Fig. 4.

Impact of SVs on genome organization at the population scale. a Browser view of a 1-Mb genomic segment with a deletion identified in a part of the human population. The deletion removes a CTCF anchor with enhancer located in an intron of KIAA0391. CTCF ChIP-seq signals from 10 lymphoblastoid cells of different genotypes are presented for comparison. For each track, ChIP-seq signal values (originally in RPMs) were divided by the maximal value of the signal in the visualized region. The highest signal peak in the genomic region covered by the deletion is marked in each signal track. b Close-up on ChIA-PET interactions at the deletion site displayed above the ChIP-seq profiles of histone modifications for GM12878—no deletion and GM18526—homozygous deletion. H3K4me1 is primarily associated with active enhancers, H3K27ac—with active promoters and enhancers, H3K4me3—with promoters. Compare with Additional file 2: Figure S7. c Differences in gene transcription rates between genotypes defined by the deletion. Genes exhibiting the differences in transcription which pass Mann-Whitney test with p value < 0.1 were reported, see Fig. 2c for box plot description. n = 346, 85, 14 sample points. d 3D models of the domain shown in a without the deletion (left column) and with the deletion (right column). Schematic drawings of loops shown in b (first row); 3D models with loops colored as on schematic drawings (second row); 3D models with NFKBIA and PPP2R3C genes (arrows are pointing toward the TSSs) and enhancers marked (third row). Every picture has its duplicated zooming in on the deletion site. e Distance in 3D Euclidean space between the NFKBIA promoter and enhancer E1 and between the PPP2R3C promoter and enhancer E2. In green, distribution of distances calculated in 3D models of the reference structure (REF), in purple—in models with the deletion introduced (DEL). For each case, 100 models were generated. The differences between REF and DEL groups are statistically significant (p values much less than 0.001), see Fig. 2c for box plot description. f Enrichment/depletion of genomic structural elements with SVs of different types and of different VAF (VAF < 0.001 and VAF ≥ 0.001). In case of CCD borders, only these fully imbedded in SV intervals are counted as affected, whereas for other structural elements ≥ 1 bp overlaps are counted. Error bars represent SD. g Enrichment/depletion of genomic structural elements with the 1000 Genomes Project SNPs (ALL 1kGP), all GWAS SNPs (ALL GWAS), GWAS SNPs associated with hematological parameters (HP), and with autoimmune diseases (AI). Error bars represent SD