动机行为频谱的因果遗传位点 精神疾病风险基因
bioRxiv : the preprint server for biology
|September 21, 2023
概括
这项研究揭示了斑马鱼幼虫冒险行为的遗传基础. 全基因组关联研究确定了影响动机的关键基因和与人类精神疾病的潜在联系.
科学领域:
- 神经遗传学 神经遗传学
- 行为遗传学 行为遗传学
- 进行比较基因组学.
背景情况:
- 包括承担风险在内的行为多样性对于人口健康至关重要.
- 在不同物种中观察到动机行为的个体差异,例如避开黑暗.
- 这些行为差异的遗传基础和保护在很大程度上仍未被探索.
研究的目的:
- 在斑马鱼幼虫中研究动机行为的遗传结构,特别是避开黑暗的行为.
- 识别与个人差异相关的基因和基因组区域 - - 避免冲突.
- 建立一个可扩展的模型系统来研究与精神疾病相关的动机的神经遗传基础.
主要方法:
- 利用大脑范围的成像来捕捉斑马鱼幼虫的神经活动差异,表现出各种黑暗避开倾向.
- 在一大群 (∼6,000) 幼虫斑马鱼上进行了全基因组关联研究 (GWAS).
- 采用CRISPR基因编辑功能评估候选基因,包括血清素受体-1b (htr1b),氧化合成酶-1 (nos1) 和压力诱导的蛋白-1 (stip1).
主要成果:
- 在倾向于接近和倾向于回避的斑马鱼之间发现了神经活动模式的显著差异.
- 发现了34个与黑暗避开行为相关的基因组区域,其中含有参与突触传播的基因,并与人类精神疾病有关.
- 通过CRISPR介导的基因研究验证了htr1b,nos1和stip1的作用.
- 发现了52个具有66个显著GWAS变异的保存元素,包括影响nos1表达的调控元素.
结论:
- 在斑马鱼中揭示了与有动机的行为和冒险相关的新型遗传位置.
- 建立了幼虫斑马鱼作为一个强大而可扩展的系统来剖析动机的遗传机制.
- 提供了关于动物行为与人类精神疾病之间的遗传联系的见解.
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