Why do repeated DNA sequences make genome assembly difficult?

In the context of the Human Genome Project, repetitive DNA sequences present a significant challenge for de novo genome assembly because they create ambiguity during the reconstruction process.1

During assembly, computer programs attempt to stitch together short DNA fragments by identifying overlapping identical sequences. When a genome contains repetitive elements—which are a general property of complex genomes—these identical sequences can appear in multiple locations. Because these repeats are indistinguishable from one another, it becomes difficult for assembly algorithms to determine the correct order and orientation of the surrounding unique DNA segments.12

To overcome this, scientists often require DNA reads of sufficient length and quality to span these repetitive regions, or they utilize hierarchical shotgun sequencing to create physical maps that help anchor the fragments in their proper genomic context.1