Mutation spectrum of Drosophila CNVs revealed by breakpoint sequencing

Genome Biology

Andrew G Clark¹  J Roman Arguello¹  Margarida Cardoso-Moreira¹ 

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

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

Others  :  866944
DOI  :  10.1186/gb-2012-13-12-r119

 received in 2012-05-31, accepted in 2012-12-22,  发布年份 2012

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2013 Cardoso-Moreira et al.; licensee BioMed Central Ltd.

【 图 表 】

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