News & Comment

  • 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
  • Editorial |

    With new ways to examine the effects of mutations on gene expression within the 3D genome and increased emphasis on finding these variants by sequencing whole genomes, we would really like to know more about the rules that govern noncoding and regulatory sequences.

  • 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
  • Editorial |

    Largely owing to inequitable distribution of resources, the United States is failing its population in healthcare, for which it vastly overspends relative to other wealthy countries. We advocate extending research in genetic epidemiology to oversample poor people, underserved ancestry groups and ethnic minorities, as well as to use genetic predisposition as a baseline from which to examine environmental influences on the costly comorbidities of common diseases.

  • 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
  • Correspondence |

    • Nicole A. Vasilevsky
    • , Erin D. Foster
    • , Mark E. Engelstad
    • , Leigh Carmody
    • , Matt Might
    • , Chip Chambers
    • , Hugh J. S. Dawkins
    • , Janine Lewis
    • , Maria G. Della Rocca
    • , Michelle Snyder
    • , Cornelius F. Boerkoel
    • , Ana Rath
    • , Sharon F. Terry
    • , Alastair Kent
    • , Beverly Searle
    • , Gareth Baynam
    • , Erik Jones
    • , Pam Gavin
    • , Michael Bamshad
    • , Jessica Chong
    • , Tudor Groza
    • , David Adams
    • , Adam C. Resnick
    • , Allison P. Heath
    • , Chris Mungall
    • , Ingrid A. Holm
    • , Kayli Rageth
    • , Catherine A. Brownstein
    • , Kent Shefchek
    • , Julie A. McMurry
    • , Peter N. Robinson
    • , Sebastian Köhler
    •  & Melissa A. Haendel
  • 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
  • Editorial |

    The multiple standardized clinical measurements that make up one’s lifetime path through health and disease are essential information for yourself and your healthcare system. Aggregated into a population cohort study across a single-payer network, these data become an extraordinary tool for improving the efficiency of healthcare delivery and new discoveries in genomic medicine.

  • Editorial |

    The reconstruction of the genome of a woman of African ancestry from her European descendants, across eight generations, connects living people to a documented saga, drawing attention to the individuals who participated in historic events at a time when the legal, cultural and ethical implications of individual human rights began to gain currency. It is also a technical achievement that extends the methodologies for understanding our interwoven genomic and social histories.

  • 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
  • Editorial |

    This issue features epigenetic analysis of cell commitment at many levels in mammalian genomes: during early embryonic development, in stem cells, and in cancer cells. The establishment, propagation and dynamic robustness of cell states is addressed by comprehensive interrogation of the coordination of DNA methylation with the marks and organization of chromatin and programs of gene expression. Understanding this landscape of commitment is essential to interpretation of the functional consequences of genome variation.

  • 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
  • Editorial |

    In the motivation, conduct and reporting of science, there is no substitute for reason, and it must prevail whenever scientific methods are used. Similarly, scientific recommendations can only be useful if they meet with rational decision-making. Because people come to decisions from diverse viewpoints and values, listening to the values and views of scientists and non-scientists—while explicitly refraining from debate and persuasion—may point the way to determining when and where scientific ideas are of interest and likely to be adopted.

  • 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