Bioinformatics analysis of SV breakpoints
The performed analysis showed that all breakpoints had at least a significant DBS stimulator motif. The contingency of DNA motifs found within each interval around the breakpoints from the deletion and duplication are shown in Table 1.
Repetitive elements were found in 4/8 breakpoint junctions of the SVs, among them LTR (n=1), LINE L1 (n=3) (Table 1). On the other hand, only 1/8 breakpoints presented a non-B DNA structure. A cruciform DNA motif was found in the last 3’ breakpoint of the duplication (Table 1). Regarding the analysis by mfold algorithm, every breakpoint junction showed to adopt a secondary DNA structure. However, 7/8 were counted as positives, those in which the breakpoint co-localize with the secondary structure itself (Table 1, Figure 3). The most stable identified structures presented heterogeneous ∆G values, ranging from -5.01 to -0.27 with an average value of -1.77kcal (Figure 3).
Based on the hypothesis for the deletion´s origin of a non-allelic non-homologous inter-chromosomal recombination assisted by events of ectopic synapsis between repeats, we broaden the analysis of the breakpoint junctions with Dfam to a 5kb interval. The Dfam algorithm detected, at least, 8 partial- and full-length repetitive elements (LINEs, Alus, LTRs and MIRs, etc.) that may be involved in the formation of the ectopic synapsis (Figure 4). Furthermore, 2 tandem (TG)n and (T)n repeats were found in the analyzed interval, which may act as DNA breaks stimulators (Figure 4).