染色体构造揭示了人类大脑发育中的调节关系
Hyejung Won1, Luis de la Torre-Ubieta1, Jason L Stein1
1Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, California 90095, USA.
Nature
|October 28, 2016
概括
这项研究绘制了人类大脑发育过程中的3D基因组组织图,揭示了新的基因调控网络. 发现这些网络与认知进化和精神分裂症等神经发育障碍有关.
科学领域:
- 基因组学
- 神经科学
- 发育生物学
背景情况:
- 染色体的三维组织可以动态调节基因表达.
- 在人类大脑发育和神经发育障碍中,3D基因组结构的作用在很大程度上是未知的.
研究的目的:
- 在人类皮质生成过程中生成高分辨率的3D染色体接触图.
- 确定影响人类认知和疾病的调节关系,特别是神经发育障碍.
主要方法:
- 在人类皮质生成过程中高分辨率的3D染色体接触映射.
- 将染色体接触数据与来自精神分裂症全基因组关联研究 (GWAS) 的非编码变体整合.
- 在人类神经祖先中进行基因编辑以验证基因调节.
主要成果:
- 数百个与特定基因增强剂相互作用的基因被发现, 其中许多与认知功能有关.
- 突出了候选精神分裂症风险基因和途径,包括神经发生转录因子和胆固醇信号分子.
- 一个远端精神分裂GWAS位点被证明可以调节神经前代的FOXG1表达.
结论:
- 这项工作为理解人类大脑发育和认知进化中的非编码调节元素提供了框架.
- 发现神经精神疾病的新机制,如精神分裂症.
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