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Aaron Jex and colleagues report whole-genome sequencing of adult male and female whipworm, Trichuris suis, from experimentally infected pigs. They also report stage-, sex- and tissue-specific transcriptomes and provide insights into host-parasite interactions.
Jie Luo, Xingming Lian and colleagues report results of a large genome-wide association study of metabolic variation in rice. They identify hundreds of common variants influencing metabolite levels and illustrate how this approach can complement classical trait mapping and provide insights into pathways of physiological and nutritional importance.
Alexander Stark and colleagues use STARR-seq, a quantitative enhancer assay, to determine enhancer activity profiles for the genomes of five Drosophila species in Drosophila melanogaster S2 cells. They find that a large fraction of D. melanogaster enhancers are functionally conserved and enhancer activity is frequently gained.
Scott Jackson, Jeremy Schmutz, Phillip McClean and colleagues report the genome sequence of the common bean (Phaseolus vulgaris) and resequenced wild individuals and landraces from Mesoamerican and Andean gene pools, showing that common bean underwent two independent domestications.
Tomas Ganz and colleagues identify a new regulator of iron metabolism, erythroferrone, that is produced by erythroblasts in response to erythropoietin and suppresses hepcidin expression during stress erythropoiesis. They further show that erythroferrone levels are highly elevated in a mouse model of β-thalassemia, contributing to hepcidin suppression and iron overload in this model.
Wei Zheng and colleagues report the results of a large-scale genome-wide association study of colorectal cancer in East Asians. They identify six new susceptibility loci, including variants near TCF7L2 and TGFB1.
Yu-Xian Zhu, Jun Wang, Shuxun Yu and colleagues report sequencing and assembly of the genome of cultivated cotton, Gossypium arboreum. Comparison with the Gossypium raimondii genome sequence provides insights into genome evolution and speciation, and identifies two shared whole-genome duplication events occurring before the speciation event around 2–13 million years ago.
Suet Yi Leung, Mao Mao and colleagues report whole-genome sequencing of 100 gastric cancers and DNA copy number, gene expression and methylation profiling of these tumors. They identify new recurrently mutated genes and find mutation of RHOA in 14% of diffuse-type gastric cancers.
Nissim Benvenisty and colleagues use induced pluripotent stem cells (iPSCs) derived from individuals with Prader-Willi syndrome (PWS) to model PWS in vitro. By comparison to parthenogenetic human iPSCs, they find that the PWS-associated noncoding RNA IPW regulates maternally expressed genes at the DLK1-DIO3 imprinted region through its effect on H3K9me3 histone marks in that region.
Nicole Soranzo, Tim Spector, Gabi Kastenmüller and colleagues report a large-scale analysis of genetic variants influencing human blood metabolite levels. They identify genome-wide significant associations at 145 loci, providing a framework for exploring relationships between genetic variation, metabolism and complex disease.
Piero Carninci and colleagues report the discovery of a large class of noncoding RNAs, non-annotated stem cell transcripts (NASTs), which are implicated in the regulation of stem cell properties. The authors identify 8,873 mouse and 3,042 human NASTs and functionally validate 4 as having an important role in the maintenance of pluripotency.
Fred Wright, Patrick Sullivan and colleagues present the results of a large expression QTL study of peripheral blood using a classic twin design with follow-up replication in independent samples. Their results enable a more precise estimate of the heritability of gene expression and provide a useful resource for exploring the genetic control of transcription.
Cristen Willer, Kristian Hveem and colleagues use an exome array to identify a coding variant in TM6SF2 that is associated with total cholesterol levels. They further show that transient overexpression of TM6SF2 or knockdown of Tm6sf2 in mice alters serum lipid profiles, implicating TM6SF2 as a causal regulator of lipid traits.
Christina Warinner and colleagues report a high-resolution characterization of the oral microbiome isolated from the dental tissues of adult skeletons dating to 1100 CE and showing evidence of periodontal disease. They show the long-term carriage of a diverse range of opportunistic pathogens in the oral cavity and reconstruct the genome of the periodontal pathogen Tannerella forsythia.
Christian Steidl and colleagues identify recurrent somatic mutations in the PTPN1 gene in primary mediastinal B cell lymphoma and Hodgkin lymphoma. They show that mutant PTPN1 leads to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members.
Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.
Charles Swanton and colleagues used multiregion exome sequencing to study the evolutionary histories of ten clear cell renal cell carcinomas. They observed marked intratumoral heterogeneity in all cases, with extensive evidence of parallel evolution of tumor subclones and only a small number of truncal driver events.
Tannishtha Reya and colleagues show that Lis1, a key mediator of asymmetric cell division, is required for blood formation and hematopoietic stem cell function. The authors also show that the directed control of asymmetric division is a critical regulator of malignant hematopoietic development.
Songlin Chen and colleagues sequenced the whole genomes of a male (ZZ) and a female (ZW) Chinese half-smooth tongue sole, Cynoglossus semilaevis. Their analysis provides insights into the structure and evolution of the sex chromosomes and adaptation to the benthic lifestyle of this flatfish.
Francis Drobniewski and colleagues report the whole-genome sequencing of 1,000 Mycobacterium tuberculosis strains obtained prospectively from patients over a 2-year period in Samara, Russia, a region with a high incidence of multidrug-resistant (MDR) tuberculosis. They compare these strains to a diverse panel of strains isolated from across the UK and characterize the patterns of the emergence and evolution of drug resistance.
