Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Recent studies have revealed a ubiquitous role for genome architecture in the formation of structural variants at a given locus, both in DNA recombination-based and in DNA replication-based processes. These reports showcase the influence of repeat sequences on genomic stability and structural variant complexity and the tremendous plasticity and dynamic nature of our genome.
Genome-wide approaches have advanced the study into mechanisms triggering autoimmunity. This Review illustrates how this has been achieved for twelve common autoimmune diseases, and discusses recent functional genomics approaches that have the potential to help define key immune molecular traits, cell types and cell states.
RNA-guided endonucleases have the potential to revolutionize the engineering of synthetic gene drives, which may be particularly useful for the control of vector-borne diseases. Here, the authors review different types of engineered gene drives and their potential applications, as well as considerations regarding the safety and regulation of gene drives for the manipulation of wild populations.
Phenotypic data from electronic health records and epidemiological studies can be exploited to study the impact of genetic variation on the phenome. This Review highlights challenges that need to be overcome for the characterization of the complex human genome–phenome relationship using phenome-wide association studies (PheWAS).
Single-cell genome sequencing can provide detailed insights into the composition of single genomes that are not readily apparent when studying bulk cell populations. This Review discusses the considerable technical challenges of amplifying and interrogating genomes from single cells, emerging innovative solutions and various applications in microbiology and human disease, in particular in cancer.
Genomic analyses of cancer genomes have largely focused on mutations in protein-coding regions, but the functional importance of alterations to non-coding regions is becoming increasingly appreciated through whole-genome sequencing. This Review discusses our current understanding of non-coding sequence variants in cancer — both somatic mutations and germline variants, and their interplay — including their identification, computational and experimental evidence for functional impact, and their diverse mechanisms of action for dysregulating coding genes and non-coding RNAs.
Why does the rate of evolution vary among sites within proteins? The authors review the current understanding of site-specific variation, discuss possible limitations of current methods and models, and propose directions for future research.
Technical differences between the many variant methods that are based on restriction site-associated DNA sequencing (RADseq) lead to trade-offs in experimental design and analysis. Here, the authors comprehensively review the various RADseq approaches and provide general considerations for designing a RADseq study.
