News & Comment

  • Editorial |

    A solution to screening for recessive heritable disorders and identifying genetic influences on common diseases is to be found in the history of one of the world's most populous regions. Large South Asian populations are a mosaic of smaller populations, many of which have founder effects as extreme as those in the European isolates that first inspired genetic medicine.

  • News and 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 and 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 and 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
  • Editorial |

    This month's research articles span the range of scales of gene-regulatory mechanisms, from a deceptively simple gene therapy vector, via synthetic gene expression circuits, to extremely intricate epigenetic switches. We encourage investigation of synthetic circuits exploring the functions of the 3D genome.

  • News and 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 and 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 and 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 and 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
  • Editorial |

    This journal and Scientific Data are calling for submissions containing linked open data models that embody and extend the FAIR principles: that data should be findable, accessible, interoperable and reusable by both humans and machines. These principles are achievable with existing resources, languages and vocabularies to enable computers to combine and reanalyze data sets automatically and lead humans to new discoveries.

  • News and 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 and 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 and Views |

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

    • Ane Iturbide
    •  & Maria-Elena Torres-Padilla
  • Editorial |

    Understanding of how epigenetic information is acquired, processed and transmitted through cell division, and potentially across generations, remains limited. Mechanistic studies aiming to elucidate the molecular underpinnings of these phenomena may provide insights into development, disease susceptibility and evolution.

  • News and Views |

    A DNA modification—methylation of cytosines and adenines—has important roles in diverse processes such as regulation of gene expression and genome stability, yet until recently adenine methylation had been considered to be only a hallmark of prokaryotes. A new study identifies abundant adenine methylation of transcriptionally active genes in early-diverging fungi that, together with recent other work, emphasizes the importance of adenine methylation in eukaryotes.

    • Michael F Seidl
  • News and Views |

    New work reports that both derepressed and hyper-repressed chromatin states in animals can be transmitted to progeny for many generations. Transmission depends on genomic architecture and histone modifications.

    • Vincenzo Pirrotta
  • News and Views |

    An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV) infection confirms the innate and adaptive arms of the immune system as drivers of viral evolution. Viral adaptation has a critical role in the interaction between host and pathogen and has important clinical implications for infection outcome.

    • Silvana Gaudieri
    •  & Michaela Lucas
  • Editorial |

    With the advent of precision genome editing, the ability to modify living organisms has proceeded with remarkable speed and breadth. Any application of this technology to the human germ line must be tightly coupled to deliberate consideration of the consequences, both scientific and social, of introducing heritable alterations to the human population. We recommend constant oversight and evaluation of human germline genome editing to balance prudence with discovery, and risk with progress.

  • News and Views |

    A new resequencing analysis of weedy rice (Oryza sativa L.) biotypes illuminates distinct evolutionary paths and outcomes of de-domestication and ferality. This largest effort to date in weedy plant genomics gives a better understanding of weediness while also providing a promising source of alleles for rice breeding.

    • C Neal Stewart Jr
  • News and Views |

    Mammalian SWI/SNF complexes have critical roles in development and differentiation, and are implicated in the pathogenesis of several diseases; however, the mechanisms underpinning disease manifestation and the specificity of the subunits mutated are incompletely understood. Newly identified loss-of-function mutations in the SMARCD2 gene (part of the SMARCD1, SMARCD2 and SMARCD3 paralog family) reveal an evolutionarily conserved role specifically for the SMARCD2 subunit in granulopoiesis, and further investigation implicates the CEBPɛ transcription factor as a key effector of this specific function.

    • Brittany C Michel
    •  & Cigall Kadoch
  • News and Views |

    The newly described de novo goat genome sequence is the most contiguous diploid vertebrate assembly generated thus far using whole-genome assembly and scaffolding methods. The contiguity of this assembly is approaching that of the finished human and mouse genomes and suggests an affordable roadmap to high-quality references for thousands of species.

    • Kim C Worley