Current Affiliation Organization 【 display / non-display 】

Current Affiliation Organization 【 display / non-display 】

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Published Papers 【 display / non-display 】

• Identification of potential disease-associated variants in idiopathic generalized epilepsy using targeted sequencing

  Gamirova, R; Shagimardanova, E; Sato, T; Kannon, T; Gamirova, R; Tajima, A

  JOURNAL OF HUMAN GENETICS ( Journal of Human Genetics )  69 ( 2 ) 59 - 67   2024.02 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.

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• Nutrigenetic Interaction Between Apolipoprotein C3 Polymorphism and Fat Intake in People with Nonalcoholic Fatty Liver Disease

  Reina Yamamoto, Yumie Takeshita, Hiromasa Tsujiguchi, Takayuki Kannon, Takehiro Sato, Kazuyoshi Hosomichi, Keita Suzuki, Yuki Kita, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Tatsuya Yamashita, Shuichi Kaneko, Atsushi Tajima, Hiroyuki Nakamura, Toshinari Takamura

  Current Developments in Nutrition ( Elsevier BV )  7 ( 4 ) 100051 - 100051   2023.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Genetic factors associated with serum amylase in a Japanese population: combined analysis of copy-number and single-nucleotide variants

  Zannatun Nayema, Takehiro Sato, Takayuki Kannon, Hiromasa Tsujiguchi, Kazuyoshi Hosomichi, Hiroyuki Nakamura, Atsushi Tajima

  Journal of Human Genetics ( Springer Science and Business Media LLC )    2023.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Abstract Amylase activity and levels in humans are heritable quantitative traits. Although many studies exist on the effects of copy-number variants (CNVs) in amylase genes (AMY) on human phenotypes, such as body mass index (BMI), the genetic factors controlling interindividual variation in amylase levels remain poorly understood. Here, we conducted a genome-wide association study (GWAS) of serum amylase levels (SAL) in 814 Japanese individuals to identify associated single-nucleotide variants (SNVs), after adjusting for non-genetic factors. Diploid copy numbers (CN) of AMY (AMY1, AMY2A, and AMY2B) were measured using droplet digital PCR to examine the association between each diploid CN and SAL. We further assessed the relative contribution of the GWAS-lead SNV and AMY CNVs to SAL. GWAS identified 14 significant SNVs (p < 5 × 10⁻⁸) within a linkage disequilibrium block near the AMY cluster on chromosome 1. The association analyses of AMY CNVs and SAL showed a significant association between AMY1 diploid CN and SAL (p = 1.89 × 10⁻¹⁹), while no significant association with SAL was found for AMY2A CN (p = 0.54) or AMY2B CN (p = 0.15). In a joint association analysis with SAL using the GWAS-lead SNV and AMY1 diploid CN, AMY1 CN remained significant (p = 5.4 ×10⁻¹³), while the association of the lead SNV was marginal (p = 0.08). We also found no association between AMY1 diploid CN and BMI (p = 0.14). Our results indicate that AMY1 CNV is the major genetic factor for Japanese SAL, with no significant association with BMI.

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• Genetic Characteristics Contributing to Lipoprotein(a) Levels in the Japanese Population

  Kan Yamagami, Hayato Tada, Takehiro Sato, Akihiro Nomura, Kenji Sakata, Soichiro Usui, Masa-aki Kawashiri, Atsushi Tajima, Masayuki Takamura

  Journal of Coronary Artery Disease ( The Japanese Coronary Association )  29 ( 4 ) 104 - 108   2023 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia.

