St Laurent Georges, Vyatkin Yuri, Kapranov Philipp
St, Laurent Institute, 317 New Boston St, Suite 201, Woburn, MA 01801, USA.
BMC Med. 2014 Jun 12;12:97. doi: 10.1186/1741-7015-12-97.
In the past decade, numerous studies have made connections between sequence variants in human genomes and predisposition to complex diseases. However, most of these variants lie outside of the charted regions of the human genome whose function we understand; that is, the sequences that encode proteins. Consequently, the general concept of a mechanism that translates these variants into predisposition to diseases has been lacking, potentially calling into question the validity of these studies. Here we make a connection between the growing class of apparently functional RNAs that do not encode proteins and whose function we do not yet understand (the so-called 'dark matter' RNAs) and the disease-associated variants. We review advances made in a different genomic mapping effort - unbiased profiling of all RNA transcribed from the human genome - and provide arguments that the disease-associated variants exert their effects via perturbation of regulatory properties of non-coding RNAs existing in mammalian cells.
在过去十年中，众多研究已将人类基因组中的序列变异与复杂疾病易感性联系起来。然而，这些变异大多位于我们已知功能的人类基因组图谱区域之外，即编码蛋白质的序列之外。因此，一直缺乏一种将这些变异转化为疾病易感性的机制的总体概念，这可能会让人质疑这些研究的有效性。在此，我们将一类不断增加的、不编码蛋白质且功能尚不清楚的明显具有功能的RNA（即所谓的“暗物质”RNA）与疾病相关变异联系起来。我们回顾了在一项不同的基因组图谱研究中取得的进展——对从人类基因组转录的所有RNA进行无偏差分析，并提出论据表明，疾病相关变异是通过干扰哺乳动物细胞中存在的非编码RNA的调控特性来发挥作用的。
