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Outline of our achievements

Chromosome Engineering Team

About our research

Purpose of our research

  To date, various human diseases have been elucidated at the gene level, and genetic analyses are performed in clinical practice. Meanwhile, research aimed at identifying genes responsible for remaining human diseases is being performed by using accumulated human DNA sequence data from patients. Even diseases with similar symptoms can be distinguished by identification of genes responsible for the diseases. Analysis of mutations in the human genome can inform us about the risk that an individual will be predisposed to a certain disease. Our team is also producing mouse models of human disease by introducing the relevant genetic mutations into the mouse genome. The availability of excellent mouse models of human disease, in conjunction with our genome engineering technology, will provide a greater understanding of human disease. We would be pleased if the information and knowledge resulting from our research were able to promote development of therapeutic medicines and diagnostic methods.

Characteristics of our research

  As the pathogenic mechanism of various types of human disease is elucidated, more complicated and precise genome engineering technologies are needed to produce mouse models of complex human diseases. We have developed two novel site-specific recombination systems that can eliminate or invert any DNA region on the genome; these technologies have been patented. We have successfully used these novel site-specific recombination systems to modify the mouse genome. We are developing an improved human artificial chromosome (HAC) technology by adapting these site-specific recombination systems. As described above, we are focusing on developing genome engineering technologies.
 As a collaboration with an outside research institution, we are proceeding with a project called “Establishment of pipe-line system for systematical production of conditional knockout mice to identify genes responsible for human common disease.”  Via this collaboration, we hope to make a specific contribution to solving human health problems.

Expected fields of application

  We are attempting to generate mouse models of human disease by introducing the single-nucleotide polymorphisms (SNPs) related to human disease (i.e., SNPs identified in current or future patients) into the mouse genome. Such research will help to determine whether these SNPs are responsible for the disease. From the results of these studies, we will obtain useful basic information and knowledge regarding human disease, and this knowledge will in turn contribute to the development of novel therapeutic approaches. By improving an existing high-throughput DNA sequencing system using clinical samples from patients or healthy individuals, we are aiming at developing a system capable of generating diagnostic DNA data that will be useful in clinical practice in the future.
 We will provide our technical know-how, accumulated during the production of disease models in mice, to research institutes and private companies inside and outside Chiba prefecture because we hope to aggressively promote cooperation with the industrial sector.

Members

Manabu Nakayama team leader nmanabu at kazusa.or.jp