自然変異アレルはマウスの変異スペクトルの変化を形作る

Thomas A Sasani¹, David G Ashbrook², Annabel C Beichman¹

¹Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Nature

|May 11, 2022

まとめ

共通する遺伝的変異はゲルムラインの変異率に影響する. 研究者らは,マウスのC>A変異に影響を与えるDNA修復遺伝子,Mutyhを特定し,自然遺伝的変異が変異性に影響することを示唆しました.

科学分野:

遺伝学
ゲノミクス
進化生物学

背景:

ゲルムラインの変異率とスペクトルは,種間の多様性を表しています.
自然集団における突然変異率の共通遺伝変異因子を特定することは,依然として課題です.

研究の目的:

ゲルムライン変異に影響を与える遺伝的位置を特定する.
哺乳類における変異率の調節における遺伝的変異の役割を調査する.

主な方法:

C57BL / 6JとDBA / 2Jの株から派生したBXD再結合性マウスラインを使用しました.
既知の遺伝子背景で50年にわたって蓄積された de novo 変異を分析した.
変異率に関連した染色体4の定量的な特徴の位置 (QTL) を調査した.

主要な成果:

染色体4のQTLでDハプロタイプを持つマウスは,Bハプロタイプを持つマウスと比較して,C>Aの生殖線変異率が50%高かった.
この増加した変異率は,C>Aが支配する変異シグネチャーSBS18と関連していた.
特定されたQTLハプロタイプは,DNA修復遺伝子Mutyhの異なるアレルをコードする.

結論:

一般的な遺伝的変異,特に異なるMutyhアレルは,マウスの生殖線変異を調節する.
実験室の株と野生のマウスの集団 (Mus musculus domesticus) の両方で見つかった変異性アレルは,自然選択が変異率に作用することを示唆している.
この発見は,モデル哺乳類の変異率の遺伝的制御の証拠を提供し,遺伝的な癌の傾向を理解するための意味を持っています.

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