アイスランドの1,548のトリオにおけるヒトの生殖系統のデノボ変異に対する親の影響

Hákon Jónsson¹, Patrick Sulem¹, Birte Kehr¹

¹deCODE genetics/Amgen Inc., 101 Reykjavik, Iceland.

Nature

|September 30, 2017

まとめ

両親の年齢はヒトゲノム配列決定における de novo 変異に大きく影響する. 特定のゲノム領域におけるC>Gの突然変異の種類を変化させる.

科学分野:

人間の遺伝子
進化生物学
ゲノム不安定性

背景:

遺伝的多様性の起源を理解することは,医学遺伝学と進化論の研究にとって極めて重要です.
デノボ変異 (新しい遺伝的変異) は人間の配列の多様性の主要な源である.
親の年齢と性別は変異率に影響する要因として知られています

研究の目的:

遺伝子を伝達する親の年齢と性別が,新しい変異の発生率と特徴にどのように影響するか調べる.
親の年齢によって影響される特定のゲノム領域と変異型を特定する.

主な方法:

1,548人のアイスランド人,その両親,そしてその子供たちのサブセット (225) のゲノムシーケンシングを35倍にしました.
10万8000以上のデノボ変異 (単核酸多形化とインデル) の識別と原産物の決定.
変異率,クラスタリング,タイプ,親の年齢とゲノム位置との相関性の分析.

主要な成果:

両親の年齢に伴い,デノボ変異の割合は増加し,父親は母親よりも毎年多くの変異を寄与します.
母親の年齢は変異群の増加と変異型の変化,特にC>G変異の増加と関連しています.
年齢に関係する突然変異は均一ではないが,染色体8pのような特定の領域では,母親のC>G突然変異率が著しく高い.
特定の地域におけるC>Gの過剰な変動は古くから存在し,霊長類に共通しており,長期の進化過程を示唆している.

結論:

親の年齢,性別,変異型,ゲノム位置が相互作用して人間の配列の多様性を形作ります
特定のゲノム領域は,母親の年齢によって異なる変異パターンを示し,局所的な変異プロセスを示します.
観察された配列多様性のパターンは,ヒトと霊長類のゲノムに共通する特徴を持つ進化的根源を持っています.

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