News & Comment

  • Editorial |

    Genetic tools can help uncover evolutionary histories, migration patterns and admixture events of domesticated animals and their wild ancestors. The genetic window into the past can help shape breeding strategies and inform animal agricultural practices that should lead to a more resilient and sustainable future.

  • News & Views |

    FOXA1 is a key pioneer factor in androgen-receptor activity but has been an elusive drug target. A new study shows that inhibition of the associated cofactor LSD1 modifies the methylation state of FOXA1, thus resulting in chromatin dissociation and tumor inhibition, even in models of treatment-resistant prostate cancer.

    • Soleilmane Omarjee
    •  & Jason S. Carroll
  • News & Views |

    How do boundary elements divide chromosomes into domains? A new study uses random genomic insertions to show how small genomic fragments can shape chromatin folding through the interplay of loop extrusion and compartmentalization. Spoiler: context matters.

    • Erika C. Anderson
    •  & Elphège P. Nora
  • Comment |

    The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms to inform effective vaccine and drug development. Despite the novelty of the virus, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations in infection, host immunity and drug development, we have developed COVID-3D ( http://biosig.unimelb.edu.au/covid3d/ ).

    • Stephanie Portelli
    • , Moshe Olshansky
    • , Carlos H. M. Rodrigues
    • , Elston N. D’Souza
    • , Yoochan Myung
    • , Michael Silk
    • , Azadeh Alavi
    • , Douglas E. V. Pires
    •  & David B. Ascher
  • Comment |

    The WashU Virus Genome Browser is a web-based portal for efficient visualization of viral ‘omics’ data in the context of a variety of annotation tracks and host infection responses. The browser features both a phylogenetic-tree-based view and a genomic-coordinate, track-based view in which users can analyze the sequence features of viral genomes, sequence diversity among viral strains, genomic sites of diagnostic tests, predicted immunogenic epitopes and a continuously updated repository of publicly available genomic datasets.

    • Jennifer A. Flynn
    • , Deepak Purushotham
    • , Mayank N. K. Choudhary
    • , Xiaoyu Zhuo
    • , Changxu Fan
    • , Gavriel Matt
    • , Daofeng Li
    •  & Ting Wang
  • Comment |

    The UCSC SARS-CoV-2 Genome Browser ( https://genome.ucsc.edu/covid19.html ) is an adaptation of our popular genome-browser visualization tool for this virus, containing many annotation tracks and new features, including conservation with similar viruses, immune epitopes, RT–PCR and sequencing primers and CRISPR guides. We invite all investigators to contribute to this resource to accelerate research and development activities globally.

    • Jason D. Fernandes
    • , Angie S. Hinrichs
    • , Hiram Clawson
    • , Jairo Navarro Gonzalez
    • , Brian T. Lee
    • , Luis R. Nassar
    • , Brian J. Raney
    • , Kate R. Rosenbloom
    • , Santrupti Nerli
    • , Arjun A. Rao
    • , Daniel Schmelter
    • , Alastair Fyfe
    • , Nathan Maulding
    • , Ann S. Zweig
    • , Todd M. Lowe
    • , Manuel Ares Jr
    • , Russ Corbet-Detig
    • , W. James Kent
    • , David Haussler
    •  & Maximilian Haeussler
  • Editorial |

    Increasing amounts of crop genomic resources, along with new technical achievements in genome analysis, can facilitate basic and translational research in agriculture, and expand the ability to meet the global challenge of food production and security.

  • News & Views |

    The role of N6-methyladenosine (m6A) is still not fully understood. Two new studies advance understanding of this RNA modification. One shows that m6A modification of nascent messenger RNA promotes transcription by recruiting the histone H3 K9 demethylase KDM3B. Another study identifies genetic variants that affect m6A deposition and human disease.

    • Dalen Chan
    •  & Pedro J. Batista
  • News & Views |

    Binding of RNA to the gene expression regulator Polycomb repressive complex 2 (PRC2) has been proposed to antagonize PRC2’s chromatin recruitment. A new study now shows that RNA is in fact critical for correct recruitment of PRC2 at its target genes in human pluripotent stem cells and suggests that interplay of PRC2 and RNA can fine-tune PRC2’s regulatory role.

