Volume 53 Issue 7, July 2021

R-loops—nucleic acid structures composed of an RNA:DNA hybrid and displaced single-stranded DNA—are abundant in the genome and may impair progression of the replication fork, thus leading to accumulation of DNA damage and genome instability. A new study demonstrates that SWI/SNF chromatin-remodeling complexes are instrumental in resolving such R-loop-mediated transcription–replication conflicts, highlighting the importance of these chromatin remodelers in R-loop homeostasis and the maintenance of genome integrity.

The UK Biobank Exome Sequencing Consortium aims to sequence all the exomes of approximately 500,000 UK Biobank participants. This Perspective describes the results from approximately 200,000 exomes and discusses the lessons learned from this UK Biobank–biopharmaceutical company collaboration.

An association model that estimates dominance and additive effects applied to imputed whole-genome data from cattle allows for the mapping of recessive syndromes in the absence of disease classification by using proxy phenotypes such as body weight.

PHYTOCHROME-INTERACTING FACTORs reshape the H2A.Z epigenetic landscape in response to light quality changes in Arabidopsis thaliana, through an interaction with the INO80 chromatin remodeling complex.

A large-scale genetic analysis of type 1 diabetes identifies new susceptibility variants, highlights potential regulatory mechanisms and provides genetic support for therapeutic targets for immune intervention.

An analytical framework based on transcriptome-wide association and electronic medical records provides insights into the relationship between plasma lipids and complex diseases on a phenome-wide scale.

An analysis of the UK Biobank identifies 227 new associations between mitochondrial DNA (mtDNA) variants and phenotypes. mtDNA genetic architecture reflects regional UK nuclear genome ancestry.

A multi-tissue atlas of alternative polyadenylation (APA) quantitative trait loci (3′aQTLs) identifies approximately 0.4 million common genetic variants associated with the APA of target genes. Approximately 16% of trait-associated variants colocalize with 3′aQTLs.

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

The histone H3K4 methyltransferase SET1B is recruited to a subset of hypoxia-inducible genes by the HIF complex. Loss of SET1B reduces HIF transcriptional activity in hypoxia and impairs tumor formation in xenograft models.

Genetic manipulation of poised enhancers (PEs) shows that orphan CpG islands promote physical and functional communication between PEs and distally located developmental genes.

The SWI/SNF complex helps resolve R-loop-mediated transcription–replication conflicts, as depletion of SWI/SNF complex member BRG1 increases R-loops, R-loop-dependent DNA breaks and transcription–replication conflicts.

The insulation potency of CTCF depends on the number of binding sites in tandem and on upstream flanking sequences. Insulators form local chromatin domain boundaries and weaken enhancer–promoter contacts.

Hi-C and single-molecule sequencing analysis provide an improved assembly of the Xenopus tropicalis genome and insights into three-dimensional genome dynamics throughout embryogenesis.

Radiotherapy induces small and large deletions as well as inversions across the genome in multiple cancer types. The genomic changes associated with radiotherapy correlate with poorer clinical outcomes.

REGENIE is a whole-genome regression method based on ridge regression that enables highly parallelized analysis of quantitative and binary traits in biobank-scale data with reduced computational requirements.

QUILT is a method for rapid genotype imputation and phasing from low-coverage whole-genome sequence data using a large haplotype reference panel. QUILT enables highly accurate imputation across a range of coverages and data types.