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Mutation spectrum of Drosophila CNVs revealed by breakpoint sequencing

Margarida Cardoso-Moreira*, J Roman Arguello and Andrew G Clark

Author Affiliations

Department of Molecular Biology and Genetics, Cornell University, 526 Campus Road, Ithaca, NY 14853-2703, USA

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Genome Biology 2012, 13:R119  doi:10.1186/gb-2012-13-12-r119

Published: 22 December 2012



The detailed study of breakpoints associated with copy number variants (CNVs) can elucidate the mutational mechanisms that generate them and the comparison of breakpoints across species can highlight differences in genomic architecture that may lead to lineage-specific differences in patterns of CNVs. Here, we provide a detailed analysis of Drosophila CNV breakpoints and contrast it with similar analyses recently carried out for the human genome.


By applying split-read methods to a total of 10x coverage of 454 shotgun sequence across nine lines of D. melanogaster and by re-examining a previously published dataset of CNVs detected using tiling arrays, we identified the precise breakpoints of more than 600 insertions, deletions, and duplications. Contrasting these CNVs with those found in humans showed that in both taxa CNV breakpoints fall into three classes: blunt breakpoints; simple breakpoints associated with microhomology; and breakpoints with additional nucleotides inserted/deleted and no microhomology. In both taxa CNV breakpoints are enriched with non-B DNA sequence structures, which may impair DNA replication and/or repair. However, in contrast to human genomes, non-allelic homologous-recombination (NAHR) plays a negligible role in CNV formation in Drosophila. In flies, non-homologous repair mechanisms are responsible for simple, recurrent, and complex CNVs, including insertions of de novo sequence as large as 60 bp.


Humans and Drosophila differ considerably in the importance of homology-based mechanisms for the formation of CNVs, likely as a consequence of the differences in the abundance and distribution of both segmental duplications and transposable elements between the two genomes.

Copy number variants; CNVs; Non-allelic homologous-recombination; NAHR; Single-strand annealing; SSA; Non-homologous end-joining; NHEJ; Replication-associated repair; Alternative end-joining; Microhomology-mediated end-joining; MMEJ; Filler DNA