Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human traits and on other model organisms, including mouse, fly, nematode and yeast. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
The genetic determinants of progression from premalignant Barrett's esophagus to esophageal adenocarcinoma are not known. A new study reports genomic sequence analyses of this progression and uses the insights gained to identify high-risk Barrett's esophagus in a new non-endoscopic test.
An international effort, the 1000 bull genomes project, aims to resequence the genomes of a large number of key ancestor bulls of the most important domestic cattle breeds. A new study reports on the first results of this important initiative based on the analysis of the first 234 bovine whole-genome sequences.
The influence of Epstein-Barr virus (EBV) on cancer is not well understood. High-throughput sequencing of nasopharyngeal carcinoma (NPC) illustrates the influences of EBV on oncogenesis and identifies driver pathways that might be therapeutically useful for NPC treatment.
Marco Tartaglia, Raoul Hennekam and colleagues show that de novo mutations in ZBTB20 cause Primrose syndrome, a disorder characterized by tall stature, macrocephaly, intellectual disability, diabetes, deafness, progressive muscle wasting and ectopic calcifications.
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.
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.
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.
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.
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.
De-Chen Lin and colleagues report whole-exome sequencing, targeted sequencing and SNP array analysis of 128 cases of nasopharyngeal carcinoma (NPC), a tumor type connected to Epstein-Barr virus infection. Their results identify a distinct mutational signature with nine significantly mutated genes and mutations enriched in cellular processes, including chromatin modification and autophagy.
Yingbin Liu, Yun Liu, Hui Wang and colleagues perform whole-exome and targeted gene sequencing of gallbladder carcinoma. They identify recurrent somatic alterations in components of the ErbB signaling pathway and show that these alterations are associated with poor clinical outcomes.
Bin Tean Teh and colleagues report exome sequencing of 8 breast fibroadenomas and follow-up targeted sequencing in 90 additional samples. They find that 59% of samples contain somatic mutations in exon 2 of MED12, a mutational pattern shared with another female-specific benign tumor, uterine leiomyoma.
Joseph Buxbaum and colleagues use an epidemiological sample from Sweden to investigate the genetic architecture of autism spectrum disorders. They conclude that most inherited risk for autism is determined by common variation and that rare variation explains a smaller fraction of total heritability.
Qiuyin Cai and colleagues report a genome-wide association analysis for breast cancer in 22,780 cases and 24,181 controls from 14 studies as part of the Asia Breast Cancer Consortium. They identify three loci newly associated with breast cancer susceptibility.
Ana Vega and colleagues report the results of a three-stage genome-wide association study of radiotherapy toxicity following treatment for prostate cancer. They find that susceptibility to late radiation-induced toxicity is associated with variants in the TANC1 gene at 2q24.1.
Marc Rothenberg, John Harley and colleagues present the results of a genome-wide association study of eosinophilic esophagitis. They discover an association with variants near CAPN14 and show that CAPN14 is expressed specifically in the esophagus and is upregulated in esophageal biopsies of individuals with active disease.
Johannes Schumacher and colleagues report the results of a genetic association study of idiopathic achalasia, a rare motility disorder of the esophagus. They show that common variation in the HLA-DQ region is strongly associated with achalasia risk, implicating immune-mediated processes in this disorder.
Maxence Nachury, Christel Thauvin-Robinet and colleagues identify mutations in C2CD3 in two families with oral-facial-digital syndrome. They further show that C2CD3 localizes to the distal end of centrioles and acts as a positive regulator of centriole elongation.
Gerton Lunter and colleagues report Platypus software, which combines a haplotype-based multi-sample variant caller with local sequence assembly in a Bayesian statistical framework. They demonstrate applications to exome and whole-genome data sets, to the identification de novo mutations in parent-offspring trios and to the genotyping of HLA loci.
Stephan Schiffels and Richard Durbin report the multiple sequentially Markovian coalescent (MSMC) method for inferring human population size and separation history from multiple genome sequences. Their application to the whole-genome sequences of 34 individuals from 9 populations allows inferences about events in human population history as recent as 2,000 years ago.