Applied Genomics

• Project/Area Number: 16065101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: TSUJI Shoji The University of Tokyo, 医学部附属病院, 教授 (70150612)
• Co-Investigator(Kenkyū-buntansha): 笹月 健彦 東京大学, 国立国際医療センター, 総長 (50014121) ; 菅野 純夫 東京大学, 医科学研究所, 教授 (60162848) ; 小笠原 直毅 奈良先端科学技術大学院大学, 情報科学研究科, 教授 (10110553) ; 林 健志 九州大学, 生体防御医学研究所, 教授 (00019671) ; 猪子 英俊 東海大学, 医学部, 教授 (10101932)
• Co-Investigator(Renkei-kenkyūsha): SASATSUKI Takehiko 東京大学, 国立国際医療センター, 総長 (50014121) ; SUGANO Sumio 東京大学, 大学院・新領域創成科学研究科, 教授 (60162848) ; OGASAWAEA Naotake 奈良先端科学技術大学院大学, 情報科学研究科, 教授 (10110553) ; GOJOBORI Takashi 国立遺伝学研究所, 生命情報・DDBJ研究センター, 教授 (50162136) ; INOUE Itsuro 東海大学, 医学部, 教授 (00192500) ; HAYASHI Tetsuya 宮崎大学, フロンティア科学実験総合センター, 教授 (10173014) ; KATO KAZUTO 京都大学, 人文科学研究所, 准教授 (10202011) ; INOKO Hidetoshi 東海大学, 医学部, 教授 (10101932) ; HAYASHI Kenshi 九州大学, 生体防御医学研究所, 教授 (00019671) ; FUKUSHIMA YOSHIMITU 信州大学, 医学部, 教授 (70273084) ; HATA Akira 千葉大学, 大学院・医学研究院・公衆衛生, 教授 (00244541) ; TAKAKU Humimaro 自治医科大学, 学長 (40048955) ; YOSHIDA Mituaki 東京大学, 大学院・新領域創成科学研究科, 教授 (80012607) ; KATUKI Motoya 自然科学研究機構 (20051732) ; YOSHIDA Teruhiko 国立がんセンター, 研究所 (10191602) ; NAKAMURA Yusuke 東京大学, 医科学研究所ヒトゲノム解析センター, 所長 (70217909) ; BEPPU Teruhiko 日本大学, 大学院・総合科学研究科, 教授 (80011873) ; IDA Ryuiti 京都大学, 大学院・公共政策連携研究部, 教授 (40127543) ; TAKAGI Toshihisa 東京大学, 大学院・新領域創成科学研究科, 教授 (30110836)
• Project Period (FY): 2004 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥232,300,000 (Direct Cost: ¥232,300,000); Fiscal Year 2009: ¥45,000,000 (Direct Cost: ¥45,000,000); Fiscal Year 2008: ¥45,000,000 (Direct Cost: ¥45,000,000); Fiscal Year 2007: ¥48,600,000 (Direct Cost: ¥48,600,000); Fiscal Year 2006: ¥41,600,000 (Direct Cost: ¥41,600,000); Fiscal Year 2005: ¥48,600,000 (Direct Cost: ¥48,600,000); Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
• Keywords: 疾患関連遺伝子 / ゲノムワイド関連解析 / ヒトゲノム配列再解析 / メディカルインフォマティクス / 微生物ゲノム / 産業微生物ゲノム / ゲノム / 遺伝子 / 臨床 / 微生物 / 社会医学 / 分子遺伝学 / 多型解析 / 有用微生物 / 病原微生物 / ゲノムインフォーマティック / 生命倫理 / 遺伝医学 / ゲノムインフォーマティックス

Research Abstract

This study has focused on application of genome-based studies for better understanding the molecular mechanisms of diseases, for better understanding mechanisms of production of substances useful for human life by microorganisms, and for better understanding the molecular basis of pathogenecity of virulent microorganisms. This study has also focused on various issues arising between the genome research and the society. In the study for better understanding the molecular mechanisms of diseases, we have identified causative genes for various diseases including erebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL),Costello syndrome,and cardio-facio-cutaneous (CFC) syndrome. For polygenic diseases, we have identified disease-susceptibility genes for a number of diseases including diabetes mellitus, cerebral aneurysms, rheumatoid arthritis and Parkinson disease. In the research focusing on production of useful substances by microorganisms, we have elucidated the molecular basis for production of substances for human life based on the genome structures of Aspergillus oryzae and Actinomyces. With regard to the molecular basis of virulent microorganisms, we have elucidated molecular basis of virulence of O157 (Enterohemorrhagic Escherichia coli). In the research field of society-genome interactions, we have focused on science communication of genome research activities. We have also put our effort to encourage collection of genomic resources by introducing the education and certification systems for genome medical research coordinators.

