顔写真

マキノ サトシ
牧野 悟士
Satoshi Makino
所属
東北メディカル・メガバンク機構 ゲノム解析部門
職名
助教
学位
  • 博士(医学)(徳島大学)

  • 修士(理学)(信州大学)

e-Rad 研究者番号
30423403

所属学協会 1

  • アメリカ人類遺伝学会

    2005年10月 ~ 継続中

研究分野 1

  • ライフサイエンス / 分子生物学 /

論文 43

  1. Heterozygous calcyclin-binding protein/Siah1-interacting protein (CACYBP/SIP) gene pathogenic variant linked to a dominant family with paucity of interlobular bile duct 査読有り

    Miyako Kanno, Mitsuyoshi Suzuki, Ken Tanikawa, Chikahiko Numakura, Shu-ichi Matsuzawa, Tetsuya Niihori, Yoko Aoki, Yoichi Matsubara, Satoshi Makino, Gen Tamiya, Satoshi Nakano, Ryo Funayama, Matsuyuki Shirota, Keiko Nakayama, Tetsuo Mitsui, Kiyoshi Hayasaka

    Journal of Human Genetics 67 (7) 393-397 2022年7月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s10038-022-01017-0  

    ISSN:1434-5161

    eISSN:1435-232X

  2. dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project 査読有り

    Soichi Ogishima, Satoshi Nagaie, Satoshi Mizuno, Ryosuke Ishiwata, Keita Iida, Kazuro Shimokawa, Takako Takai-Igarashi, Naoki Nakamura, Sachiko Nagase, Tomohiro Nakamura, Naho Tsuchiya, Naoki Nakaya, Keiko Murakami, Fumihiko Ueno, Tomomi Onuma, Mami Ishikuro, Taku Obara, Shunji Mugikura, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Akito Tsuboi, Shu Tadaka, Fumiki Katsuoka, Akira Narita, Mika Sakurai, Satoshi Makino, Gen Tamiya, Yuichi Aoki, Ritsuko Shimizu, Ikuko N. Motoike, Seizo Koshiba, Naoko Minegishi, Kazuki Kumada, Takahiro Nobukuni, Kichiya Suzuki, Inaho Danjoh, Fuji Nagami, Kozo Tanno, Hideki Ohmomo, Koichi Asahi, Atsushi Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Masayuki Yamamoto, Michiaki Abe, Yayoi Aizawa, Yuichi Aoki, Koichi Chida, Inaho Danjoh, Shinichi Egawa, Ai Eto, Takamitsu Funayama, Nobuo Fuse, Yohei Hamanaka, Yuki Harada, Hiroaki Hashizume, Shinichi Higuchi, Sachiko Hirano, Takumi Hirata, Masahiro Hiratsuka, Atsushi Hozawa, Kazuhiko Igarashi, Jin Inoue, Noriko Ishida, Naoto Ishii, Tadashi Ishii, Mami Ishikuro, Kiyoshi Ito, Sadayoshi Ito, Maiko Kageyama, Fumiki Katsuoka, Hiroshi Kawame, Junko Kawashima, Masahiro Kikuya, Kengo Kinoshita, Kazuyuki Kitatani, Tomomi Kiyama, Hideyasu Kiyomoto, Tomoko Kobayashi, Eiichi Kodama, Mana Kogure, Kaname Kojima, Sachie Koreeda, Seizo Koshiba, Shihoko Koyama, Hisaaki Kudo, Kazuki Kumada, Shigeo Kure, Miho Kuriki, Shinichi Kuriyama, Yoko Kuroki, Norihide Maikusa, Satoshi Makino, Hiroko Matsubara, Hiroyuki Matsui, Hirohito Metoki, Takahiro Mimori, Naoko Minegishi, Kazuharu Misawa, Masako Miyashita, Satoshi Mizuno, Hozumi Motohashi, Ikuko N. Motoike, Satoshi Nagaie, Masato Nagai, Fuji Nagami, Masao Nagasaki, Sachiko Nagase, Naoki Nakamura, Tomohiro Nakamura, Naoki Nakaya, Keiko Nakayama, Akira Narita, Ichiko Nishijima, Takahiro Nobukuni, Kotaro Nochioka, Taku Obara, Soichi Ogishima, Noriaki Ohuchi, Gervais Olivier, Noriko Osumi, Hiroshi Otsu, Akihito Otsuki, Daisuke Saigusa, Sakae Saito, Tomo Saito, Masaki Sakaida, Mika Sakurai-Yageta, Yuki Sato, Yukuto Sato, Atsushi Sekiguchi, Chen-Yang Shen, Tomoko F. Shibata, Ritsuko Shimizu, Kazuro Shimokawa, Matsuyuki Shirota, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Shu Tadaka, Makiko Taira, Takako Takai-Igarashi, Yuji Takano, Yasuyuki Taki, Gen Tamiya, Osamu Tanabe, Hiroshi Tanaka, Yukari Tanaka, Shunsuke Teraguchi, Takahiro Terakawa, Teiji Tominaga, Hiroaki Tomita, Akito Tsuboi, Naho Tsuchiya, Ichiro Tsuji, Masao Ueki, Akira Uruno, Nobuo Yaegashi, Junya Yamagishi, Yumi Yamaguchi-Kabata, Chizuru Yamanaka, Riu Yamashita, Jun Yasuda, Junji Yokozawa, Kazunori Waki, Makoto Sasaki, Junko Akai, Ryujin Endo, Akimune Fukushima, Ryohei Furukawa, Tsuyoshi Hachiya, Kouhei Hashizume, Jiro Hitomi, Yasushi Ishigaki, Shohei Komaki, Yuka Kotozaki, Takahiro Mikami, Motoyuki Nakamura, Naoyuki Nishiya, Satoshi Nishizuka, Yoko Nomura, Kuniaki Ogasawara, Hideki Ohmomo, Shinichi Omama, Ryo Otomo, Kotaro Otsuka, Kotaro Oyama, Kiyomi Sakata, Ryohei Sasaki, Mamoru Satoh, Namie Sato, Atsushi Shimizu, Yu Shiwa, Yoichi Sutoh, Nobuyuki Takanashi, Noriko Takebe, Fumitaka Tanaka, Ryoichi Tanaka, Kozo Tanno, Tomoharu Tokutomi, Kayono Yamamoto, Fumio Yamashita, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto

    Human Genome Variation 8 (1) 44 2021年12月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s41439-021-00175-5  

    eISSN:2054-345X

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    <title>Abstract</title>To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called “dbTMM” that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts.

