Review Articles

Next-generation sequencing methods can be used to examine features of chromatin biology, although the outputs of these methods can be subject to various potential biases. This Review describes the ways in which biases can be introduced to such experiments and outlines methods to detect and mitigate their effect.

Genome-wide association studies have been extensively used to uncover genetic variants that independently influence complex traits, including diseases. This Review describes advances in computational approaches to detect interactions (epistasis) between genetic variants underlying complex traits, including the different promises and pitfalls of the methods. Additionally, the authors summarize current empirical evidence on how pervasive epistasis is in complex traits and its wider biological implications.

This Review provides insights into the use of eusocial insect species as models to study the role of epigenetic processes in regulating behaviour.

Recent developments and refinements to DNA methylation assays have led to the availability of several methods to detect and quantify cytosine modifications. This Review discusses the principles behind the newly developed techniques, compares the strengths and weaknesses of the different methods, and provides guidelines for selecting the most appropriate methods for particular experimental contexts.

Forward genetic screens have a long history of uncovering the genetic mutations underlying phenotypes of interest. This Review describes how next-generation sequencing technology can be integrated into forward genetic screens not only to enhance their efficiency but also to allow them to be carried out using expanded repertoires of species, populations and experimental strategies.

RNA-binding proteins (RBPs) influence alternative splicing in a highly context-sensitive and combinatorial manner, and it is therefore difficult to predict their actions on the basis of genomic sequence. However, recent progress in understanding alternative splicing, particularly using global approaches, has revealed new sets of rules for deciphering these patterns. This Review outlines the function of RBPs at different levels and describes the emerging rules of alternative splicing.

Understanding disease pathogenesis and developing potential therapies require accurate and genetically tractable models. This Review discusses how human stem cells — including embryonic stem cells, adult stem cells and induced pluripotent stem cells — can provide informative models of diverse human diseases. Such methods can also be extended through gene editing, co-culture or infectious agent approaches.

DNA and histone modifications undergo extensive reprogramming to reset the epigenomic state between generations. This Review discusses the mechanisms and consequences of epigenetic reprogramming during plant sexual reproduction. Despite various similarities to the equivalent process in mammals, a key difference is the seemingly incomplete reprogramming of plant epigenomes, which has implications for evolution and transgenerational epigenetic inheritance.

This Review introduces the biological barriers to gene deliveryin vivoand discusses recent advances in material sciences, nanotechnology and nucleic acid chemistry that have yielded promising non-viral systems for the delivery of DNA, mRNA, small interfering RNAs and microRNAs, some of which are currently undergoing testing in clinical trials.

This Review discusses the main experimental approaches for microRNA (miRNA) target identification, as well as the modulators and the consequences of miRNA–target interactions. It also highlights the role of computational modelling in furthering the conceptual understanding of miRNA functions in gene regulatory networks.

The field of cancer genomics has been transformed by recent advances in sequencing and the development of new computational methods. This Review outlines the available cancer genomics software and describes recent insights gained from the application of these tools.

Among rodent species, there is a wide diversity in lifespans and cancer susceptibilities, which makes comparative studies of rodents an attractive strategy for identifying molecular mechanisms that underlie ageing and cancer. This Review describes the various biological insights provided by comparative rodent genomics, including those from whole-genome sequencing of long-lived and highly cancer-resistant species. Such progress has potential implications for understanding and modulating human disease.

Mutagenic processes leave characteristic imprints on the cancer genome that can help to identify the underlying DNA damaging components as well as DNA repair and replicative pathways that are active or disrupted. This Review discusses these mutational signatures according to different classes of mutations and summarizes how different components contribute mechanistically to produce each signature type.

Imprinted genes influence a wide range of biological processes, the effects of which extend from prenatal stages to adulthood. This Review discusses the role of imprinted genes, with a focus on postnatal and adult phenotypes, and their contribution to common diseases such as intrauterine growth restriction, obesity, psychiatric disorders and cancer.

The role of telomeric factors as guardians of chromosome ends from threats to genome integrity (such as degradation and inappropriate DNA damage response activation) has long been appreciated. This Review discusses the extratelomeric activity of these factors and how they can regulate the transcription of genes involved in metabolism, immunity and differentiation.

Gene-regulatory DNA elements control complex spatiotemporal patterns of gene expression, and alterations to these sequences are commonly associated with inter-individual phenotypic variation and human disease. This Review discusses our latest understanding of how different layers of information in these sequences control the binding of regulators and influence gene expression outcomes.

A central topic in biology concerns how genotypes determine phenotypes and functions of organisms that affect their evolutionary fitness. This Review discusses recent advances in the development of empirical fitness landscapes and their contribution to theoretical analyses of the predictability of evolution.

Recent technological advances have enabled the probing of RNA structure across the transcriptomes of various speciesin vitro and in vivo. This Review discusses our latest understanding of how RNA structure influences various steps of gene expression, including translation, mRNA localization and microRNA-mediated gene regulation.

RNA-directed DNA methylation (RdDM) is a major mechanism of transcriptional gene silencing in plants that is mediated through small interfering RNAs (siRNAs) and plant-specific RNA polymerases. This Review summarizes our latest understanding of RdDM, including its genomic targets, molecular mechanisms (such as emerging non-canonical pathways) and diverse biological roles.

Data sharing in genetics is essential to ensure research progress. However, concerns about the impact on privacy of data originators have been raised. This Review summarizes privacy breaching strategies and potential mitigation methods for privacy-preserving dissemination of sensitive data, and highlights different cases that are relevant to genetic applications.