Nature: Generate a complete human X chromosome sequence!

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist.

Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), have produced the first end-to-end DNA sequence of a human chromosome. The results, published in the journal Nature on July 14, 2020, show that generating a precise, base-by-base sequence of a human chromosome is now possible, and will enable researchers to produce a complete sequence of the human genome.

In this study, researchers present a de novo human genome assembly that surpasses the continuity of GRCh38, along with the first 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 their efforts on the human X chromosome, we reconstructed the ~3.1 megabase centromeric satellite DNA array and closed all 29 remaining gaps in the current reference, including new sequence from the human pseudoautosomal regions and cancer-testis ampliconic gene families (CT-X and GAGE). These novel sequences will be integrated into future human reference genome releases. Additionally, a complete chromosome X, combined with the ultra-long nanopore data, allowed them to map methylation patterns across complex tandem repeats and satellite arrays for the first time. 

Their results demonstrate that finishing the entire human genome is now within reach and the data presented here will enable ongoing efforts to complete the remaining human chromosomes.

References

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