Reviews & Analysis

Telomeres have long been implicated in processes of cellular ageing. This Review discusses how a diverse range of human diseases are now known to be caused by mutations that result in defective telomere maintenance and shortened telomeres. It describes the unique inheritance patterns of telomere defects and how telomere biology sheds light into several disease mechanisms.

Recent measurements of the human mutation rate using next-generation sequencing have revealed a value of approximately half of that previously derived from fossil calibration. Here, the authors discuss the implications of this revised mutation rate in relation to our understanding of human evolution.

Epigenetic alterations, notably in DNA hypermethylation, are emerging as consistent biomarkers for disease. Here, with a focus on cancer, the authors discuss the identification of these biomarkers and their use in disease diagnosis, prognosis and response to therapy.

There are many different methods and tools available for the analysis of next-generation sequencing data. The challenges towards applying these analysis tools in a transparent and reproducible manner are presented, and a way forward for analysing these data in life sciences research is discussed.

Seasonal cues, such as day length and temperature, influence the developmental programme of plants. Recent genetic research has shed light on the pathways that lead to seasonal responses in flowering. The regulation of these pathways inArabidopsis thaliana, their conservation throughout other species and comparative analysis of annual and perennial plants are considered here.

How do transcription factors lead to defined developmental programs? The ways in which transcription factors act at enhancer elements and how enhancer activity is established during development are discussed in this Review, which brings together genetic and genomic evidence.

The Notch signalling network is highly conserved in Metazoa and is crucial for various cell-fate decisions. Focusing onDrosophila melanogaster, this Review summarizes and integrates various recent studies, including large-scale genetic and proteomic screens that have provided a new appreciation of the complexity of Notch signalling.

This Review sets out the emerging potential of next-generation sequencing in the context of clinical microbiology. Using bacterial genome sequencing as an example, the authors discuss the options and challenges for species identification, testing for virulence and drug resistance and monitoring outbreaks.

Twin studies have long been used for dissecting the relative contributions of genetics and other factors to various phenotypes. This Review discusses how these traditional studies are now being integrated with modern omics technologies to provide a wide range of biological insights.

Biological processes are inherently dynamic and therefore capturing data about gene expression at multiple time points can provide valuable insights into biological systems. This Review discusses experimental and analytical considerations for studies of gene expression dynamics, and the possibilities for integration with other data sets.

Recent family-based genomic studies are providing a window into the incidence of new mutations in human genomes. This Review discusses our understanding of various types ofde novomutation, including the determinants and consequences of their occurrence rates, and the challenges both for their detection and for linking them to disease pathogenesis.

Genome-wide association studies have recently furthered the understanding of the genetics of osteoporosis. The authors here present the major findings from these studies, the pathways that have been highlighted in the progress of the disease and strategies for future diagnosis and therapy development.

This Review considers recent findings — from genome-wide association studies, structural variant studies and exome sequencing — about the genetics of nine psychiatric disorders. The authors evaluate the implications of our current picture of the genetic architectures of these conditions for future research strategies.

Is ageing in our genes? In this Viewpoint, six experts present their views on the extent to which ageing is genetic and discuss future strategies for research into ageing and longevity.

Various studies (such as genetic linkage or 'omics'-based approaches) generate large lists of candidate genes, of which only a minority may be biologically relevant for a phenotype or disease of interest. This Review discusses computational tools for gene prioritization, emphasizing key considerations for how biologists can incorporate these tools into their research, and it includes hands-on tutorials.

Several approaches exist for identifyingcis-regulatory modules, which are the regions in the genome that regulate gene expression. The authors describe these strategies and assess how they perform (either alone or in combination) and how they can be improved.

Gene expression levels can now be compared among species at greater resolution. Focusing on work in primates, the authors discuss the evolution of gene expression, ways of exploring mechanisms that underlie expression changes and complementary work in model organisms on the functional effects of expression changes.

Aneuploidy is the leading cause of congenital defects in humans and nearly always results from errors occurring in oocytes. Here, the authors review the evidence pointing towards the mechanistic basis of meiotic defects leading to aneuploidy and discuss the potential role of environmental factors.

This Review introduces the core concepts of using biological building blocks to carry out computation. The author explains models of computation, experimental examples — sometimes inspired by the complex computation that is part of natural biological systems — and potential applications.

Our understanding of the function of DNA methylation is developing now that we are able to look beyond CpG-rich regions at transcriptional start sites. The emerging picture is of a complex relationship between DNA methylation and transcription and of possible additional roles of methylation.