Research Products

• [Journal Article] Familial Ischemic Cerebral Small-Vessel Disease, Alopecia, and Spondylosis Caused by Mutations in the HTRA1 Gene (2009)
  • Author(s): Hara K, Shiga A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A, Kawata H, Koyama A, Arima K, Takahashi T, Ikeda M, Shiota H, Tamura M, Shimoe Y, Hirayama M, Arisato T, Yanagawa S, Tanaka A, Nakano I, Ikeda S, Yoshida Y, Yamamoto T, Ikeuchi T, Kuwano R, Nishizawa M, Tsuji S, Onodera O.
  • Journal Title: New Engl J Med 360 Pages: 1729-1739
• [Journal Article] Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease (2009)
  • Author(s): Hara K, Shiga A, Fukutake T, et al.
  • Journal Title: New Engl.J.Med. 360 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease (2009)
  • Author(s): Sidransky E, Nalls MA, Aasly JO, et al.
  • Journal Title: New Engl.J.Med. 361 Pages: 1651-1661
  • Peer Reviewed
• [Journal Article] SNP haplotype mapping in a small ALS family (2009)
  • Author(s): Krueger KA, Tsuji S, Fukuda Y, et al.
  • Journal Title: PLoS One 4
  • Peer Reviewed
• [Journal Article] Development of high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis (2008)
  • Author(s): Takahashi Y, Seki N, Ishiura H, Mitsui J, Matsukawa T, Kishino A, Onodera O, Aoki M, Shimozawa M, Murayama S, Itoyama Y, Suzuki Y, Sobue S, Nishizawa M, Goto J and Tsuji S.
  • Journal Title: Arch Neurol 65 Pages: 1326-32
  • Peer Reviewed
• [Journal Article] Appropriate data cleaning methods for genome-wide association study (2008)
  • Author(s): Miyagawa T, Nishida N, Ohashi J, Kimura R, Fujimoto A, Kawashima M, Koike A, Sasaki T, Tanii H, Otowa T, Momose Y, Nakahara Y, Goto J, Okazaki Y, Tsuji S and Tokunaga K.
  • Journal Title: J Hum Genet 53 Pages: 886-93
  • Peer Reviewed
• [Journal Article] Multiplex families with multiple system atrophy (2007)
  • Author(s): Hara K, Momose Y, Tokiguchi S, Shimohata M, Terajima K, Onodera O, Kakita A, Yamada M, Takahashi H, Hirasawa M, Mizuno Y, Ogata K, Goto J, Kanazawa K, Nishizawa M, and Tsuji S
  • Journal Title: Arch. Neurol 64 Pages: 545-551
  • Peer Reviewed
• [Journal Article] Aprataxin, causative gene product for EAOH/AOA1, repairs DNA single-strand breaks with 3 f-phosphate and 3 f-phosphoglycolate ends. (2007)
  • Author(s): Takahashi T, Tada M, Igarashi S, Koyama A, Date H, Yokoseki A, Shiga A, Yoshida Y, Tsuji S, Nishizawa M. *Onodera O.
  • Journal Title: Nucleic Acids Res. 35 Pages: 3797-3809
  • Peer Reviewed
• [Journal Article] Analysis of KRAP expression and localization, and genes regulated by KRAP in a human colon cancer cell line (2007)
  • Author(s): Fujimoto, T., Koyanagi, M., Baba, I., Nakabayashi, K, Kato, N., Sasazuki, T., Shirasawa, S.
  • Journal Title: J. Hum. Genet. 52 Pages: 978-984
  • NAID: 10020022213
  • Peer Reviewed
• [Journal Article] Comparasite : a database for comparative study of transcriptomes of parasites defined by full-length cDNAs. (2007)
  • Author(s): Watanabe, J., Wakaguri, H., Sasaki, M., Suzuki, Y., Sugano, S.
