Figure 3

Interpreting enhancer variants. Various strategies for interpreting enhancer variants. (Top) Single- or high-throughput reporter assays can be used to test whether a putative enhancer is functional. (Middle) Gene targets of enhancers can be identified through experimental approaches such as fluorescence in situ hybridization and chromosome conformation capture assays, or through computational methods. (Bottom) The impact of a single nucleotide polymorphism (SNP) on enhancer function can be evaluated through CRISPR/Cas9-based DNA editing approaches, followed by measures of enhancer activity or target gene expression. The effect of a risk SNP on transcriptional activity and chromatin architecture can be evaluated through reporter assays and chromosome-conformation-capture-based experiments. Effects of the risk SNP on allele-specific expression and transcription factor binding can also be studied through quantitative ChIP and expression studies. Expression quantitative trait loci (eQTL) analysis can be performed to determine the effect of risk SNPs on gene expression levels.