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.
Data sharing provides research with an essential opportunity for error correction by collaborators and disinterested parties alike. Public deposition ensures the useful formatting and recording of essential metadata.
A new study describes a tool, Lentihop, for somatic insertional mutagenesis in human cells and uses this system in combination with cancer genome data to define new genes and pathways involved in sarcoma development. Gene discovery in this way suggests that we are far from a complete catalog of cancer drivers.
Polycomb/Trithorax response elements (PRE/TREs) are genetic elements that can stably silence or activate genes. A new study describes how long noncoding RNAs (lncRNAs) transcribed from opposite strands of the Drosophila melanogaster vestigial PRE/TRE throw the switch between these two opposing epigenetic states.
The domestication of African rice, Oryza glaberrima, occurred separately from that of the much more widespread Asian rice species Oryza sativa. Analysis of the whole-genome sequence for O. glaberrima shows the extent to which the same genes were involved in these distinct but parallel evolutionary events.
Dina Paltoo, Laura Lyman Rodriguez, Michael Feolo and colleagues present their analysis of the usefulness and impact of the first seven years of data sharing via the dbGaP repository and announce the extension of data-sharing provisions to other types of research funded by the NIH.
Trey Ideker and colleagues report a comprehensive genome-wide analysis of head and neck squamous cell carcinoma, reporting that TP53 mutations are frequently accompanied by loss of chromosome 3p. Their data indicate that the combination of these two events has a stronger negative effect on survival rate than either event alone.
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.
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.
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.
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.
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.
Andrew Singleton and colleagues report a large-scale meta-analysis of genome-wide association data in Parkinson's disease using over 13,000 cases and 95,000 controls plus additional samples for replication. They identify 6 new risk loci and replicate 28 independent risk variants for Parkinson's disease across 24 loci.
Dongxin Lin, Philip Taylor, Li-Dong Wang and colleagues have now pooled three genome-wide association analyses of esophageal squamous cell carcinoma, finding two new risk loci at genome-wide significance and an HLA class II locus of significance in high-risk populations. They reanalyze the strength of evidence for previously published risk loci.
Peizeng Yang, Zhenglin Yang and colleagues report results of a genome-wide association study of Vogt-Koyanagi-Harada syndrome. They confirm strong association with the HLA region and identify two new susceptibility loci, including variants near IL23R.
Shiro Ikegawa and colleagues report the results of a genome-wide association study for ossification of the posterior longitudinal ligament of the spine in a Japanese cohort. They identify six new loci, three of which showed decreased expression in a mouse model of endochondral ossification.
Kyuyoung Song and colleagues report the results of a two-stage association study of thiopurine-induced early leukopenia in individuals undergoing treatment for Crohn's disease. They find a missense variant in NUDT15 associated with substantially higher risk of developing this life-threatening complication to thiopurine therapy.
Christoph Klein and colleagues identify homozygous mutations in the JAGN1 gene in families and individuals with severe congenital neutropenia. They show that JAGN1 is necessary for the differentiation and survival of neutrophil granulocytes.
Josef Penninger and colleagues generate mice with conditional knockout of Jagn1 in hematopoietic cells. They show that the mice have a defective neutrophil-mediated immune response to Candida albicans, and GM-CSF treatment restored the defective fungicidal activity.
Björn Usadel and colleagues report the genome sequence of the wild tomato species Solanum pennellii. The authors identify genes important for stress tolerance, metabolism and fruit maturation and suggest that transposable elements have had an important role in the evolution of the S. penellii stress response.