Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Nat Rev Genet. 2019 Jan;20(1):51-63. doi: 10.1038/s41576-018-0066-2.
Heredity has a major role in autism spectrum disorder (ASD), yet underlying causal genetic variants have been defined only in a fairly small subset of cases. The enormous genetic heterogeneity associated with ASD emphasizes the importance of identifying convergent pathways and molecular mechanisms that are responsible for this disorder. We review how recent transcriptomic analyses have transformed our understanding of pathway convergence in ASD. In particular, deep RNA sequencing coupled with downstream investigations has revealed that a substantial fraction of autistic brains possess distinct transcriptomic signatures. These signatures are in part a consequence of altered neuronal activity and have a particular impact on pre-mRNA alternative splicing patterns.
遗传在自闭症谱系障碍(ASD)中起着重要作用,但仅在相当一小部分病例中确定了潜在的因果遗传变异。与 ASD 相关的巨大遗传异质性强调了确定导致这种疾病的趋同途径和分子机制的重要性。我们回顾了最近的转录组分析如何改变了我们对 ASD 中途径趋同的理解。特别是,深度 RNA 测序与下游研究相结合,揭示了相当一部分自闭症大脑具有独特的转录组特征。这些特征部分是神经元活动改变的结果,对前体 mRNA 可变剪接模式有特殊影响。