  3. Japonica Array NEO with increased genome-wide coverage and abundant disease risk SNPs 査読有り

    Mika Sakurai-Yageta, Kazuki Kumada, Chinatsu Gocho, Satoshi Makino, Akira Uruno, Shu Tadaka, Ikuko N Motoike, Masae Kimura, Shin Ito, Akihito Otsuki, Akira Narita, Hisaaki Kudo, Yuichi Aoki, Inaho Danjoh, Jun Yasuda, Hiroshi Kawame, Naoko Minegishi, Seizo Koshiba, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    The Journal of Biochemistry 170 (3) 399-410 2021年5月13日

    出版者・発行元:Oxford University Press (OUP)

    DOI: 10.1093/jb/mvab060  

    ISSN:0021-924X

    eISSN:1756-2651

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    <title>Abstract</title> Ethnic-specific SNP arrays are becoming more important to increase the power of genome-wide association studies in diverse population. In the Tohoku Medical Megabank Project, we have been developing a series of Japonica Arrays (JPA) for genotyping participants based on reference panels constructed from whole-genome sequence data of the Japanese population. Here, we designed a novel version of the SNP array for the Japanese population, called Japonica Array NEO (JPA NEO), comprising a total of 666,883 markers. Among them, 654,246 tag SNPs of autosomes and X chromosome were selected from an expanded reference panel of 3,552 Japanese, 3.5KJPNv2, using pairwise r2 of linkage disequilibrium measures. Additionally, 28,298 markers were included for the evaluation of previously identified disease risk markers from the literature and databases, and those present in the Japanese population were extracted using the reference panel. Through genotyping 286 Japanese samples, we found that the imputation quality r2 and INFO score in the minor allele frequency bin &amp;gt;2.5–5% were &amp;gt;0.9 and &amp;gt;0.8, respectively, and &amp;gt;12 million markers were imputed with an INFO score &amp;gt;0.8. From these results, JPA NEO is a promising tool for genotyping the Japanese population with genome-wide coverage, contributing to the development of genetic risk scores.

  4. ALOX12 mutation in a family with dominantly inherited bleeding diathesis 査読有り

    Tetsuo Mitsui, Satoshi Makino, Gen Tamiya, Hiroko Sato, Yuki Kawakami, Yoshitaka Takahashi, Toru Meguro, Hiroko Izumino, Yosuke Sudo, Ikuo Norota, Kuniaki Ishii, Kiyoshi Hayasaka

    Journal of Human Genetics 2021年2月10日

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s10038-020-00887-6  

    ISSN:1434-5161

    eISSN:1435-232X

  5. Construction and integration of three de novo Japanese human genome assemblies toward a population-specific reference 査読有り

    Jun Takayama, Shu Tadaka, Kenji Yano, Fumiki Katsuoka, Chinatsu Gocho, Takamitsu Funayama, Satoshi Makino, Yasunobu Okamura, Atsuo Kikuchi, Sachiyo Sugimoto, Junko Kawashima, Akihito Otsuki, Mika Sakurai-Yageta, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto, Gen Tamiya

    Nature Communications 12 (1) 226 2021年1月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s41467-020-20146-8  

    eISSN:2041-1723

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    <title>Abstract</title>The complete human genome sequence is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the reference genome (e.g., GRCh37) due to its bias toward European and African ancestries. Here, we perform de novo assembly of three Japanese male genomes using &gt; 100× Pacific Biosciences long reads and Bionano Genomics optical maps per sample. We integrate the genomes using the major allele for consensus and anchor the scaffolds using genetic and radiation hybrid maps to reconstruct each chromosome. The resulting genome sequence, JG1, is contiguous, accurate, and carries the Japanese major allele at most loci. We adopt JG1 as the reference for confirmatory exome re-analyses of seven rare-disease Japanese families and find that re-analysis using JG1 reduces total candidate variant calls versus GRCh37 while retaining disease-causing variants. These results suggest that integrating multiple genomes from a single population can aid genome analyses of that population.

  6. Clustering by phenotype and genome-wide association study in autism 査読有り

    Akira Narita, Masato Nagai, Satoshi Mizuno, Soichi Ogishima, Gen Tamiya, Masao Ueki, Rieko Sakurai, Satoshi Makino, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Hiroko Matsubara, Yasutaka Kuniyoshi, Keiko Murakami, Fumihiko Ueno, Aoi Noda, Tomoko Kobayashi, Mika Kobayashi, Takuma Usuzaki, Hisashi Ohseto, Atsushi Hozawa, Masahiro Kikuya, Hirohito Metoki, Shigeo Kure, Shinichi Kuriyama

    Translational Psychiatry 10 (1) 290 2020年12月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s41398-020-00951-x  

    eISSN:2158-3188

  7. Genome-wide association study identifies new loci for albuminuria in the Japanese population 査読有り

    Hiroshi Okuda, Koji Okamoto, Michiaki Abe, Kota Ishizawa, Satoshi Makino, Osamu Tanabe, Junichi Sugawara, Atsushi Hozawa, Kozo Tanno, Makoto Sasaki, Gen Tamiya, Masayuki Yamamoto, Sadayoshi Ito, Tadashi Ishii

    Clinical and Experimental Nephrology 24 (8) 1-9 2020年8月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1007/s10157-020-01884-x  

    ISSN:1342-1751

    eISSN:1437-7799

  8. 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome 査読有り

    Shu Tadaka, Fumiki Katsuoka, Masao Ueki, Kaname Kojima, Satoshi Makino, Sakae Saito, Akihito Otsuki, Chinatsu Gocho, Mika Sakurai-Yageta, Inaho Danjoh, Ikuko N. Motoike, Yumi Yamaguchi-Kabata, Matsuyuki Shirota, Seizo Koshiba, Masao Nagasaki, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Atsushi Shimizu, Jun Yasuda, Nobuo Fuse, Gen Tamiya, Masayuki Yamamoto, Kengo Kinoshita

