87 results on '"Tadasu Shin-I"'
Search Results
2. Idiotope-Driven T-Cell/B-Cell Collaboration-Based T-Cell Epitope Prediction Using B-Cell Receptor Repertoire Sequences in Infectious Diseases
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Yukio Nakamura, Meng Ling Moi, Takashi Shiina, Tadasu Shin-I, and Ryuji Suzuki
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T-cell epitope ,antigen ,idiotype network ,repertoire analysis ,anti-idiotypic antibody ,idiotope-driven T-B collaboration ,Microbiology ,QR1-502 - Abstract
T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore, important for understanding diverse immune responses and controlling T-cell immunity. A number of bioinformatic tools exist that predict T-cell epitopes; however, many of these methods highly rely on evaluating conventional peptide presentation by major histocompatibility complex (MHC) molecules, but they ignore epitope sequences recognized by T-cell receptor (TCR). Immunogenic determinant idiotopes are present on the variable regions of immunoglobulin molecules expressed on and secreted by B-cells. In idiotope-driven T-cell/B-cell collaboration, B-cells present the idiotopes on MHC molecules for recognition by idiotope-specific T-cells. According to the idiotype network theory formulated by Niels Jerne, such idiotopes found on anti-idiotypic antibodies exhibit molecular mimicry of antigens. Here, by combining these concepts and defining the patterns of TCR-recognized epitope motifs (TREMs), we developed a T-cell epitope prediction method that identifies T-cell epitopes derived from antigen proteins by analyzing B-cell receptor (BCR) sequences. This method allowed us to identify T-cell epitopes that contain the same TREM patterns between BCR and viral antigen sequences in two different infectious diseases caused by dengue virus and SARS-CoV-2 infection. The identified epitopes were among the T-cell epitopes detected in previous studies, and T-cell stimulatory immunogenicity was confirmed. Thus, our data support this method as a powerful tool for the discovery of T-cell epitopes from BCR sequences.
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- 2023
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3. Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
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Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, and Tatsuo Ichinohe
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Medicine ,Science - Abstract
Abstract To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
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- 2017
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4. Genome sequence and analysis of the Japanese morning glory Ipomoea nil
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Atsushi Hoshino, Vasanthan Jayakumar, Eiji Nitasaka, Atsushi Toyoda, Hideki Noguchi, Takehiko Itoh, Tadasu Shin-I, Yohei Minakuchi, Yuki Koda, Atsushi J. Nagano, Masaki Yasugi, Mie N. Honjo, Hiroshi Kudoh, Motoaki Seki, Asako Kamiya, Toshiyuki Shiraki, Piero Carninci, Erika Asamizu, Hiroyo Nishide, Sachiko Tanaka, Kyeung-Il Park, Yasumasa Morita, Kohei Yokoyama, Ikuo Uchiyama, Yoshikazu Tanaka, Satoshi Tabata, Kazuo Shinozaki, Yoshihide Hayashizaki, Yuji Kohara, Yutaka Suzuki, Sumio Sugano, Asao Fujiyama, Shigeru Iida, and Yasubumi Sakakibara
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Science - Abstract
Japanese morning glory (Ipomoea nil) has diverse flowering traits. Here, the authors describe the reference genome sequence of I. nil, annotations of genes and transposons, and compare evolution of the I. nilgenome to other Convolvulaceae and Solanales genomes.
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- 2016
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5. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein
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Takuma Hashimoto, Daiki D. Horikawa, Yuki Saito, Hirokazu Kuwahara, Hiroko Kozuka-Hata, Tadasu Shin-I, Yohei Minakuchi, Kazuko Ohishi, Ayuko Motoyama, Tomoyuki Aizu, Atsushi Enomoto, Koyuki Kondo, Sae Tanaka, Yuichiro Hara, Shigeyuki Koshikawa, Hiroshi Sagara, Toru Miura, Shin-ichi Yokobori, Kiyoshi Miyagawa, Yutaka Suzuki, Takeo Kubo, Masaaki Oyama, Yuji Kohara, Asao Fujiyama, Kazuharu Arakawa, Toshiaki Katayama, Atsushi Toyoda, and Takekazu Kunieda
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Science - Abstract
Tardigrades are resistant to extreme environmental conditions including dehydration, radiation and the vacuum of space. Here the authors present a high-quality genome which displays minimal horizontal gene transfer, and identify the unique tardigrade protein Dsup which suppresses DNA damage.
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- 2016
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6. Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host–Gut Microbiome Interactions
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Tatsuo Ichinohe, Takahiko Miyama, Takakazu Kawase, Yasuko Honjo, Kazutaka Kitaura, Hiroyuki Sato, Tadasu Shin-I, and Ryuji Suzuki
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next-generation immune repertoire sequencing ,B-cell receptors ,T-cell receptors ,single-cell transcriptomics ,human microbiome ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host–microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.
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- 2018
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7. Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia
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Takero Shindo, Kazutaka Kitaura, Hiroshi Ureshino, Kazuharu Kamachi, Masaharu Miyahara, Kazuko Doi, Tatsuro Watanabe, Eisaburo Sueoka, Tadasu Shin-I, Ryuji Suzuki, and Shinya Kimura
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adult t cell leukemia ,mogamulizumab ,t cell receptor ,immune reconstitution ,next generation sequencing ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+ T cells and oligoclonal CD8+ T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.
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- 2018
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8. Polycystic kidney disease in the medaka (Oryzias latipes) pc mutant caused by a mutation in the Gli-Similar3 (glis3) gene.
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Hisashi Hashimoto, Rieko Miyamoto, Naoki Watanabe, Dai Shiba, Kenjiro Ozato, Chikako Inoue, Yuko Kubo, Akihiko Koga, Tomoko Jindo, Takanori Narita, Kiyoshi Naruse, Kazuko Ohishi, Keiko Nogata, Tadasu Shin-I, Shuichi Asakawa, Nobuyoshi Shimizu, Tomotsune Miyamoto, Toshio Mochizuki, Takahiko Yokoyama, Hiroshi Hori, Hiroyuki Takeda, Yuji Kohara, and Yuko Wakamatsu
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Medicine ,Science - Abstract
Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients.
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- 2009
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9. Supplementary Table 1 from Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Shinya Kimura, Shimon Sakaguchi, Ryuji Suzuki, Tadasu Shin-I, Masaharu Miyahara, Susumu Kusunoki, Makoto Samukawa, Hiromi Kimura, Kotaro Nagase, Kazuko Doi, Hiroaki Kitamura, Kazutaka Kitaura, Natsuko Satoh, Eri Watanabe, Nobukazu Watanabe, Hiroyoshi Nishikawa, Takero Shindo, and Hiroshi Ureshino
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Adaptor ligation and PCR primer sequences
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- 2023
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10. Supplementary Figure 2 from Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Shinya Kimura, Shimon Sakaguchi, Ryuji Suzuki, Tadasu Shin-I, Masaharu Miyahara, Susumu Kusunoki, Makoto Samukawa, Hiromi Kimura, Kotaro Nagase, Kazuko Doi, Hiroaki Kitamura, Kazutaka Kitaura, Natsuko Satoh, Eri Watanabe, Nobukazu Watanabe, Hiroyoshi Nishikawa, Takero Shindo, and Hiroshi Ureshino
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Histopathological findings of the skin rash and the brain (Case 2)
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- 2023
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11. Data from Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Shinya Kimura, Shimon Sakaguchi, Ryuji Suzuki, Tadasu Shin-I, Masaharu Miyahara, Susumu Kusunoki, Makoto Samukawa, Hiromi Kimura, Kotaro Nagase, Kazuko Doi, Hiroaki Kitamura, Kazutaka Kitaura, Natsuko Satoh, Eri Watanabe, Nobukazu Watanabe, Hiroyoshi Nishikawa, Takero Shindo, and Hiroshi Ureshino
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The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA–Foxp3++CCR4+ phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644–9. ©2016 AACR.
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- 2023
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12. Supplementary Table 2 from Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Shinya Kimura, Shimon Sakaguchi, Ryuji Suzuki, Tadasu Shin-I, Masaharu Miyahara, Susumu Kusunoki, Makoto Samukawa, Hiromi Kimura, Kotaro Nagase, Kazuko Doi, Hiroaki Kitamura, Kazutaka Kitaura, Natsuko Satoh, Eri Watanabe, Nobukazu Watanabe, Hiroyoshi Nishikawa, Takero Shindo, and Hiroshi Ureshino
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The numbers of sequence reads
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- 2023
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13. Supplementary Figure 1 from Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Shinya Kimura, Shimon Sakaguchi, Ryuji Suzuki, Tadasu Shin-I, Masaharu Miyahara, Susumu Kusunoki, Makoto Samukawa, Hiromi Kimura, Kotaro Nagase, Kazuko Doi, Hiroaki Kitamura, Kazutaka Kitaura, Natsuko Satoh, Eri Watanabe, Nobukazu Watanabe, Hiroyoshi Nishikawa, Takero Shindo, and Hiroshi Ureshino
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Histopathological findings of the skin (Case 1)
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- 2023
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14. UTGB/medaka: genomic resource database for medaka biology.
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Budrul Ahsan, Daisuke Kobayashi, Tomoyuki Yamada, Masahiro Kasahara, Shin Sasaki, Taro L. Saito, Yukinobu Nagayasu, Koichiro Doi, Yoichiro Nakatani, Wei Qu, Tomoko Jindo, Atsuko Shimada, Kiyoshi Naruse, Atsushi Toyoda, Yoko Kuroki, Asao Fujiyama, Takashi Sasaki, Atsushi Shimizu, Shuichi Asakawa, Nobuyoshi Shimizu, Shin-ichi Hashimoto, Jun Yang, Yongjun Lee, Kouji Matsushima, Sumio Sugano, Mitsuru Sakaizumi, Takanori Narita, Kazuko Ohishi, Shinobu Haga, Fumiko Ohta, Hisayo Nomoto, Keiko Nogata, Tomomi Morishita, Tomoko Endo, Tadasu Shin-I, Hiroyuki Takeda, Yuji Kohara, and Shinichi Morishita
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- 2008
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15. YAMATO and ASUKA: DNA database management system.
