Inherited retinal degenerations are diverse and debilitating blinding diseases. Genetic tests and exome sequencing have identified mutations in many protein-coding genes associated with such diseases, but causal sequence variants remain to be found in many retinopathy cases. Since 99% of our genome does not code for protein but contains cis-regulatory elements (CREs) that regulate the expression of essential genes, CRE variants might hold the answer for some of these cases. However, identifying functional CREs within the noncoding genome and predicting the pathogenicity of CRE variants pose a significant challenge. Here, we review the development of massively parallel reporter assays in the mouse retina, its use in dissecting retinal cis-regulatory networks, and its potential application for developing therapies.
Keywords: CRE-seq; CRX; Cis-regulatory element; High-throughput functional analysis; Massively parallel reporter assay (MPRA); NRL; Noncoding DNA; Retina transcription factor; Transcriptional regulation.