mutation spectrum of drosophila cnvs revealed by breakpoint sequencing果蝇的突变谱基因拷贝数异变了断点测序.pdfVIP

Cardoso-Moreira et al. Genome Biology 2012, 13:R119 /2013/13/12/R119 RESEARCH Open Access Mutation spectrum of Drosophila CNVs revealed by breakpoint sequencing * Margarida Cardoso-Moreira , J Roman Arguello and Andrew G Clark Abstract 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 mec