Reviews & Analysis

Advances in genomic technologies have enabled investigations into a wide range of species. In this Review, the authors describe recent studies in both non-model and model organisms that illustrate the diversity of animal sex chromosomes with respect to their evolutionary histories and mechanistic roles in sex-determination systems.

RNA-binding proteins regulate the lifecycle of RNA, and their dysregulation is associated with diseases such as cancer and neurodegeneration. Using methods based on ultraviolet crosslinking followed by immunoprecipitation (CLIP), we can now begin to decode the mechanisms of the interactions between RNA-binding proteins and RNA. This Review discusses recent insights from and future applications of these methodologies.

Single-cell, spatial and multi-omic profiling technologies generate large-scale data that reveal the output of genome-scale experiments across diverse cells, tissues and organisms. Cole Trapnell reviews the underlying core statistical challenges that need to be tackled to harness the power of these technologies and advance our understanding of gene function in health and disease.

In this Review, Pfeifer and Jin discuss currently available methods for genome-wide mapping of DNA damage and rare mutations and illustrate how these technologies are being used to study mechanisms of mutagenesis linked to the aetiology of human diseases.

In this Review, Pinto and Bhatt provide an overview of DNA-sequencing and RNA-sequencing approaches that can be used to study the composition, structure, and function of microbiomes and discuss the biological insights they provide.

In this Review, Pamula and Lehmann describe how distinct membraneless germ granules organize the germ cell cytoplasm at different stages of the germline life cycle to determine germ cell identity, maintain genome integrity and regulate gamete differentiation.

In this Review, the authors summarize DNA packaging in bacteriophage, bacteria and eukaryotic cells. They describe the difficulties each system faces when packaging its DNA, outline the molecular motor components involved, and provide insights from new studies that reveal how DNA organization is achieved.

Filtering genomic data is a crucial step to ensure the quality and reliability of downstream analyses. The authors provide guidance on the choice of filtering strategies and thresholds, including filters that remove sequencing bases or reads, variants, loci, genotypes or individuals from genomic datasets to improve accuracy and reproducibility.

Despite their impact on human complex traits and diseases, gene–environment interactions (G × E) remain challenging to assess statistically. The authors review considerations for the conceptualization, methodology, interpretation and reporting of G × E studies, and provide recommendations on how to avoid common pitfalls.

In this Review, Stanley summarizes the role of genetics in mammalian glycosylation, highlighting how advances in genetic and genomic technologies are helping to characterize the genes involved and contributing to the development of therapies for diseases related to glycosylation.

Targeted genome modification using CRISPR–Cas genome editing, base editing or prime editing is driving base research in plants and precise molecular breeding. The authors review the technological principles underlying these methods, approaches for their delivery in plants, and emerging crop-breeding strategies based on targeted genome modification.

In this Review, Li and Durbin discuss how to generate telomere-to-telomere assemblies for large haploid or diploid genomes using currently available data types and algorithms, and outline remaining challenges in resolving highly repetitive sequences and polyploid genomes.

In this Review, the authors summarize our current understanding of nuclear pre-mRNA and mRNA decay pathways. They describe how aberrantly processed mRNAs are targeted for decay in the nucleus and how this process is regulated to finely control gene expression.

In this Perspective, Werner and colleagues discuss the many potential mechanisms by which natural antisense transcripts (NATs) can regulate expression of their complementary sense transcripts, the biological implications of their regulatory effects and the potential of NATs for therapeutic applications.

Genetic variants acquired early during embryogenesis can affect numerous tissues. The authors review the phenomenon of embryonic mosaicism, with a focus on small variants, and discuss mechanisms of cell competition that allow mosaic clones to expand, as well as the functional consequences of mosaicism for embryo viability and the health of the organism.

In this Review, Mackay and Anholt discuss how epistasis and pleiotropy contribute to the genetic architecture of quantitative traits and outline factors that might explain observed differences in their prevalence between model organisms and humans.

In this Review, the authors compare the characteristics and detection methods of germline and somatic variants. Furthermore, they outline how the interplay between the two types of genetic variation can affect human health.

Plants have uniquely adapted to manage endoplasmic reticulum stress triggered by protein misfolding. The authors review the dynamics of gene expression regulation underlying the unfolded protein response in plants, highlighting recent insights provided by systems-level approaches and omics data.

This Review highlights the diversity in sequence composition of disease-related short tandem repeats. The authors discuss how to detect non-canonical motifs in repeat sequences from sequencing data and review the molecular and clinical consequences of sequence composition changes.

In this Review, Sayers et al. summarize findings from recent large-scale genetic epidemiology studies on the genetic underpinnings of chronic respiratory diseases. Furthermore, they outline how insights gained from such studies can improve treatment approaches.