    Human Genome Variation 6 (1) 2019年12月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s41439-019-0059-5  

    eISSN:2054-345X

  9. Outlier detection for questionnaire data in biobanks 査読有り

    Rieko Sakurai, Masao Ueki, Satoshi Makino, Atsushi Hozawa, Shinichi Kuriyama, Takako Takai-Igarashi, Kengo Kinoshita, Masayuki Yamamoto, Gen Tamiya

    International Journal of Epidemiology 48 (4) 1305-1315 2019年8月1日

    出版者・発行元:Oxford University Press (OUP)

    DOI: 10.1093/ije/dyz012  

    ISSN:0300-5771

    eISSN:1464-3685

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    <title>Abstract</title> <sec> <title>Background</title> Biobanks increasingly collect, process and store omics with more conventional epidemiologic information necessitating considerable effort in data cleaning. An efficient outlier detection method that reduces manual labour is highly desirable. </sec> <sec> <title>Method</title> We develop an unsupervised machine-learning method for outlier detection, namely kurPCA, that uses principal component analysis combined with kurtosis to ascertain the existence of outliers. In addition, we propose a novel regression adjustment approach to improve detection, namely the regression adjustment for data by systematic missing patterns (RAMP). </sec> <sec> <title>Result</title> Application to epidemiological record data in a large-scale biobank (Tohoku Medical Megabank Organization, Japan) shows that a combination of kurPCA and RAMP effectively detects known errors or inconsistent patterns. </sec> <sec> <title>Conclusions</title> We confirm through the results of the simulation and the application that our methods showed good performance. The proposed methods are useful for many practical analysis scenarios. </sec>

  10. Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare. 国際誌 査読有り

    Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

    Journal of biochemistry 165 (2) 139-158 2019年2月1日

    DOI: 10.1093/jb/mvy096  

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    Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms of medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, medical genetics and prospective cohort studies to develop a critical infrastructure for the establishment of PHC. To date, a TMM CommCohort (adult general population) and a TMM BirThree Cohort (birth+three-generation families) have conducted recruitments and baseline surveys. Genome analyses as part of the TMM Project will aid in the development of a high-fidelity whole-genome Japanese reference panel, in designing custom single-nucleotide polymorphism (SNP) arrays specific to Japanese, and in estimation of the biological significance of genetic variations through linked investigations of the cohorts. Whole-genome sequencing from >3,500 unrelated Japanese and establishment of a Japanese reference genome sequence from long-read data have been done. We next aim to obtain genotype data for all TMM cohort participants (>150,000) using our custom SNP arrays. These data will help identify disease-associated genomic signatures in the Japanese population, while genomic data from TMM BirThree Cohort participants will be used to improve the reference genome panel. Follow-up of the cohort participants will allow us to test the genetic markers and, consequently, contribute to the realization of PHC.

  11. Female Japanese quail visually differentiate testosterone-dependent male attractiveness for mating preferences 査読有り

    Gen Hiyama, Shusei Mizushima, Mei Matsuzaki, Yasuko Tobari, Jae-Hoon Choi, Takashi Ono, Masaoki Tsudzuki, Satoshi Makino, Gen Tamiya, Naoki Tsukahara, Shoei Sugita, Tomohiro Sasanami

    Scientific Reports 8 (1) 2018年12月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1038/s41598-018-28368-z  

    eISSN:2045-2322

  12. Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole-exome sequencing analysis 査読有り

    Daisuke Ogino, Taeko Hashimoto, Motoshi Hattori, Noriko Sugawara, Yuko Akioka, Gen Tamiya, Satoshi Makino, Kentaro Toyota, Tetsuo Mitsui, Kiyoshi Hayasaka

    JOURNAL OF HUMAN GENETICS 61 (2) 137-141 2016年2月

    出版者・発行元:NATURE PUBLISHING GROUP

    DOI: 10.1038/jhg.2015.122  

    ISSN:1434-5161

    eISSN:1435-232X

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    Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in similar to 20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment.

  13. Waardenburg syndrome type IIE in a Japanese patient caused by a novel missense mutation in the SOX10 gene 査読有り

    Ken Okamura, Naoki Oiso, Gen Tamiya, Satoshi Makino, Daishi Tsujioka, Yuko Abe, Masakazu Kawaguchi, Yutaka Hozumi, Yoshikazu Shimomura, Tamio Suzuki

    JOURNAL OF DERMATOLOGY 42 (12) 1211-1212 2015年12月

    出版者・発行元:WILEY-BLACKWELL

    DOI: 10.1111/1346-8138.13095  

    ISSN:0385-2407

    eISSN:1346-8138

  14. Whole-exome sequencing confirmation of a novel heterozygous mutation in RUNX1 in a pregnant woman with platelet disorder 査読有り

    Miyuki Obata, Seiji Tsutsumi, Satoshi Makino, Kanako Takahashi, Norikazu Watanabe, Takayuki Yoshida, Gen Tamiya, Hirohisa Kurachi

    Platelets 26 (4) 364-369 2015年6月1日

    出版者・発行元:Informa Healthcare

    DOI: 10.3109/09537104.2014.912750  

    ISSN:1369-1635 0953-7104

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    We describe a successful pregnancy and delivery in a patient with platelet disorder. Prophylactic platelet transfusions ensured that there were no bleeding complications during and after cesarean section. Following delivery, we performed whole exome sequencing, using next generation sequencing, to analyze the DNA samples of the patient and her family, and to identify the disease-causing mutation or variant. To identify de-novo mutations systematically, we also analyzed DNA isolated from the parents of the patient and the neonate. We successfully identified a causative novel mutation c.419G&gt A (p.S140N) in RUNX1 in the patient and the neonate. Mutations of RUNX1 have been reported to be associated with familial platelet disorder and with a predisposition for myelodysplasia and/or acute myeloid leukemia. The patient and the neonate require careful long-term hematological follow-up. Identification of mutations by a through whole-exome analysis using next-generation sequencing may be useful in the determination of a long-term follow-up schedule for the patient.

