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Mutagenesis and Genomics Team
Yoichi GONDO
Team Leader
Yoichi GONDO (Ph.D.)
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Research Areas

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 developed bioresources. The Mutagenesis and Genomics Team will develop a high-throughput and high-resolution mutation discovery system in particular to detect unknown newly-arizen mutations in the whole genome of higher eukaryotes. At the same time, we will develop useful mutagenesis infrastructure and technology and indeed provide useful bioresources such as model mice for human diseases to the research community. We use 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 target genes. Contrary to ordinary genetics, it is called "reverse genetics" or "gene-driven mutagenesis", which provide 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 elucidate the mechanism of the diseases. In particular, so-called "next-generation sequencing technology" is currently being developed at the astonishing pace and scale. We integurate 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 now enable to establish new model mice encomappsing the gene-to-gene interaction(s). The feasiblity of polygenic model mice have already shown by the comprehensive discovery of all the coding mutations by the next-generation sequencers with the whole mouse coding-exon enrichment system.

Research Subject

  1. Development of ENU-based gene-driven mutagenesis and modeling human diseases in the mouse.
  2. Development of the mutation discovery system for newly-arizen mutations and polymorphisms with next-generation techonologies.
  3. Development of resources for the functional genomics including human and mouse gene-to-gene interactions.
  4. Maintenance of bioresource based on mutations, recombinations and rearrangements of the genome.
  5. Development of model systems for the highly conserved noncoding genomic sequences in the genome.

Related links

  1. RIKEN BioResource Center Website_Laboratories PageNew Window
  2. Individual Website Laboratory PageNew Window
  3. NEXT-GENERATION GENE-TARGETING PageNew Window

Press release

September 10, 2008
Developing a method for sophisticated genome function analysis at the single base level

List of Selected Publications

  1. Janes DE, Chapus C, Gondo Y, Clayton DF, Sinha S, Blatti CA, Organ CL, Fujita MK, Balakrishnan CN, Edwards SV.:
    "Reptiles and mammals have differentially retained long conserved non-coding sequences from the amniote ancestor."
    Genome Biol Evol 3: 102-113, 2011.
  2. Gondo, Y., Fukumura, R., Murata, T., Makino, S.:
    "ENU-based gene-driven mutagenesis in the mouse: a next-generation gene-targeting system."
    Exp Anim. 59(5): 537-548, 2010.
  3. Gondo, Y.:
    "Now and future of mouse mutagenesis for human disease models."
    J Genet Genomics 37(9): 559-572, 2010.
  4. Gondo, Y.:
    "Do Long and Highly Conserved Noncoding Sequences in Vertebrates Have Biological Functions?"
    Evolutionary Biology: Concepts, Molecular and Morphological Evolution, pp.187-206, 2010.
  5. Gondo, Y., Fukumura, R.:
    "ENU-induced mutant mice for a next-generation gene-targeting system."
    Progress in Brain Research 179: 29-34, 2009
  6. Viviane, L., Fukumura, R., Rastogi, A., Fick, L.J., Wang, W., Boutros, P.C., Kennedy, J.L., Semeralul, M.O., Lee, F.H., Baker, G.B., Belsham, D.D., Barger, S.W., Gondo, Y., Wong, A.H.C., Roder, J.C.:
    "Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model."
    Human Molecular Genetics 18(17): 3227-3243, 2009.
  7. Gondo, Y.:
    "Trends in large-scale mouse mutagenesis: from genetics to functional genomics."
    Nature Reviews Genetics 9: 803-810, 2008.
  8. Erickson, R.P., McQueen, C.A., Chau, B., Gokhale, V., Uchiyama, M., Toyoda, A., Ejima, F., Maho, N., Sakaki, Y., Gondo, Y.:
    "An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice."
    Biochem. Biophys. Res. Commun. 370: 285-288, 2008.
  9. Clapcote, S.J., Lipina, T.V., Millar, J.K., Mackie, S.., Christie, S., Ogaawa, F., Lerch, J.P., Trimble, K., Uchiyama, M., Sakuraba, Y., Kaneda, H., Shiroishi, T., Houslay, M.D., Henkelman, R.M., Sled, J.G., Gondo, Y., Porteous, D.J., Roder, J.C.:
    "Behavioral phenotypes of Disc1 missense mutations in mice."
    Neuron 54: 387-402, 2007.
  10. Masuya, H., Sezutsu, H., Sakuraba, Y., Sagai, T., Hosoya, M., Kaneda, H., Miura, I., Kobayashi, K., Sumiyama, K., Shimizu, A., Nagano, J., Yokoyama, H., Kaneko, S., Sakurai, N., Okagaki, Y., Noda, T., Wakana, S., Gondo, Y., Shiroishi, T.:
    "A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud."
    Genomics 89(2): 207-214, 2007.

Members

Principal Investigator

Yoichi GONDO
Team Leader

Staff Scientist

Takuya MURATA
Research and Development Scientist
Ryutaro FUKUMURA
Research and Development Scientist
Shigeru MAKINO
Research and Development Scientist
Yuji NAKAI
Technical Scientist

Technical Assistant

Hayato KOTAKI
Technical Staff 2
Yuichi ISHITSUKA
Technical Staff 2