Genetic techniques articles within Nature Reviews Genetics

Featured

  • Review Article |

    Targeted genome modification using CRISPR–Cas genome editing, base editing or prime editing is driving base research in plants and precise molecular breeding. The authors review the technological principles underlying these methods, approaches for their delivery in plants, and emerging crop-breeding strategies based on targeted genome modification.

    • Boshu Li
    • , Chao Sun
    •  & Caixia Gao

  • Journal Club |

    Magda Bienko highlights a landmark paper by Lieberman-Aiden et al., which in 2009 reported the development of high-throughput chromosome conformation capture (Hi-C), revolutionizing the field of 3D genome biology.

    • Magda Bienko

  • Research Highlight |

    A new study in Nature Methods describes a computational method named UTAG (unsupervised discovery of tissue architecture with graphs) that aims to identify and quantify higher-level tissue domains from biological images without previous knowledge.

    • Linda Koch

  • Research Highlight |

    A microscopy-based pooled CRISPR screening approach described in Cell enables the cellular functions of thousands of genes to be assessed at remarkable phenotypic depth.

    • Dorothy Clyde

  • Review Article |

    Spatial omics methods enable the charting of cellular heterogeneity, complex tissue architectures and dynamic changes during development and disease. The authors review the developing landscape of in situ spatial transcriptome, genome and proteome technologies and highlight their impact on basic and translational research.

    • Jeffrey R. Moffitt
    • , Emma Lundberg
    •  & Holger Heyn

  • Review Article |

    Large-scale genetic datasets and deep learning approaches are being used to model the structures of proteins or protein complexes. This Review describes approaches based on coevolution, deep mutational scanning and genome-scale genetic or chemical–genetic interaction mapping and their application and integration to inform structural modelling.

    • Hannes Braberg
    • , Ignacia Echeverria
    •  & Nevan J. Krogan

  • Research Highlight |

    Two recent studies demonstrate that putative nucleases encoded by IS200/IS605 family transposons are programmable RNA-guided DNA endonucleases, which could represent a new source of genome-editing enzymes for biotechnological applications.

    • Grant Otto

  • Research Highlight |

    A study in Nature describes single-cell ribosome sequencing, which advances single-cell genomics by enabling the measurement of translational dynamics in single cells.

    • Katharine H. Wrighton

  • Research Highlight |

    Three recent studies report the generation of miniature CRISPR systems based on compact Cas effector proteins, showing high efficiency of genome editing or transcriptional regulation in mammalian cells.

    • Linda Koch

  • In Brief |

    A new method called CIM-seq analyses pairwise co-occurrences of cell types across multiplets to identify cells that are in physical contact with each other in intact tissues.

    • Linda Koch

  • Review Article |

    Combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics can localize transcriptionally characterized single cells within their native tissue context. This Review discusses methodologies and tools to integrate scRNA-seq with spatial transcriptomics approaches, and illustrates the types of insights that can be gained.

    • Sophia K. Longo
    • , Margaret G. Guo
    •  & Paul A. Khavari

  • In Brief |

    Park et al. describe in Cell how CRISPR–Cas9 genome editing can be used as a time recorder in mammalian cells in vitro and in vivo, including reporting the timescales of cellular events such as chemical exposure and inflammation.

    • Darren J. Burgess

  • In Brief |

    The TOPMed consortium report whole-genome sequencing data from 53,831 ethnically diverse participants. They describe the key features of the genetic variation and produce data resources for future medical research by the wider scientific community.

    • Darren J. Burgess

  • Research Highlight |

    A recent study in Nature presents a method that integrates data from chromosome imaging, nuclear bodies and chromatin states to build a picture of the nuclear layout at the single-cell level.

    • Ingrid Knarston

  • In Brief |

    In this study in Molecular Cell, Clarke et al. describe a system that enables multiple Cas9-mediated genome edits to be introduced into cells in a defined, sequential order.

    • Dorothy Clyde

  • Research Highlight |

    A study in Nature reports that adenine base editors can correct the mutation that causes Hutchinson–Gilford progeria syndrome in a mouse model of this disease, extending lifespan.

    • Katharine H. Wrighton

  • In Brief |

    The CRISPR–Cas13 system can be used to knock down circular RNAs (circRNAs) without any impact on related mRNAs, reports a study in Nature Methods.

    • Linda Koch

  • Research Highlight |

    Two new reports in Cell use genome-wide CRISPR screens to uncover host determinants of coronavirus infection, identifying potential leads for antiviral therapeutics.

    • Darren J. Burgess

  • 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
    •  & Jin-Soo Kim

  • Comment |

    Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects on the promisesthat this voyage of discovery bore. Its success should be measured by how this project transformed the rules of research, the way of practising biological discovery and the ubiquitous digitization of biological science.

    • Richard A. Gibbs

  • Research Highlight |

    Three new studies in Nature Biotechnology combine the adenine and cytosine deaminase activities of single base editors to generate dual base editor systems for combinatorial editing in human cells.

