News & Comment

  • 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
  • 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
  • Editorial |

    Citation of prior publications is essential both to claim that knowledge is needed in your area of research and to establish that you have indeed advanced understanding substantially in that area. The journal deplores and will decline to consider manuscripts that fail to identify the key findings of published articles and that—deliberately or inadvertently—omit the reason the prior work is cited.

  • Commentary |

    • Jennifer A Brody
    • , Alanna C Morrison
    • , Joshua C Bis
    • , Jeffrey R O'Connell
    • , Michael R Brown
    • , Jennifer E Huffman
    • , Darren C Ames
    • , Andrew Carroll
    • , Matthew P Conomos
    • , Stacey Gabriel
    • , Richard A Gibbs
    • , Stephanie M Gogarten
    • , Namrata Gupta
    • , Cashell E Jaquish
    • , Andrew D Johnson
    • , Joshua P Lewis
    • , Xiaoming Liu
    • , Alisa K Manning
    • , George J Papanicolaou
    • , Achilleas N Pitsillides
    • , Kenneth M Rice
    • , William Salerno
    • , Colleen M Sitlani
    • , Nicholas L Smith
    • , NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
    • , The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
    • , TOPMed Hematology and Hemostasis Working Group
    • , CHARGE Analysis and Bioinformatics Working Group
    • , Susan R Heckbert
    • , Cathy C Laurie
    • , Braxton D Mitchell
    • , Ramachandran S Vasan
    • , Stephen S Rich
    • , Jerome I Rotter
    • , James G Wilson
    • , Eric Boerwinkle
    • , Bruce M Psaty
    •  & L Adrienne Cupples
  • 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
  • Commentary |

    Genetic variants have been associated with myriad molecular phenotypes that provide new insight into the range of mechanisms underlying genetic traits and diseases. Identifying any particular genetic variant's cascade of effects, from molecule to individual, requires assaying multiple layers of molecular complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx project to combine gene expression with additional intermediate molecular measurements on the same tissues to provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.

    • eGTEx Project
    • , Barbara E Stranger
    • , Lori E Brigham
    • , Richard Hasz
    • , Marcus Hunter
    • , Christopher Johns
    • , Mark Johnson
    • , Gene Kopen
    • , William F Leinweber
    • , John T Lonsdale
    • , Alisa McDonald
    • , Bernadette Mestichelli
    • , Kevin Myer
    • , Brian Roe
    • , Michael Salvatore
    • , Saboor Shad
    • , Jeffrey A Thomas
    • , Gary Walters
    • , Michael Washington
    • , Joseph Wheeler
    • , Jason Bridge
    • , Barbara A Foster
    • , Bryan M Gillard
    • , Ellen Karasik
    • , Rachna Kumar
    • , Mark Miklos
    • , Michael T Moser
    • , Scott D Jewell
    • , Robert G Montroy
    • , Daniel C Rohrer
    • , Dana R Valley
    • , David A Davis
    • , Deborah C Mash
    • , Sarah E Gould
    • , Ping Guan
    • , Susan Koester
    • , A Roger Little
    • , Casey Martin
    • , Helen M Moore
    • , Abhi Rao
    • , Jeffery P Struewing
    • , Simona Volpi
    • , Kasper D Hansen
    • , Peter F Hickey
    • , Lindsay F Rizzardi
    • , Lei Hou
    • , Yaping Liu
    • , Benoit Molinie
    • , Yongjin Park
    • , Nicola Rinaldi
    • , Li Wang
    • , Nicholas Van Wittenberghe
    • , Melina Claussnitzer
    • , Ellen T Gelfand
    • , Qin Li
    • , Sandra Linder
    • , Rui Zhang
    • , Kevin S Smith
    • , Emily K Tsang
    • , Lin S Chen
    • , Kathryn Demanelis
    • , Jennifer A Doherty
    • , Farzana Jasmine
    • , Muhammad G Kibriya
    • , Lihua Jiang
    • , Shin Lin
    • , Meng Wang
    • , Ruiqi Jian
    • , Xiao Li
    • , Joanne Chan
    • , Daniel Bates
    • , Morgan Diegel
    • , Jessica Halow
    • , Eric Haugen
    • , Audra Johnson
    • , Rajinder Kaul
    • , Kristen Lee
    • , Matthew T Maurano
    • , Jemma Nelson
    • , Fidencio J Neri
    • , Richard Sandstrom
    • , Marian S Fernando
    • , Caroline Linke
    • , Meritxell Oliva
    • , Andrew Skol
    • , Fan Wu
    • , Joshua M Akey
    • , Andrew P Feinberg
    • , Jin Billy Li
    • , Brandon L Pierce
    • , John A Stamatoyannopoulos
    • , Hua Tang
    • , Kristin G Ardlie
    • , Manolis Kellis
    • , Michael P Snyder
    •  & Stephen B Montgomery
  • 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
  • Editorial |

    This issue highlights a range of genetic techniques and cell biological models required to begin to understand the levels of long-range regulation of gene expression as it occurs during cell differentiation. Explanations based on the specificity of covalent modifications and binding interactions intersect with evidence for conjectured mechanisms of topological loop creation and maintenance by transcription and motile protein activities.

  • 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