131 人の脳における体内変異の分析は,老化に関連した超変異性を明らかにする
Taejeong Bae1, Liana Fasching2, Yifan Wang1
1Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
まとめ
大抵の人の脳には 肉体の変異は少ないが 何百もの変異があり 癌の遺伝子やクローンの膨張と 関連しています 自閉症の脳には MEISの転写因子に影響する特定の変異がありました
科学分野:
- 神経遺伝学
- ゲノム医学
- 発達神経科学
背景:
- 体内の変異 つまり受胎後のDNAの変化は ヒトの脳細胞に生涯蓄積されます
- 健康な脳と病気の脳における これらの変異のパターンと影響を 理解することは 神経科学と医学にとって 極めて重要です
研究 の 目的:
- ニューロタイプとトゥレット症候群,統合失調症,自閉症を含む多様な人間の脳内の体内変異を包括的に分析する.
- 身体変異の負担,特定の遺伝的変異,神経発達障害,特に自閉症スペクトル障害との関連を調査する.
主な方法:
- 単核酸変異と構造的変異を検出するために,131人の脳を高度に解析した.
- 高変異性,年齢との関連性,がんに関連する遺伝子,クローン拡張,複製を含む変異パターンの分析.
- 転写因子結合モチーフに焦点を当てて,自閉症の脳における特定の変異型と影響を受けた調節要素の特定.
主要な成果:
- 大半の脳は20〜60の体内変異を示し,約6%は数百の変異を示し,年齢と癌に関連した遺伝子の変異と相関していました.
- 脳の約5%で体内複製が観察され,これは発達中の背景変異を示しています.
- 自閉症の脳は増強器の領域に変異を示し,脳発達中の遺伝子調節における役割を示唆するMEIS (骨髄外ウイルス統合部位) 転写因子の結合モチーフを生み出しました.
結論:
- 人間の脳における体内の変異のパターンは大きく変化し,その一部は老化と癌の経路に関連した超変異性を表している.
- 発達過程は健康な脳と病気の脳の両方に体内複製を促します
- 自閉症に関連した脳変異における特定されたMEIS転写因子の失調は,疾患の発生に寄与する潜在的なメカニズムを強調しています.
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