進化的選択とヒトの膝の軟骨細胞の調節に対する制約 骨関節炎のリスクへの影響
Daniel Richard1, Zun Liu1, Jiaxue Cao2
1Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Cell
|March 30, 2020
まとめ
双脚症に対するヒトの膝の進化は 軟骨細胞の発達を変化させ 骨格関節炎の危険性をもたらしました 制御要素に影響する遺伝的変異が この一般的な関節疾患に寄与します
科学分野:
- 進化生物学
- 遺伝学
- 整形外科
背景:
- 双脚症に対する人間の膝の進化は 軟骨細胞の発達に変化をもたらしました
- 骨格関節炎は2億5千万人に影響し 遺伝的危険因子には 軟骨細胞の遺伝子が関係しています
- 軟骨細胞の遺伝子付近の非コード遺伝子は,骨格関節炎の遺伝性と関連しています.
研究 の 目的:
- 膝の進化的適応と 骨格関節炎の病原性との関係を調べる
- 進化的選択と制約に関連した関節軟骨細胞の表遺伝的変化を調査する.
- 骨格関節炎のリスクと遺伝性に影響を与える特定の遺伝子変異を特定する.
主な方法:
- 関節軟骨細胞のエピジェネティックプロファイリング
- 古代の選択,制約,および膝の規制要素の漂流の分析
- マウスモデルにおける因果増強剤の変種 (rs6060369) の識別と機能的検証
主要な成果:
- エピジェネティックプロファイリングは 進化の選択と膝の規制要素の制約を明らかにしました
- 骨格関節炎のリスク変異は,これらの制限された機能的配列と重なり合っています.
- GDF5-UQCC1の因果増強剤の変種 (rs6060369) はマウスの膝の形状と関節炎に影響する.
結論:
- 膝の発達中に許容される 制御要素の遺伝的変異は 成人の骨格関節炎を引き起こす可能性があります
- この研究は 人間の膝の進化的適応と 骨関節炎の感受性を関連付けています
- この発見は 人間の進化に根ざした 骨関節炎の病原性を理解するためのモデルです
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