Opinion in 2009

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.

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.

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.

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.

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.

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.

Stable, non-genetically variant cells can arise in clonal populations owing to gene expression noise and the multi-stability of gene networks. This Perspective proposes that such non-genetic yet heritable heterogeneity contributes to tumour evolution, and might explain the acquisition of traits such as drug resistance.

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.

Diverse lines of evidence link replication timing with epigenetic marks and transcriptional potential. The authors of this article propose a model in which mechanisms that bring about coordinated changes in replication timing also provide a platform for reprogramming the epigenome.

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.

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.

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.