統合失調症の脳における体的モザイク主義は,産前変異過程を明らかにする
Eduardo A Maury1,2,3, Attila Jones4,5, Vladimir Seplyarskiy6,7
1Division of Genetics and Genomics, Manton Center for Orphan Disease, Boston Children's Hospital, Boston, MA 02115, USA.
まとめ
脳のニューロンのモザイクソマティック変異は 統合失調症のリスクを高めます これらの変異は,特に発達の遺伝子部位では,対照群よりも統合失調症の症例ではより一般的でした.
科学分野:
- 神経科学
- 遺伝学
- ゲノミクス
背景:
- ゲルムライン変異は統合失調症 (SCZ) リスクに影響することが知られている.
- SCZの病原性におけるモザイクソマティック変異の役割はあまり理解されていない.
研究 の 目的:
- 統合失調症患者の脳ニューロンのモザイク体変異の存在と影響を調査する.
- 産前神経発達の間にSCZに関連した特定の変異パターンを特定する.
主な方法:
- 61人のSCZ患者と25人の対照群からの死後の脳ニューロンの深層全ゲノムシーケンシング (239×).
- オープンクロマチン領域と転写因子結合部位 (TFBS) を中心に体内の変異を分析する.
主要な成果:
- SCZ症例は,対照群と比較して,オープンクロマチンの体内変異の負担が増加した.
- SCZでは,CpG変異と発達期TFBSにおけるT> G変異を含む特定の変異タイプが増加した.
- SCZリスク遺伝子や神経発達遺伝子を含む遺伝子発現に影響した変種が特定されました.
結論:
- モザイクソマティック変異は,特に発達の転写因子結合部位で発生する変異は,統合失調症の危険に寄与する可能性があります.
- これらの発見は,SCZ病因における神経発達の過程における体内変異の潜在的な役割を強調しています.
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