Articles in 2014

The Malaria Genomic Epidemiology Network reports a large multicenter association study for severe malaria due to Plasmodium falciparum in 11,890 cases and 17,441 controls from 12 locations in Africa, Asia and Oceania. They examine 27 loci previously associated with severe malaria and replicate associations at the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but they fail to replicate other previously reported associations.

Xiaowen Sun and colleagues report the whole-genome sequencing of the common carp, Cyprinus carpio. They also resequenced 33 representative accessions from a worldwide collection and provide insights into population structure and evolution.

Evan Eichler and colleagues report an expanded copy number variation (CNV) morbidity map of developmental delay, with additional resequencing of candidate genes in regions implicated by large CNVs. They identify several new disease-associated CNVs and show how their combined approach facilitates discovery of new developmental syndromes and disease genes.

Frank Geller and colleagues report the results of a large genome-wide association study of hypospadias. They identify 18 susceptibility regions for this common congenital condition, many of which harbor genes important for embryonic development.

Rama Khokha and colleagues report a new mutagenesis method, called Lentihop, for creating spontaneous, genetically tractable tumors from normal human cells. Through genetic analysis of Lentihop-derived tumors, they find known drivers of sarcomas and identify new candidate tumor suppressor genes, including HDLBP and ADARB2.

Josef Prchal and colleagues identify a mutation in EGLN1 associated with adaptation to high altitude in Tibetan individuals. Their functional studies suggest a mechanism acting to reduce the erythropoietic response to hypoxia.

Mingsheng Chen, Klaus Mayer, Steve Rounsley, Rod Wing and colleagues report the genome sequence of African rice (Oryza glaberrima), a different species than Asian rice. The authors resequenced 20 O. glaberrima accessions and 94 Oryza barthii accessions (the putative progenitor species of O. glaberrima), and their analyses support the hypothesis that O. glaberrima was domesticated in a single region along the upper Niger river.

Mark Daly and colleagues present a statistical framework to evaluate the role of de novo mutations in human disease by calibrating a model of de novo mutation rates at the individual gene level. The mutation probabilities defined by their model and list of constrained genes can be used to help identify genetic variants that have a significant role in disease.

Leonie Ringrose and colleagues show that a switch between forward and reverse noncoding transcription at the Drosophila melanogaster vestigial Polycomb/Trithorax response element switches the status of the element between silencing and activation. They further show that strand switching of noncoding RNAs occurs at several hundred PcG-binding sites in flies and vertebrates, suggesting that this regulatory mechanism could be widespread.

Stephen DiFazio and colleagues report the genome sequences and population genomic analyses of 544 black cottonwood trees (Populus trichocarpa) along the Northwest coast of North America. They find evidence for climate-driven selection on adaptive traits, including genes related to drought, photoperiod and stress.

Matthew Webster and colleagues report whole-genome sequencing of 140 honeybees from 14 worldwide populations. Their analyses provide insights into the evolutionary history and genetic basis of local adaptation in honeybees.

Scott Keeney, Bernard de Massy, Maria Jasin and colleagues report a method to perform tetrad analysis (analysis of all four chromatids from a single meiosis) in mouse and analyzed two recombination hotspots in mouse oocytes and spermatocytes. They show that gene conversion frequently spares the binding site of the hotspot-specifying protein PRDM9.

Kim Worley and colleagues report the whole-genome sequence of the common marmoset, Callithrix jacchus, the first New World monkey to be sequenced.

Ben Hayes and colleagues report the whole-genome sequencing of 234 bulls as phase one of the 1000 bull genomes project. They identify 28.3 million variants in the cattle sequences and also report genome-wide association studies for complex traits, including milk production and curly coat.

Paul de Bakker, Cisca Wijmenga and colleagues report on The Genome of the Netherlands Project, including whole-genome sequencing of 769 individuals of Dutch ancestry from 250 parent-offspring families and construction of a phased haplotype map. Their intermediate-coverage population sequencing data set provides a complementary resource to other publicly available data sets, including the 1000 Genomes Project.

Giuseppe Giaccone and colleagues identify a recurrent missense mutation in GTF2I in a high percentage of thymic epithelial tumors. The mutation occurs more commonly in type A and AB thymomas and is associated with a more favorable clinical outcome.

Rebecca Fitzgerald and colleagues used genome sequence analyses to study the progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) and found that the majority of recurrently mutated genes in EAC were also mutated in precursor lesions and that only mutations in TP53 and SMAD4 were stage specific.

Christopher Newton-Cheh and colleagues report genome-wide association analyses for QT interval, an electrocardiographic measure reflecting myocardial repolarization, in 100,000 individuals. They identify 35 loci associated with QT interval and highlight a role for calcium regulation in myocardial repolarization.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

Matthew Berriman and colleagues report the whole-genome sequences of the human-infective whipworm Trichuris trichiura and the mouse-infective laboratory model Trichuris muris. Their transcriptome analyses and examination of T. muris infection in mice provide insights into host response to infection and potential drug targets for this major soil-transmitted helminth.