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This Review provides a comprehensive overview of epidemiology and molecular determinants of relapsed rhabdoid and other non-nephroblastoma childhood and adolescent kidney tumours, which are usually rare and challenging to cure. The most updated results in this field are discussed to highlight how understanding tumour biology can be used to inform therapeutic strategies in these patient populations.

A peer-to-peer website aims to disrupt the author-services industry.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

Evan Eichler and colleagues explore the structural diversity and ancestral origins of the 17q21.31 inversion region. They find that complex duplication architectures have arisen independently on both inversion haplotypes and have recently reached high frequencies among Europeans, either through extraordinary genetic drift or selective sweeps.

Single cell genome sequencing approaches have identified somatic copy number variants (CNVs) in human neurons, but small sample sizes (<100 neurons) have limited the power to find recurrent patterns such as CNV hotspots in a single individual. Here, the authors develop an approach to map CNVs in 2097 neurons from a neurotypical individual, finding that >10% neurons contain at least one somatic CNV, and enabling deeper investigation of these events.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

A comparative segmental duplication map of four primate genomes that allows the evolutionary history of all human segmental duplications to be reconstructed is presented. It reveals a fourfold acceleration of segmental duplication accumulation during the speciation of human, chimpanzee and gorilla at a time when other mutational processes were slowing, and also provides a detailed evolutionary history of all human segmental duplications as a resource to the human genetics community.

The European continent is thought to have played a major role in the origins of modern dogs. Here, analysing two ancient dog genomes from Germany, the authors find significant genetic continuity throughout the Neolithic period and time dog domestication to ∼20,000–40,000 years ago.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Evan Eichler and colleagues present an analysis of how well current commercial SNP platforms accurately capture copy number variants (CNVs). Although they were able accurately predict from Illumina Human 1M genotype data many sites identified in their recent study assessing CNVs in nine human individuals with a fosmid paired-end sequence approach, they find that commonly used platforms offer limited coverage for a large fraction of CNVs.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.

Harnessing information from whole genome sequencing in 185 individuals, this study generates a high-resolution map of copy number variants. Nucleotide resolution of the map facilitates analysis of structural variant distribution and identification of the mechanisms of their origin. The study provides a resource for sequence-based association studies.

This study presents OncoTreat, a framework for the prioritization of compounds targeting mechanistic tumor dependencies in individual patients.

This paper examines eight individual genomes using a clone-based sequencing approach, for structural variants of 8,000 nucleotides or more. One of the first high-quality inversion maps for the human genome is generated, and it is demonstrated that previous estimates of variation of this sort have been too high.

Evan Eichler and colleagues identify a recurrent microdeletion on 16p12.1 associated with developmental, cognitive and neuropsychiatric phenotypes. They also show that more severe phenotypes are frequently correlated with the presence of a second large genomic rearrangement, supporting a complex model of pathogenesis that may underlie the variable expressivity typical of many microdeletion syndromes.

Evan Eichler and colleagues identify a large, complex structural polymorphism at 16p12.1 in a region previously associated with neurocognitive disease. They further show that the region has experienced dynamic structural evolution in primates and that disease-associated microdeletions arise on the more common human haplotype.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

High-coverage sequencing of 79 (wild and captive) individuals representing all six non-human great ape species has identified over 88 million single nucleotide polymorphisms providing insight into ape genetic variation and evolutionary history and enabling comparison with human genetic diversity.

Evan Eichler and colleagues have developed an algorithm called mrFAST to map short, next-generation sequence reads across the genome that allows for the accurate prediction of copy-number variation.

Nearly 50% of the sequence of mammalian genomes is derived from mobile elements that inserted into the genome over millions of years of evolution. A recent mobile element insertion, found only in some individuals with European genetic ancestry, contributes to decreased skin pigmentation and increased sunburn frequency and skin cancer risk.

Evan Eichler and colleagues present a sequence assembly of the inverted H2 haplotype of human chromosome 17q21.31 and show that the inversion is polymorphic in other great ape species. Their analyses suggest that the H2 configuration represents the ancestral state in great apes and that inversions have occurred independently in the human and chimpanzee lineages.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

The genome of the southeast Asian orang-utan has been sequenced. The draft assembly of a Sumatran individual alongside sequence data from five Sumatran and five Bornean orang-utan genomes is presented. The resources and analyses described offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

Until now, fully sequenced human genomes of the indigenous hunter-gatherer peoples of southern Africa have been limited to recently diverged populations. The complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and of a Bantu from southern Africa are now presented. The extent of whole-genome and exome diversity is characterized; the observed genomic differences may help to pinpoint genetic adaptations to an agricultural lifestyle.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

Rodin and Dou et al. characterized genome-wide somatic mutation in autistic and control brains, revealing that even unaffected individuals may possess dozens of brain somatic mutations and providing insight into the role of somatic mutation in autism.

A comprehensive analysis of brain somatic mosaicism across the neocortex demonstrates the origins and distribution patterns of cells within the human brain.

Zhu et al. discover that in human brain there is widespread anatomic distribution of low-frequency somatic, mosaic L1 insertions, using deep whole-genome sequencing of neuronal and glial fractions and machine-learning analysis.

A deep learning model detects low frequency mosaic variants with improved accuracy.