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Hajime Kitakami, Tadasu Shin-I, Kazuho Ikeo, Yoshihiro Ugawa, Naruya Saitou, Takashi Gojobori, and Yoshio Tateno
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- 1995
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16. Construction of complete Tupaia belangeri transcriptome database by whole-genome and comprehensive RNA sequencing
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Kyoko Tsukiyama-Kohara, Mohammad Enamul Hoque Kayesh, Yasuhiro Yasutomi, Tadasu Shin-I, Yumiko Shiogama, Daisuke Yamane, Takahiro Sanada, Naoki Yamamoto, Kazuho Ikeo, Michinori Kohara, Masashi Mizokami, Jun-ichiro Takano, and Takashi Gojobori
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0301 basic medicine ,Male ,Hepatitis B virus ,Sequence analysis ,lcsh:Medicine ,Biology ,computer.software_genre ,Genome ,Article ,Transcriptome ,Genomic analysis ,03 medical and health sciences ,Tupaia belangeri ,Open Reading Frames ,0302 clinical medicine ,Databases, Genetic ,Animals ,RNA, Messenger ,lcsh:Science ,Gene ,Tupaia ,Multidisciplinary ,Database ,Base Sequence ,Sequence Analysis, RNA ,lcsh:R ,RNA ,Reproducibility of Results ,biology.organism_classification ,Hepatitis B ,genomic DNA ,030104 developmental biology ,Gene Ontology ,Type I interferon signaling pathway ,Gene Expression Regulation ,Liver ,Organ Specificity ,Interferon Type I ,lcsh:Q ,computer ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The northern tree shrew (Tupaia belangeri) possesses high potential as an animal model of human diseases and biology, given its genetic similarity to primates. Although genetic information on the tree shrew has already been published, some of the entire coding sequences (CDSs) of tree shrew genes remained incomplete, and the reliability of these CDSs remained difficult to determine. To improve the determination of tree shrew CDSs, we performed sequencing of the whole-genome, mRNA, and total RNA and integrated the resulting data. Additionally, we established criteria for the selection of reliable CDSs and annotated these sequences by comparison to the human transcriptome, resulting in the identification of complete CDSs for 12,612 tree shrew genes and yielding a more accurate tree shrew genome database (TupaiaBase: http://tupaiabase.org). Transcriptome profiles in hepatitis B virus infected tree shrew livers were analyzed for validation. Gene ontology analysis showed enriched transcriptional regulation at 1 day post-infection, namely in the “type I interferon signaling pathway”. Moreover, a negative regulator of type I interferon, SOCS3, was induced. This work, which provides a tree shrew CDS database based on genomic DNA and RNA sequencing, is expected to serve as a powerful tool for further development of the tree shrew model.
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- 2019
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17. Pharmacological MEK inhibition promotes polyclonal T-cell reconstitution and suppresses xenogeneic GVHD
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Akifumi Takaori-Kondo, Kazutaka Kitaura, Seiji Okada, Takero Shindo, Tadasu Shin-I, Hiroyuki Muranushi, Ryuji Suzuki, Shinya Kimura, and Hidekazu Itamura
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Pyridones ,T cell ,T-Lymphocytes ,Immunology ,Transplantation, Heterologous ,Clone (cell biology) ,Receptors, Antigen, T-Cell ,Graft vs Host Disease ,chemical and pharmacologic phenomena ,Mice, SCID ,Pyrimidinones ,Biology ,Tacrolimus ,Mice ,Immune system ,immune system diseases ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,Cells, Cultured ,Trametinib ,Mice, Knockout ,Mitogen-Activated Protein Kinase Kinases ,MEK inhibitor ,T-cell receptor ,Hematopoietic Stem Cell Transplantation ,Janus Kinase 3 ,medicine.disease ,Clone Cells ,surgical procedures, operative ,Graft-versus-host disease ,medicine.anatomical_structure ,Humanized mouse ,Cancer research ,Immunosuppressive Agents - Abstract
Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. The MEK inhibitor trametinib ameliorated GVHD and enabled engraftment of diverse T-cell clones. Furthermore, trametinib also ameliorated GVHD sparing diverse T cell repertoire, even when it was given from day 15 through 28. Although tacrolimus also reduced development of GVHD, it disturbed diverse T cell reconstitution and resulted in skewed TCR repertoire. Thus, trametinib not only suppresses GVHD-inducing T cells but also promotes human T cell reconstitution in vivo, providing a novel rationale for translational studies targeting human GVHD.
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- 2020
18. Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
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Kazutaka Kitaura, Masashi Shibata, Tadasu Shin-I, Atsushi Muraguchi, Kumi Oshima, Ren Chishaki, Ryuji Suzuki, Hiroshi Hamana, Tatsuo Ichinohe, Takahiko Miyama, Hiroh Saji, Hiroyuki Kishi, Takakazu Kawase, and Kiyotaka Kuzushima
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0301 basic medicine ,Cellular immunity ,Science ,Receptors, Antigen, T-Cell ,Gene Expression ,T-Cell Antigen Receptor Specificity ,chemical and pharmacologic phenomena ,Immunogenetics ,Biology ,Lymphocyte Activation ,Deep sequencing ,Article ,Cell Line ,Immunophenotyping ,Viral Matrix Proteins ,03 medical and health sciences ,Antigen ,HLA Antigens ,Transduction, Genetic ,Humans ,Genetics ,Immunity, Cellular ,Precursor Cells, T-Lymphoid ,Multidisciplinary ,Effector ,Repertoire ,T-cell receptor ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Phosphoproteins ,030104 developmental biology ,Immunology ,Medicine ,Immunologic Memory ,Biomarkers - Abstract
To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
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- 2017
19. Epstein-Barr virus-related diffuse large B-cell lymphoma in mogamulizumab-treated adult T-cell leukemia with incomplete T-cell reconstitution
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Tadasu Shin-I, Kazutaka Kitaura, Masaharu Miyahara, Kazuharu Kamachi, Shinya Kimura, Ryuji Suzuki, Koichi Oshima, Takero Shindo, and Michiaki Akashi
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Adult ,medicine.medical_specialty ,Herpesvirus 4, Human ,T cell ,T-Lymphocytes ,T-cell leukemia ,medicine.disease_cause ,Antibodies, Monoclonal, Humanized ,Central Nervous System Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Mogamulizumab ,medicine ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Child ,Hematology ,business.industry ,medicine.disease ,Epstein–Barr virus ,Lymphoma ,Clone Cells ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C–C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein–Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.
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- 2018
20. Hepatitis B Virus Genotype and Mutations Related to Clinical Outcome
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Tadasu Shin-I, Masashi Mizokami, and Masaya Sugiyama
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Hepatitis B virus ,Hepatitis B virus genotype ,HBsAg ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,virus diseases ,Acute infection ,medicine.disease_cause ,Virology ,digestive system diseases ,Epidemiology ,Genotype ,Medicine ,Risk factor ,business ,education - Abstract
Hepatitis B virus (HBV) infection is a high risk factor on severe liver diseases. HBV is currently divided into ten genotypes based on the genetic sequence of HBV, which has regional characteristics on clinical outcomes. Recently, cross-border incursion of HBV genotypes occurs worldwide. The nationwide epidemiological study in Japan showed that the number of acute hepatitis B patients was about 8000–8400 people per year. Interestingly, the European–US genotype HBV/A2 has made up an increasing proportion of acute HB cases over 50% in Japan. And 29% of acute HB patients infected with HBV/A became negative for HBsAg within 6–12 months, which were considered “prolonged,” rather than chronic hepatitis B. The acute infection of HBV/A2 is more likely to become chronic compared to HBV/B or C in Japanese population. The invasion of HBV genotypes into other region or country could provide new insights on clinical outcomes of HBV genotypes. The observation of long-term prognosis is needed to collect the clinical evidences on the infection of new genotype into a population.
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- 2017
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21. The MEK Inhibitor Trametinib Enhances Diverse T Cell Reconstitution with Suppressing Xenogeneic Graft-Versus-Host-Disease
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Kazutaka Kitaura, Takero Shindo, Ryuji Suzuki, Akifumi Takaori-Kondo, Shinya Kimura, Hiroyuki Muranushi, Hidekazu Itamura, Seiji Okada, and Tadasu Shin-I
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Trametinib ,Severe combined immunodeficiency ,business.industry ,MEK inhibitor ,T cell ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Transplantation ,Graft-versus-host disease ,Immune system ,medicine.anatomical_structure ,medicine ,business - Abstract
Introduction: Early immune reconstitution without severe graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We showed that MEK inhibitors suppress GVHD but retain antiviral immunity and graft-versus-tumor (GVT) effects (Shindo, Blood2013; Itamura, Shindo, JCI Insight2016). Furthermore, we have shown that they attenuate graft rejection but spare thymic function following rat lung transplantation (Takahagi, Shindo, Am J Respir Cell Mol Biol2019). Here we analyzed their effects on human polyclonal T cell reconstitution in xenogeneic transplant by evaluating T-cell receptor (TCR) repertoire diversity. Methods: As a xenogeneic GVHD model, human PBMCs were infused to NOD/Scid/JAK3null mice, immunodeficient mice lacking T/B/NK cells, after total body irradiation. Vehicle, tacrolimus, or the MEK inhibitor trametinib was administered from day 0 through 28 or day 15 through 28. Human TCR repertoire diversity was evaluated by an adapter ligation PCR method with next generation sequencing (Shindo, Oncoimmunol2018) in the liver, lung, and spleen. The assignment and frequencies of TCRαV/J clones were determined at the single-cell level. Their diversity and clonality were evaluated by Inv. Simpson's index 1/λ. Results: Trametinib prolonged their survival compared with vehicle (median survival: 88 vs 46 days, p Conclusions:GVHD can be characterized with skewed TCR repertoire diversity and expansion of pathological T cell clones in the target tissues. Trametinib suppresses GVHD but maintains polyclonal T cell reconstitution, even in established GVHD. These results explain the facts that MEK inhibitors separate GVHD from GVT effects/antimicrobial immunity. Furthermore, MEK inhibition enhances immune reconstitution after allo-HSCT, which would avoid post-transplant complications. Disclosures Shindo: Novartis: Research Funding. Kitaura:Repertoire Genesis Inc.: Employment. Okada:Bristol-Myers Squibb: Research Funding; Japan Agency for Medical Research and Development: Research Funding. Shin-I:BITS Co., Ltd: Equity Ownership. Suzuki:Repertoire Genesis Inc.: Equity Ownership. Takaori-Kondo:Celgene: Honoraria, Research Funding; Novartis: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Ono: Research Funding; Takeda: Research Funding; Kyowa Kirin: Research Funding; Chugai: Research Funding; Janssen: Honoraria; Pfizer: Honoraria. Kimura:Ohara Pharmaceutical Co.: Research Funding; Novartis: Honoraria, Research Funding.
