title: High-throughput sequencing of DNA G-quadruplex structures in the human genome.
abstract: G-quadruplexes (G4s) are nucleic acid secondary structures that form within guanine-rich DNA or RNA sequences. G4 formation can affect chromatin architecture and gene regulation and has been associated with genomic instability, genetic diseases and cancer progression. Here we present a high-resolution sequencing-based method to detect G4s in the human genome. We identified 716,310 distinct G4 structures, 451,646 of which were not predicted by computational methods. These included previously uncharacterized noncanonical long loop and bulged structures. We observed a high G4 density in functional regions, such as 5' untranslated regions and splicing sites, as well as in genes previously not predicted to contain these structures (such as BRCA2). G4 formation was significantly associated with oncogenes, tumor suppressors and somatic copy number alterations related to cancer development. The G4s identified in this study may therefore represent promising targets for cancer intervention.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Vicki S
authors.identifier: 0000000333391813
authors.initials: VS
authors.lastname: Chambers
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsico
authors.affiliation: Illumina Cambridge Ltd., Chesterford Research Park, Little Chesterford, Saffron Walden, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Boutell
authors.affiliation: 1] Department of Chemistry, University of Cambridge, Cambridge, UK. [2] Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Antonio
authors.affiliation: Illumina Cambridge Ltd., Chesterford Research Park, Little Chesterford, Saffron Walden, UK.
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Smith
authors.affiliation: 1] Department of Chemistry, University of Cambridge, Cambridge, UK. [2] Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK. [3] School of Clinical Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D004247:DNA / Q000235:genetics*; D054856:G-Quadruplexes; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA