Review Articles in 2009

There is an increasing demand for next-generation sequencing technologies that rapidly deliver high volumes of accurate genome information at a low cost. This Review provides a guide to the features of the different platforms, and describes the recent advances in this fast-moving area.

How did the intricate adaptive immune system of mammals arise? New clues have recently emerged from studies of the immune systems of non-mammalian vertebrates. Here, these findings are integrated with current knowledge of macroevolutionary events and selective pressures.

The recent increase in available human population genetic data is revealing signatures of selection at immunity-related genes. This Review discusses how studies of genome evolution are contributing to our understanding of how pathogens have shaped the human genome and immune response.

Vertebrate limb development is a classic developmental model. In this Review the authors discuss how existing models of this process might be integrated and might form a framework for a systems approach to understanding organogenesis.

Recent transcriptomic studies have revealed that diverse small RNAs are transcribed from the regions around gene promoters. This Review considers questions prompted by the discovery of these transcripts; for example, what is their origin and are they functional?

The article highlights how the process of engineering biological systems has contributed to our understanding of how endogenous systems are put together and function — from a quantitative description of gene expression and signal transduction to controlling spatial organization and cell–cell interactions.

In addition to the core hypoxic transcriptional pathway, several mechanisms exist to allow transcriptional diversity and specificity. This Review highlights recent advances in our understanding of the mechanisms and factors that contribute to the tailoring of the appropriate hypoxic transcriptional response.

Increasing evidence suggests that animal sexual dimorphisms are produced by the combined action of transcriptional effectors of sex-determination pathways and other transcription factors oncis-regulatory elements. These findings have led to new insights into how differences between sexes evolve.

The genetic basis of inbreeding depression and of the related phenomenon, heterosis, has been a puzzle for many decades. Based on recent studies in many species, the authors argue that both phenomena are predominantly caused by the presence of recessive deleterious mutations in populations.

Although humans are genetically similar, marked geographic patterns exist for many heritable traits. The investigation of spatial patterns at loci under selection can address fundamental questions about geographically variable traits in humans and give new insights into human adaptation.

Dozens of new genes with causal roles in motor neuron diseases have recently been identified, which has moved the field beyond the previous focus on superoxide dismutase 1 mutations. These findings implicate several additional pathways in motor neuron diseases, including RNA processing, axonal transport and mitochondrial function.

Inherited mutations in the nucleotide excision DNA repair pathway cause an unusually diverse range of clinical abnormalities; even mutations in the same gene can cause markedly different phenotypes. Recent structural, genetic and clinical studies are helping to explain this variability.

Alterations in microRNA function contribute to the pathogenesis of many cancers. Recent studies have shown that such changes can result not only from mutations but also from epigenetic silencing or the dysregulation of transcription factors that target specific microRNAs.

The ability of mobile genetic elements to move and multiply means that they have a unique influence on genome sequences. Developments in comparative genomics have shown how important non-long terminal repeat retrotransposons have been in shaping the human genome.

Bayesian analyses are increasingly being used in genetics, particularly in the context of genome-wide association studies. This article provides a guide to using Bayesian analyses for assessing single-SNP associations and highlights the advantages of these methods compared with standard frequentist analyses.

Disparate fields have provided advances in our understanding of the impact of protein-synthesis errors on cellular fitness, disease and evolution. Although organisms show adaptations to minimize the deleterious effects of such errors, erroneous protein synthesis can also be exploited for the organism's benefit.

Coupling next-generation sequencing to chromatin immunoprecipitation has transformed the resolution and genomic coverage of DNA-binding protein and nucleosome mapping studies. However, successful ChIP–seq requires careful consideration of the experimental and analytical approaches; this Review evaluates the current strategies and challenges.

F_STdescribes the processes that lead to genetic differentiation among and within populations and is widely used in population and evolutionary genetics. This article describes the meaning ofF_STand how it should be estimated and interpreted.

Advances in mass spectrometry-based proteomics have led to an increasing use of proteomics data for the analysis of mutant phenotypes. Integrating this proteomic information with genomics and phenomics data into networks represents a promising route for modelling how phenotypes emerge.

Genome-wide maps of transcription factor binding are prompting the re-examination of traditional concepts of transcriptional regulation. Current challenges centre on understanding which binding events are functional, how transcription factors cooperate and how to integrate the genomic and chromatin context into models of gene regulation.