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- 2019
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22. Genome sequence and analysis of the Japanese morning glory Ipomoea nil
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Hiroshi Kudoh, Atsushi J. Nagano, Atsushi Toyoda, Eiji Nitasaka, Yuki Koda, Yutaka Suzuki, Motoaki Seki, Sachiko Tanaka, Hideki Noguchi, Asako Kamiya, Atsushi Hoshino, Tadasu Shin-I, Yoshihide Hayashizaki, Piero Carninci, Yuji Kohara, Takehiko Itoh, Yasubumi Sakakibara, Satoshi Tabata, Masaki Yasugi, Yasumasa Morita, Sumio Sugano, Hiroyo Nishide, Shigeru Iida, Kyeung-Il Park, Toshiyuki Shiraki, Kohei Yokoyama, Asao Fujiyama, Yoshikazu Tanaka, Vasanthan Jayakumar, Ikuo Uchiyama, Kazuo Shinozaki, Erika Asamizu, Yohei Minakuchi, and Mie N. Honjo
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0301 basic medicine ,Science ,General Physics and Astronomy ,Transposases ,Ipomoea ,Genes, Plant ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Article ,Evolution, Molecular ,03 medical and health sciences ,parasitic diseases ,Brassinosteroids ,Ipomoea nil ,Gene ,Whole genome sequencing ,Comparative genomics ,Genetics ,Multidisciplinary ,biology ,Base Sequence ,fungi ,food and beverages ,Reproducibility of Results ,Molecular Sequence Annotation ,General Chemistry ,Sequence Analysis, DNA ,biology.organism_classification ,Solanales ,030104 developmental biology ,DNA Transposable Elements ,Convolvulaceae ,Genome, Plant - Abstract
Ipomoea is the largest genus in the family Convolvulaceae. Ipomoea nil (Japanese morning glory) has been utilized as a model plant to study the genetic basis of floricultural traits, with over 1,500 mutant lines. In the present study, we have utilized second- and third-generation-sequencing platforms, and have reported a draft genome of I. nil with a scaffold N50 of 2.88 Mb (contig N50 of 1.87 Mb), covering 98% of the 750 Mb genome. Scaffolds covering 91.42% of the assembly are anchored to 15 pseudo-chromosomes. The draft genome has enabled the identification and cataloguing of the Tpn1 family transposons, known as the major mutagen of I. nil, and analysing the dwarf gene, CONTRACTED, located on the genetic map published in 1956. Comparative genomics has suggested that a whole genome duplication in Convolvulaceae, distinct from the recent Solanaceae event, has occurred after the divergence of the two sister families., Japanese morning glory (Ipomoea nil) has diverse flowering traits. Here, the authors describe the reference genome sequence of I. nil, annotations of genes and transposons, and compare evolution of the I. nil genome to other Convolvulaceae and Solanales genomes.
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- 2016
23. A new high-throughput sequencing method for determining diversity and similarity of T cell receptor (TCR) α and β repertoires and identifying potential new invariant TCR α chains
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Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, and Tadasu Shin-I
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0301 basic medicine ,Adult ,Male ,Receptors, Antigen, T-Cell, alpha-beta ,Immunology ,chemical and pharmacologic phenomena ,Computational biology ,Biology ,Peripheral blood mononuclear cell ,Polymerase Chain Reaction ,DNA sequencing ,Immune profiling ,law.invention ,03 medical and health sciences ,Similarity (network science) ,Japan ,law ,Next generation sequencing ,Humans ,Repertoire ,Invariant (mathematics) ,Gene ,Polymerase chain reaction ,Invariant TCRα ,Aged ,T-cell receptor ,Computational Biology ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Molecular biology ,Healthy Volunteers ,Clone Cells ,030104 developmental biology ,Leukocytes, Mononuclear ,Female ,T cell receptor ,Research Article - Abstract
Background High-throughput sequencing of T cell receptor (TCR) genes is a powerful tool for analyses of antigen specificity, clonality and diversity of T lymphocytes. Here, we developed a new TCR repertoire analysis method using 454 DNA sequencing technology in combination with an adaptor-ligation mediated polymerase chain reaction (PCR). This method allows the amplification of all TCR genes without PCR bias. To compare gene usage, diversity and similarity of expressed TCR repertoires among individuals, we conducted next-generation sequencing (NGS) of TRA and TRB genes in peripheral blood mononuclear cells from 20 healthy human individuals. Results From a total of 267,037 sequence reads from 20 individuals, 149,216 unique sequence reads were identified. Preferential usage of several V and J genes were observed while some recombinations of TRAV with TRAJ appeared to be restricted. The extent of TCR diversity was not significantly different between TRA and TRB, while TRA repertoires were more similar between individuals than TRB repertoires were. The interindividual similarity of TRA depended largely on the frequent presence of shared TCRs among two or more individuals. A publicly available TRA had a near-germline TCR with a shorter CDR3. Notably, shared TRA sequences, especially those shared among a large number of individuals’, often contained TCRα related with invariant TCRα derived from invariant natural killer T cells and mucosal-associated invariant T cells. Conclusion These results suggest that retrieval of shared TCRs by NGS would be useful for the identification of potential new invariant TCRα chains. This NGS method will enable the comprehensive quantitative analysis of TCR repertoires at a clonal level. Electronic supplementary material The online version of this article (doi:10.1186/s12865-016-0177-5) contains supplementary material, which is available to authorized users.
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- 2016
24. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein
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Toru Miura, Yohei Minakuchi, Takuma Hashimoto, Takeo Kubo, Asao Fujiyama, Yuki Saito, Yuji Kohara, Sae Tanaka, Hiroshi Sagara, Hiroko Kozuka-Hata, Toshiaki Katayama, Tadasu Shin-I, Ayuko Motoyama, Koyuki Kondo, Atsushi Enomoto, Masaaki Oyama, Kiyoshi Miyagawa, Atsushi Toyoda, Tomoyuki Aizu, Takekazu Kunieda, Shigeyuki Koshikawa, Yuichiro Hara, Kazuko Ohishi, Yutaka Suzuki, Hirokazu Kuwahara, Shin-ichi Yokobori, Daiki D. Horikawa, and Kazuharu Arakawa
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0301 basic medicine ,Gene Transfer, Horizontal ,DNA damage ,Science ,General Physics and Astronomy ,Bioinformatics ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Stress, Physiological ,Gene expression ,Peroxisomes ,Tardigrada ,Gene family ,Animals ,Humans ,Gene ,Whole genome sequencing ,Multidisciplinary ,biology ,X-Rays ,Aquatic animal ,General Chemistry ,biology.organism_classification ,Adaptation, Physiological ,Cell biology ,030104 developmental biology ,HEK293 Cells ,Tardigrade ,DNA Damage - Abstract
Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms., Tardigrades are resistant to extreme environmental conditions including dehydration, radiation and the vacuum of space. Here the authors present a high-quality genome which displays minimal horizontal gene transfer, and identify the unique tardigrade protein Dsup which suppresses DNA damage.
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- 2016
25. Hepatitis C Virus Genotypes and Their Evolution
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Masaya Sugiyama, Tadasu Shin-I, and Masashi Mizokami
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0301 basic medicine ,Genetics ,Hepatitis C virus ,HCV genotypes ,virus diseases ,Biology ,medicine.disease_cause ,Genome ,Geographic distribution ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Genotype ,medicine ,030211 gastroenterology & hepatology ,Genetic variability ,Nomenclature - Abstract
The hepatitis C virus (HCV) genome is highly heterogeneous. Its genetic variability (genotypes and subtypes) is related to its biological and clinical properties. In 2005, a consensus was reached regarding a unified nomenclature system for HCV genotypes and subtypes. Since then, many complete genome sequences have been reported, resulting in the identification of new genotypes and subtypes. To determine the current status of HCV genotypes, complete genome sequences and their annotations were retrieved from public databases. These viral sequences were arranged according to genotype/subtype and geographical distribution and analyzed phylogenetically to determine the relationships between classification and geography. In addition, the relationships between the HCV genome and the genomes of various related viruses were analyzed phylogenetically to determine the HCV origin. These analyses showed that the viruses evolved along with their hosts and that, worldwide, HCV should be classified into seven major genotypes with their serial subtypes.
