Fig. 1.

Inversion polymorphisms with respect to a complete T2T reference show pericentromeric bias. A An ideogram showing the position and inverted allele frequency (dot size) of all balanced inversions from 41 human samples mapped to T2T-CHM13 reference (n = 296). Inversions that fall within pericentromeric regions (CENSAT annotation, ± 1 Mbp) are shown as red dots (n = 61) while other inversions are shown as black dots (n = 235). Inversions with ≥ 90% reciprocal overlap with nonsyntenic regions between GRCh38 and T2T-CHM13 or that failed to map to the GRCh38 reference are highlighted as open circles (n = 63). B Permutation analysis shows pericentromeric enrichment for specific chromosomes. Permuted counts of pericentromeric inversions are shown as black violin plots as compared to observed counts (red dots). C The read-coverage profiles of Strand-seq data over a chromosome 1 centromeric region summarized as binned (bin size: 50 kbp step size: 10 kbp) read counts represented as bars above (teal; Crick read counts) and below (orange; Watson read counts) the midline with respect to centromere repeat annotation. Dotted lines highlight the novel centromeric inversion detected on chromosome 1 only with respect to T2T-CHM13. Note: equal coverage of Watson and Crick counts represent a heterozygous inversion (one homologue inverted) while reads aligned only in the Watson orientation signify a homozygous inversion (both homologs inverted). Pie charts show frequency of inverted (bright blue) and directly oriented (light blue) alleles across all haplotypes (n = 82) from all unrelated individuals (n = 41) for a given centromeric inversion (dotted lines). D A “backgammon” plot showing the inversion status of each defined region reported as colored arrowheads (dark blue—direct, bright blue—inverted, see the legend) for chromosome 7 region with respect to GRCh38 (chr7:57456486–61949954; top) and T2T-CHM13 (chr7:57700000–60400000; bottom). HSATs human satellites, HOR higher-order repeat