G4‐associated human diseases

Abstract

Recent research has established clear connections between G-quadruplexes and human disease. Features of quadruplex struc-tures that promote genomic instability have been determined. Quadruplexes have been identified as transcriptional, translational and epigenetic regulatory targets of factors associated with human genetic disease. An expandable GGGGCC motif that can adopt a G4 structure, located in the previously obscure C9ORF72 locus, has been shown to contribute to two well-recognized neurodegener-ative diseases, amyotrophic lateral sclerosis (ALS) and frontotem-poral dementia (FTD). This review focuses on these advances, which further dispel the view that genomic biology is limited to the confines of the canonical B-form DNA duplex, and show how quad-ruplexes contribute spatial and temporal dimensionalities to linear sequence information. This recent progress also has clear practical ramifications, as prevention, diagnosis, and treatment of disease depend on understanding the underlying mechanisms.