Journal Article

High-throughput identification of human SNPs affecting regulatory element activity

FitzPatrick, Vincent D., Franke, Lude, de Wit, Elzo, Teunissen, Hans, van Arensbergen, Joris, Comoglio, Federico, Võsa, Urmo, Bussemaker, Harmen J., de Haas, Marcel, Pagie, Ludo, van Steensel, Bas, Baltissen, Marijke P., van der Weide, Robin H., Vermeulen, Michiel

2019

نظرة عامة

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. Application of SuRE reporter technology to survey the effect of 5.9 million SNPs in the human genome on enhancer and promoter activity identifies over 30,000 SNPs that alter the activity of putative regulatory elements.

• الناشر: Nature Publishing Group US,Nature Publishing Group
• موضوع: 13/106 / 38 / 38/90 / 45 / 45/23 / 45/47 / 45/91 / 631/114/2163 / 631/208/200 / 631/61/191 / Agriculture / Animal Genetics and Genomics / Biomedical and Life Sciences / Biomedicine / Blood / Cancer Research / Deoxyribonucleic acid / DNA / Gene expression / Gene Function / Genetic Predisposition to Disease / Genome, Human / Genome-wide association studies / Genome-Wide Association Study / Genomes / Hep G2 Cells / High-Throughput Nucleotide Sequencing / Human Genetics / Humans / K562 Cells / Liver cancer / Peptides / Phenotype / Plasmids / Polls & surveys / Polymorphism, Single Nucleotide / Proteins / Proteomics / Quantitative Trait Loci / Regulatory Elements, Transcriptional / Regulatory sequences / RNA polymerase / Screens / Single-nucleotide polymorphism / Transcription factors / Transcription Factors - genetics / Transcription Factors - metabolism