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Replicative mechanisms for CNV formation are error prone.

ABSTRACT: 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.

SUBMITTER: Carvalho CM

PROVIDER: S-EPMC3821386 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Replicative mechanisms for CNV formation are error prone.

Carvalho Claudia M B CM Pehlivan Davut D Ramocki Melissa B MB Fang Ping P Alleva Benjamin B Franco Luis M LM Belmont John W JW Hastings P J PJ Lupski James R JR

Nature genetics 20130922 11

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. ...[more]

PMID: 24056715

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