Annual review of genomics and human genetics

Gene Regulatory Elements, Major Drivers of Human Disease.

PMID 28399667


Gene expression changes, the driving forces for cellular diversity in multicellular organisms, are regulated by a diverse set of gene regulatory elements that direct transcription in specific cells. Mutations in these elements, ranging from chromosomal aberrations to single-nucleotide polymorphisms, are a major cause of human disease. However, we currently have a very limited understanding of how regulatory element genotypes lead to specific phenotypes. In this review, we discuss the various methods of regulatory element identification, the different types of mutations they harbor, and their impact on human disease. We highlight how these variations can affect transcription of multiple genes in gene regulatory networks. In addition, we describe how novel technologies, such as massively parallel reporter assays and CRISPR/Cas9 genome editing, are beginning to provide a better understanding of the functional roles that these elements have and how their alteration can lead to specific phenotypes. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 18 is August 31, 2017. Please see for revised estimates.