在人类皮层神经发生过程中的开放色素的动态景观
Luis de la Torre-Ubieta1, Jason L Stein2, Hyejung Won1
1Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|January 9, 2018
概括
科学家绘制了人类大脑发育中的非编码元素, 这些因素将神经精神疾病和认知特征的遗传风险与早期大脑形成联系起来.
科学领域:
- 基因组学
- 神经科学
- 发育生物学
背景情况:
- 非编码区域构成了大部分的人类基因组.
- 这些区域包含许多神经精神疾病的风险基因,但它们的功能基本上是未知的.
- 了解这些元素对于解读复杂的人类特征和疾病至关重要.
研究的目的:
- 创建一个高分辨率地图的非编码元素调节人类皮质神经发生.
- 确定这些调节元件所准的基因及其在大脑发育中的作用.
- 研究这些元素中与认知特征和疾病相关的遗传变异的丰富性.
主要方法:
- 在发育中的人类大脑中对比染色质可访问性和基因表达数据.
- 使用染色体相互作用数据将远端调节元件 (DREs) 与目标基因联系起来.
- 对关键基因预测增强功能 (FGFR2,EOMES) 的实验验证.
主要成果:
- 产生了涉及人类皮质神经发生的非编码元素的详细地图.
- 人类获得的增强剂 (HGE) 被确定为对皮质发育至关重要的调节基因,并富含外部辐射质.
- 与教育程度,神经精神疾病风险和内体积相关的遗传变异在这些神经发育调节元素中显著丰富.
结论:
- 非编码元素在人类皮质神经发生过程中起着关键作用.
- HGE及其目标基因与人类大脑的进化和发育有关.
- 这些元素在早期发育过程中的失调会导致神经精神疾病和成年人的认知变化.
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