PhaseDancer: a novel targeted assembler of segmental duplications unravels the complexity of the human chromosome 2 fusion going from 48 to 46 chromosomes in hominin evolution

Abstract

Abstract Resolving complex genomic regions rich in segmental duplications (SDs) is challenging due to the high error rate of long-read sequencing. Here, we describe a targeted approach with a novel genome assembler PhaseDancer that extends SD-rich regions of interest iteratively. We validate its robustness and efficiency using a golden-standard set of human BAC clones and in silico-generated SDs with predefined evolutionary scenarios. PhaseDancer enables extension of the incomplete complex SD-rich subtelomeric regions of Great Ape chromosomes orthologous to the human chromosome 2 (HSA2) fusion site, informing a model of HSA2 formation and unravelling the evolution of human and Great Ape genomes.

Keywords

• De-novo assembly
• Segmental duplications
• Long-read PacBio sequencing
• Chromosomal fusion
• Complex genomic rearrangements