Review Articles in 2010

The detailed characterization of the genomes and transcriptomes of diverse species has enabled advances in our understanding of how alternative splicing and alternatively spliced genes have evolved. Evolutionary studies are also contributing insights into how exons are defined and how splicing is regulated.

The transmission of epigenetic information through cell divisions is crucial for maintaining cellular identity. Inheritance seems to involve multiple, cooperative mechanisms, including non-coding RNAs and feedback loops among chromatin modifications and modifiers.

A hallmark of cancer cells is their ability to prevent telomere shortening. Sometimes this is achieved without telomerase by a process known as alternative lengthening of telomeres (ALT). Recent progress has been made in understanding how ALT occurs.

Retinal degeneration due to photoreceptor cell death is a major cause of visual impairment in adults. Over one hundred genes have been implicated, so how does this genetic heterogeneity converge on a shared phenotype? The emerging insights have implications for therapy.

Despite the yield of genome-wide association studies, the variants identified explain little of the heritability of most complex diseases. This unexplained heritability could be partly due to gene–environment (G×E) interactions. This Review provides a guide to designs and analytical approaches for studying specific G×E interactions.

This article describes the important advances in our understanding of recombination in humans and mice, from the properties and activity of individual hot spots to the control of the recombination landscape along chromosomes and between the sexes.

'Omics' technologies are making it possible to simultaneously measure a substantial portion of the molecular components of a cell. This article describes the challenges that need to be confronted to develop and refine genome-scale reconstructions of signalling networks.

Expansions of repeat sequences cause some of the most common inherited neurological diseases. But how do repeats in DNA lead to pathogenesis? This Review considers the diverse mechanisms that are now emerging, including aberrant splicing, post-translational modification and autophagy.

Recent studies have increased our understanding of how DNA methylation is accurately targeted, maintained and modified. Mechanistic similarities between plants and animals have emerged, including key roles for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases.

The CRISPR system uses small RNAs to provide bacteria and archaea with an adaptive defence mechanism against foreign nucleic acids. Recent studies have increased the understanding of mechanisms of CRISPR interference, its roles in microbial physiology and evolution and its potential applications.

Mapping DNA methylation is vital for understanding the importance of this epigenetic mark in health and disease. Recent years have seen rapid progress in the development of techniques for genome-scale methylation profiling; this Review introduces and evaluates the available methods.

Theoretical, anthropological and genetic studies suggest that human evolution has been shaped by gene–culture interactions. This Review collates data from these diverse fields, and highlights the potential for cross-disciplinary exchange to provide novel insights into how culture has shaped the human genome.

The classical model of gene activation by a unidirectional switch from co-repressor binding to co-activator binding is changing. This Review discusses emerging themes in the interplay among co-repressor complexes, enzymatic functions and chromatin modifications in controlling gene repression.

Genome-wide association studies are not widespread in Africa, partly because of the challenges of dealing with population structure and high genomic diversity. New approaches in statistical imputation and whole-genome sequencing are now set to exploit these features for fine mapping causal variants.

Meiosis is a necessary part of gamete formation and sexual reproduction. It has been examined extensively in yeast but, although key components are evolutionarily conserved, studies in mammals are revealing important differences, and such work will enable progress towards the treatment of human infertility.

Despite their importance, little is known about how gene duplications are fixed and maintained in genomes. This comprehensive Review of theoretical models of gene-duplication evolution and the data that can distinguish between them provides a foundation for answering these crucial questions.

mRNA repertoires can be diversified by many mechanisms, including alternative splicing and alternative polyadenylation. Technological advances are now allowing genome–wide insights into the extent of RNA processing, the actions of RNA–binding proteins and how regulation at the RNA level helps to control biological systems.

Protein kinases are one of the largest gene families in humans. Through a comprehensive survey of kinase mutations the authors highlight the structure–function relationships that control the activities of these proteins and their contribution to a varied set of human diseases.