Reviews & Analysis

Next-generation sequencing has allowed an unprecedented genomic characterization of diverse cancer types. This Review describes our latest understanding of cancer genomes, including methods to interpret the mutation data, and the emerging biological and clinical implications.

The identification of mutations that underlie rare diseases has dramatically accelerated in recent years thanks to next-generation sequencing. This Review discusses strategies for further identification studies, insights into disease mechanisms and the clinical implications of the rapid progress in this field of research.

Genes that have originated in recent evolution are present in only a subset of organisms and are often assumed to be dispensable or redundant. This Review discusses our latest understanding of how new genes in diverse species have actually evolved to have important functions in diverse developmental and physiological processes in various organisms.

This Review considers mechanisms by which information is transmitted over short and long distances during plant development and how different modes of signalling integrate with gene regulatory networks to allow plants to respond to their environment.

High-throughput technologies are starting to be applied to assess the complex molecular changes that occur with increasing age in humans. This Progress article introduces the emerging findings for transcriptomics, epigenomics, metabolomics and other 'omics' approaches.

Increasing evidence suggests that parent-of-origin effects, particularly genomic imprinting, contribute to complex traits. This Review discusses how such effects can be identified in order to expand our understanding of their roles in phenotypes such as human diseases and traits important for agriculture.

Technologies that are based on next-generation sequencing are increasingly being used to study individual cells. The authors discuss the application of this approach to single-cell genomics and transcriptomics, and explore the implications for both basic research and medicine.

In this article, the authors present a synthesis of the emerging field of evolutionary biochemistry. This field has profited from the development of experimental techniques that allow the study of the physical mechanisms and evolutionary processes that have constrained and shaped biological molecules.

Despite the impact of genome-wide association studies (GWASs) on disease genetics, there has been scepticism about their usefulness in clinical translation. This Review highlights pertinent examples in which clinical application has been achieved or is likely and considers the wider potential for translation.

Our understanding of transcription is being improved through single-molecule and genome-wide approaches. Quantitative models are also required to provide insights into the underlying mechanisms of transcription, and the authors discuss how experimental results and models can be brought together.

This Review discusses roles for microRNAs in adult animals — including in adult stem cells, metabolism and in cancer — and how functions in adults can be distinguished from developmental roles using a range of methods. Understanding adult-specific functions has implications for therapeutic manipulation of miRNAs.

The authors discuss strategies and challenges of population-based studies of epigenetic variation. Such studies should contribute to our understanding of the contribution of epigenetic factors to human disease, but need to be performed and interpreted with consideration of their limitations.

PIWI-interacting RNAs (piRNAs) have important roles in various species, particularly in silencing transposons in the germ line. This Review describes our latest understanding of various steps in this process, from the specification of piRNA-producing loci to piRNA processing and nuclear effector functions, including a role in transgenerational epigenetic inheritance.

Recent advances have allowed the genomic characterization of the extent and regulation of alternative polyadenylation. Here, the biological processes with which alternative polyadenylation has been associated, the mechanisms of its regulation and its involvement in disease are discussed.

The data from genome-wide association studies can be applied to genotype data to predict the phenotype of a complex trait. Here the authors discuss the potential pitfalls of such analyses and the inherent limitations of the method.

Next-generation sequencing is now poised for the discovery of genetic variants involved in common and rare diseases. Here, the authors present considerations for the workflow of these studies in order to identify true associations of disease and mutation.

Modern genomic studies are revealing widespread associations between single genetic variants and multiple distinct traits, including diseases. This Review discusses the biological underpinnings of such pleiotropy and the available bioinformatic tools for the detection and characterization of these effects, as well as the implications for understanding human disease.

Heterosis, also known as hybrid vigour, is an intriguing phenomenon that has particularly important implications for agriculture. The molecular basis of this vigour is poorly understood, but progress is being made through the use of genomic, transcriptomic and epigenomic approaches.

Argonaute proteins are vital components of small-RNA-guided modes of gene regulation. Recent studies have provided important details about classical modes of Argonaute function, such as their structure and loading with small RNAs, and have also revealed unexpected roles in other cellular functions.

The authors review current technologies for clinical genetic testing. Moves are being made towards whole-genome and whole-exome sequencing in the clinic, although other technologies will continue to be of value.