Latest Reviews

  • Review Article |

    MicroRNAs (miRNA) exert essential functions in mammalian development and physiology. The authors review recent insights from the phenotypic analysis of miRNA knockouts in mice that emphasize roles for these non-coding RNAs at different developmental stages and in adults, and illustrate the importance of functional miRNA targets, miRNA dosage, miRNA interactions and cellular context.

    • Brian DeVeale
    • , Jennifer Swindlehurst-Chan
    •  & Robert Blelloch
  • Review Article |

    Shadow enhancers regulate a common target gene and drive expression patterns that overlap spatiotemporally. The authors review recent insights into the prevalence and role of shadow enhancers in metazoans, as well as their mechanisms of action to fine-tune gene expression. They also discuss the evolution of shadow enhancers and their implication in disease.

    • Evgeny Z. Kvon
    • , Rachel Waymack
    • , Mario G. Elabd
    •  & Zeba Wunderlich
  • Review Article |

    Africa is a continent with deep evolutionary history, which has implications for the genetic underpinnings of disease. In this Review, the authors discuss how genetic features of African populations provide both challenges and opportunities for understanding disease genetics in Africa. They describe how this genetic knowledge — combined with initiatives including capacity-building, data sharing and increased representation of African genomes in genetic variation databases — can be leveraged towards achieving precision medicine approaches in African healthcare.

    • Luisa Pereira
    • , Leon Mutesa
    • , Paulina Tindana
    •  & Michèle Ramsay
  • Review Article |

    Our evolutionary history has resulted in highly complex and sophisticated human physiology. Yet evolutionary footprints have also left us prone to diseases. In this Review, the authors discuss how events from the earliest history of life on Earth through to modern human evolution influence many disease traits and outcomes. They describe how an understanding and application of evolutionary frameworks can inform precision medicine initiatives.

    • Mary Lauren Benton
    • , Abin Abraham
    • , Abigail L. LaBella
    • , Patrick Abbot
    • , Antonis Rokas
    •  & John A. Capra
  • Review Article |

    The ability to reprogramme cellular translation and genomes to produce non-canonical biopolymers has wide-ranging applications, including in therapeutics, but has yet to be fully realized. In this Review, de la Torre and Chin discuss recent advances towards achieving this goal.

    • Daniel de la Torre
    •  & Jason W. Chin
  • Review Article |

    Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.

    • Giuliana Ferrari
    • , Adrian J. Thrasher
    •  & Alessandro Aiuti
  • Review Article |

    Infectious diseases are an ever-present global threat. In this Review, Kwok, Mentzer and Knight discuss our latest understanding of how human genetics influence susceptibility to disease. Furthermore, they discuss emerging progress in the interplay between host and pathogen genetics, molecular responses to infection and vaccination, and opportunities to bring these aspects together for rapid responses to emerging diseases such as COVID-19.

    • Andrew J. Kwok
    • , Alex Mentzer
    •  & Julian C. Knight
  • Perspective |

    Although cancer genetics analyses have often focused on individual mutations of classic cancer genes, a wealth of cancer sequencing data are allowing a more comprehensive understanding of the cumulative effects of mutations genome-wide. In this Perspective article, the authors propose how the burden of different types of mutation — from point mutations to large-scale chromosomal aberrations — has distinct and compensatory effects on tumour fitness and selection during different stages of cancer evolution.

    • Erez Persi
    • , Yuri I. Wolf
    • , David Horn
    • , Eytan Ruppin
    • , Francesca Demichelis
    • , Robert A. Gatenby
    • , Robert J. Gillies
    •  & Eugene V. Koonin
  • Review Article |

    In this Review, Carter and Zhao discuss how single-cell sequencing technologies are being applied to investigate epigenetic heterogeneity among seemingly homogeneous populations of cells and how this epigenetic variability relates to cell–cell differences in gene expression.

