The discovery and resolution of genetic variation is critical to understanding disease and evolution. Our most recent work sequences diverse human and nonhuman primate genomes using both ultra-long and high-fidelity long-read sequencing technologies. Advances in this area have made possible the first telomere-to-telomere assemblies of the human genome and much more complete chimp, gorilla and orangutan genomes providing new biological insights into regions typically excluded from human genetic and comparative studies. We have discovered mega basepairs of duplicated sequence and/or rapidly evolving sequence present in humans that are absent from other non-human primates. These changes have predisposed our species to recurrent rearrangements associated with disease but also have led to the emergence of new genes important in the expansion of the human frontal cortex of the brain. Our data suggest that large-scale genome structural variation has played and continues to play a crucial role in the evolution of the human species. (#38297)