukumura R, Ishitsuka Y, Kotaki H, Matsumaru D, Ishii S, Hui CC, Gondo Y:
    "T396I Mutation of Mouse Sufu Reduces the Stability and Activity of Gli3 Repressor."
    PLoS One 10(3):e0119455 (2015) doi: 10.1371/journal.pone.0119455
  5. Murata T, Ishitsuka Y, Karouji K, Kaneda H, Toki H, Nakai Y, Makino S, Fukumura R, Kotaki H, Wakana S, Noda T, Gondo Y:
    "β-CateninC429S mice exhibit sterility consequent to spatiotemporally sustained Wnt signalling in the internal genitalia."
    Scientific Reports 4:6959 (2014) doi: 10.1038/srep06959.
  6. SEQC/MAQC-III Consortium.:
    "A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium."
    Nature Biotechnol 32(9):903-14 (2014) doi: 10.1038/nbt.2957
  7. Rivkin E, Almeida SM, Ceccarelli DF, Juang YC, MacLean TA, Srikumar T, Huang H, Dunham WH, Fukumura R, Xie G, Gondo Y, Raught B, Gingras AC, Sicheri F, Cordes SP:
    "The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis."
    Nature 498(7454):318-24 (2013) doi: 10.1038/nature12296
  8. Gondo Y:
    "Do long and highly conserved noncoding sequences in vertebrates have biological functions?"
    in Evolutionary Biology – Concepts, Molecular and Morphological Evolution (Ed. by P. Pontarotti), pp.187-206 (2010)
  9. Gondo Y, Fukumura R:
    "ENU-induced mutant mice for a next-generation gene-targeting system."
    Prog Brain Res 179:29-34 (2009) doi: 10.1016/S0079-6123(09)17904-9
  10. Gondo Y:
    "Trends in large-scale mouse mutagenesis: from genetics to functional genomics."
    Nature Reviews Genetics 9(10):803-10 (2008) doi: 10.1038/nrg2431

Lab Members

Principal Investigator

Yoichi Gondo
Team Leader

Core Members

Ryutaro Fukumura
Research and Development Scientist
Shigeru Makino
Research and Development Scientist
Yuji Nakai
Technical Scientist
Yuichi Ishitsuka
Technical Staff II
Hayato Kotaki
Technical Staff II

Contact information

3-1-1 Koyadai
Tsukuba, Ibaraki
305-0074 Japan

Email: enu-target [at] brc.riken.jp

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