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Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Complex structural variations and rearrangements in cancer are identified using long-read sequencing.

A complete genome assembly of a crab-eating macaque, revealing 46% fewer segmental duplications and 3.83 times longer centromeres than those of humans, is presented, enhancing understanding of lineage-specific phenotypes, adaptation and primate evolution.

A vaccine to generate durable HIV broadly neutralizing antibodies (bnAb) from engineered B cells holds promise as an HIV functional cure. Here, the authors show that CRISPR/Cas-modified B cells expressing bnAbs as functional antigen receptors can be immunized to generate long-lived, germinal centre matured bnAb memory and plasma cells in mice.

Izumo and Juno are receptors on sperm and eggs respectively required for fusion, but other factors for sperm-egg fusion are poorly studied. Here, the authors report that phosphatidylserine, found mainly on cells marked for death, is also present on motile sperm, recognized by egg receptors, and is required for sperm-egg fusion.

High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

DNA variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve genotyping accuracy, however this increases computational complexity. Here the authors develop an approximate haplotagging method that simplifies the process and enables state-of-the-art variant calling performance with multiple sequencing platforms.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

Repetitive DNA intervals play important roles in the nucleus but are difficult to study due to their reiterated nature. Tigerfish introduces a novel computational platform for the design of interval-specific in situ hybridization probes.

Cleveland and colleagues report a DNA-replication-dependent error correction mechanism that acts in S phase to remove ectopically loaded CENP-A outside the centromeres, while retaining centromere-bound CENP-A.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

A human genome is sequenced and assembled de novo using a pocket-sized nanopore device.

Here we describe an open collaborative effort termed the ‘Ruminant T2T Consortium’. It aims to generate complete diploid assemblies for many species of ruminants to examine chromosomal evolution in the context of natural selection and domestication.

DiMeLo-seq uses native long-read sequencing to examine protein–DNA interactions by mapping exogenous methylation marks generated by a nonspecific DNA methyltransferase, as well as profile endogenous CpG methylation simultaneously.

Variant detection in problematic genes is facilitated with a curated benchmark.

The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.

High contiguity human genomes can be assembled de novo in 6 h using nanopore long-read sequences and the Shasta toolkit.

This work introduces a wet lab and computational pipeline, Napu, for small variant calling and de novo assembly of Nanopore sequencing data, which leads to comparable performances to short-read sequencing and allows for large-scale long-read sequencing projects.

The PEPPER-Margin-DeepVariant pipeline achieves highly accurate variant calling using nanopore and other long-read sequencing data.

Since the human genome was published in 2001, many of the gaps in the original sequence have been filled in, offering a more detailed understanding of genome regulation, structure and function.

The work describes the validation and polishing strategies developed by the telomere-to-telomere consortium for evaluating and improving the first complete human genome assembly.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

Clonal hematopoiesis, often caused by mutations in DNMT3A and TET2, is associated with blood cancer and coronary artery disease. Here, the authors conduct an epigenome-wide association study, finding that clonal hematopoiesis caused by DNMT3A vs. TET2 mutations has directionally opposing changes in DNA methylation profiles, with both promoting stem cell self-renewal.

Improved error assessment and read alignment on the MinION nanopore sequencing platform allow for calling of single-nucleotide variants and resolving the repeat structure of an assembly gap in the human X chromosome.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Advances in long-read sequencing technologies have broadened our understanding of genetic variation in the human population, uncovered new complex structural variants and offered an opportunity to elucidate new variant associations with disease.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Repeat regions in the human Y chromosome centromere are assembled using long-read nanopore sequencing.

Variant calling is the process of identifying genetic variants, which is important for characterizing population genetic diversity and for identifying disease-associated variants in clinical sequencing projects. In this Review, the authors discuss the state-of-the-art in variant calling, focusing on challenging types of genetic variants, advances in both sequencing technologies and computational pipelines, and benchmarking strategies to assess the robustness of variant-calling strategies.

The Human Pangenome Reference Consortium aims to offer the highest quality and most complete human pangenome reference that provides diverse genomic representation across human populations.