2019 Fiscal Year Final Research Report
Construction of high-dimensional Japanese genome reference sequences suitable for the search for disease-associated mutations
| Project/Area Number |
17K07255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical genome science
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| Research Institution | Kansai Medical University (2018-2019)
Kyoto University (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ヒトゲノム構造多様性 |
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| Outline of Final Research Achievements |
The current human reference genome is a linear haploid DNA sequence. This reference structure poses practical limitations due to the prevalence of genetic diversity in human populations because any given human genome has millions of variations compared with the reference genome. Therefore, a strategy to reconstruct a more complete version of the reference sequence will be essential. To construct a state-of-the-art reference sequence, we elucidated the complex genetic components from whole genome-sequencing data of 3,135 Japanese individuals and integrated them into the current reference sequence as a graph structure. The Japanese graph reference sequence significantly contributed to the precise characterization of variants. The integration of accumulating knowledge of genetic variation into the current reference sequence is a promising strategy to develop a leading-edge reference structure appropriate for interpretation of pathogenic variants towards precision medicine.
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| Free Research Field |
ゲノム解析
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| Academic Significance and Societal Importance of the Research Achievements |
現在、精密医療を目指し世界中で進められている大規模ゲノム解析は、欧米人を対象とした情報の収集に偏っている。本課題では、日本人の遺伝的多様性を網羅する3,135人を対象に全ゲノム配列解析を行い、44,757,785箇所の変異を検出した。そのうちアレル頻度1％未満の98.9％の変異が今まで報告のない変異であることが判明した。またこれらの情報を活用することにより、正確な遺伝子型の推定や変異の同定が可能であることが分かった。本知見は、民族的に多様な集団からの遺伝的変異を既存のゲノム情報に統合することが、あらゆる人種を対象とした精密医療を実現するために不可欠であることを示唆するものである。
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