    • Benjamin Carter
    •  & Keji Zhao
  • Review Article |

    RNA-binding proteins (RBPs) are critical effectors of gene expression, and their malfunction underlies many diseases. The authors review the role of RBPs in human genetic disorders, both Mendelian and somatic, discuss the molecular mechanisms of disease and highlight emerging therapeutic interventions that target RBPs.

    • Fátima Gebauer
    • , Thomas Schwarzl
    • , Juan Valcárcel
    •  & Matthias W. Hentze
  • Review Article |

    In this Review, Oudelaar and Higgs discuss the relationship between genome structure and gene regulation, with a focus on whether genome organization has an instructive role or largely reflects the activity of regulatory elements.

    • A. Marieke Oudelaar
    •  & Douglas R. Higgs
  • Perspective |

    This Perspective reviews efforts to map six different RNA modifications — pseudouridine (Ψ), 5-methylcytidine (m5C), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), ribose methylations (Nm) and N7-methylguanosine (m7G) — and how they differ from N6-methyladenosine (m6A). The authors discuss the technical and analytical challenges of characterizing the epitranscriptome and provide their own conclusions on the abundance and distribution of these modifications.

    • David Wiener
    •  & Schraga Schwartz
  • Review Article |

    Cell–cell interactions and communication can be inferred from RNA sequencing data of, for example, ligand–receptor pairs. The authors review insights gained and the methods and tools used in studies of cell–cell interactions based on transcriptomic data.

    • Erick Armingol
    • , Adam Officer
    • , Olivier Harismendy
    •  & Nathan E. Lewis
  • Review Article |

    The effects of genetic variation on the adaptive potential of species depend on the frequencies of alleles at other loci in the individual or in the population, and the patterns of spatio-temporal co-occurrence between alleles in interacting species. This Review explores these population and community genomic contexts and their direct and indirect effects on biodiversity, ecosystems and people.

    • Madlen Stange
    • , Rowan D. H. Barrett
    •  & Andrew P. Hendry
  • Perspective |

    Recent studies have demonstrated that concomitant activity of de novo methylation and demethylation machineries results in rapid turnover of DNA methylation in certain contexts. The authors review this phenomenon and propose that DNA methylation turnover may facilitate key lineage decisions.

    • Aled Parry
    • , Steffen Rulands
    •  & Wolf Reik
  • Review Article |

    Deep resequencing has revealed extreme genetic variation in mitochondrial genomes at multiple levels. This heterogeneity has implications for the origins of human mitochondrial DNA mutations as well as their impact on rare and common human diseases, including cancer.

    • James B. Stewart
    •  & Patrick F. Chinnery
  • Review Article |

    In this Review, Cenik and Shilatifard focus on two families of Trithorax group proteins: COMPASS histone H3 lysine 4 methyltransferase complexes and SWI/SNF chromatin remodelling complexes. They discuss the roles of these complexes in gene regulation, development and disease.

    • Bercin K. Cenik
    •  & Ali Shilatifard
  • Review Article |

    Various cellular metabolites provide the chemical moieties for DNA and histone modifications, resulting in a complex interplay between metabolism and epigenetics. In this Review, Dai, Ramesh and Locasale discuss the metabolic regulation of diverse types of chromatin modifications and the functional consequences of these modifications at the molecular, cellular and organismal levels, as well as influences from diet and microbiota.

    • Ziwei Dai
    • , Vijyendra Ramesh
    •  & Jason W. Locasale
  • Review Article |

    Host–parasite co-evolution is expected to leave signatures of selection in the genome of both antagonists. Ebert and Fields discuss what is known about these signatures, how they relate to co-evolutionary processes and how they can help identify the genes underlying the co-evolving phenotypes.

    • Dieter Ebert
    •  & Peter D. Fields
  • Review Article |

    In this Review, Suhre, McCarthy and Schwenk describe how combining genetics with plasma proteomics is providing notable insights into human disease. As changes in the circulating proteome are often an intermediate molecular readout between a genetic variant and its organismal effect, proteomics can enable a deeper understanding of disease mechanisms, clinical biomarkers and therapeutic opportunities.

