Articles in 2013

Eric Rahrmann and colleagues performed a transposon-based somatic mutagenesis screen for genes involved in malignant peripheral nerve sheath tumors (MPNSTs). They identified many recurrent transposon insertions and nominate Foxr2 as a new oncogene in MPNSTs.

Dongxin Lin and colleagues report a genome-wide association study identifying common variants in SLC39A6 associated with length of survival in individuals with esophageal squamous-cell carcinoma (ESCC). Higher expression of SLC39A6 in esophageal tissues was correlated reduced survival time in individuals with ESCC.

Nicholas Croucher and colleagues report whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae, a major cause of pneumonia, bacteremia and meningitis. They examine the impact of the introduction of the pneumococcal conjugate vaccine PCV7 on pneumococcal population dynamics.

Dominic Kwiatkowski and colleagues report analysis of genetic variation in 826 Plasmodium falciparum samples collected from 10 locations in West Africa and southeast Asia. They characterize the population structure of this parasite in Cambodia and find evidence for multiple distinct subpopulations showing high levels of genetic differentiation and artemisinin resistance.

Jamel Chelly, Nicholas Cowan and colleagues report mutations in TUBG1, DYNC1H1, KIF2A and KIF5C in individuals with malformations of cortical development and microcephaly. Their findings emphasize the importance of centrosomal and microtubule-related proteins for normal brain development.

David Ellison and colleagues report whole-genome sequencing of pediatric low-grade gliomas, the most common pediatric brain tumor. They identify a range of genomic alterations, including recurrent and mutually exclusive duplications of the FGFR1 region encoding the tyrosine kinase domain and rearrangements of MYB.

Tasha Fingerlin, David Schwartz and colleagues report a genome-wide association study of fibrotic idiopathic interstitial pneumonia. Their results confirm known risk variants at MUC5B and TERT and identify several new regions associated with disease susceptibility.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The International Peach Genome Initiative reports the high quality draft genome sequence of peach (Prunus persica). They also resequenced ten additional P. persica accessions, as well as those of Prunus ferganensis, Prunus kansuensis, Prunus davidiana and Prunus mira.

Thomas Nutman and colleagues report the draft genome of the filarial pathogen Loa loa, the African eyeworm. They also report coverage of two other filarial pathogens, Wuchereria bancrofti and Onchocerca volvulus. Unlike most filariae, L. loa lacks an obligate intracellular Wolbachia endosymbiont, and comparative genomic analyses suggest that the L. loa genome does not contain new metabolic synthesis or transport pathways compared to other filariae.

Adam Bass, Gad Getz and colleagues report whole-exome sequencing of 149 esophageal adenocarcinomas (EACs) and whole-genome sequencing of 15 EACs. They identify a mutational signature defined by a high prevalence of A>C transversions, as well as 26 genes mutated at high frequency in EACs.

Steven McCarroll, Giulio Genovese and colleagues report a new approach to help complete maps of the human genome reference sequence. They use a population-based admixture mapping approach and report the successful mapping of ~4 Mb of unplaced human euchromatic sequences.

Jeramiah Smith, Weiming Li and colleagues report the whole-genome sequence of the sea lamprey, Petromyzon marinus, representing a vertebrate lineage diverged from humans ~500 million years ago. Their analyses define key evolutionary events in vertebrate lineages and provide evidence for two whole-genome duplication events occurring before the divergence of the ancestral lamprey and jawed vertebrate (gnathostome) lineages.

Neil Hunter and colleagues show that RNF212 is essential for crossing-over during mammalian meiosis and functions to couple chromosome synapsis to the formation of crossover-specific recombination complexes. They further show that selective localization of RNF212 to a subset of recombination sites is a key step in the crossover designation process that serves to stabilize meiosis-specific recombination factors at these sites.

Tim Chan and colleagues report the identification of recurrent somatic mutations in FAT1 in glioblastoma, colon cancer and head and neck cancer and show that inactivation of FAT1 promotes Wnt signaling and tumorigenesis.

Heymut Omran, Mary Porter and colleagues identify the nexin link–dynein regulatory complex subunit DRC1 from Chlamydomonas and show that mutations in the human DRC1 homolog CCDC164 cause primary ciliary dyskinesia. Their analyses show that loss of DRC1 results in distinct axonemal defects and altered ciliary beat patterns.