    • Darren J. Burgess

  • Research Highlight |

    Two new studies in Nature Biotechnology demonstrate the feasibility of functional genomics systems beyond Cas9: a combinatorial DNA editing system involving both Cas9 and Cas12a, and an RNA-targeted system based on Cas13.

    • Darren J. Burgess

  • Research Highlight |

    A new study in Cell reports a mammalian genetic screening strategy that combines CRISPR libraries with in situ sequencing to read out both complex cellular phenotypes and genetic perturbations using microscopy.

    • Darren J. Burgess

  • Research Highlight |

    A new genome editing strategy called prime editing uses a catalytically impaired Cas9 fused to an engineered reverse transcriptase to write desired genetic sequence information directly into a target locus.

    • Linda Koch

  • Research Highlight |

    A study in Nature retraces the convergent evolution of resistance to cardiac glycosides in insects, pinpointing the adaptive alleles and their functional consequences.

    • Linda Koch

  • Review Article |

    In eukaryotes, circular RNAs (circRNAs) carry out important biological roles by acting as microRNA or protein sponges, regulating protein function or through cap-independent translation. New technologies for identifying and characterizing circRNAs will increase our knowledge of their biogenesis and function in health and disease.

    • Lasse S. Kristensen
    • , Maria S. Andersen
    •  & Jørgen Kjems

  • Research Highlight |

    A study in Nature Methods describes a light-activated dynamic looping (LADL) system, which consists of a synthetic architectural protein that rapidly induces long-range chromatin interactions in response to blue light.

    • Linda Koch

  • Research Highlight |

    A new technique named ChIA-Drop combines chromatin interaction analysis (ChIA) with droplet-based and barcode-linked high-throughput sequencing to capture multiplex chromatin interactions at the single-molecule level.

    • Linda Koch

  • Research Highlight |

    A study in Nature shows the feasibility of using the CRISPR–Cas9 system for efficient and precise genotypic correction of pathogenic mutations without a donor template.

    • Ross Cloney

  • Research Highlight |

    Two studies in Nature describe the full data set of the UK Biobank resource, which contains genome-wide genetic data, clinical measurements and health records for ~500,000 individuals, and reveal insights into the brain’s genetic architecture.

    • Orli G. Bahcall

  • Review Article |

    Genome editing through direct editing of bases holds promise for achieving precise genomic changes at single-nucleotide resolution while minimizing the occurrence of potentially mutagenic double-strand DNA breaks. In this Review, Rees and Liu provide a comprehensive account of the state of the art of base editing of DNA and RNA, including the progressive improvements to methodologies, understanding and avoiding unintended edits, cellular and organismal delivery of editing reagents and diverse applications in research and therapeutic settings.

    • Holly A. Rees
    •  & David R. Liu

  • Research Highlight |

    Two studies report the application of high-throughput genome editing approaches to engineer many precise genetic variants and determine their functional impact in human and yeast cells.

    • Michelle Trenkmann

  • Review Article |

    In this Review, Sheth and Wang describe emerging synthetic biology approaches for using DNA as a memory device for recording cellular events, including the various methodological steps from detecting diverse signals, converting them into DNA alterations and reading out and interpreting the recorded information. Furthermore, they discuss potential applications as biotechnological and environmental biosensors.

    • Ravi U. Sheth
    •  & Harris H. Wang

  • Review Article |

    Fine-mapping is the process by which a trait-associated region from a genome-wide association study (GWAS) is analysed to identify the particular genetic variants that are likely to causally influence the examined trait. This Review discusses the diverse statistical approaches to fine-mapping and their foundations, strengths and limitations, including integration of trans-ethnic human population data and functional annotations.

    • Daniel J. Schaid
    • , Wenan Chen
    •  & Nicholas B. Larson

  • Review Article |

    Although the field of functional genomics is increasingly adopting genome-scale approaches, a comprehensive understanding of gene functions requires the parallel development of deep phenotyping platforms. This Review discusses strategies for broad-based mouse phenomics, applied both to gene knockout collections and to diverse strains harbouring natural genetic variation. The authors discuss technical challenges, analysis pipelines and insights into human disease genetics.

    • Steve D. M. Brown
    • , Chris C. Holmes
    •  & Sara Wells

  • Review Article |

    The rapid development of CRISPR-based gene manipulation has enabled various approaches for high-throughput functional genomics. This Review guides users through the practicalities of CRISPR-based functional genomics screens, including study design options, best-practice approaches, pitfalls to avoid and data analysis strategies.

    • John G. Doench

  • Opinion |

    Advances in genome sequencing, editing and synthetic biology have enhanced the feasibility of large-scale genome engineering, termed genome writing. In this Opinion article, Chari and Church discuss the strengths and limitations of diverse strategies for genome writing, including extensively modifying existing genomes versus synthesizing genomesde novo, and they provide future visions for writing large genomes.

    • Raj Chari
    •  & George M. Church

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