    • Karsten Suhre
    • , Mark I. McCarthy
    •  & Jochen M. Schwenk
  • Viewpoint |

    To celebrate the first 20 years of Nature Reviews Genetics, we asked 12 leading scientists to reflect on the key challenges and opportunities faced by the field of genetics and genomics.

    • Amy L. McGuire
    • , Stacey Gabriel
    • , Sarah A. Tishkoff
    • , Ambroise Wonkam
    • , Aravinda Chakravarti
    • , Eileen E. M. Furlong
    • , Barbara Treutlein
    • , Alexander Meissner
    • , Howard Y. Chang
    • , Núria López-Bigas
    • , Eran Segal
    •  & Jin-Soo Kim
  • Review Article |

    Both genetic and non-genetic factors underlie the intratumoural heterogeneity that fuels cancer evolution. This Review discusses the application of single-cell multi-omics technologies to the study of cancer evolution, which capture and integrate the different layers of heritable information and reveal their complex interplay.

    • Anna S. Nam
    • , Ronan Chaligne
    •  & Dan A. Landau
  • Review Article |

    The growth and survival of cells within tissues can be influenced by competition between different cell clones. Genetic and cell biological studies suggest that cell competition may occur through the molecular recognition of ‘different’ cells, signalling imbalances between cell populations or the mechanical consequences of differential growth rates.

    • Nicholas E. Baker
  • Review Article |

    Genome instability can lead to a number of human diseases, including neurodegeneration and cancer. In this Review, Zong et al. discuss the various ways in which RNA can both promote genome instability and contribute to genome maintenance.

    • Dali Zong
    • , Philipp Oberdoerffer
    • , Pedro J. Batista
    •  & André Nussenzweig
  • Review Article |

    Gene expression is typically measured at the level of either mRNAs or proteins. In this Review, Buccitelli and Selbach discuss how large-scale comparative studies are characterizing the degree to which mRNA and protein levels correlate. They discuss technical and biological reasons why mRNA and protein levels may be particularly concordant or disconnected, as well as the different biological information provided by these non-redundant readouts of gene expression.

    • Christopher Buccitelli
    •  & Matthias Selbach
  • Review Article |

    Data sharing can maximize the benefit and reach of genomics research. However, sharing must occur in a responsible manner, particularly when there are privacy risks to human participants. In this Review, the authors discuss the principles of data sharing, strategies for assessing and mitigating privacy risks, as well as practical guidelines for researchers and wider stakeholders.

    • James Brian Byrd
    • , Anna C. Greene
    • , Deepashree Venkatesh Prasad
    • , Xiaoqian Jiang
    •  & Casey S. Greene
  • Expert Recommendation |

    In this Expert Recommendation, the authors review the definitions of classic concepts relating to bacterial gene regulation, with a focus on transcription initiation, and suggest up-to-date, precise definitions to provide a reference for knowledge representation, modelling and future research on bacterial gene regulation.

    • Citlalli Mejía-Almonte
    • , Stephen J. W. Busby
    • , Joseph T. Wade
    • , Jacques van Helden
    • , Adam P. Arkin
    • , Gary D. Stormo
    • , Karen Eilbeck
    • , Bernhard O. Palsson
    • , James E. Galagan
    •  & Julio Collado-Vides
  • Perspective |

    Increased capacities for sequencing and genotyping are enabling a more comprehensive understanding of the genetics of adaptation for diverse species. In this Perspective, Barghi, Hermisson and Schlötterer describe how polygenic adaptation can be studied using a framework of ‘adaptive architecture’ that unifies principles from the traditionally disparate fields of quantitative genetics and molecular population genetics.

    • Neda Barghi
    • , Joachim Hermisson
    •  & Christian Schlötterer
  • Review Article |

    Computational tools to analyse RNA sequencing data often disregard or even misinterpret reads derived from transposable elements. This Review highlights the main challenges associated with the detection of transposable element expression, including mappability, sequence polymorphisms and transcript diversity, and discusses the experimental and computational strategies to overcome them.

