News & Views

  • News & Views |

    Chromatin loops and domains are major organizational hallmarks of chromosomes. New work suggests, however, that these topological features of the genome are poor global predictors of gene activity, raising questions about their function.

    • Elizabeth H. Finn
    •  & Tom Misteli
  • News & Views |

    Genetics has played a key role in understanding the relationship between the DNA sequence encoding a protein and the protein’s three-dimensional structure. Two new studies present similar analytical approaches to predict three-dimensional structure on the basis of genetic interaction data.

    • Melissa Chiasson
    •  & Douglas M. Fowler
  • News & Views |

    Although human genetics can help identify new drug targets, the best way to prioritize genes as therapeutic targets is uncertain. A new study describes a framework to prioritize potential targets by integrating genome-wide association data with genomic features, disease ontologies and network connectivity.

    • Robert M. Plenge
  • News & Views |

    Fhb1 is the most effective and most widely deployed source of durable resistance against Fusarium graminearum, a devastating toxin-producing fungal pathogen affecting wheat. Two new studies identify Fhb1 as an atypical disease resistance gene; this discovery is expected to fuel discussion on the molecular nature of this important disease-resistance locus.

    • Evans S. Lagudah
    •  & Simon G. Krattinger
  • News & Views |

    Epigenetic heterogeneity underlies the diversity of cell states found in health and disease. A new study presents a method for profiling of histone modifications in single cells and applies it to identify rare chromatin states, possibly predisposed to drug resistance, within patient-derived tumor xenografts.

    • Anna Minkina
    •  & Jay Shendure
  • News & Views |

    The conserved ligand–receptor pair CLAVATA1–CLAVATA3, which maintains homeostasis in shoot apical meristems, responds differently to perturbation in tomato, Arabidopsis and maize. Active compensation occurs in CLE signaling peptides in tomato, but compensation is passive in Arabidopsis.

    • Elizabeth A. Kellogg
  • News & Views |

    Resolving variant-to-function relationships is a key challenge faced by human geneticists. A new study combining statistical fine-mapping with cell-type-specific functional annotations advances the understanding of the regulatory consequences of genetic variants associated with variations in blood-cell traits.

    • Manuel Tardaguila
    •  & Nicole Soranzo
  • News & Views |

    More than one dozen hereditary ataxias are caused by repeat expansions. A newly discovered expansion may be the first known common genetic cause of late-onset ataxia.

    • Vikram Shakkottai
    •  & Henry Paulson
  • News & Views |

    The origin of strawberry is truly global, involving both natural processes and human intervention. The strawberry genome sequence provides support for an influential hypothesis of genome dominance.

    • David J. Bertioli
  • News & Views |

    Contemporary genomics and informatics technologies were used to provide a meaningful and insightful overview of more than 20,000 wild and domesticated barley genotypes from one of the largest crop germplasm collections. The data provide a framework for the rational exploitation of genetic resources in crop improvement, which will be central to addressing global food security.

    • Peter Langridge
    •  & Robbie Waugh
  • News & Views |

    The genomes for essentially all worm parasites of humans are in hand thanks to a new study. Now we have to use them.

    • Paul W. Sternberg
  • News & Views |

    A new study identifies loss-of-function mutations in HAVCR2, which encodes TIM-3, in patients with a rare cutaneous T cell lymphoma associated with aberrant immunological activation. These mutations lead to loss of the TIM-3 immunological checkpoint, thus promoting inflammation and malignancy.

    • Karen O. Dixon
    • , Madhumita Das
    •  & Vijay K. Kuchroo
  • News & Views |

    The availability of various public resources has hastened the discovery of type 2 diabetes–associated loci in the largest genome-wide association study of the disease reported to date. In addition, these resources have also enabled researchers to get closer to determining the culprit genetic variants and therefore closer to the target effector genes driving these associations.

    • Diana L. Cousminer
    •  & Struan F. A. Grant
  • News & Views |

    Patient-derived cancer cell lines could address two major challenges in oncology: real-time drug response prediction and the creation of massive knowledge banks. A new study showcases the power of this approach for precision oncology.