    • Ivano Mocavini
    •  & Luciano Di Croce
  • Editorial |

    Gene nomenclature can be complicated, and the official naming of genes requires rational standards to avoid confusion and to maximize clarity. The HUGO Gene Nomenclature Committee has released updated guidelines for the naming of human genes, and we encourage the community to adopt these recommendations.

  • Comment |

    Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in health care, the need for a consistent language to refer to human genes becomes ever more essential. Here, we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding genes but also RNA genes and pseudogenes, and we outline the changes in approach and ethos that have resulted from the discoveries of the past few decades.

    • Elspeth A. Bruford
    • , Bryony Braschi
    • , Paul Denny
    • , Tamsin E. M. Jones
    • , Ruth L. Seal
    •  & Susan Tweedie
  • News & Views |

    Genomes are highly organized in space and time. Compartments, topologically associating domains (TADs) and loops are three dimensional (3D) genome features that have been extensively studied. Among these three levels of organization, TADs have sparked the most debate. New microscopy data shed light on how TADs and their leaky borders contribute to gene regulation.

    • Irene Farabella
    •  & Marc A. Marti-Renom
  • Editorial |

    When the status quo in science continues to perpetuate ingrained systems of discrimination, inequality and racism, the beneficiaries of these systems must not only reexamine their collective practices but also redress historical injustices through consequential, concrete actions that will lead to change. We cannot focus only on the first steps of listening and learning to build a better, fairer scientific community. We at Nature Genetics fully commit to pledging our energy and efforts toward long-term goals explicitly designed to fundamentally transform how science and its dissemination are conducted.

  • News & Views |

    How ‘difficult’ is it for somatic evolution to produce a cell that is capable of leaving the primary tumor and growing in a distant organ? In this issue, Reiter et al. assess genetic diversity across metastatic lesions and identify a tight selective bottleneck preceding distant metastasis.

    • Trevor A. Graham
    •  & Darryl Shibata
  • News & Views |

    Pachytene Piwi-interacting RNAs (piRNAs) are abundant small non-coding RNAs expressed in mammalian germ lines. A new study indicates that, among the diverse pool of piRNA sequences, a small number act as highly selective guides that induce cleavage of coding and non-coding transcripts, thus promoting piRNA generation and regulating gene expression.

    • Alexei A. Aravin
  • Editorial |

    One of the many consequences of the global COVID-19 pandemic is the need for the scientific community to adapt to the cancellation of conferences and events because of travel restrictions and social-distancing guidelines. We have seen a very swift conversion to online meetings, which have allowed for this established form of science communication to continue and opened new avenues for innovation in the reporting of research and discussion of ideas.

  • News & Views |

    TET2 and DNMT3A mutations lead to similar long-term outcomes in blood cancers despite the antagonistic biochemical functions of their encoded proteins. A new study highlights the opposing effects of TET2 and DNMT3A mutations in shaping the early erythroid or myeloid bias of hematopoietic progenitors.

    • Isaac F. López-Moyado
    •  & Anjana Rao
  • News & Views |

    Many normal tissues are populated by clonal expansions that compete for space. Colom et al. now show that mutant clones keep other mutant clones in check by effectively annulling one another’s advantages.

    • Kamila Naxerova
  • Editorial |

    The promise of personalized medicine lies in the tailored treatment of individual patients, a process requiring detailed phenotypic and genetic information. Although the widespread collection of such data can help to advance the implementation of precision healthcare, the genomic sequencing data being amassed also include private information that could potentially be used as a basis for genetic discrimination. It is important for the genetics community to be aware of these risks and to contribute to policies designed to monitor and mitigate threats to the equitable treatment of individuals or populations on the basis of genetics.

  • News & Views |

    A new study addresses whether transcription of enhancers and the resulting enhancer RNAs (eRNAs) play a role in mediating long-range interactions between enhancers and promoters. Studying the immunoglobulin heavy chain (Igh) locus, the authors find that transcription of the enhancers per se is required to establish but not maintain these interactions, and this mechanism may apply to a subset of other enhancer–promoter interactions.

    • Douglas R. Higgs
  • News & Views |

    A new study identifies sorbitol dehydrogenase (SORD) deficiency as a slowly progressive hereditary motor axonopathy caused by a genetic defect in the second step of the polyol pathway, thus leading to elevated tissue and blood sorbitol. SORD deficiency is the most common recessive cause of neuropathy, for which therapeutic intervention with aldose reductase inhibitors may have potential.