    • Sophie Lanciano
    •  & Gael Cristofari
  • Review Article |

    The development of successful anticancer therapies relies on identifying drug targets that are genuine cancer-specific vulnerabilities. In this article, Lin and Sheltzer discuss how the different genetic and pharmacological methods for identifying and characterizing cancer dependencies each have important strengths and limitations. Responsible and orthogonal use of these methods holds promise for maximizing the ability of preclinical research to translate into clinical benefit.

    • Ann Lin
    •  & Jason M. Sheltzer
  • Review Article |

    In this Review, several experts discuss progress in the decade since the development of transposon-based approaches for bacterial genetic screens. They describe how advances in both experimental technologies and analytical strategies are resulting in insights into diverse biological processes.

    • Amy K. Cain
    • , Lars Barquist
    • , Andrew L. Goodman
    • , Ian T. Paulsen
    • , Julian Parkhill
    •  & Tim van Opijnen
  • Review Article |

    The role of DNA methylation in genomic imprinting and X-chromosome inactivation (XCI) is well documented, but other imprinting mechanisms exist. Here, the authors review the role of oocyte-derived histone H3 lysine 27 trimethylation in establishing autosomal imprinting and imprinted XCI.

    • Zhiyuan Chen
    •  & Yi Zhang
  • Review Article |

    Long-read sequencing is becoming more accessible and more accurate. In this Review, Logsdon et al. discuss the currently available platforms, how the technologies are being applied to assemble and phase human genomes, and their impact on improving our understanding of human genetic variation.

    • Glennis A. Logsdon
    • , Mitchell R. Vollger
    •  & Evan E. Eichler
  • Review Article |

    The capacity to regenerate tissue varies across different species and tissue types. The poor regenerative capacity of organs such as the heart and nervous system contributes to the aetiology of a number of serious diseases, including heart failure and Alzheimer disease. In this Review, Goldman and Poss discuss how genetic programmes of regeneration are regulated and how the control mechanisms might be adapted to treat human disease.

    • Joseph A. Goldman
    •  & Kenneth D. Poss
  • Review Article |

    Genetic recombination is a fundamental biological process generating genetic variation by shuffling combinations of alleles. In this Review, Peñalba and Wolf focus on how sequencing-based approaches are providing diverse insights into recombination rate variation across levels of biological organization and timescales, from individual gametes of single individuals to populations through evolutionary history.

    • Joshua V. Peñalba
    •  & Jochen B. W. Wolf
  • Review Article |

    Wilkinson and colleagues discuss haematopoietic stem cell (HSC) self-renewal in mice and humans. Experimental techniques for assaying HSC self-renewal are addressed, along with biological mechanisms regulating HSC self-renewal in vivo and ex vivo, and the therapeutic implications of this understanding.

    • Adam C. Wilkinson
    • , Kyomi J. Igarashi
    •  & Hiromitsu Nakauchi
  • Review Article |

    Understanding evolutionary relationships between species requires the generation of accurate phylogenetic trees. In this Review, Kapli, Yang and Telford discuss the principles, steps and computational tools for phylogenetic tree building. They describe the impact of burgeoning genomic datasets as well as the diverse sources of errors and how they can be mitigated.

    • Paschalia Kapli
    • , Ziheng Yang
    •  & Maximilian J. Telford
  • Review Article |

    Colour traits have been useful for studying the genetics underlying adaptive evolution. This Review discusses how genomic technologies are providing a deeper understanding of these traits, revealing fresh insights into their genetic architecture, evolvability and origins of adaptive variation.

    • Anna Orteu
    •  & Chris D. Jiggins
  • Roadmap |

    A curated list of genes that are relevant to autism spectrum disorder (ASD) would greatly benefit clinical genetic testing. This Roadmap discusses the need for an evidence-based framework for gene curation that is based on the level of information supporting a clinically relevant relationship between a given gene and ASD.

