Which difficult genome regions include centromeres and telomeres?

The difficult genome regions that include centromeres and telomeres are heterochromatic regions.

Heterochromatin is DNA packed into a relatively condensed state and is commonly rich in repetitive sequences. Centromeres, which help chromosomes separate correctly during cell division, contain extensive satellite-DNA arrays. Telomeres cap chromosome ends and contain repeated TTAGGG sequences in humans, along with adjacent subtelomeric DNA.

These repeats created a distinctive technical problem for the HGP. Short sequencing reads could not reliably determine how many repeat units were present or where a nearly identical sequence belonged. Repetitive DNA could also be unstable or difficult to maintain in cloning vectors such as bacterial artificial chromosomes.

The original HGP consequently concentrated on euchromatin and left much heterochromatin unresolved. The later Telomere-to-Telomere effort used long-read sequencing and improved assembly methods to close major centromeric and other repetitive gaps. Heterochromatin is not simply “junk DNA”: centromeres are essential for chromosome segregation, and telomeres protect chromosome ends.