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Genome-wide sequencing (GWS) is the most sensitive test available for detecting pathogenic genetic variants but it generates complex results. It is important, therefore, that individuals undergoing GWS are offered both pre-test and post-test genetic counselling.
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.
Two new studies in Nature provide insight into the role of nucleosomes in gene regulation. One describes the genome-wide organization of nucleosomes and the other details how transcription factor binding to DNA is affected by the presence of nucleosomes.
A study in Nature Genetics reports the analysis of transcriptomes of the ageing brain and highlights the impact of genetic variation underlying altered mRNA splicing in Alzheimer disease.
CRISPR–Cas genome editing and next-generation sequencing are driving advances in cancer modelling and functional cancer genomics. Their application to autochthonous mouse models of human cancer to generate and analyse multiplexed and/or combinatorial alterations in vivo is reviewed here.
The virulence of viruses is a major determinant of the health burden of viral infections in humans and other species. In this article, Geoghegan and Holmes discuss how largely disparate research fields — theoretical modelling of virulence evolution and experimental dissection of genetic virulence determinants in laboratory model systems — can be bridged by considering real genomic data of viral evolution in a phylogenetic context. They describe the underlying principles of virulence evolution and how they apply to real-world viral infections and outbreaks of global importance.
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.
High-resolution studies of chromosome conformation are revealing that the 3D genome is organized into smaller structural features than was previously supposed and is primarily composed of compartmental domains and CTCF loops. In this Perspectives article Rowley and Corces describe the latest views on the organizational drivers and principles of the 3D genome, and the interplay between genome activity and organization.