    • Christian P. Schaaf
    • , Catalina Betancur
    • , Ryan K. C. Yuen
    • , Jeremy R. Parr
    • , David H. Skuse
    • , Louise Gallagher
    • , Raphael A. Bernier
    • , Janet A. Buchanan
    • , Joseph D. Buxbaum
    • , Chun-An Chen
    • , Kira A. Dies
    • , Mayada Elsabbagh
    • , Helen V. Firth
    • , Thomas Frazier
    • , Ny Hoang
    • , Jennifer Howe
    • , Christian R. Marshall
    • , Jacques L. Michaud
    • , Olivia Rennie
    • , Peter Szatmari
    • , Wendy K. Chung
    • , Patrick F. Bolton
    • , Edwin H. Cook
    • , Stephen W. Scherer
    •  & Jacob A. S. Vorstman
  • Review Article |

    Genetic improvement of production traits in aquaculture has great potential to help meet the rising seafood demands driven by human population growth. The authors review how genomics is being applied to aquaculture species at all stages of the domestication process to optimize selective breeding.

    • Ross D. Houston
    • , Tim P. Bean
    • , Daniel J. Macqueen
    • , Manu Kumar Gundappa
    • , Ye Hwa Jin
    • , Tom L. Jenkins
    • , Sarah Louise C. Selly
    • , Samuel A. M. Martin
    • , Jamie R. Stevens
    • , Eduarda M. Santos
    • , Andrew Davie
    •  & Diego Robledo
  • Review Article |

    Improvements in DNA extraction methods and sequencing technologies have led to the successful sequencing of numerous whole ancient genomes. In this Review, the authors provide an overview of how ancient DNA has informed our understanding of the domestication of various animal species, including dogs, pigs, cattle, goats and chickens.

    • Laurent A. F. Frantz
    • , Daniel G. Bradley
    • , Greger Larson
    •  & Ludovic Orlando
  • Perspective |

    In this Perspective article, the authors discuss how Indigenous Peoples' desires for greater involvement and oversight when participating in genomic research projects can be balanced against calls for unrestricted data access. They provide practical recommendations for the handling and sharing of Indigenous genomic data, with the aim of achieving mutual benefit for the research community and participating Indigenous communities.

    • Maui Hudson
    • , Nanibaa’ A. Garrison
    • , Rogena Sterling
    • , Nadine R. Caron
    • , Keolu Fox
    • , Joseph Yracheta
    • , Jane Anderson
    • , Phil Wilcox
    • , Laura Arbour
    • , Alex Brown
    • , Maile Taualii
    • , Tahu Kukutai
    • , Rodney Haring
    • , Ben Te Aika
    • , Gareth S. Baynam
    • , Peter K. Dearden
    • , David Chagné
    • , Ripan S. Malhi
    • , Ibrahim Garba
    • , Nicki Tiffin
    • , Deborah Bolnick
    • , Matthew Stott
    • , Anna K. Rolleston
    • , Leah L. Ballantyne
    • , Ray Lovett
    • , Dominique David-Chavez
    • , Andrew Martinez
    • , Andrew Sporle
    • , Maggie Walter
    • , Jeff Reading
    •  & Stephanie Russo Carroll
  • Review Article |

    Understanding developmental trajectories has recently been enabled by progress in modern lineage-tracing methods that combine genetic lineage analysis with omics-based characterization of cell states (particularly transcriptomes). In this Review, Wagner and Klein discuss the conceptual underpinnings, experimental strategies and analytical considerations of these approaches, as well as the biological insights gained.

    • Daniel E. Wagner
    •  & Allon M. Klein
  • Review Article |

    Electronic health records (EHRs) linked to biobanks provide new opportunities for developing and applying polygenic risk scores in the clinic. The authors review the opportunities and challenges that arise when using EHR data for the systematic evaluation of patient disease susceptibilities.

    • Ruowang Li
    • , Yong Chen
    • , Marylyn D. Ritchie
    •  & Jason H. Moore