Abstract
Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 130 bp of microhomology, whereas 33% of deletion breakpoints contain 1367 bp of inserted sequence. The co-occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible.
Original language | English (US) |
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Pages (from-to) | 385-391 |
Number of pages | 7 |
Journal | Nature genetics |
Volume | 42 |
Issue number | 5 |
DOIs | |
State | Published - May 2010 |
Externally published | Yes |
ASJC Scopus subject areas
- Genetics