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

Miga, Karen H

Koren, Sergey

Rhie, Arang

Vollger, Mitchell R

Gershman, Ariel

Bzikadze, Andrey

Brooks, Shelise

Howe, Edmund

Porubsky, David

Logsdon, Glennis A

Schneider, Valerie A

Potapova, Tamara

Wood, Jonathan

Chow, William

Armstrong, Joel

Fredrickson, Jeanne

Pak, Evgenia

Tigyi, Kristof

Kremitzki, Milinn

Markovic, Christopher

Maduro, Valerie

Dutra, Amalia

Bouffard, Gerard G

Chang, Alexander M

Hansen, Nancy F

Wilfert, Amy B

Thibaud-Nissen, Françoise

Schmitt, Anthony D

Belton, Jon-Matthew

Selvaraj, Siddarth

Dennis, Megan Y

Soto, Daniela C

Sahasrabudhe, Ruta

Kaya, Gulhan

Quick, Josh

Loman, Nicholas J

Holmes, Nadine

Loose, Matthew

Surti, Urvashi

Risques, Rosa Ana

Graves Lindsay, Tina A

Fulton, Robert

Hall, Ira

Paten, Benedict

Howe, Kerstin

Timp, Winston

Young, Alice

Mullikin, James C

Pevzner, Pavel A

Gerton, Jennifer L

Sullivan, Beth A

Eichler, Evan E

Phillippy, Adam M

2022-04-01T14:27:16Z

2022-04-01T14:27:16Z

2020-09

2022-04-01T14:27:15Z

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 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.

10.1038/s41586-020-2547-7

0028-0836

1476-4687

https://hdl.handle.net/10161/24764

eng

Springer Science and Business Media LLC

Nature

10.1038/s41586-020-2547-7

Testis

Chromosomes, Human, X

Centromere

Telomere

Humans

Hydatidiform Mole

DNA, Satellite

Reproducibility of Results

DNA Methylation

CpG Islands

Pregnancy

Genome, Human

Female

Male

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

Journal article

Sullivan, Beth A|0000-0001-5216-4603

79

84

7823

Duke

School of Medicine

Basic Science Departments

Institutes and Centers

Molecular Genetics and Microbiology

Duke Cancer Institute

Institutes and Provost's Academic Units

Initiatives

Duke Science & Society

Published

585