ヒトの体細胞と生殖細胞の変異の景観

Luiza Moore^1,2, Alex Cagan¹, Tim H H Coorens¹

¹Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.

Nature

|August 26, 2021

まとめ

人間の細胞は生涯にわたって変異を蓄積しますこの研究では,体細胞と生殖細胞の29種で異なる変異パターンを明らかにし,精子細胞で最も低い変異率が観察されました.

科学分野:

ゲノミクス
細胞生物学
人間の生理学

背景:

体細胞と生殖細胞は一人の生涯にわたって変異を蓄積する.
これらの変異を理解することは遺伝的多様性や病気を理解するために極めて重要です
以前の研究では変異の特徴が示されましたが同じ個体からの多数の細胞タイプを総合的に比較することは欠けています

研究の目的:

29種類のヒト細胞の変異パターンを比較する
これらの細胞タイプ内の普遍的および特定の変異シグネチャを特定し,定量化します.
spermatogoniaの変異率と人間の遺伝的多様性への影響を調査する.

主な方法:

複数の個体における29種類の細胞のDNAにおける変異シグネチャーの比較分析.
変異を特定し分類するために全ゲノム配列データを利用した.
異なる変異シグネチャー (例えば,SBS1,SBS5/40,SBS18) が全体的な変異負荷に与える影響を定量化した.

主要な成果:

2つの変異シグネチャーSBS1とSBS5/40は,ほとんどの細胞タイプで優勢だったが,その比率は著しく変化した.
SBS18と暴露に関連した他のシグネチャは,特定の細胞タイプの変異に寄与しました.
細胞分裂率が低下したため,精子菌は最も低い変異率を示した.

結論:

ゲルムラインとソマの維持には,突然変異の蓄積に影響を与える共有されたと異なる分子メカニズムが含まれる.
spermatogoniaの低変異率は,ヒトの遺伝的変異の起源に重大な影響を及ぼします.
この研究は,細胞型特異性を強調したヒト細胞変異の地図を包括的に提供しています.

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