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

Abstract

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 persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, 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 chromosome3, 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.

• Authors: Karen H Miga, Sergey Koren, Arang Rhie, Mitchell R Vollger, Ariel Gershman, Andrey Bzikadze, Shelise Brooks, Edmund Howe, David Porubsky, Glennis A Logsdon, Valerie A Schneider, Tamara Potapova, Jonathan Wood, William Chow, Joel Armstrong, Jeanne Fredrickson, Evgenia Pak, Kristof Tigyi, Milinn Kremitzki, Christopher Markovic, Valerie Maduro, Amalia Dutra, Gerard G Bouffard, Alexander M Chang, Nancy F Hansen, Amy B Wilfert, Françoise Thibaud-Nissen, Anthony D Schmitt, Jon-Matthew Belton, Siddarth Selvaraj, Megan Y Dennis, Daniela C Soto, Ruta Sahasrabudhe, Gulhan Kaya, Josh Quick, Nicholas J Loman, Nadine Holmes, Matthew Loose, Urvashi Surti, Rosa Ana Risques, Tina A Graves Lindsay, Robert Fulton, Ira Hall, Benedict Paten, Kerstin Howe, Winston Timp, Alice Young, James C Mullikin, Pavel A Pevzner, Jennifer L Gerton, Beth A Sullivan, Evan E Eichler, Adam M Phillippy
• Journal: Nature (Nature) Vol. 585 Issue 7823 Pg. 79-84 (09 2020) ISSN: 1476-4687 [Electronic] England
• PMID: 32663838 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Satellite

Topics

• Centromere (genetics)
• Chromosomes, Human, X (genetics)
• CpG Islands (genetics)
• DNA Methylation
• DNA, Satellite (genetics)
• Female
• Genome, Human (genetics)
• Humans
• Hydatidiform Mole (genetics)
• Male
• Pregnancy
• Reproducibility of Results
• Telomere (genetics)
• Testis (metabolism)