Volume 55 Issue 7, July 2023

Single large-scale mitochondrial DNA deletions cause a spectrum of disease with differing severities and tissue expressivity. Quantification of single-cell deletion levels with multi-modal cellular readouts provides insights into hematopoietic cell fate and disease manifestation.

Cross-ancestry genome-wide association meta-analyses of neuroimaging genetics data from European and East Asian populations identified 339 genetic variant–hippocampal volumetric trait associations (23 new). Further cross-ancestry analyses revealed similar genetic effects on hippocampal volumetric traits between ancestries, with improved fine-mapping precision and predictive accuracy of polygenic scores in the under-represented East Asian population.

GLIMPSE2 is an improved method using sparse models for accurate, efficient and cost-effective genotype imputation in low-coverage whole-genome sequencing data.

Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand–receptor pairs, prioritizing potential new drug targets.

A genome-wide association study of thoracic aortic aneurysms and dissections (TAAD) in the Million Veteran Program identifies 17 new risk loci and demonstrates that the genetic architecture of TAAD mirrors that of other complex traits.

Multitrait genome-wide association analyses identify hundreds of risk loci for primary open-angle glaucoma. Integration with other data types highlights potential new drug targets, including proteins likely to act via the optic nerve.

Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

GATA2 regulatory mutations are associated with hereditary congenital facial paresis in humans. A genetically engineered mouse model recapitulates the human phenotype, showing altered neuron-specific Gata2 expression and a bias in formation of inner-ear efferent neurons over facial branchial motor neurons.

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed transcription of more posterior-located genes.

Slide-seq profiling of mouse embryos at the onset of organogenesis (embryonic days 8.5–9.5) coupled with a new three-dimensional reconstruction and visualization tool (sc3D) provides high-resolution maps of spatiotemporal gene expression dynamics.

Transcriptomic analysis of BCR-ABL1 lymphoblastic leukemia identifies three subgroups, each associated with a maturation arrest at a specific stage of B-cell progenitor differentiation and distinct genetic and clinical features.

Single-cell analyses of immune cells from patients with pathogenic, single large-scale mitochondrial DNA (mtDNA) deletions including Pearson syndrome describe heteroplasmy dynamics consistent with purifying selection, as well as T-cell state-specific regulatory mechanisms and metabolic vulnerabilities.

A comparison of fetal hemoglobin gene editing strategies using human sickle cell disease donor cells and in vivo transplantation finds that adenine base editing of the –175A>G site in the γ-globin gene promoters results in durable and potent expression.

A complete telomere-to-telomere genome assembly of the maize Mo17 inbred line uncovers structural features of the highly complex maize genome.

Setaria pan-genome constructed using genome assemblies of 110 representative accessions and variation analyses provides insights into foxtail millet domestication and the genetic basis for crop improvement.

SHAPEIT5, a phasing method that accurately processes large sequencing datasets, was applied on the UK Biobank whole-genome and whole-exome sequencing data to generate reference panels of haplotypes that boost imputation accuracy and enable the detection of compound heterozygous loss-of-function events for 549 genes.