Collins and Talkowski provide a broad overview of structural variation in the human genome that covers their mutational properties, the dynamics of population genetics and functional consequences in disease as well as promising directions for future research.

Epigenetic clocks based on DNA methylation data are machine learning tools used to estimate chronological and biological age. The authors review computational and statistical challenges that must be addressed for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.

Circular RNAs have gained attention for their stability, immunological advantages and regulatory functions, making them a promising modality in multiple therapies. This Review discusses the therapeutic prospects of circular RNA-based approaches and the emerging role of circular RNAs as biomarkers in disease.

Recent genomic approaches are providing unprecedented opportunity to disentangle how genotype and environment affect organismal traits. The authors review the role of epigenetic variation in mediating the genotype–phenotype map across three scales: among individuals within a generation, across one or multiple generations, and long term over evolutionary time.

Controlling for phylogeny is essential in comparative genomics studies, because species, genomes and genes are not independent data points within statistical tests. The authors review the application of phylogeny-based comparative methods to genomic data to control for non-independence and how to test for causal hypotheses.

Loss of Y chromosome (LOY), the most commonly occurring post-zygotic (somatic) mutation in male individuals, affects immune activity and is associated with cancer, neurodegeneration, cardiovascular disease and infection. LOY is dynamic over time and has cell-type-specific effects, suggesting its potential as a biomarker and therapeutic target.

Studying germline variants and somatic mutations in cancer using omics technologies helps identify both heritable traits and molecular features of cancer genomes. Population-specific cancer genomics can reduce disparities and ensure equity across racial and ethnic groups for personalized medicine and public health approaches.

Kojima, Hoppe and Giraldez provide this cross-species Review of the cytoplasmic and nuclear remodelling that occurs after fertilization to permit zygotic genome activation (ZGA) and enable the shift from maternal to zygotic control of development (the maternal-to-zygotic transition).

Recent advances in genome engineering are enabling the recording of cellular histories into genomes, with single-cell and spatial omics technologies enabling their reconstruction into cellular lineages, states and exposures. This Perspective explores the rationale and technical basis of DNA recording, what aspects of cellular biology can be recorded and how, and the types of discovery that DNA recording will enable when studying development and disease.

Biobanks help centralize specimen collections, store and disseminate data, and facilitate large-scale analyses. This Review discusses how biobanks facilitate genetics research towards advancing precision medicine and overviews potential solutions to their current limitations.

Genomic and pangenomic data are yielding insights into the evolution of plant pattern recognition receptors (PRRs) and their molecular triggers. Recent advances in in silico and in vivo methods, alongside protein structure prediction, are helping to harness these insights for PRR engineering, offering sustainable solutions for broad-spectrum plant disease resistance.

In this Review, James et al. provide an overview of approaches for planning, constructing, and fine-tuning synthetic genomes and describe their potential applications.

Biomolecular condensates are membraneless cellular compartments that concentrate molecules such as proteins and nucleic acids. In this Review, the authors discuss how complementation experiments, a classic genetics approach, have provided valuable insights into the functions of biomolecular condensates.

With SNP-based genome-wide association studies (GWAS) nearing signal saturation, exploring copy number variation (CNV) can offer new insights into the genetic architecture of complex traits. The authors review recent advances that enable large-scale CNV-based GWAS and their likely impact on downstream analyses, such as polygenic risk scoring and drug target identification.

Global genomic data sharing enhances precision medicine. In this Roadmap, the authors outline evolving data-sharing models, best practices and policy impacts, and propose 12 actions to systematically scale up genomic data sharing.

This Review describes how increasingly sophisticated omics data and computational models of the splicing code are paving the way to more accurate, context-specific splicing predictions, while also providing insights into the regulatory mechanisms and therapeutic applications of alternative splicing.

Ancestral recombination graphs (ARGs) are revolutionizing population genetics by elucidating genetic processes such as demography, migration and selection. This Review introduces ARG structure, compares estimation methods and illustrates their application to understanding population dynamics.

Metabologenomics integrates multi-omics data into genome-scale metabolic models (GEMs) to analyse complex metabolic networks. Mardinoglu and Palsson review advancements in GEMs at the global, cell- and tissue-specific, microbiome and whole-body levels, with insights into their applications towards improving health care.

Toxicogenomics leverages molecular data to predict toxicological effects. In this Review, the authors summarize innovations in transcriptomics and emerging methods, such as single-cell technologies and multi-omics, that offer detailed insights into toxicological mechanisms to enhance hazard prediction and risk assessment.

Mosaic variegated aneuploidy is a rare condition in which the copy number of different chromosomes varies across some cells within an individual. In this Review, the authors discuss the genetic underpinnings and clinical manifestations of this condition and relate these findings to the consequences of chromosomal instability more broadly.