  15. A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease 査読有り

    Gen Tamiya, Satoshi Makino, Makiko Hayashi, Akiko Abe, Chikahiko Numakura, Masao Ueki, Atsushi Tanaka, Chizuru Ito, Kiyotaka Toshimori, Nobuhiro Ogawa, Tomoya Terashima, Hiroshi Maegawa, Daijiro Yanagisawa, Ikuo Tooyama, Masayoshi Tada, Osamu Onodera, Kiyoshi Hayasaka

    AMERICAN JOURNAL OF HUMAN GENETICS 95 (3) 294-300 2014年9月

    出版者・発行元:CELL PRESS

    DOI: 10.1016/j.ajhg.2014.07.013  

    ISSN:0002-9297

    eISSN:1537-6605

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    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6de1CACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT.

  16. Visualizing Hepatic Copper Release in Long–Evans Cinnamon Rats Using Single-Photon Emission Computed Tomography 査読有り

    Eric M. Yezdimer, Tomohiro Umemoto, Hiroshi Yamada, Satoshi Makino, Ikuo Tooyama

    Applied Biochemistry and Biotechnology 170 (5) 1138-1150 2013年7月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1007/s12010-013-0252-9  

    ISSN:0273-2289

    eISSN:1559-0291

  17. Generation of a Monoclonal Antibody Specifically Reacting with Neuron-specific TATA-Box Binding Protein-Associated Factor 1 (N-TAF1) 査読有り

    Satoshi Makino, Chiaki Masuda, Satoshi Ando, Gen Tamiya, Ikuo Tooyama

    Antibodies 2 (4) 1-8 2012年12月21日

    出版者・発行元:MDPI AG

    DOI: 10.3390/antib2010001  

    eISSN:2073-4468

  18. In Vivo Detection of Copper Ions by Magnetic Resonance Imaging Using a Prion-Based Contrast Agent 査読有り

    Satoshi Makino, Tomohiro Umemoto, Hiroshi Yamada, Eric M. Yezdimer, Ikuo Tooyama

    APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY 168 (3) 504-518 2012年10月

    出版者・発行元:HUMANA PRESS INC

    DOI: 10.1007/s12010-012-9792-7  

    ISSN:0273-2289

    eISSN:1559-0291

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    Abnormal distributions of transition metals inside the body are potential diagnostic markers for several diseases, including Alzheimer's disease, Parkinson's disease, Wilson's disease, and cancer. In this article, we demonstrate that P57/Gd, a novel prion-based contrast agent, can selectively image tissues with excessive copper accumulation using magnetic resonance imaging (MRI). P57/Gd selectivity binds copper(II) over other physiologically relevant cations such as zinc, iron, manganese, and calcium. To simulate a metabolic copper disorder, we treated mice with an intraperitoneal injection of a CuSO4 solution to induce a renal copper overload. The MRI signal intensities from the renal cortex and medulla of copper spiked animals that were administered P57/Gd were found to correlate with the ex vivo copper concentrations determined by inductively coupled plasma mass spectrometry.

  19. Sustained expression of a neuron-specific isoform of the Taf1 gene in development stages and aging in mice 査読有り

    Jamiyansuren Jambaldorj, Satoshi Makino, Batmunkh Munkhbat, Gen Tamiya

    Biochemical and Biophysical Research Communications 425 (2) 273-277 2012年8月

    出版者・発行元:Elsevier BV

    DOI: 10.1016/j.bbrc.2012.07.081  

    ISSN:0006-291X

  20. UBR5 Gene Mutation Is Associated with Familial Adult Myoclonic Epilepsy in a Japanese Family 査読有り

    Takeo Kato, Gen Tamiya, Shingo Koyama, Tomohiro Nakamura, Satoshi Makino, Shigeki Arawaka, Toru Kawanami, Ikuo Tooyama

    ISRN Neurology 2012 1-4 2012年

    出版者・発行元:Hindawi Limited

    DOI: 10.5402/2012/508308  

    eISSN:2090-5513

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    The causal gene(s) for familial adult myoclonic epilepsy (FAME) remains undetermined. To identify it, an exome analysis was performed for the proband in a Japanese FAME family. Of the 383 missense/nonsense variants examined, only c.5720G&gt;A mutation (p.Arg1907His) in the <italic>UBR5</italic> gene was found in all of the affected individuals in the family, but not in the nonaffected members. Such mutation was not found in any of the 85 healthy individuals in the same community nor in any of the 24 individuals of various ethnicities. The present study demonstrated an FAME-associated mutation in the <italic>UBR5</italic> gene, which is located close to the reported locus linked to Japanese FAME families.

  21. Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina 査読有り

    Hisae Maebayashi, Shigako Takeuchi, Chiaki Masuda, Satoshi Makino, Kenji Fukui, Hiroshi Kimura, Ikuo Tooyama

    ACTA HISTOCHEMICA ET CYTOCHEMICA 45 (1) 15-23 2012年

    出版者・発行元:Japan Society of Histochemistry & Cytochemistry

    DOI: 10.1267/ahc.11015  

    ISSN:0044-5991

    eISSN:1347-5800

  22. Infiltration of T Lymphocytes and Expression of ICAM-1 in the Hippocampus of Patients with Hippocampal Sclerosis 査読有り

    Hiroaki Nakahara, Yoshihiro Konishi, Thomas G. Beach, Naoto Yamada, Satoshi Makino, Ikuo Tooyama

    ACTA HISTOCHEMICA ET CYTOCHEMICA 43 (6) 157-162 2010年

    出版者・発行元:Japan Society of Histochemistry & Cytochemistry

    DOI: 10.1267/ahc.10022  

    ISSN:0044-5991

    eISSN:1347-5800

  23. The mRNA Distribution of C7orf24, a γ-Glutamyl Cyclotransferase, in Rat Tissues 査読有り

    Keisuke Oda, Satoshi Makino, Chiaki Masuda, Tatsuhiro Yoshiki, Yoshihisa Kitamura, Kazuyuki Takata, Daijiro Yanagisawa, Takashi Taniguchi, Ikuo Tooyama

