Replicative mechanisms for CNV formation are error prone

Nat Genet. 2013 Nov;45(11):1319-26. doi: 10.1038/ng.2768. Epub 2013 Sep 22.


We investigated 67 breakpoint junctions of gene copy number gains in 31 unrelated subjects. We observed a strikingly high frequency of small deletions and insertions (29%) apparently originating from polymerase slippage events, in addition to frameshifts and point mutations in homonucleotide runs (13%), at or flanking the breakpoint junctions of complex copy number variants. These single-nucleotide variants were generated concomitantly with the de novo complex genomic rearrangement (CGR) event. Our findings implicate low-fidelity, error-prone DNA polymerase activity in synthesis associated with DNA repair mechanisms as the cause of local increase in point mutation burden associated with human CGR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Breaks*
  • DNA Copy Number Variations / genetics*
  • DNA Repair / genetics*
  • DNA Replication / genetics*
  • Frameshift Mutation
  • Gene Rearrangement / genetics*
  • Genetic Variation
  • Genotype
  • Humans
  • Sequence Analysis, DNA
  • Sequence Deletion

Associated data

  • GEO/GSE49447