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Andrew Feinberg and colleagues report whole-genome bisulfite sequencing of three colon cancers and matched normal tissue and two adenomatous polyps. The authors identify large blocks of relative hypomethylation over half of the genome.
Ruth Loos and colleagues use genome-wide association to identify common variants influencing body fat percentage. Unexpectedly, they show that a body-fat–decreasing allele near IRS1 is associated with an impaired metabolic profile, including increased risk of type 2 diabetes and coronary artery disease.
Chia-Lin Wei, Yijun Ruan and colleagues used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to determine the CTCF-chromatin interactome in mouse embryonic stem cells.
Stefan Somlo and colleagues show that the polycystic liver disease genes Prkcsh and Sec63 are required for the proper biogenesis of polycystin complexes. They further show that a Pkd1 transgene can rescue the cystic phenotype of Prkcsh and Sec63 mutant mice, identifying polycystin-1 as the central determinant of cyst formation.
David Wong, Howard Chang and colleagues report the identification of long noncoding RNAs transcribed from the promoters of cell cycle genes. Many of these RNAs have periodic expression during the cell cycle and are regulated by oncogenic stimuli, stem cell differentiation or DNA damage.
Fernando Pardo-Manuel de Villena, Gary Churchill and colleagues provide a high-resolution phylogenetic map of mouse inbred strains based on comparisons to wild-caught mice. They show that the genomes of classical strains are overwhelmingly derived from Mus musculus domesticus whereas wild-derived laboratory strains include a broad sampling of diversity from multiple subspecies with pervasive introgression. The subspecific origin, haplotype diversity and identity-by-descent map of laboratory strains can be visualized at http://msub.csbio.unc.edu/PhylogenyTool.html.
Balázs Papp and colleagues construct a genetic interaction map of yeast metabolism and use a genome-scale systems biology model to examine the structure of the metabolic network. They use an automated machine-learning method to reconcile differences between the experimental and computational genetic interaction maps. In contrast to previous studies, they do not find evidence for prevalent positive interactions in essential metabolic genes.
Garry Cutting and colleagues report a genome-wide association and linkage study for loci that affect lung disease severity in cystic fibrosis. They identify two loci that influence lung function in individuals with cystic fibrosis.
Norihiro Kato and colleagues perform a meta-analysis of genome-wide association studies to identify common variants associated with blood pressure variation in east Asians. They identify five new genome-wide significant signals and replicate seven loci previously discovered in populations of European ancestry.
Kathryn Anderson and colleagues use mouse genetics to define unexpected relationships between the retrograde ciliary motor gene Dync2h1 and other genes required for trafficking in primary cilia. Their findings argue that the mutant phenotypes in these models result from defects in cilia architecture rather than direct roles in signaling.
Ido Golding and colleagues examine transcriptional time series in Escherichia coli, characterizing mRNA copy number statistics for 20 promoters at single transcript resolution. They find that the degree of burstiness depends primarily on the level of gene expression.
Michel Georges and colleagues report fine mapping and functional characterization of a quantitative trait locus with a large effect on bovine stature. They show that the likely causal variants at this locus modulate expression of a chromosomal domain encompassing PLAG1 and several other genes.
Julia Zeitlinger, Alexander Stark and colleagues report genome-wide binding profiles for the transcription factor Twist across six Drosophila species. They find that the binding pattern is highly conserved across species, suggesting strong functional constraints at the enhancers that Twist regulates.
Zhu Chen, Sai-Juan Chen and colleagues report exome sequencing of acute monocytic leukemia, a subtype of acute myeloid leukemia. They identified somatic mutations of DNMT3A, which encodes a DNA methyltransferase, in 20% of cases.
Ali Gharavi, Rick Lifton and colleagues report a genome-wide association study for IgA nephropathy, a major cause of kidney failure. They identify five susceptibility loci.
Hilma Holm et al. report a rare missense variant MYH6 that is associated with a high risk of sick sinus syndrome in Icelanders. This heart condition is found most often in elderly people and is the most frequent reason a heart pacemaker is implanted.
Richard Wilson and colleagues report the genome sequence of Trichinella spiralis, a food-borne parasitic nematode that diverged early in the evolution of the phylum Nematoda. T. spiralis is the most common cause of human trichinellosis.
Geneviève Almouzni and colleagues report that SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin in mouse. They identify long nuclear non-coding transcripts at major satellite repeats and show that they specifically associate with SUMO-modified HP1 proteins.
Josef Penninger and colleagues show that deletion of the stress kinase MKK7 in mouse models of lung and mammary tumors accelerates tumor onset and reduces overall survival. The study suggests that MKK7 is a sensor of oncogenic stress.