    • Ultan McDermott
  • News & Views |

    A new study uncovers novel copy number signatures in ovarian cancer genomes. This work sheds light on mutational processes driving ovarian cancer, reveals the distribution of copy number features across the patient population and identifies new genomic properties related to treatment response.

    • Sohrab P. Shah
  • News & Views |

    Two new studies show that a plant-specific complex composed of EBS, or its homolog SHL, and EMF1 acts as a chromatin reader within the Polycomb pathway and effects gene repression. Two domains of EBS and SHL bind distinct chromatin modifications that are associated with active and repressed chromatin.

    • Kristin Krause
    •  & Franziska Turck
  • News & Views |

    Individual genome-wide polygenic risk scores (GPSs) for assessing disease susceptibility have been shown to yield both reliable and clinically meaningful results. However, certain impediments and outdated ways of thinking about health maintenance must be overcome before GPSs are adopted in routine care streams.

    • Andrew J. Schork
    • , M. Anthony Schork
    •  & Nicholas J. Schork
  • News & Views |

    Roses have held an attraction for people all over the world as ornamental plants. Now genome sequencing of the highly heterozygous Rosa chinensis and resequencing of major genotypes open the door to a greater understanding of rose evolutionary history and the regulatory mechanisms determining rose flower color and scent.

    • Qing Xu
    •  & Zhong-Jian Liu
  • News & Views |

    The ability to visualize and study the 3D folding of chromosomes in cells has been propelled forward by several major technological advances in the past two decades. Two new studies now further expand the scientific toolbox for studying chromosome conformation by providing novel methodologies for accurate mapping of genome topology and predicting the topological effects of genomic structural variation.

    • Ralph Stadhouders
  • News & Views |

    The triplet code underpins analyses of rare and de novo mutations in exome sequencing data, but analysis of the noncoding genome is much more challenging. A new analytical framework for common, complex diseases highlights the need for very large samples to overcome the unavoidable multiple-testing burden and hence provides preemptive warnings against underpowered studies.

    • Naomi R. Wray
    •  & Jacob Gratten
  • News & Views |

    In vivo verification of tumor suppressors and their interactions with each other has required complex experiments. A report in this issue uses a novel CRISPR–Cas9 technology with barcodes to test, in parallel, the tumorigenic potential of functional loss of multiple tumor-suppressor genes in the context of a genetically engineered mouse model of lung adenocarcinoma with mutant Kras.

    • James Kim
    •  & John D. Minna
  • News & Views |

    Noncoding expanded repeats have been implicated in a wide range of diseases. A new report uncovers expanded TTTCA and TTTTA repeats in an intronic region of SAMD12, and at least two other genes, in individuals with benign adult familial myoclonic epilepsy.

    • Marka van Blitterswijk
    •  & Rosa Rademakers
  • News & Views |

    The switch from fetal to adult hemoglobin relies on repression or silencing of the upstream γ-globin gene, but identification of the transcriptional repressors that bind to the sites at which a cluster of naturally occurring variants associated with HPFH (hereditary persistence of fetal hemoglobin) are found has been elusive. A new study provides mechanistic evidence for the direct binding of BCL11A and ZBTB7A, two previously identified γ-globin gene repressors.

    • Xunde Wang
    •  & Swee Lay Thein
  • News & Views |

    Alterations in craniofacial size and shape are apparent in many monogenic diseases and syndromes, but remarkably little is known about the genetics of face shape within healthy populations. This may be set to change following publication of a study that combines unsupervised hierarchical spectral clustering and canonical correlation analysis to help identify common genetic variants associated with craniofacial shape.

    • David M. Evans
  • News & Views |

    Maternal high-fat diet has a negative impact on fertility—including an apparent direct effect on early development. In this issue, a new study connects this phenotype to depletion of Stella protein in oocytes, demonstrating environmental regulation of a maternal-effect gene.