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- 2016
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26. Comprehensive Functional Analyses of Expressed Sequence Tags in Common Wheat (Triticum aestivum)
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Alagu Manickavelu, Kanako Kawaura, Yasunari Ogihara, Beat Keller, Kazuko Oishi, Taishi Nagayama, Reina Abe, Kentaro Yano, Tadasu Shin-I, Yuji Kohara, Ayako Suzuki, Nabila Yahiaoui, University of Zurich, and Ogihara, Y
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DNA, Complementary ,SNP ,Biology ,580 Plants (Botany) ,Genes, Plant ,Polymorphism, Single Nucleotide ,correspondence analysis ,10126 Department of Plant and Microbial Biology ,1311 Genetics ,Gene Expression Regulation, Plant ,Complementary DNA ,wheat ,transcription factors ,Databases, Genetic ,Genetics ,1312 Molecular Biology ,Genomic library ,Common wheat ,Molecular Biology ,Triticum ,miRNA ,Gene Library ,Expressed Sequence Tags ,Expressed sequence tag ,cDNA library ,ESTs ,Gene Expression Profiling ,food and beverages ,Computational Biology ,Molecular Sequence Annotation ,General Medicine ,Sequence Analysis, DNA ,Full Papers ,Gene expression profiling ,annotation ,Functional genomics - Abstract
About 1 million expressed sequence tag (EST) sequences comprising 125.3 Mb nucleotides were accreted from 51 cDNA libraries constructed from a variety of tissues and organs under a range of conditions, including abiotic stresses and pathogen challenges in common wheat (Triticum aestivum). Expressed sequence tags were assembled with stringent parameters after processing with inbuild scripts, resulting in 37 138 contigs and 215 199 singlets. In the assembled sequences, 10.6% presented no matches with existing sequences in public databases. Functional characterization of wheat unigenes by gene ontology annotation, mining transcription factors, full-length cDNA, and miRNA targeting sites were carried out. A bioinformatics strategy was developed to discover single-nucleotide polymorphisms (SNPs) within our large EST resource and reported the SNPs between and within (homoeologous) cultivars. Digital gene expression was performed to find the tissue-specific gene expression, and correspondence analysis was executed to identify common and specific gene expression by selecting four biotic stress-related libraries. The assembly and associated information cater a framework for future investigation in functional genomics.
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- 2012
27. Molecular cloning and characterization of the repetitive DNA sequences that comprise the constitutive heterochromatin of the W chromosomes of medaka fishes
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Asao Fujiyama, Yoichi Matsuda, Yuji Kohara, Tadasu Shin-I, Yusuke Asada, Satoshi Hamaguchi, Kiyoshi Naruse, Mitsuru Sakaizumi, and Yusuke Takehana
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Male ,Heterochromatin ,Oryzias ,Molecular Sequence Data ,Homology (biology) ,Species Specificity ,RNA, Ribosomal, 28S ,RNA, Ribosomal, 18S ,Genetics ,Animals ,Constitutive heterochromatin ,Cloning, Molecular ,In Situ Hybridization, Fluorescence ,Phylogeny ,Repetitive Sequences, Nucleic Acid ,Sex Chromosomes ,Autosome ,biology ,Chromosome Mapping ,Chromosome ,Genes, rRNA ,Sex Determination Processes ,biology.organism_classification ,W chromosome ,Female ,Oryzias javanicus - Abstract
Among the medaka fishes of the genus Oryzias, most species have homomorphic sex chromosomes, while some species, such as Oryzias hubbsi and Oryzias javanicus, have heteromorphic ZW sex chromosomes. In this study, a novel family of repetitive sequence was molecularly cloned from O. hubbsi and characterized by chromosome in situ and filter hybridization, respectively. This repetitive element, which we designated as a BstNI family element, localized at heterochromatin regions on the W chromosome, as well as on two pairs of autosomes. Homologous sequences to this element were found only in O. javanicus, which is a sister species of O. hubbsi, suggesting that this repeated element originated in the common ancestor of these two species. However, the intensity of the hybridization signals was lower in O. javanicus than in O. hubbsi, and the chromosomal location of this element in O. javanicus was confined to heterochromatin regions on one pair of autosomes. Thus, we hypothesize that this repetitive element was extensively amplified in the O. hubbsi lineage, especially on its W chromosome, after the separation of the O. javanicus lineage. In addition, we also found the W chromosomal location of the 18S-28S ribosomal RNA genes in both O. hubbsi and O. javanicus. Our previous studies showed no linkage homology of the sex chromosomes in these species, indicating that the RNA genes were shared between W chromosomes of different origins. This situation may be explained by a translocation of the sex-determining region with the ribosomal RNA genes in either species or an independent accumulation of the RNA genes as a convergent process during W chromosome degeneration.
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- 2011
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28. Easy-to-use phylogenetic analysis system for hepatitis B virus infection
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Motokazu Mukaide, Kiyoaki Ito, Makoto Nakanishi, Masaya Sugiyama, Naohiko Masaki, Ayano Inui, Tomoo Fujisawa, Tadasu Shin-I, Masashi Mizokami, Haruki Komatsu, and Kazumoto Murata
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Hepatitis B virus ,Genetics ,medicine.medical_specialty ,Hepatology ,Phylogenetic tree ,Biology ,medicine.disease_cause ,Disease cluster ,law.invention ,Infectious Diseases ,Transmission (mechanics) ,Genetic distance ,law ,Molecular genetics ,Genotype ,medicine ,Gene - Abstract
Aim: The molecular phylogenetic analysis has been broadly applied to clinical and virological study. However, the appropriate settings and application of calculation parameters are difficult for non-specialists of molecular genetics. In the present study, the phylogenetic analysis tool was developed for the easy determination of genotypes and transmission route. Methods: A total of 23 patients of 10 families infected with hepatitis B virus (HBV) were enrolled and expected to undergo intrafamilial transmission. The extracted HBV DNA were amplified and sequenced in a region of the S gene. Results: The software to automatically classify query sequence was constructed and installed on the Hepatitis Virus Database (HVDB). Reference sequences were retrieved from HVDB, which contained major genotypes from A to H. Multiple-alignments using CLUSTAL W were performed before the genetic distance matrix was calculated with the six-parameter method. The phylogenetic tree was output by the neighbor-joining method. User interface using WWW-browser was also developed for intuitive control. This system was named as the easy-to-use phylogenetic analysis system (E-PAS). Twenty-three sera of 10 families were analyzed to evaluate E-PAS. The queries obtained from nine families were genotype C and were located in one cluster per family. However, one patient of a family was classified into the cluster different from her family, suggesting that E-PAS detected the sample distinct from that of her family on the transmission route. Conclusions: The E-PAS to output phylogenetic tree was developed since requisite material was sequence data only. E-PAS could expand to determine HBV genotypes as well as transmission routes.
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- 2011
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29. Sequence Analysis of the Genome of an Oil-Bearing Tree, Jatropha curcas L
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Sachihiro Matsunaga, Shusei Sato, Nobuko Ohmido, Alipour Atefeh, Atsushi Toyoda, Tomoyuki Aizu, Hisano Tsuruoka, Tsutomu Kohinata, Shigemi Sasamoto, Tadasu Shin-I, Eigo Fukai, Shin'ichiro Kajiyama, Kiichi Fukui, Shinobu Nakayama, Naoki Wada, Mitsuyo Kohara, Nakako Shibagaki, Hideki Hirakawa, Suguru Tsuchimoto, Asao Fujiyama, Satoshi Tabata, Naomi Nakazaki, Kumiko Kawashima, Eri Makigano, Akiko Watanabe, Chiharu Minami, Akiko Muraki, Yohei Minakuchi, Joyce A. Cartagena, Yoshie Kishida, Shota Yuasa, Yuji Kohara, Sachiko Isobe, Manabu Yamada, Midori Kato, and Chika Takahashi
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cDNA sequencing ,Sequence analysis ,Jatropha ,UniGene ,Biology ,Genome ,DNA sequencing ,symbols.namesake ,Jatropha curcas L ,Genetics ,Molecular Biology ,Plant Proteins ,Sanger sequencing ,food and beverages ,General Medicine ,Sequence Analysis, DNA ,Full Papers ,microsatellite markers ,biology.organism_classification ,genome sequencing ,symbols ,Pyrosequencing ,Jatropha curcas ,Genome, Plant - Abstract
Shusei Sato, Hideki Hirakawa, Sachiko Isobe, Eigo Fukai, Akiko Watanabe, Midori Kato, Kumiko Kawashima, Chiharu Minami, Akiko Muraki, Naomi Nakazaki, Chika Takahashi, Shinobu Nakayama, Yoshie Kishida, Mitsuyo Kohara, Manabu Yamada, Hisano Tsuruoka, Shigemi Sasamoto, Satoshi Tabata, Tomoyuki Aizu, Atsushi Toyoda, Tadasu Shin-i, Yohei Minakuchi, Yuji Kohara, Asao Fujiyama, Suguru Tsuchimoto, Shin'ichiro Kajiyama, Eri Makigano, Nobuko Ohmido, Nakako Shibagaki, Joyce A. Cartagena, Naoki Wada, Tsutomu Kohinata, Alipour Atefeh, Shota Yuasa, Sachihiro Matsunaga, Kiichi Fukui, Sequence Analysis of the Genome of an Oil-Bearing Tree, Jatropha curcas L., DNA Research, Volume 18, Issue 1, February 2011, Pages 65–76, https://doi.org/10.1093/dnares/dsq030., The whole genome of Jatropha curcas was sequenced, using a combination of the conventional Sanger method and new-generation multiplex sequencing methods. Total length of the non-redundant sequences thus obtained was 285 858 490 bp consisting of 120 586 contigs and 29 831 singlets. They accounted for ∼95% of the gene-containing regions with the average G + C content was 34.3%. A total of 40 929 complete and partial structures of protein encoding genes have been deduced. Comparison with genes of other plant species indicated that 1529 (4%) of the putative protein-encoding genes are specific to the Euphorbiaceae family. A high degree of microsynteny was observed with the genome of castor bean and, to a lesser extent, with those of soybean and Arabidopsis thaliana. In parallel with genome sequencing, cDNAs derived from leaf and callus tissues were subjected to pyrosequencing, and a total of 21 225 unigene data have been generated. Polymorphism analysis using microsatellite markers developed from the genomic sequence data obtained was performed with 12 J. curcas lines collected from various parts of the world to estimate their genetic diversity. The genomic sequence and accompanying information presented here are expected to serve as valuable resources for the acceleration of fundamental and applied research with J. curcas, especially in the fields of environment-related research such as biofuel production. Further information on the genomic sequences and DNA markers is available at http://www.kazusa.or.jp/jatropha/.
