Subscribe: Nature Genetics
http://www.nature.com/ng/current_issue/rss
Preview: Nature Genetics

Nature Genetics - Issue - nature.com science feeds



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



 



Combined harvest of knowledge

2016-11-29

Investment 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.



Understanding unspecific complaints through genetics

2016-11-29

Unspecific 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.



A DNA element that remembers winter

2016-11-29

Polycomb-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.



Human host range of Mycobacterium tuberculosis

2016-11-29

A 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.



Genome-wide significance testing of variation from single case exomes

2016-10-24

Donald 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.



Genome-wide analysis identifies 12 loci influencing human reproductive behavior

2016-10-31

Melinda 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.



Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction

2016-10-24

Marika 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.



Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

2016-10-24

Charles 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.



Clonal evolution of chemotherapy-resistant urothelial carcinoma

2016-10-17

Mark 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.



Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma

2016-10-17

Ming-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.



General rules for functional microRNA targeting

2016-10-24

Daehyun 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.



A cis cold memory element and a trans epigenome reader mediate Polycomb silencing of FLC by vernalization in Arabidopsis

2016-11-07

Yuehui 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.



Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

2016-10-31

Sebastien 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.



Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

2016-10-17

Paul 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.



The genomic landscape of core-binding factor acute myeloid leukemias

2016-10-31

Lars 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.



Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality

2016-10-31

Pim 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.



Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

2016-10-17

Joshua 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.



Prospective functional classification of all possible missense variants in PPARG

2016-10-17

Amit 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.



Wheat Fhb1 encodes a chimeric lectin with agglutinin domains and a pore-forming toxin-like domain conferring resistance to Fusarium head blight

2016-10-24

Bikram 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.



M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity

2016-10-24

Gill 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.



Scaling probabilistic models of genetic variation to millions of humans

2016-11-07

John 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.