Volume 54 Issue 2, February 2022

Similar to CTCF, MAZ insulates repressed posterior Hoxa genes from the spreading of anterior active regulatory cues during motoneuron differentiation. This discovery provides new perspectives to understand chromatin organization and insulation.

The function of transposable elements present in mammalian genomes remains an enigma. In this issue, Bodega, Abrignani and colleagues show that LINE1-containing transcripts are key regulators of T cell effector function and exhaustion.

This Perspective discusses the analytical issues concerning heterogeneity and power encountered in microbial genome-wide association studies and highlights potential future directions for genetic analysis of the microbiome.

This Perspective explores the spatial and genomic mobility of extrachromosomal DNA within the cell and proposes how these properties may be harnessed for therapeutic benefit.

Normal cellular processes can cause DNA breaks which become substrates for the cell’s DNA repair machinery. Focusing on neurons, this Perspective article explores the role of this ‘programmed’ DNA damage and its repair in health, ageing and neurodegenerative disease.

Multi-ancestry genome-wide analyses identify variants near UGT2A1 and UGT2A2 associated with COVID-19-related loss of smell or taste. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants.

Multi-ancestry fine-mapping of the OAS1/2/3 region shows that a splice site variant in OAS1 is likely responsible for the association of this locus with the risk of severe COVID-19.

Common mutational analyses assume that every base in the genome can only mutate once. Here, the authors report multiple violations of this infinite sites model in whole-genome data across a range of tumor types.

Genome-wide association analysis of gut microbial taxa in a single homogenous population-based cohort of 5,959 Finnish individuals identifies 567 independent SNP–taxon associations, including strong associations with LCT, ABO and MED13L.

A genome-wide association study of 207 taxa and 205 pathways representing gut microbial composition and function from 7,738 individuals of the Dutch Microbiome Project identifies genetic associations at the LCT and ABO loci.

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.

A multi-ancestry expression quantitative trait locus meta-analysis of 3,983 RNA-seq samples from 2,119 donors using the multivariate multiple QTL (mmQTL) approach characterizes the genetics of gene expression in the human brain and identifies candidate causal variants for brain-related traits.

A germline variant associated with acute lymphoblastic leukemia activates an enhancer element resulting in increased GATA3 expression, altered chromatin accessibility and changes in three-dimensional genome organization.

Non-canonical transcripts containing LINE1 transposable elements maintain naive CD4⁺ T cell quiescence and interfere with gene expression in cis. LINE1-containing transcripts are downregulated upon T cell activation.

Hi-C and live-imaging data show that nucleoprotein complexes containing the transcription factor Rok interact over long distances in the bacterium Bacillus subtilis. Rok-dependent interactions contribute to anchored chromosomal loop formation.

Genome-wide screens identify several genes, including MAZ, required for CTCF-mediated insulation. MAZ interacts with cohesin, and MAZ motif deletions derepress posterior Hox gene expression, leading to homeotic transformations in mouse.