Division of Gene Regulation, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Biological Sciences, Columbia University, New York, NY, USA.
Nat Genet. 2019 Jul;51(7):1160-1169. doi: 10.1038/s41588-019-0455-2. Epub 2019 Jun 28.
Most of the millions of SNPs in the human genome are non-coding, and many overlap with putative regulatory elements. Genome-wide association studies (GWAS) have linked many of these SNPs to human traits or to gene expression levels, but rarely with sufficient resolution to identify the causal SNPs. Functional screens based on reporter assays have previously been of insufficient throughput to test the vast space of SNPs for possible effects on regulatory element activity. Here we leveraged the throughput and resolution of the survey of regulatory elements (SuRE) reporter technology to survey the effect of 5.9 million SNPs, including 57% of the known common SNPs, on enhancer and promoter activity. We identified more than 30,000 SNPs that alter the activity of putative regulatory elements, partially in a cell-type-specific manner. Integration of this dataset with GWAS results may help to pinpoint SNPs that underlie human traits.
人类基因组中的数百万个单核苷酸多态性（SNPs）大多数是非编码的，其中许多与假定的调控元件重叠。全基因组关联研究（GWAS）已经将这些 SNPs 中的许多与人类特征或基因表达水平联系起来，但很少有足够的分辨率来确定因果 SNPs。以前，基于报告基因检测的功能筛选的通量太低，无法对可能影响调控元件活性的大量 SNPs 进行测试。在这里，我们利用调查调控元件（SuRE）报告基因技术的通量和分辨率，对包括已知常见 SNPs 的 57%在内的 590 万个 SNPs 对增强子和启动子活性的影响进行了调查。我们确定了超过 30000 个改变假定调控元件活性的 SNPs，部分以细胞类型特异性的方式。将这个数据集与 GWAS 结果整合，可能有助于确定导致人类特征的 SNPs。
