Comparison of constitutional and replication stress-induced genome structural variation by SNP array and mate-pair sequencing

ABSTRACT: Copy number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have suggested replication stress, such as that caused by the polymerase inhibitor aphidicolin, as a causative factor in CNV formation, but existing data are technically limited in the quality of the comparisons which can be made to experimentally induced variants. Here we used 1M feature single-nucleotide polymorphism (SNP) arrays and mate-pair sequencing as high resolution methods for characterizing CNVs in a common set of samples, to compare both the properties of constitutional and induced CNVs as well as the utility of the two methods in an experimental setting. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions that allowed some CNVs to be associated with inversions, ectopic duplications or LINE insertions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26121 | GEO | 2010/12/18

SECONDARY ACCESSION(S): PRJNA135363

REPOSITORIES: GEO