  • Journal Title: Nucleic Acids Res. 35 (Database issue)
• [Journal Article] The accurate replacement of long genome region more than several hundreds kilobases in Bacillus subtilis. (2007)
  • Author(s): Liu, S., Endo, K., Ara, K., Ozaki, K., Ogasawara, N.
  • Journal Title: Genes and Genetic Systems 82 Pages: 9-19
• [Journal Article] D-HaploDB : a database of definitive haplotypes determined by genotyping complete hydatidiform mole samples. (2007)
  • Author(s): Higasa, K., Miyatake K., Kukita, Y., Tahira, T., Hayashi, K.
  • Journal Title: Nucleic Acids Res. 35 (Database issue)
• [Journal Article] Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro. (2006)
  • Author(s): Furuno, K., Masatsugu, T., Sonoda, M., Sasazuki, T., Yamamoto, K.
  • Journal Title: Biochem. Biphys. Res. Commun. 345 Pages: 1051-1058
• [Journal Article] Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis. (2006)
  • Author(s): Noirot-Gros, M F., Velten, M., Yoshimura, M., McGovern, S., Morimoto, T., Ehrlich, S D., Ogasawara, N., Polard, P., Noirot, P.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 103 Pages: 2368-2373
• [Journal Article] The GTP-binding protein YlqF participates in the late step of 50 S ribosomal subunit assembly in Bacillus subtilis. (2006)
  • Author(s): Matsuo, Y., Morimoto, T., Kuwano, M., Loh, P C., Oshima, T., Ogasawara, N.
  • Journal Title: J. Biol. Chem. 281 Pages: 8110-8117
• [Journal Article] Genomewide association analysis of human narcolepsy and a new resistance gene. (2006)
  • Author(s): Kawashima, M., Tamiya, G., Oka, A., Hohjoh, H., Juji, T., Ebisawa, T., Honda, Y., Inoko, H., Tokunaga, K.
  • Journal Title: Amer. J. Hum. Genet. 79 Pages: 252-263
• [Journal Article] DataBase of Human Transcription Start Sirtes, progress report 2006. (2006)
  • Author(s): Yamashita, R., Suzuki, Y., Wakaguri, H., Tsuritani, K., Nakai, K., Sugano, S.
  • Journal Title: Nucleic Acids Res 34
• [Journal Article] The GTP-binding Protein YlqF Participates in the Late Step of 50 S Ribosomal Subunit Assembly in Bacilfus subtilis. (2006)
  • Author(s): Matsuo, Y., Morimoto, T., Kuwano, M., Loh, PC., Oshima, T., Ogasawara, N.
  • Journal Title: J Biol Chem 281 Pages: 8110-8117
• [Journal Article] Role of epiregulin in peptidoglycan-induced proinflammatory cytokine production by antigen presenting cells. Biochem Biophys (2005)
  • Author(s): Sugiyama, S., Nakabayashi, K., Baba, I., Sasazuki, T., Shirasawa, S
  • Journal Title: Res Commun 337 Pages: 271-274
• [Journal Article] Genome-wide detinitive haplotypes determined using a collection of complete hydatidirorm moles. (2005)
  • Author(s): Kukita, Y., Miyatake, K., Stokowski, R., Hinds, D.Higasa, K., Wake, N., Hirakawa, T., Kato, H., Matsuda, T., Pant, K., Cox, D., Taira, T., Hayashi, K.
  • Journal Title: Genome Res 15 Pages: 1511-1518
• [Journal Article] Whole genome association study of rheumatoid arthritis using 27039 microsatellites. (2005)
  • Author(s): Tamiya, G., Shinya, M., Imanishi, T., Ikuta, T., Makino, S., Okamoto, K., Furugaki, K., Matsumoto, T., Mano, S., Ando, S., Nozaki, Y., Yukawa, W., Nakashige, R., Yamaguchi, D., Ishibashi, H., Yonekura, M., Nakami, Y., Takayama, S., Endo, T., Saruwatari, T., Yagura, M., Yoshikawa, Y., Fujimoto, K., Oka, A., Chiku, S., Linsen, S.E., Giphart, M.J., Kulski, J.K., Fukazawa, T., Hashimoto, H., Kimura, M., Hoshina, Y., Suzuki, Y., Hotta, T., Mochida, J., Minezaki, T., Komai, K., Shiozawa, S., taniguchi, A., Yamanaka, H., Kamatani, N., Gojobori, T., Bahram, S., Inoko, H.
