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Genome-wide analysis of tandem DNA repeats in the genomes of individuals with autism spectrum disorder and control participants reveals a strong contribution of tandem repeat expansions to the genetic aetiology and phenotypic complexity of autism spectrum disorder.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Whole-genome sequencing data reveals a large number of variants for testing their associations with phenotypic traits and diseases. Here, the authors develop WGScan, a statistical method for detecting the existence and estimating the locations of the association signal at genome-wide scale.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Autism is a highly heritable neurodevelopmental disorder, and yet few specific susceptibility genes have been identified to date. A linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms is now described in a common set of 1,031 multiplex autism families. The linkage regions identified provide targets for rare variation screening whereas the discovery of a single novel association, SEMA5A, demonstrates the action of common variants.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Communities of boreal species are spreading northwards as tundra communities recede under climate change in the Arctic. Concurrently, human activities in the Arctic are increasing. This study takes a multidisclinary approach to investigate the potential future distribution of tundra species and to relate the location of refugial areas to disparate land-use practices in northern Alaska.

The surface types that comprise the dark zone of the Greenland Ice Sheet, an area of bare ice with low albedo, are unknown. Here, the authors use UAV imagery to show that, during the melt-season, biologically active surface impurities are responsible for spatial albedo patterns and the dark zone itself.

Jeramiah Smith, Weiming Li and colleagues report the whole-genome sequence of the sea lamprey, Petromyzon marinus, representing a vertebrate lineage diverged from humans ~500 million years ago. Their analyses define key evolutionary events in vertebrate lineages and provide evidence for two whole-genome duplication events occurring before the divergence of the ancestral lamprey and jawed vertebrate (gnathostome) lineages.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

A defective haemoglobin gene has been successfully replaced with a healthy copy.

Non-variceal upper gastrointestinal bleeding is a medical emergency in which bleeding develops in the oesophagus, stomach or proximal duodenum and is often caused by peptic ulcers as a result of Helicobacter pylori infection, NSAID use or low-dose aspirin use. This Primer describes how these bleeding events occur and how to resolve this common clinical problem.

Fires triggered by climate change threaten plant diversity in many biomes. Here the authors investigate how the catastrophic fires of 2019–2020 affected the vascular flora of SE Australia. They report that 816 species were highly impacted, including taxa of biogeographic and conservation interest.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

A study of the recovery potential of over 800 of the world's coral reefs shows that 83% of fished reefs are missing more than half their expected biomass, with severe consequences for key ecosystem functions; protection from fishing would allow full recovery in 35 years on average, but in 59 years for the most degraded reefs.

Submarine groundwater discharge transports nutrients from terrestrial to marine systems, but is often ignored in coastal biogeochemistry. In this Review, the fluxes, impacts and management implications of this discharge are examined and compared with riverine fluxes globally.

The study of the band structure and crystal symmetry of the semimetal bismuth indicates that this material is a higher-order topological insulator hosting robust one-dimensional metallic states on the hinges of the crystal.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Analysis of ~10,000 cases of developmental delay and autism identifies 253 candidate neurodevelopmental disease genes. Network analysis highlights cell-specific enrichments of disease-related genes in the D1⁺ and D2⁺ spiny neurons of the striatum.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Comparative study of 81 genomes of parasitic and non-parasitic worms identifies gene family births and expanded gene families at key nodes in the phylogeny that are relevant to parasitism and proteins historically targeted for drug development.

Atmospheric transport of microplastics could be a major source of plastic pollution to the ocean, yet observations currently remain limited. This Perspective quantifies the known budgets of the marine-atmospheric micro(nano)plastic cycle and proposes a future global observation strategy.

Mark Daly and colleagues present a statistical framework to evaluate the role of de novo mutations in human disease by calibrating a model of de novo mutation rates at the individual gene level. The mutation probabilities defined by their model and list of constrained genes can be used to help identify genetic variants that have a significant role in disease.

By digital profiling of residual breast tumors after neoadjuvant therapy, the authors identify gene expression patterns that correspond with a higher risk of metastasis and recurrence. Activation of the Ras-ERK pathway through loss of DUSP4 confers therapy resistance that can be overcome by combined treatment with MEK inhibitors.

The autistic spectrum disorders (ASDs) are highly heritable, yet the underlying genetic determinants remain largely unknown. Here, a genome-wide analysis of rare copy number variants (CNVs) has been carried out, revealing that ASD sufferers carry a higher load of rare, genic CNVs than do controls. Many of these CNVs are de novo and inherited. The results implicate several novel genes in ASDs, and point to the importance of cellular proliferation, projection and motility, as well as specific signalling pathways, in these disorders.

Highly bioactive supramolecular nanostructures displaying sulfated glycopeptides on their surfaces were designed in order to mimic the polysaccharides that bind and activate a plethora of proteins in mammalian biology during development and tissue regeneration.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

Daniel Chasman, Daniel Levy, Christopher Newton-Cheh, Georg Ehret and colleagues perform an association meta-analysis for blood pressure in ∼330,000 individuals and identify 31 new risk loci, implicating biological pathways related to vascular function and cardiometabolic traits. Their findings highlight potential therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

The function of adult stem cells is diminished with age but the role this dysfunction plays in the aging process is unknown. Here, the injection of muscle-derived stem/progenitor cells from young mice rescues symptoms in progeroid mice and is shown to regenerate tissues independent of engraftment.

Assessing spatial patterns of biodiversity using phylogenetic methods is a promising approach for conservation planning. Here, Mishler et al. develop a method to distinguish between recent and old endemism and provide new insights about biodiversity across space and time for the Australian Acacia.

Many traits, including susceptibilities to some diseases, are under complex genetic control. A new way of analysing the mouse genome will be a great help in understanding the interactions involved.