进化选择和对人类膝关节细胞调节的限制影响骨关节炎风险
Daniel Richard1, Zun Liu1, Jiaxue Cao2
1Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Cell
|March 30, 2020
概括
人类双脚膝盖进化改变了肌肉细胞的发育,导致骨关节炎的风险. 影响调节因素的遗传变异有助于这种常见的关节疾病.
科学领域:
- 进化生物学
- 遗传学
- 整形医学
背景情况:
- 人类双脚膝盖的进化涉及细胞发育的变化.
- 骨关节炎影响了2.5亿人,
- 冠状细胞基因附近的非编码基因变异与骨关节炎的遗传性有关.
研究的目的:
- 探索膝盖进化适应和骨关节炎发病之间的关系.
- 调查与进化选择和约束相关的关节软骨细胞的表观遗传变化.
- 确定影响骨关节炎风险和遗传性的特定遗传变异.
主要方法:
- 关节冠状细胞的表观遗传分析.
- 对古老的选择,约束和膝关节调节元素的分析.
- 在小鼠模型中识别和功能验证因果增强剂变体 (rs6060369).
主要成果:
- 表观遗传分析显示了进化选择和膝关节调节因素的约束.
- 骨关节炎风险变异与这些受限制的功能序列重叠.
- 在GDF5-UQCC1位点的因果增强剂变体 (rs6060369) 影响小鼠膝盖形状和关节炎.
结论:
- 在膝盖发育过程中能容忍的调节元件的遗传变化会导致成年人患关节炎.
- 这项研究将人类膝盖的进化适应性与骨关节炎的易感性联系起来.
- 这些发现为了解骨关节炎的发病模式提供了一个模型,
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