    • Harry G. Leitch
    •  & Petra Hajkova
  • News & Views |

    New genomic analyses indicate that pioneer transcription factors can sample a diverse repertoire of common binding sites among different cell types and become enriched where they cooperate with other factors specific to each cell. Pioneer-factor binding is mechanistically separate from, and is necessary for, subsequent phenomena of chromatin opening and epigenetic memory in vivo.

    • Kenneth S. Zaret
  • News & Views |

    Two new studies identify rare homozygous variants in ADCY3 that are causal for monogenic obesity in consanguineous families of Pakistani origin and are associated with increased risk of obesity in Greenlandic individuals. Greenlandic carriers of homozygous loss-of-function variants in ADCY3, and individuals from trans-ancestry studies with a burden of rare ADCY3 loss-of-function variants, also have increased risk of type 2 diabetes.

    • Inês Barroso
  • News & Views |

    Dysregulated lipid metabolism is a prominent feature of prostate cancers. Two papers in this issue identify novel genomic drivers of lipid metabolism in prostate cancer and provide implications for the subtyping and treatment of the disease.

    • Ninu Poulose
    • , Francesca Amoroso
    • , Rebecca E. Steele
    • , Reema Singh
    • , Chee Wee Ong
    •  & Ian G. Mills
  • News & Views |

    H3K4me1 is enriched at active and primed enhancers. However, whether H3K4me1 controls or simply correlates with enhancer activity and function has remained unclear. Several recent reports, including two in Nature Genetics, provide major mechanistic and functional insights into the role of H3K4me1 at enhancers.

    • Alvaro Rada-Iglesias
  • News & Views |

    What allows bacteria, both pathogens and mutualists alike, to survive in close association with a eukaryotic host? A new study performed a large-scale comparative genomics analysis to identify novel genetic and genomic traits that are enriched in plant-associated bacterial taxa.

    • Ryan A. Melnyk
    •  & Cara H. Haney
  • News & Views |

    A new study illustrates the power of the human induced pluripotent stem cell (hiPSC) platform by studying hiPSC-derived sensory neurons from 107 individuals. In addition to identifying thousands of quantitative trait loci influencing gene expression, chromatin accessibility and RNA splicing, the work highlights several underappreciated challenges in the hiPSC field.

    • Gabriel E. Hoffman
    •  & Kristen J. Brennand
  • News & Views |

    A new study reports genome-wide variation in 163 vervet monkeys from across their taxonomic and geographic ranges. The analysis suggests a complex history of admixture and identifies signals of repeated evolutionary selection, some of which may be linked to response to simian immunodeficiency virus.

    • Ellen M Leffler
  • News & Views |

    The CRISPR–Cas9 system enables global screens of gene function with high sensitivity and specificity, but off-target effects have been reported for CRISPR guide RNAs targeting genes that are amplified at high copy number. A new study describes a computational approach to correct for this copy number effect, increasing the specificity of CRIPSR screens to identify essential genes.

    • John Paul Shen
    •  & Trey Ideker
  • News & Views |

    A new analysis of cancer genomes identifies a decrease in the mutation burden of exons, but not introns, as compared to expectation. This difference can be explained by preferential recruitment of the DNA mismatch repair machinery to a protein modification that marks exons.

    • Dashiell J Massey
    •  & Amnon Koren
  • News & Views |

    Human-derived tumor models are becoming popular in the context of personalized medicine, but a new study shows that these models could be less representative of primary tumors than previously thought, particularly when using late passages.

    • Carlos Villacorta-Martin
    • , Amanda J Craig
    •  & Augusto Villanueva
  • News & Views |

    High-resolution maps of enhancer–promoter interactions in rare primary human T cell subsets and coronary artery smooth muscle cells link variants associated with autoimmune and cardiovascular diseases to target genes. This represents an important step forward for mapping genes involved in complex diseases.

    • Gosia Trynka
  • News & Views |

    Regulation of epigenetic factors through their recruitment to specific genomic regions is still poorly understood. A recent study demonstrates a global mechanism of tethering Polycomb group (PcG) proteins through sequence-specific DNA-binding factors.

