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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Miga, KH; Koren, S; Rhie, A; Vollger, MR; Gershman, A; Bzikadze, A; Brooks, S; Howe, E; Porubsky, D; Logsdon, GA; Schneider, VA; Potapova, T; Wood, J; Chow, W; Armstrong, J; Fredrickson, J; Pak, E; Tigyi, K; Kremitzki, M; Markovic, C; Maduro, V; Dutra, A; Bouffard, GG; Chang, AM; Hansen, NF; Wilfert, AB; Thibaud-Nissen, F; Schmitt, AD; Belton, J-M; Selvaraj, S; Dennis, MY; Soto, DC; Sahasrabudhe, R; Kaya, G; Quick, J; Loman, NJ; Holmes, N; Loose, M; Surti, U; Risques, RA; Graves Lindsay, TA; Fulton, R; Hall, I; Paten, B; Howe, K; Timp, W; Young, A; Mullikin, JC; Pevzner, PA; Gerton, JL; Sullivan, BA; Eichler, EE; Phillippy, AM

Published Date

  • September 2020

Published In

Volume / Issue

  • 585 / 7823

Start / End Page

  • 79 - 84

PubMed ID

  • 32663838

Pubmed Central ID

  • PMC7484160

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-020-2547-7


  • eng

Conference Location

  • England