    Journal of Histochemistry & Cytochemistry 57 (12) 1121-1126 2009年12月

    出版者・発行元:SAGE Publications

    DOI: 10.1369/jhc.2009.953976  

    ISSN:0022-1554

    eISSN:1551-5044

  24. Twenty-six new polymorphic microsatellite markers around the HLA-B, -C and -E loci in the human MHC class I region 査読有り

    G. Tamiya, M. Ota, Y. Katsuyama, I. Shlina, A. Oka, S. Makino, M. Kimura, H. Inoko

    Tissue Antigens 51 (4) 337-346 2008年9月30日

    出版者・発行元:Wiley

    DOI: 10.1111/j.1399-0039.1998.tb02972.x  

    ISSN:0001-2815

    eISSN:1399-0039

  25. Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity 査読有り

    Kouji Maeda, Ryuji Kaji, Katsuhito Yasuno, Jamiyansuren Jambaldorj, Hiroyuki Nodera, Hiroshi Takashima, Masanori Nakagawa, Satoshi Makino, Gen Tamiya

    Journal of Human Genetics 52 (11) 907-914 2007年11月

    出版者・発行元:Springer Science and Business Media LLC

    DOI: 10.1007/s10038-007-0193-7  

    ISSN:1434-5161

    eISSN:1435-232X

  26. Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia 査読有り

    Katsuhito Yasuno, Satoshi Ando, Shinnosuke Misumi, Satoshi Makino, Jerzy K Kulski, Tatsuyuki Muratake, Naoshi Kaneko, Hideki Amagane, Toshiyuki Someya, Hidetoshi Inoko, Hidemichi Suga, Kousuke Kanemoto, Gen Tamiya

    American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B (2) 250-253 2007年3月5日

    出版者・発行元:Wiley

    DOI: 10.1002/ajmg.b.30443  

    ISSN:1552-4841

    eISSN:1552-485X

  27. Reduced Neuron-Specific Expression of the TAF1 Gene Is Associated with X-Linked Dystonia-Parkinsonism 査読有り

    Satoshi Makino, Ryuji Kaji, Satoshi Ando, Maiko Tomizawa, Katsuhito Yasuno, Satoshi Goto, Shinnichi Matsumoto, Ma. Daisy Tabuena, Elma Maranon, Marita Dantes, Lillian V. Lee, Kazumasa Ogasawara, Ikuo Tooyama, Hiroyasu Akatsu, Masataka Nishimura, Gen Tamiya

    The American Journal of Human Genetics 80 (3) 393-406 2007年3月

    出版者・発行元:Elsevier BV

    DOI: 10.1086/512129  

    ISSN:0002-9297

  28. Tumour necrosis factor α signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice 査読有り

    K. Tomita, G. Tamiya, S. Ando, K. Ohsumi, T. Chiyo, A. Mizutani, N. Kitamura, K. Toda, T. Kaneko, Y. Horie, J. Y. Han, S. Kato, M. Shimoda, Y. Oike, M. Tomizawa, S. Makino, T. Ohkura, H. Saito, N. Kumagai, H. Nagata, H. Ishii, T. Hibi

    Gut 55 (3) 415-424 2006年3月

    DOI: 10.1136/gut.2005.071118  

    ISSN:0017-5749

    詳細を見る 詳細を閉じる

    Background: While tumour necrosis factor α (TNF-α) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. Methods: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. Results: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-α, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-α administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. Conclusions: Enhancement of the TNF-α/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.

  29. Immunohistochemical study of TAFII250 in the rat laryngeal nervous system 査読有り

    H Okano, H Bamba, Y Hisa, S Makino, S Ando, G Tamiya, S Goto, R Kaji, H Kimura, I Tooyama

    Histology and histopathology 20 (4) 1029-1035 2005年10月

  30. Whole genome association study of rheumatoid arthritis using 27 039 microsatellites 査読有り

    G Tamiya, M Shinya, T Imanishi, T Ikuta, S Makino, K Okamoto, K Furugaki, T Matsumoto, S Mano, S Ando, Y Nozaki, W Yukawa, R Nakashige, D Yamaguchi, H Ishibashi, M Yonekura, Y Nakami, S Takayama, T Endo, T Saruwatari, M Yagura, Y Yoshikawa, K Fujimoto, A Oka, S Chiku, SEV Linsen, MJ Giphart, JK Kulski, T Fukazawa, H Hashimoto, M Kimura, Y Hoshina, Y Suzuki, T Hotta, J Mochida, T Minezaki, K Komai, S Shiozawa, A Taniguchi, H Yamanaka, N Kamatani, T Gojobori, S Bahram, H Inoko

    HUMAN MOLECULAR GENETICS 14 (16) 2305-2321 2005年8月

    出版者・発行元:OXFORD UNIV PRESS

    DOI: 10.1093/hmg/ddi234  

    ISSN:0964-6906

    詳細を見る 詳細を閉じる

    A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27 039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step In our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

  31. Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism 査読有り

    Satoshi Goto, Lillian V. Lee, Edwin L. Munoz, Ikuo Tooyama, Gen Tamiya, Satoshi Makino, Satoshi Ando, Marita B. Dantes, Kazumichi Yamada, Sadayuki Matsumoto, Hideki Shimazu, Jun-Ichi Kuratsu, Asao Hirano, Ryuji Kaji

    Annals of Neurology 58 (1) 7-17 2005年7月

    出版者・発行元:Wiley

    DOI: 10.1002/ana.20513  

    ISSN:0364-5134

  32. Novel algorithm for automated genotyping of microsatellites 査読有り

    Toshiko Matsumoto, Wataru Yukawa, Yasuyuki Nozaki, Ryo Nakashige, Minori Shinya, Satoshi Makino, Masaru Yagura, Tomoki Ikuta, Tadashi Imanishi, Hidetoshi Inoko, Gen Tamiya, Takashi Gojobori

    Nucleic Acids Research 32 (20) 6069-6077 2004年11月16日

    出版者・発行元:Oxford University Press (OUP)

    DOI: 10.1093/nar/gkh946  

    eISSN:1362-4962

  33. Identification of two new C4 alleles by DNA sequencing and evidence for a historical recombination of serologically defined C4A and C4B alleles 査読有り