    • Eva Morava
  • Editorial |

    In 2015, the World Health Organization (WHO) issued guidelines for the naming of new human infectious diseases. The current global outbreak of the SARS-CoV-2 virus underscores the need to be accurate with our language, particularly as it relates to pandemics.

  • News & Views |

    Cancer cells have the extraordinary evolutionary potential to adapt and acquire resistance to most conventional and targeted therapies. In a new study, Lin et al., develop a systematic approach to identify combination therapies that produce cancer traps, in which evading the first drug makes the cancer vulnerable to the second.

    • Charles Y. Lin
  • Comment |

    Genetic discrimination is one of the most pervasive challenges resulting from research and development in human genetics. To collaboratively study and prevent this ethical issue, we established an international Genetic Discrimination Observatory comprising a network of researchers and stakeholders from more than 19 jurisdictions.

    • Yann Joly
    • , Gratien Dalpé
    • , Charles Dupras
    • , Bénédicte Bévière-Boyer
    • , Aisling de Paor
    • , Edward S. Dove
    • , Palmira Granados Moreno
    • , Calvin W. L. Ho
    • , Chih-Hsing Ho
    • , Katharina Ó Cathaoir
    • , Kazuto Kato
    • , Hannah Kim
    • , Lingqiao Song
    • , Timo Minssen
    • , Pilar Nicolás
    • , Margaret Otlowski
    • , Anya E. R. Prince
    • , Athira P. S. Nair
    • , Ine Van Hoyweghen
    • , Torsten H. Voigt
    • , Chisato Yamasaki
    •  & Yvonne Bombard
  • Comment |

    The African Orphan Crops Consortium promotes the strategic, genome-enabled improvement of under-researched crops for biodiversity-based, nutritious food solutions in Africa. The African Plant Breeding Academy empowers the continent’s plant breeders to apply advanced genetic approaches and shared genetic solutions to the task of tailoring the immense diversity of underutilized crops to the needs of Africa’s producers, processors and consumers.

    • Ramni Jamnadass
    • , Rita H. Mumm
    • , Iago Hale
    • , Prasad Hendre
    • , Alice Muchugi
    • , Ian K. Dawson
    • , Wayne Powell
    • , Lars Graudal
    • , Howard Yana-Shapiro
    • , Anthony J. Simons
    •  & Allen Van Deynze
  • Editorial |

    The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium project, led by the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), coordinated the sequencing and analysis of 2,583 tumor whole genomes across 38 cancer types. This impressively large project, comprising many working groups focusing on various molecular or genetic features of cancer, has generated valuable data for the cancer research community that will continue to be mined for many years to come.

  • News & Views |

    Efforts to systematically characterize silencers in animal genomes have been limited. Two studies in this issue of Nature Genetics bring silencers into the spotlight, identifying these elements genome wide in human and mouse cells, and providing insights into their function.

    • Monica Della Rosa
    •  & Mikhail Spivakov
  • News & Views |

    Huntington’s disease is a severe progressive neurological disorder caused by a CAG-repeat expansion in the HTT gene. A small molecule shows therapeutic potential by inducing contraction of these expanded CAG repeats in cell and mouse models of the disease.

    • Michael D. Flower
    •  & Sarah J. Tabrizi
  • Editorial |

    Given that it is based on heredity and has the ability to trace connections, genetics as a scientific discipline should be among those most attuned to diversity and global perspectives. Indigenous communities and scientists have much to contribute to genetics research, and they are making their voices heard. We celebrate these essential members of our larger genetics community, and we look forward to working together to learn from past examples, meet present challenges and support future opportunities.

  • Editorial |

    As we usher in a new year of a new decade and ponder what the future will bring for the genetics field, we wish to reflect on some specific areas related to diversity, privacy and genome editing that require attention and vigilance from the community.

  • News & Views |

    RNA:DNA hybrids that form across genomes control a wide range of biological processes. A new study shows that N6-methyladenosine (m6A) modification on the RNA moieties regulates the formation and genome integrity of these hybrids. This finding opens a new avenue of research on how RNA modifications (the ‘epitranscriptome’) can help control genome maintenance.

