News & Views in 2016

A defining characteristic of grasses, including major cereal crops, is the way in which flowers are arranged on an inflorescence. A new study finds that regulation of hormone levels during development is crucial for determining the arrangement of flowers on a barley inflorescence, opening new doors for increasing grain yield.

Our understanding of how DNA copy number changes contribute to disease, including cancer, has to a large degree been focused on the changes in gene dosage that they generate and has neglected the effects of the DNA rearrangements that lead to their formation. A new study reports an innovative analytical framework for copy number alterations that are oncogenic primarily owing to the genomic rearrangements that underlie them.

A genome-wide study of fasting insulin, HDL cholesterol and triglycerides, designed to depict insulin resistance, identified 53 independent loci associated with a limited capacity to store fat in a healthy way. The increased power of this multitrait approach provides insights into an otherwise difficult-to-grasp phenotype.

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.

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.

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.

Stabilization of p53 protein is a key step in the cellular response to DNA damage. A new study describes a long noncoding RNA, DINO, transcribed from the CDKN1A promoter region that induces stabilization of p53 protein and promotes efficient activation of p53 target genes in response to DNA damage.

Methylation of histone H3 on lysine 9 (H3K9) is a hallmark of transcriptionally inactive heterochromatin that is deregulated in pathological conditions. A new study shows that complete loss of H3K9 methylation in Caenorhabditis elegans leads to derepression of repetitive elements and formation of DNA:RNA hybrids (R loops), resulting in increased rates of repeat-specific mutation.

As the first series of genetic analyses of gut microbiome composition in humans is now emerging, the results should be met with enthusiasm, but also with caution. Findings from the initial offerings demonstrate how population-scale approaches can provide deeper insights into host–microbiome interactions while at the same time illustrating that our understanding of the architecture of highly complex microbiome 'traits' is still rudimentary.

A common ancestor of the modern codfish acquired a set of mutations that eliminated a major arm of the adaptive immune system—the MHC II pathway of antigen presentation to CD4⁺ T cells. Subsequent to this event, there was a radiation of these fish in which the number and diversity of MHC I genes increased in species-specific ways.

A new study demonstrates that genomic sequencing coverage of plasma DNA fragments around transcription start sites reflects the expression levels of genes in corresponding tumors. This approach may enable noninvasive monitoring of treatment-induced changes in gene expression for patients with cancer.

A new study based on single-nucleus sequencing reports that triple-negative breast cancers acquire copy number aberrations in short punctuated bursts in the earliest stages of tumor evolution, rather than continuously and gradually, challenging prevailing models of tumor evolution.

A new analysis has characterized a fundamental building block of complex transcribed loci. Constellations of core promoters can generally be reduced to pairs of divergent transcription units, where the distance between the pairs of transcription units correlates with constraints on genomic context, which in turn contribute to transcript fate.

A genome-wide study in Samoans has identified a protein-altering variant (p.Arg475Gln) in CREBRF as being associated with 1.3-fold increased risk of obesity and, intriguingly, 1.6-fold decreased risk of type 2 diabetes. This variant, which is common among Samoans (minor allele frequency = 26%) but extremely rare in other populations, promotes fat storage and reduces energy use in cellular models.

Study of the Greater Middle East (GME), home to approximately 10% of the world's population, has made invaluable contributions to the characterization of rare genetic disease, especially recessive conditions arising from the tradition of consanguinity and large families with multiple children. A new study now reports 1,111 unrelated exomes from the GME and provides a comprehensive view of genetic variation for enhanced discovery of disease-associated genes.

Analysis of a large whole-genome sequencing data set of 36,441 high-quality de novo mutations (DNMs) that arose in 816 family trios provides an unprecedented view into the landscape of DNMs in the germ line. This work both refines and challenges some of the views previously held on the nature and origin of DNMs.

Two new studies confirm that Plasmodium vivax populations are more diverse than Plasmodium falciparum and identify signs of recent selection at many loci, including those for drug resistance. P. vivax shows a trend of regional adaptations that poses challenges to global efforts to control and eliminate this major cause of relapsing malaria.

A new study tracks the distribution of bivalent H3K4me3/H3K27me3 chromatin in male germ cells of six vertebrate species. The results have big implications for understanding the mechanisms that specify animal development.

A new genetic disorder might be treatable through consumption of a simple sugar, but the relative contributions of endogenous and dietary sources are mostly unknown. It's time to change that.

A new analysis has identified hundreds of loci that are associated with multiple traits or diseases by comparing genome-wide association study (GWAS) data for 42 complex traits. The study uses the power of GWAS to provide evidence of pairs of traits with a likely causal relationship.