    J. Hui, A. Oka, M. Tomizawa, G. K. Tay, J. K. Kulski, W. J. Penhale, S. P.A. Iaschi, S. Makino, G. Tamiya, H. Inoko

    Tissue Antigens 63 (3) 263-269 2004年3月

    DOI: 10.1111/j.1399-0039.2004.0175.x  

    ISSN:0001-2815

    詳細を見る 詳細を閉じる

    Nucleotide polymorphisms of the C4 genes were investigated by direct sequencing of seven different homozygous typing cells from the 10IHW panels. Two novel sequences were identified within the C4d region of the C4 genes. Our sequencing analyses extend previous findings suggesting that a recombination hot spot is likely to have occurred between codon positions 1157 and 1186 within the C4d region. The classification of electrophoretically defined C4A and C4B alleles can be further subtyped by sequencing. Because the central major histocompatibility complex region that carries various copies of the C4 gene has been associated with a range of disorders further analysis at the sequence level within the C4 locus may provide informative genetic markers for the investigation of disease-associated polymorphisms.

  34. Identification of IκBL as the Second Major Histocompatibility Complex–Linked Susceptibility Locus for Rheumatoid Arthritis 査読有り

    Koichi Okamoto, Satoshi Makino, Yoko Yoshikawa, Asumi Takaki, Yumie Nagatsuka, Masao Ota, Gen Tamiya, Akinori Kimura, Seiamak Bahram, Hidetoshi Inoko

    The American Journal of Human Genetics 72 (2) 303-312 2003年2月

    出版者・発行元:Elsevier BV

    DOI: 10.1086/346067  

    ISSN:0002-9297

  35. Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC 査読有り

    Y Matsuzaka, K Tounai, A Denda, M Tomizawa, S Makino, K Okamoto, N Keicho, A Oka, JK Kulski, G Tamiya, H Inoko

    IMMUNOGENETICS 54 (5) 301-309 2002年8月

    出版者・発行元:SPRINGER-VERLAG

    DOI: 10.1007/s00251-002-0470-8  

    ISSN:0093-7711

    詳細を見る 詳細を閉じる

    Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte anticens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping. However, no genes have been recognized in this candidate region to date. In order to identify a novel candidate gene for DPB from this segment, the expressed sequence tag databases were searched using the genomic sequence. As a result, a cDNA clone was isolated from a human lung cDNA library. This gene, designated C6orf37 (Chromosorne 6 open reading frame 37), spans approximately 2.5 kb and consists of two exons encoding a 235-amino acid protein, sharing homology with the mucin-like domain of human zonadhesin, which is a sperm multiple-domain transmembrane protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR analysis detected transcripts from the anti-sense DNA strand of this C6orf37 locus. The gene designated as C6orf370S (C6orf37 Opposite Strand) and represented by these anti-sense transcripts contained no open reading frame. The transcripts from C6orf37 and C6orf370S were observed in numerous tissues, with most-abundant expression in lung, kidney, and testis. Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf370S are excellent candidate genes for DPB.

  36. Susceptibility locus for non-obstructive azoospermia is localized within the HLA-DR/DQ subregion: Primary role of DQB1*0604 査読有り

    Y. Matsuzaka, S. Makino, K. Okamoto, A. Oka, A. Tsujimura, K. Matsumiya, S. Takahara, A. Okuyama, M. Sada, R. Gotoh, T. Nakatani, M. Ota, Y. Katsuyama, G. Tamiya, H. Inoko

    Tissue Antigens 60 (1) 53-63 2002年7月1日

    DOI: 10.1034/j.1399-0039.2002.600107.x  

    ISSN:0001-2815

    詳細を見る 詳細を閉じる

    Non-obstructive azoospermia is a mate infertility characterized by no or little sperm in semen as a result of a congenital dysfunction in spermatogenesis. Previous studies have reported a higher prevalence of particular human leukocyte antigen (HLA) antigens in non-obstructive azoospermia. As the expression of the RING3 gene located in the HLA class II region was predominant in the testis, mainly around spermatids and pachytene spermatocytes, it is tempting to speculate that RING3 is one of the strong candidate genes responsible for the pathogenesis of the disease. In this study, the genetic polymorphism in the RING3 gene was investigated by the direct sequencing technique. As a result, a total of 14 single nucleotide polymorphisms were identified. Among them, six were localized in the coding region but none of them was accompanied by an amino-acid substitution. No significant difference in the allelic distribution at these 14 polymorphic sites was observed between the patients and healthy controls, suggesting that the susceptible gene for non-obstructive azoospermia is not the RING3 gene. Then, in order to map the susceptibility locus for non-obstructive azoospermia precisely within the HLA region, 11 polymorphic microsatellite markers distributed from the SACM2L gene just outside the HLA class II region (187kb telomeric of the DPB1 gene) to the OTF3 gene in the HLA class I region were subjected to association analysis in the patients. Statistical analysis of distribution in the allelic frequency at each microsatellite locus demonstrated that the pathogenic gene for non-obstructive azoospermia is located within the HLA-DR/DQ subregion. In fact, DRB1*1302 and DQB1*0604 were found to be strongly associated with non-obstructive azoospermia by polymerase chain reaction-based DNA typing. Further, haplotype analysis suggested that the DQB1*0604 allele may play a decisive rote in the pathogenesis of non-obstructive azoospermia.

  37. Association of a determinant on mouse chromosome 18 with experimental severe Plasmodium berghei malaria 査読有り

    Eiji Nagayasu, Koichi Nagakura, Mayumi Akaki, Gen Tamiya, Satoshi Makino, Yamaji Nakano, Minoru Kimura, Masamichi Aikawa

    Infection and Immunity 70 (2) 512-516 2002年

    DOI: 10.1128/IAI.70.2.512-516.2002  

    ISSN:0019-9567

    詳細を見る 詳細を閉じる

    Experimental severe malaria (ESM also known as experimental cerebral malaria) is an acute lethal syndrome caused by infection with Plasmodium berghei ANKA and associated with coma and other neurological manifestations in mice. Various inbred strains of mice exhibit differences in susceptibility to the development of ESM. For example, C57BL/6 mice are highly susceptible and DBA/2 mice are relatively resistant. We report here the results of a genomewide scan for host genomic regions that control resistance to ESM in DBA/2 mice using an F2 intercross population of susceptible and resistant strains. A region of mid-chromosome 18 was found to be a major determinant of resistance to ESM.

