title: Gene Regulatory Elements, Major Drivers of Human Disease.
abstract: 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.
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: sumantra@jhmi.edu.
authors.forename: Sumantra
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and Institute for Human Genetics, University of California, San Francisco, California 94158; email: nadav.ahituv@ucsf.edu.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
mesh_terms: D064113:CRISPR-Cas Systems; D004742:Enhancer Elements, Genetic; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods
keywords: CRISPR; enhancers; gene regulatory networks; massively parallel reporter assays; promoters; topologically associating domains