世界および日本の瞬発系・持久系選手の運動能力に関連する機能的多型の解明

2014 Fiscal Year Annual Research Report

• Project/Area Number: 25242062
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: 田中 雅嗣 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60155166)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アスリート / 全エクソン領域解析 / 全ゲノム領域解析

Outline of Annual Research Achievements

Illumina社のInfinium HumanExome BeadChipを用いて、約24万個のアミノ酸置換を伴う機能的多型を網羅的に解析した。必要なDNA量を確保するために、予めwhole genome amplificationを実施した。Jamaicaのアスリート93人と対照群306人、USAのアスリート112人と対照群200人、合計711人の試料についてBeadChip解析を終えた。このうち、レジェンド・アスリートは48人、国際大会への出場経験のあるアスリートは91人であった。日本人対照群として、平成25年度に2268人、平成26年度に913人の全エクソン領域の機能的多型を同一のBeadChipを用いて解析した。Whole genome amplification後のDNAを用いてBeadChip解析を行うと、標準クラスターを用いてgenotypingを行うことが困難であり、カスタム・クラスターを使用する必要が生じた。さらにカスタム・クラスターを使用しても判定不能となる一塩基多型が発生することが判明した。このため、次世代シークエンサーIon Protonを用いて、AmpliSeq-Exome Kitを用いて全エクソン領域の塩基配列を解析することを検討した。一方、比較的安価に全ゲノム領域塩基配列を決定する新しいシステム（Illumina社HiSeq X Ten）が開発されたので、その利用を考慮することにした。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

Whole genome amplification後のDNA試料の遺伝子型を決定する時に解析精度が低いことが判明した。

Strategy for Future Research Activity

全エクソン領の塩基配列決定、あるいは全ゲノム領域の塩基配列決定を行うことによって精度を高める。

Research Products

• [Journal Article] Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: potential interaction with smoking (2015)
  • Author(s): Miki Yamada, Noriko Sato, Shinobu Ikeda, Tomio Arai, Motoji Sawabe, Seijiro Mori, Yoshiji Yamada, Masaaki Muramatsu, Masashi Tanaka
  • Journal Title: Genes Chromosomes Cancer Volume: 54 Pages: 122-128
  • DOI: 10.1002/gcc.22227
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Polygenic risk for hypertriglyceridemia is attenuated in Japanese men with high fitness levels (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Physiol Genomics Volume: 46 Pages: 207-215
  • DOI: 10.1152/physiolgenomics.00182.2013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High cardiorespiratory fitness can reduce glycated hemoglobin levels regardless of polygenic risk for type 2 diabetes mellitus in non-diabetic Japanese men (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Ryuken Ise, Satomi Oshima, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Physiol Genomics Volume: 46 Pages: 497-504
  • DOI: 10.1152/physiolgenomics.00027.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Ryuken Ise, Satomi Oshima, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Genes Nutr Volume: 9 Pages: 416
  • DOI: 10.1007/s12263-014-0416-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes (2015)
  • Author(s): E Mikami, N Fuku, H Murakami, H Tsuchie, H Takahashi, N Ohiwa, H Tanaka, Y P Pitsiladis, M Higuchi, M Miyachi, T Kawahara, Masashi Tanaka
  • Journal Title: Intl J Sports Med Volume: 35 Pages: 172-177
  • DOI: 10.1055/s-0033-1347171
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evolution of mitochondrial power in vertebrate metazoans (2015)
  • Author(s): Yasuhiro Kitazoe, Masashi Tanaka
  • Journal Title: PloS One Volume: 9 Pages: 6.06
  • DOI: 10.1371/journal.pone.0098188
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders (2015)
  • Author(s): Natsumi Uehara, Masato Mori, Yoshimi Tokuzawa, Yosuke Mizuno, Yasunori Fujita, Masafumi Ito, Masashi Tanaka, Ken-ichi Nibu, Akira Ohtake, Yasushi Okazaki
  • Journal Title: Ann Clin Transl Neurol Volume: 1 Pages: 361-369
  • DOI: 10.1002/acn3.59
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficacy of pyruvate therapy in patients with mitochondrial disease: A semi-quantitative clinical evaluation study (2015)
  • Author(s): Tatsuya Fujii, Fumihito Nozaki, Keiko Saito, Anri Hayashi, Yutaka Nishigaki, Kei Murayama, Masashi Tanaka, Yasutoshi Koga, Ikuko Hiejima, Tomohiro Kumada
  • Journal Title: Mol Genet Metab Volume: 112 Pages: 133-138
  • DOI: 10.1016/j.ymgme.2014.04.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population (2015)
  • Author(s): Heying Zhou, Seijiro Mori, Masashi Tanaka, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Makiko Naka Mieno, Shoji Shinkai, Yoshiji Yamada, Motohiko Miyachi, Haruka Murakami, Kiyoshi Sanada, Hideki Ito
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: in press Pages: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] (2014) GDF15 is a novel biomarker to evaluate efficacy of pyruvate therapy for mitochondrial diseases (2015)
  • Author(s): Yasunori Fujita, Masafumi Ito, Toshio Kojima, Shuichi Yatsuga, Yasutoshi Koga, Masashi Tanaka
  • Journal Title: Mitochondrion Volume: 20 Pages: 34–42
  • DOI: 10.1016/j.mito.2014.10.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Toshiyuki Imasawa, Masashi Tanaka, Yutaka Yamaguchi, Takashi Nakazato, Hiroshi Kitamura, Motonobu Nishimura (2014) 7501 T > A mitochondrial DNA variant in a patient with glomerulosclerosis (2014)
  • Author(s): Toshiyuki Imasawa, Masashi Tanaka, Yutaka Yamaguchi, Takashi Nakazato, Hiroshi Kitamura, Motonobu Nishimura
  • Journal Title: Renal Failure Volume: 36 Pages: 1461-1465
  • DOI: 10.3109/0886022X.2014.945181
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pathological similarities between low birth weight-related nephropathy and nephropathy associated with mitochondrial cytopathy. (2014)
  • Author(s): Toshiyuki Imasawa, Masashi Tanaka, Naoki Maruyama, Takehiko Kawaguchi, Yutaka Yamaguchi, Rodrigue Rossignol, Hiroshi Kitamura, Motonobu Nishimura
  • Journal Title: Diagnostic Pathology Volume: 9 Pages: 181
  • DOI: 10.1186/s13000-014-0181-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant