Interchromosomal core duplicons drive both evolutionary instability and disease susceptibility of the chromosome 8p23.1 region

The chromosome 8p23.1 region is considered one of the most complex and structurally unstable regions of the human genome. It harbors a common ~4.2Mb inversion polymorphism that is thought to predispose to recurrent rearrangements associated with congenital heart defects and developmental delay. The complexity of the region and its enrichment in recent segmental duplications has complicated disease association, assembly, and studies of natural genetic variation. In order to gain insight into the genomic structure and evolution of this region, we generated a high-quality alternate reference assembly of the inverted 6.2 Mbp haplotype at the 8p23.1 locus. We discovered and characterized three separate inversion events that arose recently in human evolution (0.6-0.9 MYA).