Exome-based Variant Detection in Core Promoters.
Exome-based Variant Detection in Core Promoters.
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DOI：
10.1038/srep30716
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发表时间：
2016-07-28
影响因子：
4.6
通讯作者：
Wang SM
中科院分区：
文献类型：
--
作者：
Kim YC;Cui J;Luo J;Xiao F;Downs B;Wang SM
核心启动子控制转录的启动。核心启动子序列的改变会扰乱转录调控，导致基因表达受损，最终导致疾病。因此，对核心启动子的全面表征对于了解生物医学研究中正常和异常的基因表达是至关重要的。在这里，我们报告了基于外显子的核心启动子变异检测(EVDC)方法的发展，该方法用于基因组规模的核心-启动子序列变异分析。这种方法是基于这样一个事实，即外显子序列不仅包含编码外显子的序列，还包含非编码区的序列，包括外显子测序过程中随机碎裂产生的核心启动子。利用单个个体的三种细胞类型的CD4+T细胞、CD19+B细胞和中性粒细胞的外显子组数据，我们描述了核心启动子定位的外显子序列的特征，并分析了该个体基因组中核心-启动子的变异。我们还利用1000基因组计划产生的外显子数据比较了YRI(尼日利亚伊巴丹的约鲁巴人)群体和CEU(欧洲死者的犹他州居民)群体的核心启动子，发现YRI群体比CEU群体的变异要大得多。我们的研究表明，EVDC方法为核心启动子序列变异的基因组从头表征提供了一种简单而有力的手段。
Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data from three cell types of CD4+ T cells, CD19+ B cells and neutrophils of a single individual, we characterized the features of core promoter-mapped exome sequences, and analysed core-promoter variation in this individual genome. We also compared the core promoters between YRI (Yoruba in Ibadan, Nigeria) and the CEU (Utah residents of European decedent) populations using the exome data generated by the 1000 Genome project, and observed much higher variation in YRI population than in CEU population. Our study demonstrates that the EVDC method provides a simple but powerful means for genome-wile de novo characterization of core promoter sequence variation.