Volume 376| Issue 6588| 1 Apr 2022
Special issue – Completing the human genome
Introduction to Special Issue
Filling the gaps
BY Laura M. Zahn
31 Mar 2022: 42-43
A fully sequenced human genome was triumphantly announced more than 20 years ago. However, owing to technological limitations, some genomic regions remained unresolved. Here, Science presents research by the Telomere-to-Telomere (T2T) Consortium, reporting on the endeavor to complete a comprehensive human reference genome. Generated primarily by long-read sequencing of a hydatidiform mole, a doubly haploid growth, this effort adds ∼200 megabases of genetic information—a full chromosome’s worth—to the human genome.
Through the resolution of previously unsequenceable and unalignable regions, mostly composed of highly repetitive sequences, this reference genome allows for a detailed characterization of the centromeric satellite repeats, transposable elements, and segmental duplications. Mapping of genomic sequences, including those from previously published studies, resolves aspects of human genetic diversity, including evolutionary comparisons with our primate relatives. Furthermore, it allows for identification of how changes in methylation density differ within and among centromeres and how epigenetics can affect the transcription of repeat sequences.
These investigations have only begun to tease apart how the T2T reference genome influences the detection of biomedically relevant variants and the evolution of genomic regions that determine human traits. Although much remains to be discovered, the T2T reference genome provides another celebratory benchmark to observe as we continue to delve into the genetics that underlie our complete selves.