  Loc Thi Pham, Hui Peng, Masaya Ueno, Susumu Kohno, Atuso Kasada, Kazuyoshi Hosomichi, Takehiro Sato, Kenta Kurayoshi, Masahiko Kobayashi, Yuko Tadokoro, Atsuko Kasahara, Mahmoud I Shoulkamy, Bo Xiao, Paul F Worley, Chiaki Takahashi, Atsushi Tajima, Atsushi Hirao

  Biochemical and biophysical research communications ( Elsevier BV )  621   74 - 79   2022.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes. Although various therapeutic approaches have been developed, refractoriness of chemotherapy and relapse cause a poor prognosis of the disease and further therapeutic strategies are required. Here, we report that Ras homolog enriched in brain (RHEB), a critical regulator of mTOR complex 1 activity, is a potential target for T-ALL therapy. In this study, we established an sgRNA library that comprehensively targeted mTOR upstream and downstream pathways, including autophagy. CRISPR/Cas9 dropout screening revealed critical roles of mTOR-related molecules in T-ALL cell survival. Among the regulators, we focused on RHEB because we previously found that it is dispensable for normal hematopoiesis in mice. Transcriptome and metabolic analyses revealed that RHEB deficiency suppressed de novo nucleotide biosynthesis, leading to human T-ALL cell death. Importantly, RHEB deficiency suppressed tumor growth in both mouse and xenograft models. Our data provide a potential strategy for efficient therapy of T-ALL by RHEB-specific inhibition.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• 言語や音楽の進化は集団史を反映しているか?

  松前ひろみ, SAVAGE Patrick E, BICKEL Balthasar, CURRIE Thomas E, RANACHER Peter, BLASI Damien, 佐藤丈寛, 田嶋敦, STONEKING Mark, 清水健太郎, 清水健太郎, BROWN Steven, 太田博樹

  日本遺伝学会大会プログラム・予稿集   90th   120   2018.08

   

  J-GLOBAL

• 地域住民コホートを対象とした認知機能低下に関わるゲノムワイドgene‐set enrichment関連解析

  林幸司, 篠原もえ子, 佐藤丈寛, 觀音隆幸, 細道一善, 田嶋敦, 山田正仁

  日本人類遺伝学会大会プログラム・抄録集   63rd   359   2018

   

  J-GLOBAL

• Archaeological investigation in Hamanaka 2site, Rebun, Hokkaido (2011-2016 seasons)

  IWANAMI Ren, HIRASAWA Yu, TANEISHI Yu, NAGANUMA Masaki, FUJISAWA Takashi, TUTAYA Takumi, SATO Takehiro, FUKASE Hitoshi, KIMURA Ryousuke, YONEDA Minoru, ADACHI Noboru, SATO Takao, ISHIDA Hajime, KATO Hirofumi

  Abstracts of the 2016 Investigation Meeting of Hokkaido Archaeological Society     83 - 92   2016.12

   

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Elucidation of the human population history in boundary area between East Asia and Siberia based on ancient genome analysis

  Grant-in-Aid for Scientific Research(B)

  Project Year: 2019.04  -  2024.03 

  Direct: 13,300,000 (YEN)  Overheads: 17,290,000 (YEN)  Total: 3,990,000 (YEN)

• A feasibility study for genome analysis of ancient human skeletons excavated from the western part of Japan

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): Sato Takehiro 

  Direct: 3,900,000 (YEN)  Overheads: 5,070,000 (YEN)  Total: 1,170,000 (YEN)

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  Ancient genome analysis is necessary to investigate the genetic origin of Japanese people. In this study, we tried the screening ancient human bone samples excavated from the sites located in western part of the Japanese Archipelago, from which ancient genome data have not been reported. To extract genomic DNA from an ancient human bone, several hundreds mg of bone powder is required. To avoid such destruction of ancient human bone samples, we measured the racemization rate of aspartic acid included in collagen of bone samples at first because measuring of racemization rate can be performed using only 20 mg of bone power. We could carry out the screening of ancient bone samples without superfluous destruction, by the screening based on racemization rate.

• Grant-in-Aid for JSPS Fellows

  Project Year: 2013.04  -  2016.03 

  Direct: 3,900,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 780,000 (YEN)