    • Aline Marnef
    •  & Gaëlle Legube
  • Comment |

    The 11th International Conference on Rare Diseases and Orphan Drugs (ICORD), South Africa, included the Africa-Rare initiative launch and facilitated multi-stakeholder engagement in the challenges facing, and opportunities for, Africans living with rare diseases. The following ICORD Global Call to Action, developed in collaboration with the International Rare Diseases Research Consortium, synthesizes the outcomes of the deliberations and emphasizes the international collaborative efforts required to address the global effects of rare diseases on public health.

    • Gareth S. Baynam
    • , Stephen Groft
    • , Francois H. van der Westhuizen
    • , Safiyya D. Gassman
    • , Kelly du Plessis
    • , Emily P. Coles
    • , Eda Selebatso
    • , Moses Selebatso
    • , Boikobo Gaobinelwe
    • , Tebogo Selebatso
    • , Dipesalema Joel
    • , Virginia A. Llera
    • , Barend C. Vorster
    • , Barbara Wuebbels
    • , Benjamin Djoudalbaye
    • , Christopher P. Austin
    • , Judit Kumuthini
    • , John Forman
    • , Petra Kaufmann
    • , James Chipeta
    • , Désirée Gavhed
    • , Annika Larsson
    • , Maja Stojiljkovic
    • , Ann Nordgren
    • , Emilio J. A. Roldan
    • , Domenica Taruscio
    • , Durhane Wong-Rieger
    • , Kristen Nowak
    • , Gemma A. Bilkey
    • , Simon Easteal
    • , Sarah Bowdin
    • , Juergen K. V. Reichardt
    • , Sergi Beltran
    • , Kenjiro Kosaki
    • , Clara D. M. van Karnebeek
    • , Mengchun Gong
    • , Zhang Shuyang
    • , Ruty Mehrian-Shai
    • , David R. Adams
    • , Ratna D. Puri
    • , Feng Zhang
    • , Nicholas Pachter
    • , Maximilian Muenke
    • , Christoffer Nellaker
    • , William A. Gahl
    • , Helene Cederroth
    • , Stephanie Broley
    • , Maryke Schoonen
    • , Kym M. Boycott
    •  & Manuel Posada
  • Editorial |

    As the year comes to a close and we start to look ahead to 2020, we thought that we would highlight some of our favorite Nature Genetics papers from 2019. This snapshot also captures some of the topics and themes in genetics that we are most excited to see develop in the near future.

  • News & Views |

    A new study presents a powerful experimental approach, CRISPRi-FlowFISH, for mapping regulatory interactions, and uses it to characterize thousands of putative enhancer–gene pairs. The results suggest that most current approaches for predicting enhancer–gene interactions perform poorly, but a simple mathematical model combining distance with enhancer activity shows promise.

    • Daniel J. Gaffney
  • Comment |

    Ancestral and geographical issues underlie the need to develop Africa-specific guidelines for the return of genomics research results in Africa. In this Commentary, we outline the challenges that will inform policies and practices in the future.

    • Ambroise Wonkam
    •  & Jantina de Vries
  • Editorial |

    Popular crop plants have been bred and selected for desirable taste and color traits. Genomic approaches are increasingly being used to provide insights into the origins, evolution and biology of our favorite foods. Large-scale sequencing efforts have brought agriculture genomics into the big-data era, leading to sweet rewards.

  • Comment |

    A fundamental problem in rare-disease diagnostics is the lack of consensus as to which genes have sufficient evidence to attribute causation. To address this issue, we have created PanelApp ( https://panelapp.genomicsengland.co.uk ), a publicly available knowledge base of curated virtual gene panels.

    • Antonio Rueda Martin
    • , Eleanor Williams
    • , Rebecca E. Foulger
    • , Sarah Leigh
    • , Louise C. Daugherty
    • , Olivia Niblock
    • , Ivone U. S. Leong
    • , Katherine R. Smith
    • , Oleg Gerasimenko
    • , Eik Haraldsdottir
    • , Ellen Thomas
    • , Richard H. Scott
    • , Emma Baple
    • , Arianna Tucci
    • , Helen Brittain
    • , Anna de Burca
    • , Kristina Ibañez
    • , Dalia Kasperaviciute
    • , Damian Smedley
    • , Mark Caulfield
    • , Augusto Rendon
    •  & Ellen M. McDonagh
  • News & Views |

    Two genetic studies uncover how domestication changed fruit quality traits in melon and watermelon. The studies combine population genomic and quantitative genetic tools to study crop evolution and provide breeders with comprehensive variation maps.

