Ongoing human chromosome end extension revealed by analysis of BioNano and nanopore data

The majority of human chromosome ends remain incompletely assembled due to their highly repetitive structure. In this study, we use BioNano data to anchor and extend chromosome ends from two European trios as well as two unrelated Asian genomes. At least 11 BioNano assembled chromosome ends are structurally divergent from the reference genome, including both missing sequence and extensions. These extensions are heritable and in some cases divergent between Asian and European samples. Six out of nine predicted extension sequences from NA12878 can be confirmed and filled by nanopore data. We identify two multi-kilobase sequence families both enriched more than 100-fold in extension sequence (p-values < 1e-5) whose origins can be traced to interstitial sequence on ancestral primate chromosome 7. Extensive sub-telomeric duplication of these families has occurred in the human lineage subsequent to divergence from chimpanzees.