性差基因表达在人类皮层的发展及其与自闭症风险路径的交叉点
Lee T Kissel1, Sirisha Pochareddy2, Joon-Yong An3,4,5
1Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin.
Biological psychiatry global open science
|July 3, 2024
概括
在人类产前皮质中,性别差异性基因表达是有限的. 分析揭示了参与神经发育的性别差异表达基因 (性别DEG),但与自闭症谱系障碍 (ASD) 风险基因没有明显的重叠.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 显示出男性偏见的患病率,可能与性别差异生物学有关.
- 由于样本大小有限,人类发育中的大脑中的转录性差异尚未得到充分理解.
研究的目的:
- 调查在产前人类皮质中性别差异性基因表达和共同表达.
- 探索神经类型性差异与自闭症谱系障碍 (ASD) 生物学之间的交叉.
主要方法:
- 对273名产前大脑皮层捐赠者的大量RNA测序数据进行了元分析.
- 进行了性别差异表达和共同表达网络分析.
- 在已识别的性别差异表达基因 (性别-DEGs) 和模块中测试了ASD风险基因的丰富性.
主要成果:
- 确定了101个显著的性别DEGs,包括Y染色体,X染色体无活化影响和自体基因.
- 在已知的ASD风险基因和产前皮质性别-DEGs之间没有发现偏好重叠.
- 在一个数据集中发现了一种针对男性的共同表达模块,用于免疫信号.
结论:
- 性差基因表达在产前人类皮质中是最小的.
- 识别的性别-DEGs编码神经发育至关重要的蛋白质.
- 缺乏与ASD风险基因的重叠表明,特定于性别的ASD机制可能在其他地方或晚期发展中运作.
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