父から受け継がれるシス調節性構造変異は自閉症と関連している
William M Brandler1,2,3,4, Danny Antaki1,2,3,5, Madhusudan Gujral1,2,3
1Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Science (New York, N.Y.)
|April 21, 2018
まとめ
シス調節要素 (CRE-SVs) の希少な遺伝的構造変異は,自閉症スペクトル障害 (ASD) に子どもを誘発する可能性があります. 父から受け継がれるCRE-SVは,影響を受けた子孫に優遇的に伝染することを示し,ASDのエチオロギーにおけるノンコーディング変異の役割を示唆した.
科学分野:
- 遺伝学
- 神経発達障害
- ゲノム医学
背景:
- 自閉症スペクトル障害 (ASD) は複雑な遺伝的基盤を持ち,特定の遺伝子の新規変異が既知の役割を果たしています.
- 遺伝的な構造変異,特にシス規制要素 (CRE-SVs) のASDリスクへの寄与は,まだ理解されていない.
研究 の 目的:
- シス調節要素 (CRE-SVs) の希少な遺伝的構造変異がASDの遺伝的病因に寄与するという仮説を調査する.
- CRE-SVの自然選択と伝播の歪みの証拠を評価する.
主な方法:
- 全ゲノム配列解析は,ASDに罹患した2600人の9274人の被験者に実施された.
- 分析は,CRE-SVの減少と伝播パターンをプロモーターと翻訳されていない地域で焦点を当てました.
- 発見コホート (829家族) と独立複製コホート (1771家族) を利用した.
主要な成果:
- 変異不耐性遺伝子のプロモーターと未翻訳領域の構造変異は枯渇していることが判明した.
- 父から受け継がれるCRE-SVは,無影響の兄弟に比べて,ASDに罹患した子孫に優遇的に伝染することが示された.
- 父のCRE-SVのこの関連性は,独立したコホートで成功裏に再現されました.
結論:
- 希少な遺伝的非コーディング変種,特にCRE-SVは,ASDの潜在的な予備因子として関与しています.
- CRE-SVの父親からの遺伝はASDの感受性において重要な役割を果たしているようです.
- これらの発見は,自閉症スペクトル障害の遺伝的構造における遺伝的非コーディング変異の重要性を強調しています.
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