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  • This Opinion article argues that capturing phase information in human genomics studies is crucial for important aims such as understanding how genotype contributes to phenotypes. existing approaches for phasing will need to be improved in order to meet this goal.

    • Ryan Tewhey
    • Vikas Bansal
    • Nicholas J. Schork
  • Chronic stress is increasingly implicated as a contributing factor in common diseases, including cancer, cardiovascular disease and diabetes. This Opinion article brings together evidence supporting the idea that stress can induce epigenetic changes that alter cell behaviour and thereby lead to disease.

    • Sarah E. Johnstone
    • Stephen B. Baylin
  • Identity by descent (IBD) — the probability that two alleles descended from a common ancestor — is used in fundamental applications such as gene mapping and estimating heritability. The authors offer a solution to the confusion between IBD and identity by state (IBS) that is caused by the common practice of using dense SNPs to estimate IBD.

    • Joseph E. Powell
    • Peter M. Visscher
    • Michael E. Goddard
  • Batch effects can lead to incorrect biological conclusions but are not widely considered. The authors show that batch effects are relevant to a range of high-throughput 'omics' data sets and are crucial to address. They also explain how batch effects can be mitigated.

    • Jeffrey T. Leek
    • Robert B. Scharpf
    • Rafael A. Irizarry
  • Recent evidence indicates that gene bookmarking — the combination of mitotic retention of transcription factors at promoters, histone modifications and DNA methylation — is a novel epigenetic mechanism that sustains cellular identity after mitosis. This Opinion article discusses the importance of bookmarking in biological control and disease.

    • Sayyed K. Zaidi
    • Daniel W. Young
    • Gary S. Stein
  • Increasing evidence suggests functional similarities between promoters and insulators. The authors propose that these findings unify existing models of insulator function, provide new directions for understanding how insulators work and suggest that insulators have evolved from promoters.

    • Jesse R. Raab
    • Rohinton T. Kamakaka
  • Results from genome-wide association studies support the view that qualitative disorders can be interpreted as being the extremes of quantitative dimensions. Research on quantitative traits could have far-reaching implications for the diagnosis, treatment and prevention of the problematic extremes of these traits.

    • Robert Plomin
    • Claire M. A. Haworth
    • Oliver S. P. Davis
  • DNA methylation is a somatically heritable epigenetic mark that must be faithfully maintained through cell division. This re-examination of the evidence relating to how DNA methylation is maintained leads the authors to propose a revised model for this important biological process.

    • Peter A. Jones
    • Gangning Liang
  • The authors argue that ancient whole-genome duplications might be linked to major ecological upheavals and extinction. When established, polyploidy might lead to increased vigour, species diversity and phenotypic novelties, and could therefore contribute to the evolutionary success of a lineage.

    • Yves Van de Peer
    • Steven Maere
    • Axel Meyer
  • Genome-wide association studies have identified many cancer susceptibility alleles, but much heritable risk for this complex heterogeneous disease remains unexplained. Mouse model studies are yielding evidence that integrated analysis of genetic and genomic data might prove a fruitful strategy to meet this challenge.

    • David Quigley
    • Allan Balmain
  • The mitochondrion and plastid are derived from bacterial endosymbionts that were transformed over time into organelles. Here the authors posit an explanation for how the eukaryotic hosts controlled the evolution of these organelles through the establishment of protein-sorting systems.

    • Jeferson Gross
    • Debashish Bhattacharya
  • Comparisons between species are essential for evo–devo research, but are there benefits in focusing on organisms in which sophisticated analytical tools are available? The author of this Perspective discusses this question, and also proposes further integration of evo–devo with other areas of evolutionary research.

    • Ralf J. Sommer
  • The success of genome wide association (GWA) studies raises the hope that disease-associated markers will be useful in predicting disease risk. However, the metrics used to report effect sizes in GWA studies are not useful for determining the accuracy of genetic profiles.

    • Peter Kraft
    • Sholom Wacholder
    • Stephen Chanock
  • In mammals, errors in synapsis are associated with impaired meiosis, which is male-biased and is associated with reduced fertility. The recent discovery that asynapsed chromosome segments are transcriptionally silenced has provided fresh insight into the connection between asynapsis and meiotic impairment.

    • Paul S. Burgoyne
    • Shantha K. Mahadevaiah
    • James M. A. Turner
  • Gene regulatory networks (GRNs) are hierarchically connected sub-circuits composed of genes and thecis-regulatory sequences on which they act. The authors propose that evolutionary alterations in morphology depend on the position in the GRN hierarchy at which regulatory change occurs.

    • Douglas H. Erwin
    • Eric H. Davidson
  • Several models exist to explain the architecture of complex disease traits — each with its limitations. In this Perspective article it is proposed instead that human traits are canalized, and that their perturbation by genetic or environmental differences exposes genetic variation, leading to increased disease risk.

    • Greg Gibson
  • Selectionists and neutralists invoke different theories to explain the emergence of evolutionary innovation. Our recent understanding of molecular phenotypes makes it possible to reconcile these two views by proposing that neutral variants prepare the ground for adaptive mutations to occur.

    • Andreas Wagner
  • Current approaches for dissecting complex traits largely ignore epiallelic variation. To overcome this limitation the authors propose a quantitative approach to identifying the dynamic interplay between DNA sequence, chromatin and environmental contributions to the phenotype, across generations and developmental time points.

    • Frank Johannes
    • Vincent Colot
    • Ritsert C. Jansen