Journal Article

Telomere-to-telomere assembly of a complete human X chromosome

Pevzner, Pavel A., Pak, Evgenia, Bzikadze, Andrey, Young, Alice, Schneider, Valerie A., Holmes, Nadine, Loman, Nicholas J., Thibaud-Nissen, Françoise, Vollger, Mitchell R., Tigyi, Kristof, Schmitt, Anthony D., Potapova, Tamara, Chow, William, Wood, Jonathan, Loose, Matthew, Koren, Sergey, Armstrong, Joel, Timp, Winston, Surti, Urvashi, Paten, Benedict, Howe, Kerstin, Quick, Josh, Dennis, Megan Y., Mullikin, James C., Rhie, Arang, Markovic, Christopher, Selvaraj, Siddarth, Sahasrabudhe, Ruta, Kaya, Gulhan, Logsdon, Glennis A., Dutra, Amalia, Graves Lindsay, Tina A., Sullivan, Beth A., Wilfert, Amy B., Miga, Karen H., Risques, Rosa ana, Gershman, Ariel, Bouffard, Gerard G., Hansen, Nancy F., Fulton, Robert, Soto, Daniela C., Phillippy, Adam M., Maduro, Valerie, Eichler, Evan E., Porubsky, David, Belton, Jon-Matthew, Hall, Ira, Howe, Edmund, Brooks, Shelise, Fredrickson, Jeanne, Kremitzki, Milinn, Chang, Alexander M., Gerton, Jennifer L.

2020

Overview

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist 1 , 2 . Here we present a human genome assembly that surpasses the continuity of GRCh38 2 , along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome 3 , we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes. High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45 / 45/22 / 45/23 / 45/77 / 631/114/2785 / 631/208/212/2302 / 631/208/514/1948 / Accuracy / Arrays / Artificial chromosomes / Assembly / Centromere - genetics / Chromosomes / Chromosomes, Human, X - genetics / CpG Islands - genetics / Deoxyribonucleic acid / DNA / DNA Methylation / DNA, Satellite - genetics / Female / Gene families / Genes / Genome, Human - genetics / Genomes / Genomics / Haplotypes / Humanities and Social Sciences / Humans / Hydatidiform mole / Hydatidiform Mole - genetics / Male / multidisciplinary / Porosity / Pregnancy / Quality control / Reproducibility of Results / Ribosomal DNA / Satellite DNA / Science / Science (multidisciplinary) / Telomere - genetics / Telomeres / Testis - metabolism / Vertebrates / X chromosomes