评估了与自闭症相关的非编码单核酸多态性对人类大脑组织基因表达的调节功能
Kealan Pugsley1, Atefeh Namipashaki1, Mark A Bellgrove1
1Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
概括
研究人员确定了82种与自闭症谱系障碍 (ASD) 相关的调节性DNA变异. 然而,在人类大脑组织中的实验验证并未证实这些与自闭症相关的遗传变异对基因表达有重大影响.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 生物信息学是一种生物信息学.
背景情况:
- 常见的遗传变异解释了自闭症谱系障碍 (ASD) 的大部分遗传性.
- 全基因组关联研究 (GWAS) 已经确定了许多与ASD相关的单核酸多态 (SNP),但它们的功能作用尚不清楚.
- 这些已识别的SNP位于非编码基因组区域,这表明它们具有调节功能,而不是对基因编码的直接影响.
研究的目的:
- 通过使用全面的生物信息学管道,功能性地注释ASD相关的多态和它们的链接不平衡伙伴.
- 为了识别潜在的调节性DNA变异,有助于自闭症的发病.
- 实验验证候选变异对人类大脑组织基因表达的预测调节效应.
主要方法:
- 应用生物信息管道来注释与ASD相关的SNP及其非编码链接不平衡伙伴.
- 确定了82个具有可能调节功能的候选DNA变异.
- 用定量聚合酶链反应 (qPCR) 测量了11个高可信度候选变体及其合作伙伴对自闭症和非自闭症捐赠者的死后人类大脑组织基因表达的影响.
主要成果:
- 确定了82种与自闭症相关的潜在调节性DNA变异.
- 少数变异对基因表达有可测量的影响,但这些发现无法经受多次比较的校正.
- 对于研究的SNP-基因关联,没有观察到显著的基因型-诊断相互作用.
结论:
- 该研究发现了与自闭症相关的许多潜在的调节变异,但在人类大脑组织中的实验验证结果产生了有限的显著结果.
- 个体变异对基因表达的适度影响可能很难在死后脑样本中检测到.
- 目前GWAS数据的局限性和神经发育障碍的复杂性可能会阻碍识别对自闭症的功能遗传贡献.
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