title: Replication stress and mechanisms of CNV formation.
abstract: Copy number variants (CNVs) are widely distributed throughout the human genome, where they contribute to genetic variation and phenotypic diversity. De novo CNVs are also a major cause of numerous genetic and developmental disorders. However, unlike many other types of mutations, little is known about the genetic and environmental risk factors for new and deleterious CNVs. DNA replication errors have been implicated in the generation of a major class of CNVs, the nonrecurrent CNVs. We have found that agents that perturb normal replication and create conditions of replication stress, including hydroxyurea and aphidicolin, are potent inducers of nonrecurrent CNVs in cultured human cells. These findings have broad implications for identifying CNV risk factors and for hydroxyurea-related therapies in humans.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, United States.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Arlt
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wilson
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Glover
mesh_terms: D016590:Aphidicolin / Q000009:adverse effects; D002478:Cells, Cultured; D056905:Chromosome Breakpoints; D002877:Chromosomes, Human / Q000187:drug effects / Q000235:genetics; D056915:DNA Copy Number Variations; D004261:DNA Replication; D004777:Environment; D018816:Genes, cdc; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects; D012307:Risk Factors; D013312:Stress, Physiological
chemical_list: D016590:Aphidicolin; D006918:Hydroxyurea