Volume 56 Issue 5, May 2024

Genomic and epigenomic techniques identify a new variation type causing Mendelian disease by altering the non-coding regulatory network in thyroid cells — solving a hidden cause linked for 20 years.

By integrating spatially resolved single-cell RNA sequencing (scRNA-seq) and Stereo-seq data, two studies in this issue characterize molecular signatures of liver cell types and their interactions in homeostasis, damage, repair and regeneration.

Experimental genome evolution of normal human cells reveals an intrinsic propensity to develop cancer-associated chromosomal alterations.

This study establishes in vitro and in vivo systems to study mutagenesis and cancer genome evolution. Using microfluidics and mouse models, the method enables the dissection of co-occurring mutational processes and reveals that acute damage results in mirror-image mutation phasing between sister cells after a single mitosis.

Chromosome-level genome sequences of 69 diverse Arabidopsis thaliana strains reveal a quasi-fixed genome structure worldwide, in which large rearrangement is limited almost exclusively to the centromeric regions. Pan-genome analysis uncovered substantial diversity in gene content that, together with the genome assemblies, will fuel future genetic research.

We construct a chromosome-level genome assembly of the acorn barnacle Amphibalanus amphitrite. Using this genome together with multi-omics datasets and functional evidence, we reveal the evolution and function of two lineage-specific genes, bcs-6 and bsf, that help A. amphitrite adapt to a sessile lifestyle.

This Perspective discusses how addressing disparities in genomics can drive improvements in health equity more broadly.

Integrating human pluripotent stem cell models with population genetics and cellular genomics can help elucidate functional mechanisms underlying complex disease risk loci and uncover relationships between common genetic variation and pharmacotherapeutic phenotypes.

SBayesRC integrates genome-wide association summary statistics with functional annotations to improve polygenic prediction of complex traits. Functional partitioning highlights a major contribution of evolutionarily constrained regions to prediction accuracy.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

Genome-wide association analyses identify risk loci for breast cancer in women of African ancestry. Polygenic risk scores derived from these data improve ancestry-specific risk prediction.

A multi-ancestry genome-wide association study of liver cirrhosis and its associated endophenotypes identifies and validates 14 risk variants. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

Joint likelihood mapping across six autoimmune diseases identifies shared and distinct association signals and improves fine-mapping resolution at loci with shared effects, yielding insights into the underlying biological mechanisms.

DNA methylation data of whole blood from Han Chinese individuals are used to map mQTLs, finding that cis- and trans-mQTLs show distinct patterns of East Asians (EA) ancestry-specific colocalization with complex trait variation.

Analysis of genetic modifiers of 599 developmental disorder genes in the UK Biobank found that rare variant burden within this set, as well as the common polygenic background, can alter the expressivity of cognitive and socioeconomic traits in an additive manner.

Noncoding variants in a TTTG microsatellite on 15q26.1 are identified in Japanese patients with childhood and adult-onset thyroid abnormalities. Functional analyses suggest that these variants affect the role of the microsatellite as a potential regulator of thyroid cell growth.

Short tandem repeat mutations in a primate Alu element on chromosome 15q cause activation of a thyroid-specific enhancer, upregulating MIR7-2/MIR1179. This results in defective thyroid proliferation and thyrotropin resistance.

Amplification-free single-cell whole-genome sequencing shows that genomic, evolutionary and biophysical factors collectively drive cell-to-cell variation in mitochondrial DNA copy number.

This study examines karyotypic selection and evolution in vitro using immortalized mammary and kidney epithelial cell lines, observing aneuploidy patterns specific to each origin tissue that are correlated with frequencies in patient tumors and independent of drivers such as TP53 mutation.

A single-cell-based approach allows the daughters of a damaged cell to be separately tracked following single mitotic events. This technique highlights the different ways in which ultraviolet light and reactive oxygen species cause mutagenesis.

BEAN is a Bayesian approach for analyzing base editing screens with improved effect size quantification and variant classification. Applied to low-density lipoprotein (LDL)-associated common variants and saturation base editing of LDLR, BEAN identifies new LDL uptake genes and offers insights into variant structure–pathogenicity mechanisms.

A comprehensive time series characterization of a mouse model of cholestatic liver injury with spatial enhanced resolution omics sequencing and single-cell RNA sequencing identifies zonal responses to insult, such as cholangiocyte signaling recruiting lipid-associated macrophages.

A Stereo-seq and scRNA-seq atlas of mouse liver in homeostasis and regeneration after partial hepatectomy identifies zonated genes, pathways, cell–cell interactions and gene regulatory networks. Functional validation finds that cooperation between TBL1XR1 and β-catenin activates hepatocyte proliferation.

A new acorn barnacles genome assembly, together with transcriptomic and proteomic datasets and functional experiments, identify bcs-6 and bsf, as new genes involved in the settlement process by facilitating energy metabolism and stabilizing the alternating layers of chitin and calcites, respectively.

A pan-genome of Arabidopsis thaliana constructed using chromosome-level genome assemblies of 69 diverse accessions reveals a conserved genome structure throughout the global species range.

High-quality genome assemblies of grain and vegetable cowpeas and re-sequencing of 344 accessions characterize genomic variations between cowpea subspecies and their domestication and improvement under selection.

A comprehensive variation map constructed by deep sequencing 1,904 accessions of weedy and cultivated broomcorn millet sheds light on the genetic architecture of agronomic traits during domestication.

Genome assemblies of four filamentous Zygnematophyceae and co-expression network analyses shed light on the evolutionary roots of the mechanism for balancing environmental responses and multicellular growth.