Structural variants

Telomere-to-telomere (T2T) assembly of the CHM13 hydatidiform mole cell line, providing the first gap-resolved maps of centromeres and the full Y (from a composite). Use as a complement to GRCh38 for studying repetitive and structurally variable loci; chromosome naming and coordinates differ from GRC primary assemblies; use liftover and T2T-specific tooling where appropriate.

T2T; telomere-to-telomere; complete genome; CHM13; GRCh38 alternative

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

First-draft human pangenome from the HPRC: 47 phased diploid assemblies from diverse samples, aligned and summarized relative to GRCh38. Adds substantial euchromatic polymorphic sequence and duplicated gene content versus a single linear reference; intended for pangenome-aware alignment, variant calling, and downstream graph-based genomics (see HPRC data portal and companion software).

HPRC; pangenome; graph genome; haplotypes; GRCh38

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.