Review Articles in 2008

There are now 14 DNA polymerases in the human genome. This article explores the function of these molecules in replicating DNA, their regulation and involvement in disease, and how specific properties of each polymerase might be targeted for therapeutic ends.

It is well known that prokaryotes regularly exchange genes by horizontal transfer, but there is increasing evidence that such processes also have an important role in eukaryotic evolution, although the extent of this differs widely between lineages.

In contrast to growth control, gene expression responses to stress involve distinctive regulatory mechanisms that are characterized by high levels of noise. These features allow organisms to respond quickly to unpredictable environmental changes, and recent studies suggest that they also promote the evolvability of gene regulation.

Studies in the chick, mouse, zebrafish and other vertebrate model systems are beginning to uncover the complexities of skeletal muscle development. Distinct sets of precursor cells and various different gene regulatory networks are responsible for the spatial and temporal heterogeneity of the process.

Psychiatric genetics has been fraught with controversy owing to the irreproducibility of many claimed risk factors. There is now some cause for optimism thanks to larger sample sizes and the incorporation of intermediate traits, rare mutations and environmental risk components into the analyses.

Progress in understanding the genetic basis of susceptibility to multiple sclerosis — a debilitating and genetically complex disease — is being obtained by a combination of advances in genome studies (through genome-wide association studies) and powerful systems-level approaches.

How are the complex and varied roles of retinoic acid orchestrated at multiple developmental stages? Recent studies have highlighted the importance of tightly regulating its distribution, of switching the activities of its nuclear receptors, and of interactions with other key developmental signalling molecules.

RNAi, a common gene knockdown technique, has been widely used in a variety of genetic screens. As part of our 'art and design of genetic screens' series, the authors discuss RNAi assay design and analytical approaches for large-scale screening experiments in cells and whole-animal experiments.

Rather than being a mark of irreversible gene silencing that localizes mainly to promoters and intergenic regions, epigenomics approaches are revealing DNA methylation as a surprisingly dynamic regulator of gene expression that might also have important roles within gene bodies.

Advances in genomics and gene mapping allow sets of candidate genes to be identified for use in monitoring adaptive responses to specific environmental stresses. Such toolkits will allow us to predict the ability of species to adapt to changing environments.

Linkage disequilibrium was once a concept used little outside population genetics. However, in the genomics era it has become fundamental to our understanding of the genetic variation that is behind complex traits and evolutionary change.

Making ethanol from cellulose-containing parts of plants is a promising route to abundant biofuel production. Using genetics to decrease the need for crop pretreatment and processing, and to increase yield, will be important in making bioethanol an affordable and plentiful fuel.

The combination of environmental change and a rapidly increasing human population is putting global food supplies in danger. Crop improvements that increase yields and enable plants to withstand abiotic stresses will provide an important route to tackling this urgent problem.

The Gene Ontology project has provided a powerful tool for interpreting the biological significance of both experimental and computational data. However, some appreciation of how the database works is essential to avoid misinterpretations.

Established during embryogenesis, vertebrate segmentation is most conspicuous at the level of the periodic arrangement of vertebrae in the spine. Since the identification of the segmentation clock, which is a travelling oscillator, the generation of segmental pattern in the presomitic mesoderm has been a particular focus of attention.

Newly specified hepatic and pancreatic progenitors, which originate from common endodermal domains, are able to reverse their course and develop into gut progenitors. Understanding what underlies such programming reversal and intrinsic regenerative capacities should illuminate the basis of cellular plasticity and facilitate targeted programming of stem cells.

Genome-wide association studies have led to an improved understanding of the genetic basis of common diseases. Following the first wave of such studies, this Review takes a critical look at progress so far and considers how future studies can be optimized.

The highly heterogeneous nature of autism has made this syndrome difficult to dissect genetically. Recent work has highlighted the importance ofde novoand inherited copy number variation as well as common genetic risk variants in defining potential biological mechanisms of disease.

Tight coordination of gene expression between the nucleus and genome-containing organelles (mitochondria and chloroplasts), and between organelles themselves, is essential to the survival of a eukaryotic cell. This article reviews our current understanding of the mechanisms behind this multidirectional signalling.

Comparative genomics is a promising approach for identifying functional components of genomes. However, many challenges remain, relating to the quality and quantity of sequence data, how sequences are aligned and, ultimately, how functional elements are recognized.