The expanding genomic landscape of autism: discovering the 'forest' beyond the 'trees'
The expanding genomic landscape of autism: discovering the 'forest' beyond the 'trees'
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DOI：
10.2217/fnl.12.83
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发表时间：
2013-01-01
期刊：
影响因子：
1.3
通讯作者：
Hu, Valerie W.
中科院分区：
文献类型：
--
作者：
Hu, Valerie W.
自闭症谱系障碍是一种神经发育障碍，其特征是互惠社会互动的显著缺陷，沟通障碍和限制性重复行为。由于自闭症谱系障碍是最具遗传性的神经精神障碍之一，许多自闭症研究都集中在寻找蛋白质编码基因（即“树”）的遗传变异上。然而，没有任何一个基因可以解释超过1%的自闭症谱系障碍病例。然而，全基因组关联研究经常在不编码蛋白质的DNA区域（即基因间区域）中发现具有统计学意义的遗传变异关联。越来越多的证据表明，这些非编码区是活跃转录的，可能参与基因的调控，包括不同染色体上的基因。本文总结的证据表明，研究焦点需要扩大到包括各种表观遗传修饰以及非编码RNA（即“森林”）在内的影响深远的基因调控机制。考虑到非编码RNA在大多数细胞中代表了90%以上的转录本，我们可能只是观察到自闭症基因组景观中的“冰山一角”或“森林边缘”。
Autism spectrum disorders are neurodevelopmental disorders characterized by significant deficits in reciprocal social interactions, impaired communication and restricted, repetitive behaviors. As autism spectrum disorders are among the most heritable of neuropsychiatric disorders, much of autism research has focused on the search for genetic variants in protein-coding genes (i.e., the 'trees'). However, no single gene can account for more than 1% of the cases of autism spectrum disorders. Yet, genome-wide association studies have often identified statistically significant associations of genetic variations in regions of DNA that do not code for proteins (i.e., intergenic regions). There is increasing evidence that such noncoding regions are actively transcribed and may participate in the regulation of genes, including genes on different chromosomes. This article summarizes evidence that suggests that the research spotlight needs to be expanded to encompass far-reaching gene-regulatory mechanisms that include a variety of epigenetic modifications, as well as noncoding RNA (i.e., the 'forest'). Given that noncoding RNA represents over 90% of the transcripts in most cells, we may be observing just the 'tip of the iceberg' or the 'edge of the forest' in the genomic landscape of autism.