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- 2010
30. Mass identification of transcriptional units expressed from the Bombyx mori nucleopolyhedrovirus genome
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Yuji Kohara, Susumu Katsuma, Koji Kadota, WonKyung Kang, Tadasu Shin-I, Kazuko Ohishi, and Toru Shimada
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Gene Expression Regulation, Viral ,RNA, Untranslated ,Sequence analysis ,viruses ,Molecular Sequence Data ,Genome, Viral ,Genome ,Cell Line ,Bombycidae ,Bombyx mori ,Virology ,Transcriptional regulation ,Animals ,Genomic library ,RNA, Messenger ,Gene Library ,Genetics ,Regulation of gene expression ,biology ,cDNA library ,Gene Expression Profiling ,fungi ,Sequence Analysis, DNA ,Bombyx ,biology.organism_classification ,Nucleopolyhedroviruses ,DNA, Viral ,RNA, Viral - Abstract
In order to identify the transcriptional units expressed from an entire nucleopolyhedrovirus (NPV) genome during infection, we constructed a full-length-enriched cDNA library from Bombyx mori NPV (BmNPV)-infected BmN cells. We randomly sequenced 11,520 clones from both ends to obtain a total of 4679 BmNPV-derived transcriptional units. The data revealed a number of novel transcripts, including putative non-coding RNAs, most of which are expressed from recognized baculovirus early or late promoter motifs. These findings provide new insights into the complex transcriptional regulation of an NPV genome and suggest roles for as-yet-uncharacterized transcripts.
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- 2010
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31. Comparative Gene Expression Analysis of Susceptible and Resistant Near-Isogenic Lines in Common Wheat Infected by Puccinia triticina
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Kanako Kawaura, Kazuko Oishi, Tadasu Shin-I, Kentaro Yano, Ayako Suzuki, Nabila Yahiaoui, Yasunari Ogihara, Alagu Manickavelu, Yuji Kohara, Beat Keller, University of Zurich, and Ogihara, Y
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Molecular Sequence Data ,580 Plants (Botany) ,Biology ,Genes, Plant ,Rust ,methods ,resistance ,leaf rust ,10126 Department of Plant and Microbial Biology ,1311 Genetics ,Gene Expression Regulation, Plant ,wheat ,Gene Expression Regulation, Fungal ,Gene expression ,Botany ,1312 Molecular Biology ,Genetics ,Common wheat ,Molecular Biology ,Gene ,Triticum ,Cellular localization ,Plant Diseases ,Expressed Sequence Tags ,Regulation of gene expression ,Expressed sequence tag ,ESTs ,Basidiomycota ,Gene Expression Profiling ,food and beverages ,CDNA Library Construction ,Plant ,General Medicine ,Full Papers ,Plant Leaves ,Fungal ,Gene Expression Regulation ,Genes ,genetics/microbiology ,genetics/pathogenicity ,susceptible - Abstract
Gene expression after leaf rust infection was compared in near-isogenic wheat lines differing in the Lr10 leaf rust resistance gene. RNA from susceptible and resistant plants was used for cDNA library construction. In total, 55 008 ESTs were sequenced from the two libraries, then combined and assembled into 14 268 unigenes for further analysis. Of these ESTs, 89% encoded proteins similar to (E value ofor =10(-5)) characterized or annotated proteins from the NCBI non-redundant database representing diverse molecular functions, cellular localization and biological processes based on gene ontology classification. Further, the unigenes were classified into susceptible and resistant classes based on the EST members assembled from the respective libraries. Several genes from the resistant sample (14-3-3 protein, wali5 protein, actin-depolymerization factor and ADP-ribosylation factor) and the susceptible sample (brown plant hopper resistance protein, caffeic acid O-methyltransferase, pathogenesis-related protein and senescence-associated protein) were selected and their differential expression in the resistant and susceptible samples collected at different time points after leaf rust infection was confirmed by RT-PCR analysis. The molecular pathogenicity of leaf rust in wheat was studied and the EST data generated made a foundation for future studies.
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- 2010
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32. UTGB/medaka: genomic resource database for medaka biology
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Koichiro Doi, Shinichi Morishita, Takashi Sasaki, Hisayo Nomoto, Keiko Nogata, Shuichi Asakawa, Tomomi Morishita, Atsushi Shimizu, Hiroyuki Takeda, Tomoyuki Yamada, Wei Qu, Kazuko Ohishi, Yoko Kuroki, Atsushi Toyoda, Tomoko Endo, Yongjun Lee, Budrul Ahsan, Nobuyoshi Shimizu, Fumiko Ohta, Yukinobu Nagayasu, Kouji Matsushima, Taro I. Saito, Takanori Narita, Jun Yang, Shinobu Haga, Asao Fujiyama, Atsuko Shimada, Kiyoshi Naruse, Masahiro Kasahara, Mitsuru Sakaizumi, Tomoko Jindo, Yoichiro Nakatani, Shin-ichi Hashimoto, Shin Sasaki, Daisuke Kobayashi, Sumio Sugano, Tadasu Shin-I, and Yuji Kohara
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Genetic Markers ,Chromosomes, Artificial, Bacterial ,Oryzias ,Gene Expression ,Genomics ,Genome browser ,Biology ,computer.software_genre ,Genome ,Polymorphism, Single Nucleotide ,User-Computer Interface ,Databases, Genetic ,Genetics ,Animals ,Comparative genomics ,Whole genome sequencing ,Expressed sequence tag ,Bacterial artificial chromosome ,Internet ,Database ,fungi ,Genetic Variation ,Articles ,Fosmid ,Transcription Initiation Site ,computer ,Plasmids - Abstract
Medaka (Oryzias latipes) is a small egg-laying freshwater teleost native to East Asia that has become an excellent model system for developmental genetics and evolutionary biology. The draft medaka genome sequence (700 Mb) was reported in June 2007, and its substantial genomic resources have been opened to the public through the University of Tokyo Genome Browser Medaka (UTGB/medaka) database. This database provides basic genomic information, such as predicted genes, expressed sequence tags (ESTs), guanine/cytosine (GC) content, repeats and comparative genomics, as well as unique data resources including (i) 2473 genetic markers and experimentally confirmed PCR primers that amplify these markers, (ii) 142,414 bacterial artificial chromosome (BAC) and 217,344 fosmid end sequences that amount to 15.0- and 11.1-fold clone coverage of the entire genome, respectively, and were used for draft genome assembly, (iii) 16,519,460 single nucleotide polymorphisms (SNPs), and 2 859 905 insertions/deletions detected between two medaka inbred strain genomes and (iv) 841 235 5'-end serial analyses of gene-expression (SAGE) tags that identified 344 266 transcription start sites on the genome. UTGB/medaka is available at: http://medaka.utgenome.org/.
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- 2007
33. Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
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Eri Watanabe, Hiroshi Ureshino, Kazutaka Kitaura, Tadasu Shin-I, Kotaro Nagase, Susumu Kusunoki, Ryuji Suzuki, Natsuko Satoh, Shinya Kimura, Hiroaki Kitamura, Nobukazu Watanabe, Masaharu Miyahara, Hiromi Kimura, Takero Shindo, Makoto Samukawa, Hiroyoshi Nishikawa, Shimon Sakaguchi, and Kazuko Doi
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0301 basic medicine ,Male ,Cancer Research ,Biopsy ,Immunology ,T-cell leukemia ,Population ,Autoimmunity ,Biology ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Immunopathology ,medicine ,Mogamulizumab ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,education ,Aged ,Skin ,education.field_of_study ,Immunity ,FOXP3 ,Brain ,hemic and immune systems ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Lymphoma ,Leukemia ,030104 developmental biology ,Phenotype ,030220 oncology & carcinogenesis ,Biomarkers ,medicine.drug - Abstract
The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA–Foxp3++CCR4+ phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644–9. ©2016 AACR.
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- 2015
34. Extensive analysis of ORF sequences from two different cichlid species in Lake Victoria provides molecular evidence for a recent radiation event of the Victoria species flock
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Tokumasa Horiike, Yuji Kohara, Yoshio Tateno, Naoki Kobayashi, Tadasu Shin-I, Masakatsu Watanabe, and Norihiro Okada
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Genetics ,Expressed sequence tag ,cDNA library ,media_common.quotation_subject ,General Medicine ,Biology ,Haplochromis chilotes ,biology.organism_classification ,Genome ,Speciation ,Open reading frame ,Genetic distance ,Evolutionary biology ,Cichlid ,media_common - Abstract
The Lake Victoria Cichlid fishes have diverged very rapidly. The estimated 500 species inhabiting the lake are believed to have arisen within the last 14,000 years. The fishes' jaws and teeth have diverged markedly to adapt to different feeding behaviors and environments. To examine how the genomes of these fishes differentiated during speciation, we performed comparative analysis of expressed sequenced tag (EST) sequences. We constructed cDNA libraries derived only from the jaw portions of two cichlid species endemic to Lake Victoria. We sequenced 17,280 cDNA clones from Haplochromis chilotes and 9600 cDNA clones from Haplochromis sp. "Redtailsheller" and obtained 543 different genes common to both species. Of these genes, 441 were essentially identical between species and 102 contained base replacements in their open reading frame (ORF) or untranslated (UTR) regions. Comparative analysis of 71 selected sequences has revealed that while the degree of polymorphism is 0.0054/site for H. chilotes and 0.0047/site for H. sp. "Redtailsheller", genetic distance between the two species is 0.0031/site. The genetic distance particularly indicates that the two species diverged about 890,000 years ago.
