在自闭症谱系障碍中被破坏的神经传递和突触生物过程的识别,使用交互网络和社区检测分析
Joana Vilela1,2, Hugo Martiniano1,2, Ana Rita Marques1,2
1Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
Biomedicines
|November 25, 2023
概括
这项研究揭示了自闭症谱系障碍 (ASD) 涉及突触和神经递质通路的破坏,以及研究较少的无处不在的生物过程. 在候选基因中识别超罕见的功能丧失变异为ASD遗传学提供了新的见解.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 系统生物学 系统生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,涉及数百个候选基因,主要是神经传递和突触 (NS) 基因.
- 在ASD中,精确的遗传结构和受影响的生物学途径仍然不完全理解.
- 了解基因变异的功能影响对于破译ASD病因至关重要.
研究的目的:
- 为了澄清受NS基因变异影响的自闭症个体的生物过程.
- 绘制连接这些生物过程的全球网络.
- 确定涉及ASD的新生物学途径.
主要方法:
- 策划了1216个NS候选基因的列表.
- 在ASD全外体测序数据中搜索超罕见 (UR) 功能丧失 (LoF) 变体 (N=3938例),并使用gnomAD对照进行过 (N=60,146).
- 构建了NS基因与UR LoF变体的蛋白质-蛋白质相互作用网络,使用莱顿算法识别了社区,并探索了大脑区域的表达丰富.
主要成果:
- 在208个基因中确定了356个变异,其中PDE11A和SYTL3.3中显著的UR LoF变异.
- 表达式丰富分析突出了皮下结构,特别是基底.
- 网络分析揭示了七个社区,将突触和神经递质通路与无处不在的过程联系起来,并揭示了以前未关联的通路,如脑细胞染色体P450和线粒体代谢.
结论:
- 自闭症包括突触和神经递质通路的干扰.
- 无处不在的生物过程,传统上与ASD无关,也与此有关.
- 这种基于网络的方法可以更全面地了解ASD的遗传和生物基础.
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