Review Articles in 2011

Genome sequencing is providing a wealth of information about where and when transposons can integrate into host genomes. This Review integrates findings from eukaryotes and bacteria about patterns of transposon activity, host defence mechanisms and the developmental timing of transposition.

The recent surge in sequencing output has uncovered a wealth of genetic variation, but interpretation of these data remains a challenge. This Review discusses computational and experimental methods for estimating the deleteriousness and functional significance of genetic variants to better identify those that are potentially causal for disease.

Next-generation sequencing has now been used to produce the first ancient hominin genome sequences and is also being used to sequence modern humans from many different populations. Together with SNP genotyping, these data are transforming views of human history.

The ways in which an RNA molecule folds to form structures can be crucial to its function, and so methods for studying RNA structures make an important contribution to understanding transcriptomes. Experimental approaches in this field are being advanced by coupling them to high-throughput sequencing.

This Review describes the successful efforts of modelling approaches that combine evolutionary theory, systems biology and molecular data to interpret past evolution and, crucially, to predict evolutionary processes at the molecular and network levels.

Mammalian X-chromosome inactivation is a paradigm for understanding gene silencing by heterochromatin formation. This Review discusses recent progress and outstanding questions surrounding the initiation and maintenance of X-chromosome inactivation and its reactivation during both normal development and artificial reprogramming.

Genome-scale methods are providing increasingly detailed views of nucleosome organization and chromatin structure. This is enhancing our understanding of how DNA-based reactions occur in the context of chromatin and how they are influenced by genome accessibility.

Technological advances now allow large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation. Such epigenome-wide association studies present novel opportunities, but, as discussed here, they also create new challenges that are not encountered in genome-wide association studies.

Increasing evidence indicates that non-genetic information, as well as DNA sequence, is transmitted across generations to influence evolution. The authors review the evidence for different modes of non-genetic inheritance and discuss how they can be accounted for in evolutionary studies.

Cancer-genome sequencing is producing vast amounts of information on genetic alterations in tumours, but how can researchers uncover those changes that influence tumorigenesis? This Review describes how large-scale functional-genomics approaches using an increasing range of sophisticated tools offer a way forward.

The authors describe the best practices for a growing number of methods that use next-generation sequencing to rapidly discover and assess genetic markers across any genome, with applications from population genomics and quantitative trait locus mapping to marker-assisted selection.

Linkage studies have identified the genetic basis of several Mendelian disorders, but in recent years this method has been superseded by association mapping. The unique advantages of linkage studies support the combined use of linkage and association designs for identifying new genetic variants related to human traits.

Recent studies have greatly increased our understanding of the molecular actors that regulate X-chromosome inactivation in female mammals. A complex interplay ofcis- and trans-regulatory mechanisms ensures the differential activities of the two X chromosomes during female development.

Increasing efforts are being made to integrate electronic health records into disease genetics and genomics studies and to use the biological 'by-products' of health-care for research. Such efforts promise to decrease the cost of genomics studies and increase their clinical relevance.

An overview of the steps required in converting next-generation sequencing (NGS) data into accurate called SNPs and genotypes, a process that is crucial for the many downstream analyses of NGS data.

Circadian clocks are archetypal complex biological systems and so clock research has been at the forefront of developing and exploiting systems biology research approaches. This work has uncovered systems-level properties, such as robustness and periodicity, and provides lessons for other research fields.

The Hedgehog proteins have fundamental roles in the development of many metazoans, but comparative analyses are revealing intriguing differences, as well as similarities in the Hedgehog pathway among species. Such studies are also improving our understanding of Hedgehog regulation and how it contributes to patterning.

RNA interference can elicit specific gene silencing and so holds great potential for treating infectious or genetic diseases. Several small-RNA-based therapies have now reached clinical trials, but further work is still needed to improve delivery and efficacy.

Recent clinical and preclinical studies have described exciting results using recombinant adeno-associated virus (AAV) vectors for therapeutic gene transfer in genetic disease. This Review explores the potential for using this form of therapy in the context of different tissues and diseases.

This Review describes the state-of-the-art accomplishments that have been made with gene-based therapies and the major barriers that need to be overcome before these tools are more widely implemented by the medical community.