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- 2004
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35. Transcriptome analysis of hagfish leukocytes: a framework for understanding the immune system of jawless fishes
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Masanori Kasahara, Tadasu Shin-I, Takashi Suzuki, and Yuji Kohara
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Proteasome Endopeptidase Complex ,endocrine system ,Molecular Sequence Data ,Immunology ,Major histocompatibility complex ,Immune system ,Variable lymphocyte receptor ,biology.animal ,Leukocytes ,Eptatretus burgeri ,Animals ,Bruton's tyrosine kinase ,Amino Acid Sequence ,RNA, Messenger ,Receptors, Cytokine ,Expressed Sequence Tags ,Genetics ,biology ,Gene Expression Profiling ,biology.organism_classification ,Acquired immune system ,biology.protein ,Cytokines ,Hagfishes ,Cytokine receptor ,Transcription Factors ,Developmental Biology ,Hagfish - Abstract
Jawless fishes occupy a critical phylogenetic position in understanding the origin of the adaptive immune system. Here, we performed large-scale expressed sequence tag analysis of leukocytes isolated from the inshore hagfish Eptatretus burgeri. Although we found many immunity-related genes such as those involved in lymphocyte or hematopoietic cell signaling and development as well as cytokine and cytokine receptor genes, MHC molecules or antigen receptors were not identified. We characterized two hagfish cDNAs that closely resembled mammalian proteins with essential roles in adaptive immunity, one encoding a GATA3-like molecule and another encoding a Bruton's tyrosine kinase (Btk)-like molecule. The GATA3-like gene of hagfish was equidistant from GATA3 and GATA2 in jawed vertebrates. Similarly, the hagfish Btk-like molecule was not Btk itself, but qualified as a pre-duplicated form of Btk and Bmx in jawed vertebrates. In total, our work provides circumstantial evidence that adaptive immunity is unique to jawed vertebrates.
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- 2004
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36. Construction of a full-length cDNA library from young spikelets of hexaploid wheat and its characterization by large-scale sequencing of expressed sequence tags
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Motoaki Seki, Piero Carninci, Kanako Kawaura, Keiichi Mochida, Yuji Kohara, Kazuo Shinozaki, Yoshihide Hayashizaki, Tadasu Shin-I, Koji Murai, Yasunari Ogihara, Yukiko Yamazaki, and Asako Kamiya
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Expressed Sequence Tags ,Genetics ,Expressed sequence tag ,DNA, Complementary ,Contig ,cDNA library ,food and beverages ,General Medicine ,Biology ,Genome ,Homology (biology) ,Polyploidy ,Multigene Family ,Complementary DNA ,Common wheat ,5' Untranslated Regions ,Molecular Biology ,Gene ,Triticum - Abstract
The polyploid nature of wheat is a key characteristic of the plant. Full-length complementary DNAs (cDNAs) provide essential information that can be used to annotate the genes and provide a functional analysis of these genes and their products. We constructed a full-length cDNA library derived from young spikelets of common wheat, and obtained 24056 expressed sequence tags (ESTs) from both ends of the cDNA clones. These ESTs were grouped into 3605 contigs using the phrap method, representing expressed loci from each of the three genomes. Using BLAST, 3605 contigs were grouped into 1902 gene clusters, showing that loci of the three genomes are not always expressed. A homology search of these gene clusters against a wheat EST database (15964 gene clusters) and a rice full-length cDNA database (21447 gene clusters) revealed that a quarter of the wheat full-length cDNAs were novel. A protein database of Arabidopsis was used to examine the functional classification of these gene clusters. The GC-content in the 5 -UTR region of wheat cDNAs was compared to that of rice. Forty-three genes (3.5% of wheat cDNAs homologous to those of rice) possessed distinct GC-content in the 5 -UTR region, suggesting different breeding behaviors of wheat and rice.
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- 2004
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37. Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D
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Yasuyaki Ishii, Yu Momoyama, Naoki Sato, Sachiko Miura, Fumiko Ohta, Yamato Yoshida, Yoshiki Nishimura, Tamaki Kobayashi, Sumio Sugano, Tsuneyoshi Kuroiwa, Fumi Yagisawa, Satoko Nishizaka, Hisayo Nomoto, Tetsuya Higashiyama, Keiji Nishida, Yuji Kohara, Shinobu Haga, Manabu Takahara, Hiroyoshi Takano, Shin-ya Miyagishima, Toshiyuki Mori, Masako Sano, Shunsuke Nakao, Haruko Kuroiwa, Kimihiro Terasawa, Hisayoshi Nozaki, Niji Ohta, Naotake Ogasawara, Kan Tanaka, Motomichi Matsuzaki, Nobuyoshi Shimizu, Tomomi Morishita, Keishin Nishida, Yukihiro Kabeya, Kazuko Oishi, Osami Misumi, Shuichi Asakawa, Hiroko Hayashi, Shinichiro Maruyama, Tadasu Shin-I, Ayumi Minoda, and Yutaka Suzuki
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Molecular Sequence Data ,DNA, Mitochondrial ,DNA, Ribosomal ,Genome ,Chromosomes ,Evolution, Molecular ,Glaucophyte ,Plastids ,Plastid ,Gene ,Cyanidiophyceae ,Cell Nucleus ,Genetics ,Multidisciplinary ,biology ,Endosymbiosis ,Archaeplastida ,Algal Proteins ,Genomics ,Sequence Analysis, DNA ,biology.organism_classification ,Actins ,Introns ,Cyanidioschyzon merolae ,Rhodophyta - Abstract
Small, compact genomes of ultrasmall unicellular algae provide information on the basic and essential genes that support the lives of photosynthetic eukaryotes, including higher plants. Here we report the 16,520,305-base-pair sequence of the 20 chromosomes of the unicellular red alga Cyanidioschyzon merolae 10D as the first complete algal genome. We identified 5,331 genes in total, of which at least 86.3% were expressed. Unique characteristics of this genomic structure include: a lack of introns in all but 26 genes; only three copies of ribosomal DNA units that maintain the nucleolus; and two dynamin genes that are involved only in the division of mitochondria and plastids. The conserved mosaic origin of Calvin cycle enzymes in this red alga and in green plants supports the hypothesis of the existence of single primary plastid endosymbiosis. The lack of a myosin gene, in addition to the unexpressed actin gene, suggests a simpler system of cytokinesis. These results indicate that the C. merolae genome provides a model system with a simple gene composition for studying the origin, evolution and fundamental mechanisms of eukaryotic cells.
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- 2004
38. The Minimal Eukaryotic Ribosomal DNA Units in the Primitive Red Alga Cyanidioschyzon merolae
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Shuichi Asakawa, Osami Misumi, Yuji Kohara, Takashi Sasaki, Atsushi Shimizu, Shinichiro Maruyama, Tadasu Shin-I, Nobuyoshi Shimizu, Tsuneyoshi Kuroiwa, Hisayoshi Nozaki, Yasuyuki Ishii, and Motomichi Matsuzaki
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Chromosomes, Artificial, Bacterial ,Molecular Sequence Data ,Biology ,DNA, Ribosomal ,Genome ,Evolution, Molecular ,Genetics ,Molecular Biology ,Ribosomal DNA ,Genome size ,DNA Primers ,Gene Library ,Genomic organization ,Bacterial artificial chromosome ,Base Sequence ,Shotgun sequencing ,Chromosome Mapping ,Sequence Analysis, DNA ,General Medicine ,Ribosomal RNA ,biology.organism_classification ,Microscopy, Electron ,Gene Components ,Cyanidioschyzon merolae ,Microscopy, Fluorescence ,Rhodophyta ,Cell Nucleolus - Abstract
Cyanidioschyzon merolae is a small unicellular red alga that is considered to belong to one of the most deeply branched taxa in the plant kingdom. Its genome size is estimated to be 16.5 Mbp, one of the smallest among free-living eukaryotes. In the nucleus containing this small genome, one nucleolus is clearly observed, but the molecular basis for the intranuclear structure including ribosomal DNA organization is still unclear. We constructed a bacterial artificial chromosome library for C. merolae 10D composed of two subsets with different insert size distributions. The two subsets have average insert sizes of 97 and 48 kb, representing 10.0- and 6.9-fold genome-equivalent coverage of the haploid genome, respectively. For application to whole-genome shotgun sequencing, the termini of each clone were sequenced as sequence-tagged connectors and mapped on the contigs assigned to chromosomes. Screening for rRNA genes by conventional colony hybridization with high-density filter blots and subsequent sequencing revealed that the C. merolae genome contained the smallest number of ribosomal DNA units among all the eukaryotes examined to date. They consist of only 3 single units of rRNA genes distributed on separate chromosomal loci, representing an implication for concerted evolution. Based on these results, the origin and evolution of the nucleolus are discussed.
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- 2004
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39. Correlated clustering and virtual display of gene expression patterns in the wheat life cycle by large-scale statistical analyses of expressed sequence tags
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Yuji Kohara, Yasue Nemoto, Yasunari Ogihara, Koji Murai, Tadasu Shin-I, Yukiko Yamazaki, and Keiichi Mochida
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Regulation of gene expression ,Genetics ,Expressed sequence tag ,cDNA library ,food and beverages ,Genomics ,Cell Biology ,Plant Science ,Biology ,Gene expression profiling ,Common wheat ,Gene ,Functional genomics - Abstract
Compared to rice, wheat exhibits characteristic growth habits and contains complex genome constituents. To assess global changes in gene expression patterns in the wheat life cycle, we conducted large-scale analysis of expressed sequence tags (ESTs) in common wheat. Ten wheat tissues were used to construct cDNA libraries: crown and root from 14-day-old seedlings; spikelet from early and late flowering stages; spike at the booting stage, heading date and flowering date; pistil at the heading date; and seeds at 10 and 30 days post-anthesis. Several thousand colonies were randomly selected from each of these 10 cDNA libraries and sequenced from both 5' and 3' ends. Consequently, a total of 116 232 sequences were accumulated and classified into 25 971 contigs based on sequence homology. By computing abundantly expressed ESTs, correlated expression patterns of genes across the tissues were identified. Furthermore, relationships of gene expression profiles among the 10 wheat tissues were inferred from global gene expression patterns. Genes with similar functions were grouped with one another by clustering gene expression profiles. This technique might enable estimation of the functions of anonymous genes. Multidimensional analysis of EST data that is analogous to the microarray experiments may offer new approaches to functional genomics of plants.