  38. New polymorphic microsatellite markers in the human MHC class III region 査読有り

    Y. Matsuzaka, S. Makino, K. Nakajima, M. Tomizawa, A. Oka, S. Bahram, J. K. Kulski, G. Tamiya, H. Inoko

    Tissue Antigens 57 (5) 397-404 2001年

    DOI: 10.1034/j.1399-0039.2001.057005397.x  

    ISSN:0001-2815

    詳細を見る 詳細を閉じる

    The human major histocompatibility complex (MHC) class III region spanning approximately 760 kb is characterized by a remarkably high gene density with 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loci to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loci. However, it has been difficult to precisely localize these susceptibility loci to a single gene due to a paucity to date of polymorphic markers in the HLA class III region. To facilitate disease mapping within this region, we have analyzed 2∼5 bases short tandem repeats (microsatellites) in this region. A total of 297 microsatellites were identified from the genomic sequence, consisting of 69 di-, 62 tri-, 107 tetra-, and 59 penta-nucleotide repeats. It was noted that among them as many as 17 microsatellites were located within the coding sequence of expressed genes (NOTCH4, PBX2, RAGE, G16, LPAAT, PPT2, TNXB, P450-CYP21B, G9a, HSP70-2, HSP70-1, HSP-hom, Mu TSH5 and BAT2). Eight microsatellite repeats were collected as polymorphic markers due to their high number of alleles (11.9 on average) as well as their high polymorphic content value (PIC) (0.63). By combining the 38 and the 22 polymorphic microsatellites we have previously collected in the HLA class I and class II regions, respectively, we have now established a total of 68 novel genetic markers which are uniformly interspersed with a high density of one every 63.3 kb throughout the HLA region. This collection of polymorphic microsatellites will enable us to search for the location of any disease susceptible loci within the HLA region by association analysis.

  39. Gene structure and promoter for Crad2 encoding mouse cis-retinol/3α-hydroxysterol short-chain dehydrogenase isozyme 査読有り

    Kengo Tomita, Masahiro Sato, Kagemasa Kajiwara, Masafumi Tanaka, Gen Tamiya, Satoshi Makino, Maiko Tomizawa, Akiko Mizutani, Yuhko Kuwano, Takashi Shiina, Hiromasa Ishii, Minoru Kimura

    Gene 251 (2) 175-186 2000年6月

    出版者・発行元:Elsevier BV

    DOI: 10.1016/s0378-1119(00)00194-3  

    ISSN:0378-1119

  40. New polymorphic microsatellite markers in the human MHC class II region 査読有り

    Y. Matsuzaka, S. Makino, K. Nakajima, M. Tomizawa, A. Oka, M. Kimura, S. Bahram, G. Tamiya, H. Inoko

    Tissue Antigens 56 (6) 492-500 2000年

    DOI: 10.1034/j.1399-0039.2000.560602.x  

    ISSN:0001-2815

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    The human major histocompatibility complex (MHC) class II region spans approximately 1.1 Mb and presently contains over 30 functional genes. Susceptibility loci to numerous diseases, mainly of autoimmune nature are known to map to the this region, as assessed by associations with particular HLA class II alleles. However, it has been difficult to precisely localize these susceptibility loci to a single gene, for example DQB1 or DRB1, due to the tight linkage disequilibrium observed in the HLA class II region. To facilitate disease mapping within this region, we have analyzed 2∼5 bases short tandem repeats (microsatellites) in this same region. A total of 494 microsatellites were identified from the genomic sequence of the HLA class II region. These consist of 158 di-, 65 tri-, 163 tetra-, and 108 pentanucleotide repeats, out of which four were located within the coding sequence of expressed genes (Daxx, BING1, RXRB and COL11A2). Twenty-two repeats were selected as polymorphic markers due to their high (average) number of alleles (8.9) as well as their high polymorphic content value (PIC) (0.58). These novel polymorphic microsatellites will provide useful genetic markers in HLA-related research, such as genetic mapping of HLA class II-associated diseases, transplantation matching, population genetics, identification of recombination hot spots as well as linkage disequilibrium studies.

  41. Construction of a Linkage Map of the Medaka (Oryzias latipes) and Mapping of the Da Mutant Locus Defective in Dorsoventral Patterning 査読有り

    M Ohtsuka, S Makino, K Yoda, H Wada, K Naruse, H Mitani, A Shima, K Ozato, M Kimura, H Inoko

    Genome Research 9 (12) 1277-1287 1999年12月1日

    出版者・発行元:Cold Spring Harbor Laboratory

    DOI: 10.1101/gr.9.12.1277  

    eISSN:1088-9051

  42. Association Analysis Using Refined Microsatellite Markers Localizes a Susceptibility Locus for Psoriasis Vulgaris Within a 111 kb Segment Telomeric to the HLA-C Gene 査読有り

    A. Oka, G. Tamiya, M. Tomizawa, M. Ota, Y. Katsuyama, S. Makino, T. Shiina, M. Yoshitome, M. Iizuka, Y. Sasao, K. Iwashita, Y. Kawakubo, J. Sugai, A. Ozawa, M. Ohkido, M. Kimura, S. Bahram, H. Inoko

    Human Molecular Genetics 8 (12) 2165-2170 1999年11月1日

    出版者・発行元:Oxford University Press (OUP)

    DOI: 10.1093/hmg/8.12.2165  

    ISSN:0964-6906

    eISSN:1460-2083

  43. New polymorphic microsatellite markers in the human MHC class I region 査読有り

    G. Tamiya, T. Shiina, A. Oka, M. Tomizawa, M. Ota, Y. Katsuyama, M. Yoshitome, S. Makino, M. Kimura, H. Inoko

    Tissue Antigens 54 (3) 221-228 1999年9月

    出版者・発行元:Wiley

    DOI: 10.1034/j.1399-0039.1999.540302.x  

    ISSN:0001-2815

︎全件表示 ︎最初の5件までを表示

MISC 1

  1. だれでも使えるバイオインフォマティクスリソース 「バイオインフォマティクスはじめの一歩」

    牧野悟士

    分子精神医学 6 (1) 59-65 2006年1月

講演・口頭発表等 1

  1. Deficiency of a Neuron-specific Isoform of the TAF1 Gene Is Associated with X-linked Dystonia-Parkinsonism

    Makino S, Kaji R, Ando S, Tomizawa M, Ando H, Goto S, Matsumoto S, Tabuena D, Maranon E, Dantes M, Lee LV, Ogasawara K, Tooyama I, Akatsu H, Nishimura M, Tamiya G