    • Murukarthick Jayakodi
    • , Mona Schreiber
    •  & Martin Mascher
  • Comment |

    A generic framework for providing participant information and implementing a tiered consent process for health genomic research in Africa can help to harness global health benefits from sharing and meta-analysis of African genomic data while simultaneously respecting and upholding the autonomy and individual choices of African research participants.

    • Victoria Nembaware
    • , Katherine Johnston
    • , Alpha A. Diallo
    • , Maritha J. Kotze
    • , Alice Matimba
    • , Keymanthri Moodley
    • , Godfrey B. Tangwa
    • , Rispah Torrorey-Sawe
    •  & Nicki Tiffin
  • Editorial |

    Understanding how to biologically interpret the loci identified in genome-wide association studies is a major goal of current genetics research. To achieve this goal, we need to understand where, when and how relevant genes are expressed in specific contexts, in order to explore the mechanistic links between genetic associations and diseases or complex traits.

  • News & Views |

    A new study identifies germline NPM1 mutations in people with dyskeratosis congenita. These NPM1 mutations inhibit ribosomal RNA 2´-O-methylation by decreasing the binding of the rRNA methyltransferase FBL to small nucleolar RNAs. Thus, NPM1 influences ribosomal functions via epitranscriptomic regulation.

    • Fengbiao Zhou
    •  & Carsten Müller-Tidow
  • Correspondence |

    • Mariano J. Alvarez
    • , Pengrong Yan
    • , Mary L. Alpaugh
    • , Michaela Bowden
    • , Ewa Sicinska
    • , Chensheng W. Zhou
    • , Charles Karan
    • , Ronald B. Realubit
    • , Prabhjot S. Mundi
    • , Adina Grunn
    • , Dirk Jäger
    • , John A. Chabot
    • , Antonio T. Fojo
    • , Paul E. Oberstein
    • , Hanina Hibshoosh
    • , Jeffrey W. Milsom
    • , Matthew H. Kulke
    • , Massimo Loda
    • , Gabriela Chiosis
    • , Diane L. Reidy-Lagunes
    •  & Andrea Califano
  • Comment |

    To increase the utility of Gene Ontology (GO) annotations for interpretation of genome-wide experimental data, we have developed GO-CAM, a structured framework for linking multiple GO annotations into an integrated model of a biological system. We expect that GO-CAM will enable new applications in pathway and network analysis, as well as improve standard GO annotations for traditional GO-based applications.

    • Paul D. Thomas
    • , David P. Hill
    • , Huaiyu Mi
    • , David Osumi-Sutherland
    • , Kimberly Van Auken
    • , Seth Carbon
    • , James P. Balhoff
    • , Laurent-Philippe Albou
    • , Benjamin Good
    • , Pascale Gaudet
    • , Suzanna E. Lewis
    •  & Christopher J. Mungall
  • News & Views |

    Common genetic variants increase the risk of schizophrenia, but the downstream biological mechanisms are largely unknown. A new study demonstrates that schizophrenia risk genes cause neuronal dysfunction and have synergistic effects on gene expression.

    • Jane H. Christensen
    •  & Anders D. Børglum
  • Editorial |

    The genome of the model genetic organism Pisum sativum, or pea plant, links nineteenth-century genetics to twenty-first-century genomics, serving as a symbol of how far the genetics field has developed and how greatly technologies have advanced. Almost every student’s introduction to genetics currently involves learning Mendel’s laws; we envision that genomics and genome sequencing will become just as foundational in the education of future geneticists.

  • News & Views |

    Inferring adaptation, migration and population history would be profoundly easier if we could use the genomes that we sequence to infer the true genealogical history of each locus. Two new papers bring us close to achieving this goal.

    • Kelley Harris
  • News & Views |

    Far from being junk DNA, the pervasive retrotransposons that populate the genome have a powerful capacity to influence genes and chromatin. A new study demonstrates how the transcription of one such element, HERV-H, can modify the higher-order 3D structure of chromatin during early primate development.

    • Michael I. Robson
    •  & Stefan Mundlos