Abstract
The completion of the human genome significantly improved our ability to discover and interpret genome copy number variation. In order to understand its impact on the characterization of inversion polymorphisms, we remapped data from 41 human genomes and 10 new samples against the telomere-to-telomere (T2T) reference genome as compared to the standard GRCh38 reference. Our analysis shows a ~21% increase in sensitivity identifying and improving mapping of 63 inversions. We further identify 26 misorientations within GRCh38, and show that the T2T reference is three times more likely to represent the correct orientation of the major human allele. As a result, we report a significant bias for inversions accumulating within the pericentromeric regions of specific chromosomes and show that functional annotations around inverted regions, such as topological-associated domains, can be better interpreted.
Competing Interest Statement
E.E.E. is a scientific advisory board (SAB) member of Variant Bio, Inc. The following authors have previously disclosed a patent application (no. EP19169090) relevant to Strand-seq: J.O.K., T.M., and D.P. The other authors declare no competing interests.
Footnotes
↵* For a complete list of HPRC and HGSVC members, see Supplemental Material.
