Reviews & Analysis

The increased availability of reference genomes and the ability to obtain resequencing data in larger quantities are changing the capabilities of crop comparative genomics. Insights into the genetic basis of domestication and agriculturally important traits are emerging, and improved genomic tools have implications for crop breeders and evolutionary biologists.

Studies of the composition, dynamics and function of the human microbiome have taken off in the past two years thanks to the development of new sequencing technologies and advanced algorithms. This article provides a guide to the experimental and analytical best practices in this flourishing field.

This article describes the promising technologies for generating humanized mouse models — that is, mouse strains containing large sections of human coding and non-coding sequences — for the purposes of improving our understanding of basic genome function and disease and discovering effective therapies.

Changes incis-regulatory sequences, especially enhancers, make a substantial contribution to phenotypic diversity among and within species. Recent studies have begun to uncover the mechanisms underlying cis-regulatory divergence, such as the types of mutations that occur and their influence on transcription factor binding.

Synthetic biological devices can be engineered to achieve high levels of precision and specificity, which makes them ideally suited for use in clinical settings. Devices are being developed to meet a range of biomedical needs, including specific cancer therapies and metabolic control.

Repeat sequences in DNA remain one of the most challenging aspects of next-generation sequencing data analysis and interpretation. This Review explains the problems and current strategies for handling repeats; ignoring repeats risks missing important biological information.

Drawing on evidence from diverse species, the authors argue that aspects of gene anatomy and genome architecture have evolved to prevent or mitigate gene expression errors. These aspects range from codon usage to the arrangement of genes in the genome.

Our increasing understanding of microRNA biology, combined with sequence information from diverse animal genomes, has shed light on how microRNAs and their targets evolve and how the evolution of microRNA-containing regulatory networks has contributed to organismal complexity.

The role of non-coding RNAs (ncRNAs) in disease is best understood for microRNAs in cancer. However, there is increasing interest in the disease-related roles of other ncRNAs — including piRNAs, snoRNAs, T-UCRs and lncRNAs — and in using this knowledge for therapy.

The recent discovery of enzymes that convert 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) in mammalian genomes has led to a surge of interesting possible functions for 5hmC, from the regulation of DNA methylation to the biology of pluripotency, differentiation and brain function.

The authors review our understanding of how common genetic variation contributes to behavioural diversity, explaining how these variants modulate an organism's interaction with the environment and defining gene classes — such as those affecting sensory or neuromodulatory pathways — that are preferentially associated with behavioural variation.

Organisms are exposed to various stresses, and responding rapidly and appropriately to these changes is crucial for survival. This Review describes how gene expression is regulated at many levels in response to stresses, including through signalling to chromatin or affecting transcriptional machinery.

Systems biology is intrinsically reliant on software tools and data resources. Through looking at each stage in a systems biology workflow, this Review presents the available options and key challenges, and sets out the concept of an integrated software platform.

Various genetic and functional studies have enhanced the understanding of type 1 diabetes susceptibility genes, including their roles in the underlying immune dysfunction. This Review summarizes the current understanding of type 1 diabetes genetics from the identification of novel susceptibility loci to functional characterization of new and established risk loci.

Although many studies claim to have detected an adaptive allele, this label is not always applied rigorously. The authors argue that obtaining direct evidence that specific alleles are adaptive requires approaches which functionally connect genotype, phenotype and fitness.

Large genomic data sets are revealing that mutation rates vary across genomes at many different scales, from the effects caused by neighbouring nucleotides to patterns that affect whole chromosomes. These varying mutation rates have implications for inherited and somatic disease.

The nematode wormCaenorhabditis eleganshas long been a key model organism, not least owing to its powerful genetic toolkit. Recent technological advances — for example, in manipulating gene expression and physiology — further increase the power of the worm as a model.

Exome sequencing is a powerful approach for accelerating the discovery of the genes underlying Mendelian disorders and, increasingly, of genes underlying complex traits. This Review describes the experimental and analytical options for applying exome sequencing and the key challenges in using this approach.

Meta-analyses that use data from several genome-wide association studies are revealing more disease-associated genetic variants, but how can the privacy of study participants be protected when data are shared? This article considers ways to evaluate the risk of loss of privacy.

Recent transcriptomics studies have revealed extensive mRNA diversity generated by alternative splicing. An emerging theme is the existence of regulatory networks through which splicing promotes dynamic remodelling of the transcriptome to promote physiological changes, involving robust and coordinated alternative splicing transitions.