三代家庭:对自闭症新变异的分析
Claudia I Samogy Costa1, Gabriele da Silva Campos1, Eduarda Morgana da Silva Montenegro1
1Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano e Células-tronco, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brasil.
新变种 (DNV) 对自闭症谱系障碍 (ASD) 基因发现至关重要. 这项研究分析了巴西队列中的三代人,发现试验对象的DNV比父母和对照人高,大多数来自父亲.
科学领域:
- 遗传学 是一个遗传学.
- 神经发育障碍 神经发育障碍
背景情况:
- 新变种 (DNV) 是自闭症谱系障碍 (ASD) 基因发现的关键.
- 遗传的罕见变异也可能起作用,特别是在寡生模型中.
- 之前的研究没有在巴西ASD队列中探索DNV.
研究的目的:
- 在巴西的ASD队列中,研究新生和遗传变异在三代人中的作用.
- 分析跨世代的新变种率 (DNVr),并将其与对照组进行比较.
- 为了确定与DNVs相关的潜在的ASD候选基因.
主要方法:
- 33个巴西家庭 (231个个体:试探者,父母,祖父母) 的整体外因子测序.
- 代与代之间的DNV率和两个对照队伍 (先天性心脏病,未受影响的ASD兄弟姐妹) 的比较.
- 分析变异起源 (父/母) 和传播给试验者.
主要成果:
- 试验DNVr (1.16) 比父母 (0.60) 和对照 (0.68-0.70) 略高.
- 大多数DNV (84.6%) 是来自父亲的.
- 40%的父母传播的DNV都在ASD或候选基因中,这表明ZNF536,MSL2和HDAC9是潜在的ASD基因.
结论:
- 在ASD中,即使在后一代中,de novo变异也很重要.
- 在这个队列中,对于DNVs来说,父亲的起源占主导地位.
- 确定了潜在的新型ASD候选基因,需要进一步调查.
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