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- 2003
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40. Gene expression profiles in Ciona intestinalis cleavage-stage embryos
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Yuji Kohara, Nori Satoh, Yukihisa Maeda, Tadasu Shin-I, Naohito Takatori, Yutaka Satou, and Shigeki Fujiwara
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Expressed Sequence Tags ,Regulation of gene expression ,Genetics ,Embryology ,Expressed sequence tag ,DNA, Complementary ,Time Factors ,biology ,Gene Expression Regulation, Developmental ,Embryo ,Cell Communication ,Cell fate determination ,biology.organism_classification ,Ciona intestinalis ,Ciona ,Databases as Topic ,Multigene Family ,Ectoderm ,Gene expression ,Animals ,Gene ,In Situ Hybridization ,Transcription Factors ,Developmental Biology - Abstract
A total of 1612 expression sequence tags derived from Ciona intestinalis cleavage-stage embryos were examined to explore detailed gene expression profiles. The 3' sequences indicate that the 1612 clones can be categorized into 1066 independent clusters. DDBJ database search suggested that 496 of them showed significant matches to reported proteins with distinct functions. Among them 69 are associated with cell-cell communications and 41 with transcription factors. In situ hybridization of all 1066 clusters showed that 84 clusters exhibited blastomere-specific pattern of expression, and many of these genes seem to encode for novel proteins. One of the interesting findings is that most of them were expressed in the precursor cells of multiple tissues. Among them 28 genes were expressed in the marginal zone of the 32-cell embryo. The blastomeres in this region are thought to receive an inductive signal from the vegetal blastomeres. Many of the blastomere-specific genes did not show similarity to known proteins. The present analysis therefore provides new information for further analyses on the cell fate specification in the Ciona embryo.
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- 2002
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41. Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia
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Kazutaka Kitaura, Masaharu Miyahara, Hiroshi Ureshino, Ryuji Suzuki, Takero Shindo, Kazuko Doi, Tadasu Shin-I, Shinya Kimura, Tatsuro Watanabe, Kazuharu Kamachi, and Eisaburo Sueoka
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Immunology ,T-cell leukemia ,Biology ,lcsh:RC254-282 ,t cell receptor ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Mogamulizumab ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,next generation sequencing ,Brief Report ,mogamulizumab ,T-cell receptor ,immune reconstitution ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,adult t cell leukemia ,Antibody ,lcsh:RC581-607 ,CD8 ,medicine.drug - Abstract
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+ T cells and oligoclonal CD8+ T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.
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- 2017
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42. A cDNA resource for gene expression studies of a hemichordate, Ptychodera flava
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Akane Sasaki, Satoko Fujita, Kuni Tagawa, Asao Fujiyama, Hiroshi Kagoshima, Nori Satoh, Mizuki Izumi, Takeshi Kawashima, Asuka Arimito, Tadasu Shin-I, Yuji Kohara, and Tom Humphreys
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Genetics ,Expressed Sequence Tags ,Expressed sequence tag ,DNA, Complementary ,biology ,cDNA library ,Stomochord ,Chordate ,Hemichordate ,biology.organism_classification ,Body plan ,Gene Expression Regulation ,Chordata, Nonvertebrate ,Complementary DNA ,Botany ,Animals ,Animal Science and Zoology ,Acorn worm ,Cloning, Molecular - Abstract
Recent investigations into the evolution of deuterostomes and the origin of chordates have paid considerable attention to hemichordates (acorn worms), as hemichordates and echinoderms are the closest chordate relatives. The present study prepared cDNA libraries from Ptychodera flava, to study expression and function of genes involved in development of the hemichordate body plan. Expressed sequence tag (EST) analyses of nine cDNA libraries yielded 18,832 cloned genes expressed in eggs, 18,739 in blastulae, 18,539 in gastrulae, 18,811 in larvae, 18,978 in juveniles, 11,802 in adult proboscis, 17,259 in stomochord, 11,886 in gills, and 11,580 in liver, respectively. A set of 34,159 uni-gene clones of P. flava was obtained. This cDNA resource will be valuable for studying temporal and spatial expression of acorn worm genes during development.
- Published
- 2014
43. Co-option of Sox3 as the male-determining factor on the Y chromosome in the fish Oryzias dancena
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Koichi Kawakami, Asao Fujiyama, Yuji Kohara, Tadasu Shin-I, Satoshi Hamaguchi, Taijun Myosho, Masaru Matsuda, Kiyoshi Naruse, Yusuke Takehana, Yoko Kuroki, Mitsuru Sakaizumi, Maximiliano L. Suster, and Atsushi Toyoda
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Male ,Chromosomes, Artificial, Bacterial ,Positional cloning ,Mutant ,Molecular Sequence Data ,Oryzias ,General Physics and Astronomy ,India ,Locus (genetics) ,Biology ,Y chromosome ,Real-Time Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Animals, Genetically Modified ,Chromosome Walking ,Transforming Growth Factor beta ,Y Chromosome ,Testis ,Oryzias dancena ,Animals ,Cloning, Molecular ,In Situ Hybridization ,Genetics ,Multidisciplinary ,Sexual differentiation ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,SOXB1 Transcription Factors ,Chromosome ,Gene Expression Regulation, Developmental ,Cell Differentiation ,General Chemistry ,Sequence Analysis, DNA ,Sex Determination Processes ,Phenotype ,Biological Evolution ,Immunohistochemistry ,Mutation - Abstract
Sex chromosomes harbour a primary sex-determining signal that triggers sexual development of the organism. However, diverse sex chromosome systems have been evolved in vertebrates. Here we use positional cloning to identify the sex-determining locus of a medaka-related fish, Oryzias dancena, and find that the locus on the Y chromosome contains a cis-regulatory element that upregulates neighbouring Sox3 expression in developing gonad. Sex-reversed phenotypes in Sox3Y transgenic fish, and Sox3Y loss-of-function mutants all point to its critical role in sex determination. Furthermore, we demonstrate that Sox3 initiates testicular differentiation by upregulating expression of downstream Gsdf, which is highly conserved in fish sex differentiation pathways. Our results not only provide strong evidence for the independent recruitment of Sox3 to male determination in distantly related vertebrates, but also provide direct evidence that a novel sex determination pathway has evolved through co-option of a transcriptional regulator potentially interacted with a conserved downstream component. Sex chromosomes harbour specific sequences that determine the sexual development of the organism; yet these sequences remain unknown for many species. Here, Takehana et al. show that, similarly to mammals, Sox3 on the Y chromosome is the male-determining factor in the medaka-related fish Oryzias dancena.
- Published
- 2014
44. Profiles of Maternally Expressed Genes in Fertilized Eggs of Ciona intestinalis
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Yasuaki Mochizuki, Yuji Kohara, Takahito Nishikata, Lixy Yamada, Nori Satoh, Tadasu Shin-I, and Yutaka Satou
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DNA, Complementary ,Time Factors ,Zygote ,Population ,Gene Expression ,Mothers ,Cell Communication ,mRNA distribution patterns ,Complementary DNA ,Gene expression ,Animals ,Cluster Analysis ,Humans ,Ciona intestinalis ,Tissue Distribution ,fertilized eggs ,RNA, Messenger ,education ,Gene ,Molecular Biology ,In Situ Hybridization ,Gene Library ,Genetics ,Expressed Sequence Tags ,education.field_of_study ,Expressed sequence tag ,biology ,Models, Genetic ,Embryo ,Cell Biology ,biology.organism_classification ,EST analysis ,Ciona ,Databases as Topic ,Multigene Family ,Female ,Transcription Factors ,Developmental Biology - Abstract
A set of 1,378 expressed sequence tags (ESTs), both the 5′-most and 3′-most ends, derived from Ciona intestinalis fertilized eggs was categorized into 1,003 independent clusters. When compared with sequences in databases, 452 of the clusters showed significant matches with reported proteins, while 190 showed matches with putative proteins for which there is not enough information to categorize their function, and 361 had no significant similarities to known proteins. Sequence similarity analyses of the 452 clusters in relation to the biological function as well as the structure of the message population at this stage demonstrated that 362 of them have functions that many kinds of cells use, 65 are associated with cell–cell communication, including a candidate cDNA for sonic hedgehog, and 25 are transcription factors. Sequence prevalence distribution analysis demonstrated that the great majority (78%) of the mRNAs are rare mRNAs or are represented by a single clone/cluster. All of the 1,003 clusters were subjected to whole-mount in situ hybridization to analyze the distribution of the maternal mRNAs in fertilized eggs, and a total of 329 genes showed localized distribution of the mRNAs: 16 showed cortical localization, 12 showed mitochondrial-like distribution, 99 crescent-like distribution, 63 partial localization, and 139 weak localization. When the distribution pattern of all the maternally expressed mRNAs was examined in the 8-cell stage embryos, it became evident that 248 genes which have localized mRNA patterns at the fertilized egg stage lose their localized distribution by the 8-cell stage. In contrast, 13 genes newly gain a localized pattern by the 8-cell stage. In addition, a total of 39 genes showed distinct in situ signals in the nucleus of blastomeres of the 8-cell stage embryo, suggesting early zygotic expression of these genes by this stage. These results suggest that complicated cytoplasmic movements are associated with the characteristic distribution of maternal mRNAs, which in turn support proper embryonic axis formation and establishment of the genetic network for embryonic cell specification.
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- 2001
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45. Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans
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Michael A. Brasch, Lynn Doucette-Stamm, Jean Vandenhaute, Jean Thierry-Mieg, Nia Tzellas, Philippe Lamesch, Jérôme Reboul, Marc Vidal, Gary F. Temple, Tadasu Shin-I, Nicolas Thierry-Mieg, James L. Hartley, Troy Moore, Joseph Hitti, David E. Hill, Yuji Kohara, Cindy Jackson, Hongmei Lee, Danielle Thierry-Mieg, and Philippe Vaglio
- Subjects
Expressed Sequence Tags ,Genetics ,Expressed sequence tag ,Intron ,Biology ,biology.organism_classification ,Polymerase Chain Reaction ,Genome ,Homology (biology) ,Open Reading Frames ,Open reading frame ,Species Specificity ,Animals ,Humans ,ORFS ,Caenorhabditis elegans ,Gene ,Genes, Helminth - Abstract
The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.
