Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.
Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.
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DOI：
10.1016/j.gde.2013.10.009
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发表时间：
2013-12
影响因子：
4
通讯作者：
Raychaudhuri, Soumya
中科院分区：
文献类型：
--
作者：
Trynka, Gosia;Raychaudhuri, Soumya
虽然将基因组变异与复杂性状联系起来的研究逐渐变得越来越有成效，但这些联系背后的分子机制却很少被理解。由于只有一小部分性状相关的变异与编码序列有关，研究人员推测，许多潜在的因果等位基因影响非编码基因的调控位点。最近的研究已经成功地确定了单个位点上非编码等位基因的机制。现在，全基因组染色质分析已经在多个不同的组织、细胞类型和细胞系中产生了几十个非编码基因组的基因组注释图。这提供了一个巨大的机会，将这些注释与复杂的性状信号集成在一起，以全局解释相关的变异，并优先考虑可能的因果等位基因。在这里，我们回顾了非编码、常见等位基因导致表型的机制示例。我们讨论了整合常见性状相关变异与基因组注释的努力。最后，我们强调了这些方法的一些注意事项，并概述了未来的改进方向。
While studies to associate genomic variants to complex traits have gradually become increasingly productive, the molecular mechanisms that underlie these associations are rarely understood. Because only a small fraction of trait-associated variants can be linked to coding sequences, investigators have speculated that many of the underlying causal alleles influence non-coding gene regulatory sites. Recent studies have successfully identified examples of mechanisms for non-coding alleles at individual loci. Now, genome-wide chromatin assays have resulted in maps of dozens of genomic annotations of the non-coding genome across multiple different tissues, cell types and cell lines. This gives a tremendous opportunity to integrate these annotations with complex trait signals to globally interpret associated variants, and prioritize likely causal alleles. Here, we review the examples of mechanisms by which non-coding, common alleles result in phenotypes. We discuss the efforts to integrate common trait-associated variants with genomic annotations. Finally, we highlight some caveats of these approaches and outline future directions for improvement.
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