异构区域的低级大脑体态突变与自闭症有关,自闭症风险基因的生殖基因突变与自闭症有关
Il Bin Kim1,2, Myeong-Heui Kim2, Saehoon Jung2
1Department of Psychiatry, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, 06135, Republic of Korea.
低水平的大脑体质突变和生殖系突变可能共同导致自闭症谱系障碍 (ASD) 病理生理学. 这项研究没有发现ASD患者和对照人群之间的突变特征有显著差异,但确定了共享的遗传途径.
科学领域:
- 神经遗传学 神经遗传学
- 基因组医学是基因组医学.
- 发育神经科学的发展神经科学.
背景情况:
- 大脑中低水平的体质突变与神经系统疾病有关.
- 大脑体突变在自闭症谱系障碍 (ASD) 中的作用尚不清楚.
- 以前的研究主要集中在ASD病因学中的生殖系突变上.
研究的目的:
- 与对照人群相比,研究ASD患者中低水平脑体单核酸变体 (SNVs) 的存在和特征.
- 确定特定基因中的体和生殖系突变是否有助于ASD病理生理学.
- 探索合并的体和生殖系突变携带基因与ASD风险和发育途径的关联.
主要方法:
- 在24名自闭症患者和31名对照患者的皮质,小脑和外围组织样本上进行了高度深度的外体序列测序.
- 脑体性SNV被确定为变异性等位基频率 (VAF) 低至0.3%.
- 在ASD患者和对照者之间比较了突变概况 (数量,签名,类型). 用基因组丰富分析来评估组合体质和生殖系突变效应.
主要成果:
- 在ASD患者和对照患者中,每次大脑区域每次大脑外体检测到大约2.4个大脑体性SNV.
- 在ASD患者和对照人群之间,脑体SNV的数量,特征或类型没有显著差异.
- 在ASD患者中,具有体质或生殖系SNV的合并基因组在ASD相关的途径 (例如,状脊柱形态发生) 中显著丰富,并显示了ASD相关的时空表达模式.
结论:
- 仅脑体SNV似乎无法显著区分ASD患者与基于突变特征的对照组.
- 在特定的基因中,低水平的大脑体质SNV和破坏性生殖系SNV的联合负担可能共同导致ASD病理生理学.
- 受体和生殖系突变影响的基因显示出与ASD相关的生物学途径的显著丰富,并增加了ASD风险.
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