    American Society of Human Genetics 2005 Annual Meeting 2005年10月27日

共同研究・競争的資金等の研究課題 5

  1. 大規模コホートの調査票における新規データクリーニング手法の開発

    牧野 悟士, 田宮 元, 櫻井 利恵子

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目:Grant-in-Aid for Scientific Research (C)

    研究機関:Tohoku University

    2018年4月 ~ 2021年3月

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    東北メディカル・メガバンク機構の大規模ゲノムコホート研究では、15万人の参加者について、各種の血液検査値や画像データ、健康診断結果が計測されると同時に、同意書、生活習慣などに関する調査票といった、紙媒体の形態で収集される情報を取り扱っている。適切な調査結果の還元と医療支援への貢献、そして学術的用途としての有用性を高めるために、データの信頼性確保が必須であり、そのためには、データ入力におけるモニタリングや論理チェック、データクリーニングが重要である。しかし、膨大なデータを全て人力で確認し、調査票原本に戻って修正の必要性を調べることは事実上不可能である。そこで本研究計画では、大規模なデータクリーニングにおいて、1) 集団からの外れ値を検出する際に既知の情報を利用して主成分分析(PCA)を拡張した統計的モデルを使用する、2) 検出されたエラー候補をその性質に基づいて分類・処理する、の二つの手法をあわせ用いることにより、この問題の本質的解決を目指している。 初年度においては、同意書および調査票と、関連する特定健診データなどにおいて、期待した通りの挙動をしないデータ及びパターン(ここではエラーと呼称する)の検出を一つ目の目的とした。そのために、これまで人力により行っていたエラーの検出を、主成分分析に基づいて自動化するアルゴリズムの開発を進めてきた。主成分分析を用いたエラー検出法はすでに多く提案されているが、エラー検出の自動化を行い、さらに検出の作業効率を上げるため、統計量の一つである尖度を用いたアルゴリズムを開発した。

  2. モデルマウス呼吸鎖複合体の解析に基づく中間型CMT(CMTRID)発症機構の解明

    牧野 悟士, 田宮 元, 遠山 育夫

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目:Grant-in-Aid for Scientific Research (C)

    研究機関:Tohoku University

    2015年4月 ~ 2018年3月

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    遺伝性末梢神経障害であるCharcot-Marie-Tooth病(CMT)原因遺伝子COX6A1のノックアウトマウスが歩行障害を示し、神経伝導速度の低下、神経原性の筋萎縮、COX活性の低下を示した。一方で電子顕微鏡による神経繊維の観察では特別な所見がみられなかった。そこで、ミトコンドリアに存在する金属結合性タンパク質のミトコンドリアフェリチンに着目した。過酸化水素による酸化ストレスを与えたドパミン神経細胞において遺伝子発現量を調べたところ、ミトコンドリアフェリチンの発現量が増加し、神経細胞の保護機能をもつと考えられることがわかった。

  3. 基本転写因子TAF1が関与する転写障害と神経変性の研究

    牧野 悟士, 遠山 育夫

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    研究種目:Grant-in-Aid for Scientific Research (C)

    2012年4月 ~ 2015年3月

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    基本転写因子のサブユニットにおける転写障害が神経変性を引き起こす可能性の観点から、TAF1とその神経細胞特異的なアイソフォームにおける機能面での差異を調べる実験として、細胞周期に関する機能を喪失したハムスターのmutantセルラインを用いた実験を行った。様々な発現コンストラクトを導入した細胞をFACSによって細胞周期解析したところ、mutantセルラインがもつ細胞周期の機能に影響する点突然変異は、TAF1の神経細胞特異的な機能との関連が低いと示唆され、TAF1がもつ細胞周期関連の機能と神経細胞特異的な機能との関連について知見を得ることができた。

  4. 遺伝性ジストニアDYT3の原因遺伝子N-TAF1に関する神経細胞特異的機能の解明

    牧野 悟士

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    研究種目:Grant-in-Aid for Young Scientists (B)

    研究機関:Shiga University of Medical Science

    2010年 ~ 2011年

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    遺伝性ジストニアDYT3の原因遺伝子TAF1の神経細胞特異的なアイソフォームに関して、神経細胞における役割を明らかにすることを目的として、神経系および非神経系の哺乳類培養細胞株における強制発現を行い、細胞内局在のパターンを調べた。その結果、両者の間で局在パターンに差異のあることがわかった。また、N-TAF1が直接発現を制御する遺伝子群を明らかにする目的で、TAF1またはN-TAF1をノックダウンした細胞株を使用して、対照サンプルとの間で様々な遺伝子の発現量の変化をマイクロアレイ解析によって調べた。その結果、TAF1によって発現制御される可能性がある遺伝子の候補を見いだした。

  5. 伴性劣性ジストニアパーキンソニズムの原因遺伝子N-TAF1に関する機能解析

    牧野 悟士

    提供機関:Japan Society for the Promotion of Science

    制度名:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    研究種目:Grant-in-Aid for Young Scientists (B)

    研究機関:Shiga University of Medical Science

    2008年 ~ 2009年

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    伴性劣性ジストニアパーキンソニズムの原因遺伝子TAF1の神経細胞特異的なアイソフォームに関して、神経細胞における役割を明らかにすることを目的として、マウス胚発生期におけるN-TAF1の発現パターン解析と、N-TAF1およびTAF1タンパク質を強制発現させた培養細胞株における細胞化学的な解析を行った。その結果、N-TAF1とTAF1との問に発現パターンおよび細胞増殖へ与える影響に関して差異がみられることがわかった。