    • Eduardo March
    •  & Sara Farrona
  • News & Views |

    The functional role of repetitive elements in mammalian genomes is still largely unexplored. A new study provides evidence that LINE-1 retrotransposons regulate chromatin dynamics and are essential for normal embryonic development in mice.

    • Edward J Grow
  • News & Views |

    A new study uses a Hi-C technique to demonstrate that condensin has a major role in remodeling interphase chromatin into mitotic chromosomes. This study provides insight into the mechanism whereby a centimeters-long DNA molecule is folded into a micrometers-long rod-shaped chromosome.

    • Tatsuya Hirano
  • News & Views |

    Genetic and functional analyses of 120 mouse strains have identified a heart regeneration candidate gene that modulates the contractile sarcomeric apparatus. This gene, Tnni3k, controls the frequency of the mononuclear, diploid cardiomyocyte population, which affects cardiomyocyte proliferative potential after injury.

    • Ana Vujic
    • , Vinícius Bassaneze
    •  & Richard T Lee
  • News & Views |

    ERG overexpression in prostate cancers promotes the development of widespread changes in gene expression and chromatin landscapes, leading to redistribution of key transcription factors in prostate cancers positive for the TMPRSS2-ERG fusion gene. The overexpression of ERG is further assisted by the development of a super-enhancer in the ERG locus.

    • Deepak Babu
    •  & Melissa J Fullwood
  • News & Views |

    An innovative study analyzing genetic association across tree-structured routine healthcare data in the UK Biobank represents a new branch on a tree that is poised to grow rapidly and offer new kinds of insights on how genome variation relates to human health and disease. Indeed, this tree is likely to offer new kinds of insights into the very nature of human disease.

    • Nancy J Cox
  • News & Views |

    DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust oscillations in gene expression circuits.

    • Feilun Wu
    •  & Lingchong You
  • News & Views |

    Severe allergic disease is common, and few monogenic causes of atopy have been described. A new study that convincingly links severe atopic dermatitis to heterozygous CARD11 mutations with dominant-interfering activity serves as a timely reminder that clinicians should consider the possibility of an underlying monogenic immune disorder when caring for patients suffering from severe allergic disease.

    • Catherine M Biggs
    • , Henry Y Lu
    •  & Stuart E Turvey
  • News & Views |

    A new study reports molecular characterization of the GDF5 locus, which is associated with osteoarthritis risk and adult height in humans. This study provides evidence of positive selection for short stature at GDF5 in modern humans, as well as in archaic Neandertals and Denisovans.

    • Guillaume Lettre
  • News & Views |

    Promoters and enhancers have long been regarded as distinct elements, a notion that has been challenged more recently. Two new studies now identify promoters that function as long-range enhancers in vivo to regulate the transcription of distal genes.

    • Rui R Catarino
    • , Christoph Neumayr
    •  & Alexander Stark
  • News & Views |

    A new study shows that aberrant DNA transposase activity promotes structural alterations that are clonally selected to drive tumor development. This discovery uncovers novel mechanisms of tumor-suppressor gene inactivation and highlights a new approach to cancer gene identification.

    • Stephen C Mack
    • , Hiromichi Suzuki
    •  & Michael D Taylor
  • News & Views |

    A study in this issue demonstrates that epigenome-modifying drugs used in cancer chemotherapy induce transcription from thousands of previously unannotated transcription start sites, most of which are derived from ancient endogenous retroviruses (ERVs). This work, coupled with previous related findings, suggests that induction of ERVs, rather than direct effects on specific genes, may have a central role in the cellular responses to such agents and, in turn, their therapeutic efficacy.

    • Dixie L Mager
    •  & Matthew C Lorincz
  • News & Views |

    Three studies highlight DUX proteins as key transcription factors regulating embryonic genome activation in early mammalian development.

    • Ane Iturbide
    •  & Maria-Elena Torres-Padilla