Progress

Single-cell sequencing of uncultivated microbial species is rapidly providing a wealth of new information. Here, the authors provide an update on recent progress in capturing novel genomes, large-scale environmental studies and research relating to human health, as well as recent methodological improvements and remaining technical challenges.

Although gene delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective for numerous clinical gene therapy applications, many challenges remain. Recent advances in AAV vector development through rational design and directed evolution, as well as in the design of novel genetic cargoes, promise to extend clinical successes of AAV-mediated gene therapy.

High-throughput technologies are starting to be applied to assess the complex molecular changes that occur with increasing age in humans. This Progress article introduces the emerging findings for transcriptomics, epigenomics, metabolomics and other 'omics' approaches.

Several promising genetic approaches are being investigated for the treatment of Duchenne muscular dystrophy, including traditional gene therapy, stop codon read-through, exon skipping and increased expression of a compensatory gene. The lessons learned should also be valuable for other disorders.

The authors review new tools for studying the evolution of antibiotic resistance, including approaches to evolve resistance in the laboratory and analysis of clinical samples. Insights into pathways of evolution and the basis of resistance could inform future management of infections.

The authors discuss recent advances — mainly gained through genomic methods such as RNA sequencing — in our understanding of the causes and consequences of differences in gene expression between females and males. Areas of progress include our understanding of the roles of sexual antagonism and dosage compensation.

Recent large-scale quantitative assessment of the proteome and transcriptome has revealed that transcript abundances only partially predict protein abundances. This article discusses ways in which such studies are informing our knowledge of protein expression regulation.

Protein–RNA interactions are central to the regulation of gene expression. Emerging technologies for pinpointing these interactions, both in large complexes and between individual proteins and RNA, are discussed. Methods for analysing these data are also considered.

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.

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 increased genetic diversity in populations with recent ancestry from more than one continent may help in the identification of genetic variants underlying disease risk. This Progress article discusses recent developments in methods to study complex traits in these admixed populations, including combining SNP and admixture association signals.

RNA polymerase III is highly specialized for the production of short non-coding RNAs. This Progress article discusses the implications of recent ChIP–seq studies that reveal unprecedented genome-wide detail and unanticipated complexities of RNA polymerase III transcription, including tissue-specific transcriptional regulation and intriguing parallels to RNA polymerase II.

Planar cell polarity (PCP), the polarization of a field of cells within the plane of a cell sheet, is required for various developmental processes. This Progress article discusses recent developments in PCP — from the signals that orient polarity inDrosophila, to new insights into vertebrate collective cell movements and cilial functions.

Genetic and genomic approaches — including high-throughput sequence analysis and transcriptomics experiments — are revealing a clearer picture of the pathophysiological steps underlying the different forms of heart failure (genetic and acquired) and the genomic responses to cardiac overload.

The authors describe how the evolving designs of eQTL studies, facilitated by advances in genotyping and gene-expression-based technologies, are increasingly able to investigate the role of regulatory variation in different biological contexts.

This Progress article describes how the application of powerful technologies — based on bioinformatics, next-generation sequencing and biochemistry — has allowed us to map and characterize global adenosine-to-inosine RNA editing.

Recent technological advances are allowing genome-wide analysis of the function of individual alleles in terms of expression levels, histone modifications and DNA methylation. Approaches that discriminate between alleles offer great potential for improving our understanding ofcis-regulatory variation.

This article compares the different approaches that have been developed for detecting confounding due to population stratification, family structure and cryptic relatedness, with an emphasis on the potential of mixed models for addressing these problems simultaneously.

The use of genome-wide association (GWA) approaches to identify variants that affect drug response or reaction is increasing rapidly, with at least 12 studies appearing in 2009 alone. This article reviews these pharmacogenomics GWA studies, and the prospects for this field.

Recently, several new speciation genes have been identified that have contributed to our understanding of the molecular details of the evolution of hybrid dysfunction. This Progress article describes examples of these speciation genes in a range of species and provides insights into the mechanisms that underlie speciation.