The Human Genome Project was announced as complete in 2003, but about 8% of the genome remained unsequenced due to technological limitations. This missing portion included complex regions like centromeres, telomeres, and segmental duplications — areas critical for chromosome stability and immune function. These regions were too repetitive for early 2000s sequencing methods to resolve accurately.

In 2022, the Telomere-to-Telomere (T2T) Consortium released the first truly complete, gapless human genome sequence, named T2T-CHM13. Using advanced long-read sequencing technologies from Oxford Nanopore and PacBio HiFi, researchers filled in nearly 200 million new base pairs and identified 1,956 predicted genes — including 99 protein-coding ones. For the first time, every centromere and the short arms of acrocentric chromosomes were fully mapped.

This breakthrough was made possible by a unique cell line (CHM13) with only one copy of each chromosome, simplifying assembly. However, T2T-CHM13 represents just one individual. The next step is building a human pangenome reference that captures genetic diversity across populations, a goal now underway through the Human Pangenome Reference Consortium. While the complete sequence is now available, understanding the function of newly revealed regions remains an ongoing effort.