Comprehensive analysis of microsatellites polymorphism in the human population

• Project/Area Number: 18K19426
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: The University of Tokyo (2019-2021); Kyoto University (2018)
• Principal Investigator: Fujimoto Akihiro 東京大学, 大学院医学系研究科(医学部), 教授 (30525853)
• Project Period (FY): 2018-06-29 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクロサテライト / 人類の集団史 / 集団史 / 集団の歴史 / 人類進化

Outline of Final Research Achievements

Microsatellites have been widely used as genetic markers in population genetics and genealogy studies due to their high mutation rate and rich patterns of repeat length among individuals. However, few studies have been analyzed the genome-wide pattern of microsatellites due to methodological difficulties. To reveal the landscape of the polymorphism in microsatellites at the whole genome level, we analyzed 9 million microsatellites in approximately 4,000 whole-genome sequencing (WGS) data of four public datasets (HGDP, SGDP, ICGC, KPGP) across the various ethnic groups. We analyzed the genetic differentiation among human populations. The principal component analysis (PCA) of microsatellites showed the efficiency of microsatellites for genetic studies. Our analysis provides a comprehensive picture of microsatellite polymorphisms along with the detection method, as well as the efficiency in population genetic studies.

Academic Significance and Societal Importance of the Research Achievements

近年のゲノム解析技術の進展により、DNA多型解析アレイや全ゲノムシークエンスを用いて大量のSNP情報を得ることができる。この情報を用いて、人類の集団史を推定することができる。例えば、集団間の遺伝的関係性の推定や、過去の集団の大きさの変遷が推定されている。しかし、SNP情報を用いた研究では、極めて近い集団の関係性や最近の集団サイズの変遷を正確に推定することが難しい。本研究では、突然変異率が高いマイクロサテライトを用いることで、近縁な集団間の遺伝的関係性や最近の集団史の情報を得ることを目的とした。本研究は、マイクロサテライトを用いた集団解析のための方法論を提供する。

Research Products

• [Journal Article] Characterization of intermediate-sized insertions using whole-genome sequencing data and analysis of their functional impact on gene expression (2021)
  • Author(s): Ashouri Saeideh、Wong Jing Hao、Nakagawa Hidewaki、Shimada Mihoko、Tokunaga Katsushi、Fujimoto Akihiro
  • Journal Title: Human Genetics Volume: 140 Issue: 8 Pages: 1201-1216
  • DOI: 10.1007/s00439-021-02291-2
  • Peer Reviewed
• [Journal Article] Whole genome sequencing with long-reads reveals complex structure and origin of structural variation in human genetic variations and somatic mutations in cancer. (2021)
  • Author(s): Fujimoto A, Wong JH, Yoshii Y, Akiyama S, Tanaka A, Yagi H, Shigemizu D, Nakagawa H, Mizokami M, and Shimada M.
  • Journal Title: Genome Medicine Volume: 13 Issue: 1 Pages: 65-65
  • DOI: 10.1186/s13073-021-00883-1
  • Peer Reviewed / Open Access
• [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations. (2020)
  • Author(s): Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
  • Journal Title: EBioMedicine Volume: 53 Pages: 102659-102659
  • DOI: 10.1016/j.ebiom.2020.102659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive Analysis of Indels in Whole-genome Microsatellite Regions and Microsatellite Instability across 21 Cancer Types (2020)
  • Author(s): Fujimoto A*, Fujita M, Hasegawa T, Wong JH, Maejima K, Oku-Sasaki A, Nakano K, Shiraishi Y, Miyano S, Yamamoto G, Akagi K, Imoto S, and Nakagawa H
  • Journal Title: Genome Research Volume: 30 Issue: 3 Pages: 334-34
  • DOI: 10.1101/gr.255026.119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pan-cancer analysis of whole genomes (2020)
  • Author(s): The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
  • Journal Title: Nature Volume: 578 Issue: 7793 Pages: 82-93
  • DOI: 10.1038/s41586-020-1969-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] eVIDENCE: a practical variant filtering for low-frequency variants detection in cell-free DNA (2019)
  • Author(s): Mizuno Kei、Akamatsu Shusuke、Sumiyoshi Takayuki、Wong Jing Hao、Fujita Masashi et al.
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 15017-15017
  • DOI: 10.1038/s41598-019-51459-4
  • NAID: 120006734882
  • Peer Reviewed / Open Access
• [Journal Article] Identification of intermediate-sized deletions and inference of their impact on gene expression in a human population. (2019)
  • Author(s): Wong JH, Shigemizu D, Yoshii Y, Akiyama S, Tanaka A, Nakagawa H, Narumiya S, Fujimoto A
  • Journal Title: Genome Medicine Volume: 11 Issue: 1 Pages: 44-44
  • DOI: 10.1186/s13073-019-0656-4
  • Peer Reviewed / Open Access