Articles in 2014

We invite proposals by 1 March for pan-cancer analyses from public data sets to be submitted by the end of 2015. We will coordinate expressions of interest from the Nature family of journals and index the resulting publications prominently in a web focus and special issue of the journal.

Febrile seizures can arise in response to fevers induced by viral infection or as an adverse reaction to live-virus vaccines such as measles, mumps and rubella (MMR) vaccination. A new study has now identified common genetic variants influencing susceptibility to febrile seizures, including two loci specifically associated with MMR-related events.

A new study detects unstable nascent RNAs and uncovers thousands of transcription initiation sites in promoters and enhancers. Detailed analysis shows that these initiation sites have a similar architecture and that they are differentiated by post-transcriptional regulation rather than transcription initiation.

Characterization of the mutational landscape of tumors is important to understanding disease etiology but does not provide mechanistic insight into the functional role of specific mutations. A new study introduces a statistical mechanical framework that draws on biophysical data from SH2 domain–phosphoprotein interactions to predict the functional effects of mutations in cancer.

Stéphanie Debette and colleagues report the results of a genome-wide association study of cervical artery dissection, a major cause of ischemic stroke in young adults. They show that common variation in PHACTR1, previously associated with lower risk of migraine and increased risk of myocardial infarction, is associated with reduced risk of cervical artery dissection.

Zhong-Jian Liu, Lai-Qiang Huang, Yi-Bo Luo, Hong-Hwa Chen and Yves Van de Peer report the first genome sequence of a crassulacean acid metabolism (CAM) plant, the orchid Phalaenopsis equestris. They identify genes encoding CAM pathway enzymes and find that gene duplication was likely a key process in the evolution of CAM photosynthesis.

Cas Simons, Ryan Taft and colleagues report the identification of KCNH1 mutations in six individuals with Temple-Baraitser syndrome (TBS). Electrophysiological measurements of cells expressing mutant KCNH1 channels show decreased activation thresholds and slower deactivation in comparison to wild-type channels, suggesting that these mutations lead to gain of function of KCNH1.

Anna-Elina Lehesjoki and colleagues report exome sequencing of 84 cases of progressive myoclonus epilepsy (PME) and targeted resequencing of an additional 28 cases. They identify de novo mutations in KCNC1 in 13 cases and mutations in genes not previously associated with PME, including PRNP, SACS and TBC1D24, in additional cases.

Somasekar Seshagiri, James Brugarolas and colleagues report the mutational landscape of 167 non–clear cell renal cell carcinomas (nccRCCs) from multiple subtypes. They identify subtype-specific driver mutations and gene fusions, including ones involving MITF, which result in expression of the anti-apoptotic protein BIRC7 and might thus indicate candidates for treatment with BIRC7 inhibitors.

Rasmus Marvig and colleagues report the whole-genome sequencing of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young patients with cystic fibrosis. They identify evidence of convergent evolution in 52 genes and suggest pathways involved in within-host adaptation and pathogenesis.

Mark Walker and colleagues report the whole-genome sequencing of 132 group A Streptococcus (GAS) isolates of a sequence type that has been associated with scarlet fever. The isolates were obtained from 58 clinical cases of scarlet fever and 83 cases without scarlet fever during the course of a recent epidemic in Hong Kong.

John Lis, Adam Siepel and colleagues map transcription start sites across the genome in two human cell lines using a nuclear run-on protocol called GRO-cap. They find a common architecture of initiation at both promoters and enhancers and that transcript elongation stability provides the strongest distinction between promoters and enhancers.

Erik Larsson and colleagues present an analysis pipeline for identifying likely transcription-altering noncoding somatic mutations in cancer using publicly available data from 505 tumor genomes across 14 cancer types. They find that TERT promoter mutations show strong associations to altered transcriptional levels and identify recurrent promoter mutations in DPH3 and PLEKHS1.

Noah Zaitlen, Alkes Price and colleagues report a new approach to estimate the narrow-sense heritability of complex traits from unrelated individuals in a recently admixed population. They apply this approach to estimate the heritability for 13 quantitative or case-control phenotypes in 21,497 African-American individuals and suggest the inflation of family-based h² estimates.