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2022 Fiscal Year Final Research Report

Identification of genomic radiation signature using long-read sequencing

Research Project

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Project/Area Number 20K21718
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionNagasaki University

Principal Investigator

MITSUTAKE Norisato  長崎大学, 原爆後障害医療研究所, 教授 (50404215)

Co-Investigator(Kenkyū-buntansha) 鈴木 啓司  長崎大学, 原爆後障害医療研究所, 准教授 (00196809)
荻 朋男  名古屋大学, 環境医学研究所, 教授 (80508317)
Project Period (FY) 2020-07-30 – 2023-03-31
Keywords放射線 / ゲノム
Outline of Final Research Achievements

Two different platforms of next generation sequencing, short- and long-read sequencing, revealed the following characteristics of radiation-induced genomic variants in human normal cells: 1) Deletions of various sizes increased in a dose-dependent manner. 2) At high doses, very long deletions (hundreds of thousands to megabases or more) occurred. 3) Many of the deletions had no homology sequence at break points. Deletions by high doses often contained a distinct sequence at the junction. 4) Single nucleotide substitutions also increased but were not dose dependent. 5) Single nucleotide substitutions contained mutational signatures suggestive of oxidative damage. However, we were unable to identify mutations that were completely specific to radiation exposure.

Free Research Field

放射線影響学

Academic Significance and Societal Importance of the Research Achievements

DNA配列決定法の技術的な進歩により、DNAの配列変化をゲノムワイドに調べることが可能となってきた。放射線被ばくは、発がんリスクを上昇させることは疫学的に明らかであり、放射線によるゲノム変異がその誘因であると考えられている。本研究において、ヒト正常培養細胞で、放射線によって生じるゲノム変異の特徴の多くが詳細に明らかになった。これらの異常が、発癌の第一歩となる可能性が高い。本研究成果は、放射線による生物学的影響、遺伝子異常、発癌などの他の研究にも活かせる基盤的データとなると思われる。

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Published: 2024-01-30  

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