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- 2001
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46. The ancestor of extant Japanese fancy mice contributed to the mosaic genomes of classical inbred strains
- Author
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Tadasu Shin-I, Yoshiyuki Sakaki, Hideki Noguchi, Takanori Narita, Asao Fujiyama, Kuniya Abe, Thomas M. Keane, Kazuo Moriwaki, Toyoyuki Takada, Hironori Fujisawa, Yuji Kohara, Toshihiko Shiroishi, Toshinobu Ebata, Yuichi Obata, David J. Adams, and Atsushi Toyoda
- Subjects
Genetics ,Resource ,Genome ,Genotype ,Mosaicism ,Strain (biology) ,Molecular Sequence Data ,Introgression ,Genome project ,Sequence Analysis, DNA ,Subspecies ,Biology ,Polymorphism, Single Nucleotide ,Mice, Inbred C57BL ,Mice ,Inbred strain ,Phylogenetics ,Animals ,Inbreeding ,Genetics (clinical) ,Phylogeny ,Reference genome - Abstract
Commonly used classical inbred mouse strains have mosaic genomes with sequences from different subspecific origins. Their genomes are derived predominantly from the Western European subspecies Mus musculus domesticus, with the remaining sequences derived mostly from the Japanese subspecies Mus musculus molossinus. However, it remains unknown how this intersubspecific genome introgression occurred during the establishment of classical inbred strains. In this study, we resequenced the genomes of two M. m. molossinus–derived inbred strains, MSM/Ms and JF1/Ms. MSM/Ms originated from Japanese wild mice, and the ancestry of JF1/Ms was originally found in Europe and then transferred to Japan. We compared the characteristics of these sequences to those of the C57BL/6J reference sequence and the recent data sets from the resequencing of 17 inbred strains in the Mouse Genome Project (MGP), and the results unequivocally show that genome introgression from M. m. molossinus into M. m. domesticus provided the primary framework for the mosaic genomes of classical inbred strains. Furthermore, the genomes of C57BL/6J and other classical inbred strains have long consecutive segments with extremely high similarity (>99.998%) to the JF1/Ms strain. In the early 20th century, Japanese waltzing mice with a morphological phenotype resembling that of JF1/Ms mice were often crossed with European fancy mice for early studies of “Mendelism,” which suggests that the ancestor of the extant JF1/Ms strain provided the origin of the M. m. molossinus genome in classical inbred strains and largely contributed to its intersubspecific genome diversity.
- Published
- 2013
47. Mutations in cell elongation genes mreB, mrdA and mrdB suppress the shape defect of RodZ-deficient cells
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Fumio Ejima, Tadasu Shin-I, Hironori Niki, Atsushi Toyoda, Asao Fujiyama, Yuji Kohara, Daisuke Shiomi, and Tomoyuki Aizu
- Subjects
Penicillin binding proteins ,Escherichia coli Proteins ,Down-Regulation ,Membrane Proteins ,Periplasmic space ,Gene Expression Regulation, Bacterial ,Biology ,Microbiology ,Molecular biology ,MreB ,Cell biology ,Cell wall ,chemistry.chemical_compound ,Cytoskeletal Proteins ,Suppression, Genetic ,chemistry ,Membrane protein ,Escherichia coli ,Penicillin-Binding Proteins ,Peptidoglycan ,Cytoskeleton ,Molecular Biology ,Gene ,Gene Deletion ,Research Articles - Abstract
RodZ interacts with MreB and both factors are required to maintain the rod shape of Escherichia coli. The assembly of MreB into filaments regulates the subcellular arrangement of a group of enzymes that synthesizes the peptidoglycan (PG) layer. However, it is still unknown how polymerization of MreB determines the rod shape of bacterial cells. Regulatory factor(s) are likely to be involved in controlling the function and dynamics of MreB. We isolated suppressor mutations to partially recover the rod shape in rodZ deletion mutants and found that some of the suppressor mutations occurred in mreB. All of the mreB mutations were in or in the vicinity of domain IA of MreB. Those mreB mutations changed the property of MreB filaments in vivo. In addition, suppressor mutations were found in the periplasmic regions in PBP2 and RodA, encoded by mrdA and mrdB genes. Similar to MreB and RodZ, PBP2 and RodA are pivotal to the cell wall elongation process. Thus, we found that mutations in domain IA of MreB and in the periplasmic domain of PBP2 and RodA can restore growth and rod shape to ΔrodZ cells, possibly by changing the requirements of MreB in the process.
- Published
- 2012
48. Centromere-targeted de novo integrations of an LTR retrotransposon of Arabidopsis lyrata
- Author
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Akira Kawabe, Tasuku Ito, Akie Kobayashi, Tetsuji Kakutani, Atsushi Toyoda, Sayuri Tsukahara, Yoshiaki Tarutani, Tadasu Shin-I, Tomoyuki Aizu, and Asao Fujiyama
- Subjects
Transposable element ,Genetics ,Genome evolution ,biology ,Retroelements ,Centromere ,Arabidopsis ,Retrotransposon ,biology.organism_classification ,Genome ,Tandem repeat ,Arabidopsis thaliana ,Arabidopsis lyrata ,Developmental Biology ,Research Paper - Abstract
The plant genome evolves with rapid proliferation of LTR-type retrotransposons, which is associated with their clustered accumulation in gene-poor regions, such as centromeres. Despite their major role for plant genome evolution, no mobile LTR element with targeted integration into gene-poor regions has been identified in plants. Here, we report such targeted integrations de novo. We and others have previously shown that an ATCOPIA93 family retrotransposon in Arabidopsis thaliana is mobilized when the DNA methylation machinery is compromised. Although ATCOPIA93 family elements are low copy number in the wild-type A. thaliana genome, high-copy-number related elements are found in the wild-type Arabidopsis lyrata genome, and they show centromere-specific localization. To understand the mechanisms for the clustered accumulation of the A. lyrata elements directly, we introduced one of them, named Tal1 (Transposon of Arabidopsis lyrata 1), into A. thaliana by transformation. The introduced Tal1 was retrotransposed in A. thaliana, and most of the retrotransposed copies were found in centromeric repeats of A. thaliana, suggesting targeted integration. The targeted integration is especially surprising because the centromeric repeat sequences differ considerably between A. lyrata and A. thaliana. Our results revealed unexpectedly dynamic controls for evolution of the transposon-rich heterochromatic regions.
- Published
- 2012
49. A genomic overview of short genetic variations in a basal chordate, Ciona intestinalis
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Shota Chiba, Nori Satoh, Tadasu Shin-I, Yutaka Satou, and Yuji Kohara
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Euchromatin ,lcsh:QH426-470 ,Ascidian ,lcsh:Biotechnology ,Short genetic variations ,Genome ,Polymorphism, Single Nucleotide ,Chromosomes ,Nucleotide diversity ,Intergenic region ,INDEL Mutation ,Genetic linkage ,lcsh:TP248.13-248.65 ,Genetic variation ,Databases, Genetic ,Genetics ,Animals ,Ciona intestinalis ,Gene ,biology ,Base Sequence ,Single nucleotide polymorphisms (SNPs) ,Genetic Variation ,Reproducibility of Results ,Reference Standards ,biology.organism_classification ,lcsh:Genetics ,Mutagenesis, Insertional ,Amino Acid Substitution ,Gene Deletion ,Biotechnology ,Research Article - Abstract
Background Although the Ciona intestinalis genome contains many allelic polymorphisms, there is only limited data analyzed systematically. Establishing a dense map of genetic variations in C. intestinalis is necessary not only for linkage analysis, but also for other experimental biology including molecular developmental and evolutionary studies, because animals from natural populations are typically used for experiments. Results Here, we identified over three million candidate short genomic variations within a 110 Mb euchromatin region among five C. intestinalis individuals. The average nucleotide diversity was approximately 1.1%. Genetic variations were found at a similar density in intergenic and gene regions. Non-synonymous and nonsense nucleotide substitutions were found in 12,493 and 1,214 genes accounting for 81.9% and 8.0% of the entire gene set, respectively, and over 60% of genes in the single animal encode non-identical proteins between maternal and paternal alleles. Conclusions Our results provide a framework for studying evolution of the animal genome, as well as a useful resource for a wide range of C. intestinalis researchers.
- Published
- 2011
50. Easy-to-use phylogenetic analysis system for hepatitis B virus infection
- Author
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Masaya, Sugiyama, Ayano, Inui, Tadasu, Shin-I, Haruki, Komatsu, Motokazu, Mukaide, Naohiko, Masaki, Kazumoto, Murata, Kiyoaki, Ito, Makoto, Nakanishi, Tomoo, Fujisawa, and Masashi, Mizokami
- Abstract
The molecular phylogenetic analysis has been broadly applied to clinical and virological study. However, the appropriate settings and application of calculation parameters are difficult for non-specialists of molecular genetics. In the present study, the phylogenetic analysis tool was developed for the easy determination of genotypes and transmission route. A total of 23 patients of 10 families infected with hepatitis B virus (HBV) were enrolled and expected to undergo intrafamilial transmission. The extracted HBV DNA were amplified and sequenced in a region of the S gene. The software to automatically classify query sequence was constructed and installed on the Hepatitis Virus Database (HVDB). Reference sequences were retrieved from HVDB, which contained major genotypes from A to H. Multiple-alignments using CLUSTAL W were performed before the genetic distance matrix was calculated with the six-parameter method. The phylogenetic tree was output by the neighbor-joining method. User interface using WWW-browser was also developed for intuitive control. This system was named as the easy-to-use phylogenetic analysis system (E-PAS). Twenty-three sera of 10 families were analyzed to evaluate E-PAS. The queries obtained from nine families were genotype C and were located in one cluster per family. However, one patient of a family was classified into the cluster different from her family, suggesting that E-PAS detected the sample distinct from that of her family on the transmission route. The E-PAS to output phylogenetic tree was developed since requisite material was sequence data only. E-PAS could expand to determine HBV genotypes as well as transmission routes.
- Published
- 2011
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