2016-11-29Investment in national infrastructure should include a scalable open informatics solution for agricultural genomics, germplasm and crop traits. This is a priority measure for economic stimulus and food security. As building this knowledge harvester should be simpler than the infrastructure required for precision medicine, it will also pave the way to that goal.
2016-11-29Unspecific and unexplained medical complaints can be frustrating to both patients and clinicians. A cause for these complex symptoms and signs may now have been identified.
2016-11-29Polycomb-mediated silencing of the floral repressor gene FLC in response to long-term cold is a central event during vernalization in Arabidopsis thaliana, but how it is initiated is unclear. Two new studies identify a DNA element that mediates FLC silencing by attracting a pair of transcriptional repressors, VAL1 and VAL2, which in turn trigger epigenetic silencing by the Polycomb complex PHD–PRC2.
2016-11-29A new study demonstrates that the most widespread lineage of the causative agent of tuberculosis consists of both globally distributed and geographically restricted sublineages. The geographically restricted sublineages are likely able to infect only specific human populations, whereas the globally distributed ones likely have a broader human host range.
2016-10-24Donald Conrad and colleagues present a method, PSAP, for prioritizing potential Mendelian disease-causing variants in single human exomes using pathogenicity scores and observed allele frequencies in the unaffected population. They apply PSAP to cohorts of undiagnosed disease exomes and identify candidate disease variants for future study.
2016-10-31Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.
2016-10-24Marika Charalambous and colleagues show that, in mice, the fetus is the source of maternal circulating DLK1, which regulates the mother's metabolism during pregnancy. They also find that maternal circulating DLK1 levels predict embryonic weight in mice and associate with fetal growth restriction in a human cohort.
2016-10-24Charles Mullighan, Jinghui Zhang and colleagues characterize a subtype of B-progenitor acute lymphoblastic leukemia with deregulated DUX4 and ERG. They find that aberrant DUX4 activation results in loss of ERG function, either through deletion or by the induction a novel transforming ERG isoform, ERGalt, that inhibits wild-type ERG activity.
2016-10-17Mark Rubin, Francesca Demichelis and colleagues study the evolution of urothelial carcinomas by performing whole-exome sequencing of tumors collected from patients before and after chemotherapy. They find marked within-patient tumor heterogeneity and increased mutations involved in integrin signaling pathways and APOBEC-induced mutation signatures after treatment.
2016-10-17Ming-Rong Wang, Benjamin Berman and colleagues perform whole-exome sequencing and global methylation profiling on different tumor regions of esophageal squamous cell carcinoma. They find evidence for intratumoral heterogeneity and identify late driver mutations targeting oncogenes and early driver mutations occurring in tumor-suppressor genes.
2016-10-24Daehyun Baek and colleagues present a systematic analysis of more than 2 billion potential miRNA–gene target interactions using publicly available human microarray data. The authors find evidence for four canonical and seven non-canonical site types that show detectable downregulation of target genes, and they present functional validation for the new site types.
2016-11-07Yuehui He and colleagues show that VAL1 and VAL2 bind to a cis-regulatory element at the FLC locus and are required for its epigenetic silencing during vernalization in Arabidopsis. They further report that VAL proteins recognize the repressive histone mark H3K27me3 and are necessary for genomic binding of the Polycomb silencing partner LHP1.
2016-10-31Sebastien Gagneux and colleagues analyze a global collection of Mycobacterium tuberculosis clinical isolates to classify sublineages by phylogeography. They find globally distributed ‘generalist’ and geographically restricted ‘specialist’ sublineages of lineage 4, indicating that different evolutionary strategies were adopted to succeed in various ecological niches.
2016-10-17Paul Brennan and colleagues perform genome-wide association analysis for oral cavity and pharyngeal cancer in trans-ancestry populations. They find seven new loci across different cancer subtypes, including a protective association in the HLA region that has a stronger effect in patients with human papillomavirus–positive cancers.
2016-10-31Lars Bullinger, Jinghui Zhang, Jeffery Klco, James Downing and colleagues report a detailed genomic analysis of pediatric and adult core-binding factor acute myeloid leukemias (CBF-AMLs). They identify recurrent mutations in CCND2, MGA, DHX15 and ZBTB7A and highlight dramatic differences in the landscape of cooperating mutations between different CBF-AML subtypes.
2016-10-31Pim van der Harst and colleagues report a genome-wide association study for resting heart rate in individuals of European ancestry and identify 64 associated loci, 46 of which have not been previously reported. A genetic risk score constructed using the associated variants is significantly associated with increased mortality risk.
2016-10-17Joshua Milner and colleagues show that increased TPSAB1 copy number causes a multisystem disorder marked by elevated basal serum tryptase levels. Shared symptoms in affected individuals include irritable bowel syndrome, cutaneous flushing and pruritus, connective tissue abnormalities and dysautonomia.
2016-10-17Amit Majithia and colleagues employ a pooled assay in human macrophages to assess the functional effects of all possible missense variants in PPARG. Their study shows the value of saturation mutagenesis and prospective experimental characterization to support diagnostic interpretation of newly discovered missense variants in disease-related genes.
2016-10-24Bikram Gill and colleagues report map-based cloning of Fhb1, which confers resistance to Fusarium head blight in wheat. They show that the PFT gene at Fhb1 confers resistance and encodes a chimeric lectin with agglutinin domains and a pore-forming toxin domain, identifying a new type of durable plant-resistance gene.
2016-10-24Gill Bejerano and colleagues present M-CAP, a classifier that estimates variant pathogenicity in clinical exome data sets. They show that M-CAP outperforms other existing methods at all thresholds and correctly dismisses 60% of rare missense variants of uncertain significance at 95% sensitivity.
2016-11-07John Storey, David Blei and colleagues present a method, TeraStructure, for estimating population structure from human genomic data sets on a scale not possible with current methods. TeraStructure is able to analyze data from the Human Genome Diversity Panel and the 1000 Genomes Project in less than three hours.