DNA sequence features underlying large-scale duplications and deletions in human

Abstract

BackgroundCopy Number Variants (CNVs) may cover up to 12% of the whole genome and have substantial impact on phenotypes. We used 5 867 duplications and 33 181 deletions available from the 1000 Genomes Project to characterize genomic regions vulnerable to CNV formation and to identify sequence features characteristic for those regions.ResultsOnly 14 CNVs contained unknown nucleotides, which reflected the high quality of the analysed data. The GC content for deletions was lower and for duplications was higher than for randomly selected regions. In regions flanking deletions and downstream of duplications content was higher than in the random sequences, but upstream of duplication content was lower. In duplications, the percentage of low complexity sequences was not different from the randomized data, but in deletions it was higher. Moreover, it was significantly higher upstream of CNVs as compared to random sequences. Conversely, it was lower downstream of duplications. The majority of CNVs intersected with genic regions - mainly with introns. ConclusionsGC content may be associated with CNV formation and CNVs, especially duplications are initiated in low complexity regions. Moreover, CNVs located or overlapped with introns indicate their role in shaping intron variability. Genic CNV regions were enriched in many essential biological processes such as cell adhesion, synaptic transmission, transport, cytoskeleton organization, immune response and metabolic mechanisms what indicates that this large-scaled variants play important biological roles.