Reviews & Analysis

The authors use the well-studied example of Decapentaplegic (DPP) to illustrate key aspects of the morphogen concept. They discuss the well-established role of DPP in pattern formation as well as models for its less understood role in growth regulation.

Type 2 diabetes has been described as a geneticist's nightmare. Following a recent spate of impressive results from genome-wide association studies, the author looks at how they have advanced our understanding of this disease and informed future use of this approach towards identifying genetic variants in general.

Mutations that disrupt the splicing code, or the machinery required for splicing and its regulation, have roles in a range of diseases. It is also becoming apparent that genetic variation that affects splicing efficiency significantly contributes to disease severity and susceptibility.

Most of the differences between males and females are due to differences in expression levels of certain genes. These genes have several interesting properties, such as rapid sequence evolution and an odd distribution across the genome.

Mutations can be deleterious, neutral or, in rare cases, advantageous. The relative frequencies of these types across a genome constitutes the distribution of fitness effects. The properties of this distribution have important consequences in both medical and evolutionary genetics.

Relatively little is known about what underlies mutation rate variation at an empirical level, particularly in multicellular eukaryotes. The authors review theoretical and empirical results to provide a framework for future studies of why and how mutation rate evolves in multicellular species.

Copy number variation constitutes a major source of inter-individual genetic variation that could explain variable disease penetrance and variation in the phenotypic expression of aneuploidies, and could be an important factor in the aetiology of complex traits. Therefore, systematic exploration of both single nucleotide and copy number variation will be key to identifying the genomic contributors to polygenic traits and diseases.

Numerous inherited diseases, with a surprisingly diverse range of phenotypes, are being found to arise from mutations that affect translation. Studies of these diseases are beginning to provide new insights into the functions of the protein synthesis machinery and its regulators.

Spatial and temporal patterns of metazoan DNA replication are emerging as being dynamically regulated by tissue-specific and developmental cues, and by epigenetic modifications. These features might allow coordination with transcription and chromatin assembly, and enable changes in gene expression patterns.

Expression signatures have tremendous power to identify new cancer subtypes and to predict clinical outcomes. Using these signatures as surrogate phenotypes researchers can link diverse experimental systems to dissect the complexity of tumorigenesisin vivo.

A key challenge in gene therapy is vector targeting to specific cells, while avoiding effects on other tissues. Several strategies have been developed recently to enable targeting of the main viral vectors, moving them a step closer to clinical use.

RNA-binding proteins orchestrate the post-transcriptional co-regulation of subsets of mRNAs that encode functionally related proteins, thereby contributing to the coordination of gene expression in eukaryotes. Understanding the dynamics of such ribonucleoprotein structures might provide insights into some complex diseases and the regulation of gene expression during development.

REST can act as a hub for the recruitment of multiple chromatin-modifying enzymes. Research into its function and that of its corepressors has provided new insight into how chromatin-modifying proteins cooperate to regulate gene expression, and how alterations in this function cause disease.

Malaria is a major cause of mortality in the developing world. Genetics and genomics are now greatly assisting our understanding of this disease, through linkage and association studies of the malaria parasite,Plasmodium.

The prevailing view is that planar cell polarity is the outcome of one genetic pathway. On the basis of their observations in genetically mosaic adult flies, the authors challenge this assumption and discuss potentially far-reaching implications of their model.

The popularity ofCaenorhabditis elegans as a model organism is paralleled by the range of resources that are available to worm researchers. This Review provides a guide to existing C. elegansresources, and highlights areas for future development.

The positioning of individual genes within the nucleus affects their expression levels. The inner face of the nuclear envelope is key to this method of regulating expression, with active genes preferentially locating to nuclear pores in a manner that might be heritable.

Powerful tools for carrying out large-scale genetic-interaction screens have made budding yeast a leading model system for understanding gene networks. Studies in yeast also provide a basis for extending our understanding to networks in more complex eukaryotes.

The transcription regulation networks that control gene expression consist of a series of recurring logical wiring patterns — network motifs. By understanding the properties of these simple motifs we can start to understand the complexity of whole networks.

Although they do not get cancer naturally, genetically manipulatedDrosophila melanogasterare a useful model for studying tumours. Recent results highlight the importance of asymmetric cell division and proper spindle alignment for preventing stem cells from giving rise to tumours.