Articles in 2014

Mingliang Xu and colleagues show that a wall-associated kinase, ZmWAK, confers resistance to maize head smut, a systemic fungal disease in maize.

Giuseppe Testa and colleagues report the generation and transcriptional characterization of patient-derived induced pluripotent stem cells (iPSCs) with copy number variants at 7q11.23, which cause syndromes including neurocognitive phenotypes. They find that the dosage of the transcription factor gene GTF2I accounts for 10–20% of the transcriptional dysregulation observed in these cells.

Guido Sauter, Roland Eils, Christoph Plass, Raffaella Santoro and colleagues report that the gene encoding the epigenetic regulator BAZ2A is overexpressed in prostate cancer, where it interacts with EZH2 to induce aberrant gene silencing and cell proliferation. The authors find that BAZ2A levels are predictive of disease recurrence in patients with prostate cancer.

Roland Rad and colleagues report development of a new conditional piggyBac transposition system for performing insertional mutagenesis screens in mice. They apply the system to identify new oncogenic driver pathways for pancreatic cancer.

Martin Reincke, Martin Fassnacht and colleagues identify somatic mutations in the USP8 deubiquitinase gene in corticotroph adenomas in Cushing's disease. The mutations enhanced proteolytic cleavage and catalytic activity of USP8, which led to activation of EGF receptor signaling.

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.

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.

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.

Astrid von Mentzer, Gordon Dougan and colleagues report the whole-genome sequencing of a representative global collection of enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea, including samples from 20 countries isolated between 1980 and 2011. They find that, although ETEC isolates are widely distributed across the E. coli species and are genetically diverse, there are several discrete lineages that have contributed to overlapping global epidemics.

Tatsuhiro Shibata, David Wheeler, Hiroyuki Aburatani and colleagues report the genomic, exomic and oncoviral sequencing of hundreds of liver cancers from the United States and Japan. The authors analyzed mutation patterns and identified signatures unique to the Asian cases.

Ming Li, Ruiqiang Li and colleagues report the whole-genome sequencing of a male golden snub-nosed monkey, Rhinopithecus roxellana, as well as its relatives Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri. Their analysis provides insights into primate evolution and adaptation to a diet consisting primarily of leaves and seeds.

Bjarke Feenstra and colleagues identify common variants at six loci associated with general or MMR vaccine–related febrile seizures. The two loci specifically associated with MMR-related febrile seizures harbor the interferon-stimulated gene IFI44L and the measles virus receptor gene CD46.

Andrew Jackson, Peter Nürnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction.

Evan Eichler and colleagues present a detailed characterization of the chromosome 15q13.3 microdeletion region. They identify complex structural polymorphisms and find that the rearrangement breakpoints cluster in palindromic GOLGA8 core duplicons, providing evidence that this repeat and its palindromic architecture underlie the evolutionary and disease-related instability of this region.

Sanwen Huang and colleagues report a comprehensive analysis of genetic variation in tomato based on the genome sequencing of 360 distinct accessions. The work provides insights into the history of tomato domestication and represents a rich resource for studying the genetic basis of trait variation in this important crop plant.

Ali Gharavi and colleagues report a genome-wide association analysis of IgA nephropathy in over 20,000 individuals of European and East Asian ancestry. They identify genome-wide significant signals at three new loci near VAV3, CARD9 and ITGAM-ITGAX and correlations between genetic risk and pathogen diversity.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Fernando González-Candelas and colleagues report the whole-genome sequencing of 69 Legionella pneumophila strains linked to recurrent outbreaks in Alcoy, Spain, over the course of 11 years. They characterize the evolution and epidemiology of this environmental pathogen.