The complete sequence of a human genome

Science, Год журнала: 2022, Номер 376(6588), С. 44 - 53

Опубликована: Март 31, 2022

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

Язык: Английский

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Complete genomic and epigenetic maps of human centromeres

Science, Год журнала: 2022, Номер 376(6588)

Опубликована: Март 31, 2022

Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric centromeric repeats, constitute 6.2% the (189.9 megabases). Detailed maps these regions revealed multimegabase structural rearrangements, including in active repeat arrays. Analysis centromere-associated uncovered strong relationship between position centromere evolution surrounding DNA through layered expansions. Furthermore, comparisons X centromeres across diverse panel individuals illuminated high degrees structural, epigenetic, sequence variation complex rapidly evolving regions.

Язык: Английский

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A complete reference genome improves analysis of human genetic variation

Science, Год журнала: 2022, Номер 376(6588)

Опубликована: Март 31, 2022

Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 million base pairs of sequence, corrects thousands structural errors, and unlocks most complex regions human for clinical functional study. We show how this reference universally improves read mapping variant calling 3202 17 globally diverse samples sequenced with short long reads, respectively. identify hundreds variants per sample in previously unresolved regions, showcasing promise T2T-CHM13 evolutionary biomedical discovery. Simultaneously, eliminates tens spurious sample, including reduction false positives 269 medically relevant genes by up a factor 12. Because these improvements discovery coupled population genomic resources, is positioned replace GRCh38 as prevailing genetics.

Язык: Английский

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From telomere to telomere: The transcriptional and epigenetic state of human repeat elements

Science, Год журнала: 2022, Номер 376(6588)

Опубликована: Март 31, 2022

Mobile elements and repetitive genomic regions are sources of lineage-specific innovation uniquely fingerprint individual genomes. Comprehensive analyses such repeat elements, including those found in more complex the genome, require a complete, linear genome assembly. We present de novo discovery annotation T2T-CHM13 human reference genome. identified previously unknown satellite arrays, expanded catalog variants families for repeats mobile characterized classes composite repeats, located retroelement transduction events. detected nascent transcription delineated CpG methylation profiles to define structure transcriptionally active retroelements humans, centromeres. These data expand our insight into diversity, distribution, evolution that have shaped

Язык: Английский

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Segmental duplications and their variation in a complete human genome

Science, Год журнала: 2022, Номер 376(6588)

Опубликована: Март 31, 2022

Despite their importance in disease and evolution, highly identical segmental duplications (SDs) are among the last regions of human reference genome (GRCh38) to be fully sequenced. Using a complete telomere-to-telomere (T2T-CHM13), we present comprehensive view SD organization. SDs account for nearly one-third additional sequence, increasing genome-wide estimate from 5.4 7.0% [218 million base pairs (Mbp)]. An analysis 268 genomes shows that 91% previously unresolved T2T-CHM13 sequence (68.3 Mbp) better represents copy number variation. Comparing long-read assemblies (

Язык: Английский

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The complete sequence of a human Y chromosome

Nature, Год журнала: 2023, Номер 621(7978), С. 344 - 354

Опубликована: Авг. 23, 2023

Язык: Английский

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Epigenetic patterns in a complete human genome

Science, Год журнала: 2022, Номер 376(6588)

Опубликована: Март 31, 2022

The completion of a telomere-to-telomere human reference genome, T2T-CHM13, has resolved complex regions the including repetitive and homologous regions. Here, we present high-resolution epigenetic study previously unresolved sequences, representing entire acrocentric chromosome short arms, gene family expansions, diverse collection repeat classes. This resource precisely maps CpG methylation (32.28 million CpGs), DNA accessibility, short-read datasets (166,058 chromatin immunoprecipitation sequencing peaks) to provide evidence activity across unidentified or corrected genes reveals clinically relevant paralog-specific regulation. Probing centromeres from six individuals generated an estimate variability in kinetochore localization. analysis provides framework with which investigate most elusive granting insights into

Язык: Английский

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NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads

Genome biology, Год журнала: 2024, Номер 25(1)

Опубликована: Апрель 26, 2024

Long-read sequencing data, particularly those derived from the Oxford Nanopore platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient correction and assembly tool for noisy long reads, which achieves a level of accuracy in genome assembly. We apply NextDenovo assemble 35 diverse human genomes around world using long-read data. These allow us identify landscape segmental duplication gene copy number variation modern populations. The use should pave way population-scale

Язык: Английский

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Benchmarking challenging small variants with linked and long reads

Cell Genomics, Год журнала: 2022, Номер 2(5), С. 100128 - 100128

Опубликована: Апрель 28, 2022

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling methods. Here we use accurate linked long reads expand 7 samples include difficult-to-map regions segmental duplications that challenging for short reads. These add more than 300,000 SNVs 50,000 insertions or deletions (indels) 16% exonic variants, many challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, 92% of the autosomal GRCh38 assembly while excluding problematic benchmarking small copy number should have been previous version, which included 85% GRCh38. It identifies eight times false negatives read call set relative our benchmark. We demonstrate this benchmark reliably positives across technologies, enabling ongoing methods development.

Язык: Английский

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An efficient error correction and accurate assembly tool for noisy long reads

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 12, 2023

Abstract Long read sequencing data, particularly those derived from the Oxford Nanopore (ONT) platform, tend to exhibit a high error rate. Here, we present NextDenovo, highly efficient correction and assembly tool for noisy long reads, which achieves level of accuracy in genome assembly. NextDenovo can rapidly correct reads; these corrected reads contain fewer errors than other comparable tools are characterized by chimeric alignments. We applied quality reference genomes 35 diverse humans across world using ONT data. Based on de novo assemblies, were able identify landscape segmental duplications gene copy number variation modern human population. The use program should pave way population-scale long-read assembly, thereby facilitating construction pan-genomes,

Язык: Английский

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