  • Journal Title: Hum Mol Genet 14 Pages: 2305-2321
• [Journal Article] Interference of CREB dependent transcriptional activation expanded opolyglutamine stretches- Aumentation of transcriptional activation as a potential therapeutic strategy for polyglutarnine diseases/ (2005)
  • Author(s): Shimohata, M, Shimohata, T,.Igarashi, S, Naruse, S, Tsujil, S.
  • Journal Title: J.Neurochem 93 Pages: 654-663
• [Journal Article] Japanese SCA families with a distinct phenotype linked to a locus overlapping with SCA15 locus (2004)
  • Author(s): Hara, K, Fukushima, T, Suzuki, T, Shimohata, T, Oyake, M, Ishiguro, H, Hirota, K, Miyashita, A, Kuwano, R, Kurisaki, H, Yomono, H, Goto, J, Kanazawa, I, Tsuji, S
  • Journal Title: Neurol 62 Pages: 648-651
• [Journal Article] Dermatitis due to epiregulin deficiency and a critical role of epiregulin in immune-related responses of keratinocyte and macrophage. (2004)
  • Author(s): Shirasawa S, Sugiyama S, Baba I, Inokuchi J, Sekine S, Ogino K, Kawamura Y, Dohi T, Fujimoto M, Sasazuki T.
  • Journal Title: Proc Natl Acad Sci USA 101・38 Pages: 1391-1396
• [Journal Article] International Chicken Genome Sequencing Consortium () : Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. (2004)
  • Author(s): Hillier LW, Fulton LA, Mardis ER, Wilson RK, Inoko H, Shiina T et al.
  • Journal Title: Nature 432 Pages: 449-451
• [Journal Article] Promoter prediction analysis on the whole human genome. (2004)
  • Author(s): Bajic VB, Tan SL, Suzuki Y, Sugano S.
  • Journal Title: Nat Biotechnol. 22 Pages: 1467-1473
• [Journal Article] Zinc is a key factor in controlling alternation of two types of L31 protein in the Bacillus subtilis ribosome. (2004)
  • Author(s): Nanamiya H, Akanuma G., Natori Y, Murayama R, KosOno S, Kudo T, Kobayashi K, Ogasawara N, Park SM, Ochi K, Kawamura, F.
  • Journal Title: Mol Microbiol 52 Pages: 273-283
• [Journal Article] Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese
  • Author(s): Takei N, Miyashita A, Tsukie T, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kimura H, Kakita A, Takahashi H, Tsuji S, Kanazawa I, I hara Y, Odani S and Kuwano R.
  • Journal Title: Genomics (in press)
  • Peer Reviewed
• [Journal Article] SNP HiTLink : a high-throughput linkage analysis system employing dense SNP data
  • Author(s): Fukuda Y, Nakahara Y, Date H, Takahashi Y, Goto J, Miyashita A, Kuwano R, Adachi H, Nakamura E and Tsuji S.
  • Journal Title: BMC Bioinformatics (in press)
  • Peer Reviewed
• [Journal Article] Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or ZD4 genes.
  • Author(s): Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H.
  • Journal Title: Human Mutation (in press)
• [Presentation] Nation-Wide Survey on the Epidemiology and the Natural History of Spinocerebellar Degenerations in Japan (2009)
  • Author(s): Shoji Tsuji
  • Organizer: V International Workshop on Machado-Joseph Disese
  • Place of Presentation: S.Miguel, Portugal
• [Remarks] ホームページ等
  • URL: http://www.genome-sci.jp/
• [Remarks]
  • URL: https://www.genome-sci.jp/modules/contents1/rewrite/tc_5.html
• [Patent(Industrial Property Rights)] Association of HTRA1 mutations and familial ischemic cerebral small-vessel dieases. (2010)
  • Inventor(s): 辻省次, 小野寺理
  • Industrial Property Rights Holder: The University of Tokyo
  • Filing Date: 2010-04-20