Second, there remains a gap between the prediction and functional validation of putative enhancer elements. Thus, if a risk SNP is localized to a putative enhancer element defined through chromatin profiling, it is essential that the putative enhancer is functionally validated. In vitro and in vivo reporter assays can help in this regard. However, these assays are relatively low throughput and usually involve the use of a general promoter such as SV40 rather than the enhancer’s endogenous promoter, which complicates the interpretation of negative results. Additionally, most genes are regulated by more than one enhancer, yet typically only one enhancer is tested in a reporter assay.
