Identification of long non-coding RNAs involved in neuronal development and intellectual disability.
Identification of long non-coding RNAs involved in neuronal development and intellectual disability.
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DOI：
10.1038/srep28396
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发表时间：
2016-06-20
影响因子：
4.6
通讯作者：
Vergult S
中科院分区：
文献类型：
--
作者：
D'haene E;Jacobs EZ;Volders PJ;De Meyer T;Menten B;Vergult S
最近，外显子组测序导致16-31%的智力残疾（ID）患者的因果突变鉴定，使许多患者的潜在原因不明。在这种情况下，人类基因组的非编码部分仍然很大程度上未被探索。对于许多长链非编码rna （lncRNAs）来说，它们在神经发育和人类大脑中起着至关重要的作用。在这里，我们旨在鉴定与神经元发育和ID相关的lncrna。因此，我们应用了集成基因组学方法，利用了几个公开的表观遗传数据集。我们发现神经元特异性H3K4me3的存在赋予参与神经发育和ID的基因最高的特异性。基于这一特征的存在和GWAS对中枢神经系统疾病的命中，我们确定了53个候选lncRNA基因。对人脑样本和其他组织的广泛表达谱分析，以及随后的基因集富集分析表明，这些lncrna中至少有24种确实与突触传递、神经系统发育和神经发生等过程有关。与参与神经元过程的多个编码基因相关的双向或反义重叠方向支持这些结果。总之，我们确定了几个被认为与神经发育和中枢神经系统疾病有关的lncRNA基因，为功能研究提供了资源。
Recently, exome sequencing led to the identification of causal mutations in 16–31% of patients with intellectual disability (ID), leaving the underlying cause for many patients unidentified. In this context, the noncoding part of the human genome remains largely unexplored. For many long non-coding RNAs (lncRNAs) a crucial role in neurodevelopment and hence the human brain is anticipated. Here we aimed at identifying lncRNAs associated with neuronal development and ID. Therefore, we applied an integrated genomics approach, harnessing several public epigenetic datasets. We found that the presence of neuron-specific H3K4me3 confers the highest specificity for genes involved in neurodevelopment and ID. Based on the presence of this feature and GWAS hits for CNS disorders, we identified 53 candidate lncRNA genes. Extensive expression profiling on human brain samples and other tissues, followed by Gene Set Enrichment Analysis indicates that at least 24 of these lncRNAs are indeed implicated in processes such as synaptic transmission, nervous system development and neurogenesis. The bidirectional or antisense overlapping orientation relative to multiple coding genes involved in neuronal processes supports these results. In conclusion, we identified several lncRNA genes putatively involved in neurodevelopment and CNS disorders, providing a resource for functional studies.