Search

Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

The finding of tobacco seeds in a Pleistocene-age fire hearth suggests people learned of this plant’s intoxicant value shortly after their arrival in the Americas, initiating a long heritage of use with global societal impact.

Claudia Langenberg, James Meigs and colleagues apply a joint meta-analysis approach that accounts for differences in body mass index to identify variants associated with glycemic traits. They report six new loci associated with fasting insulin levels and provide insights into the genetic basis of insulin resistance.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

TANK binding kinase 1 (TBK1) is a non-canonical IκB kinase that regulates immunity via NF-κB. Here Pillai et al. show that TBK1 localizes to centrosomes during mitosis, and regulates microtubule dynamics and spindle formation by phosphorylating the centrosomal protein CEP170 and the mitotic apparatus protein NuMa.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

A tight-knit community and a cooperative spirit has helped San Diego to succeed. Eric Niiler checks out California's rising star.

Tisza et al. carry out a sequencing-based analysis of wastewater samples from major cities, to detect and quantify hundreds of distinct pathogenic viruses, finding striking correlations between virus abundance and local clinical cases.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Tran et al. show that environmental glutamine restriction promotes Wnt signaling and intestinal tumorigenesis, whereas supplementation of the metabolite α-ketoglutarate has the reverse effect, reducing tumor growth and extending survival.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

This broad group of authors summarizes the impact of circadian factors on metabolic biology and offers recommendations on how to account for and report biological, environmental and experimental factors affecting circadian rhythms in metabolic studies in rodents.

A single-cell transcriptomic atlas from embryonal pons and forebrain provides insights into the developmental origins of pediatric brain tumors. The study identifies impaired differentiation of specific neural progenitors as a common mechanism underlying these cancers.

PSEN1 E280A carriers develop dementia by midlife, but there is variability in disease trajectory. Cognitive decline is accelerated in E280A carriers who also have an APOE e4 allele. Educational attainment moderates the effect of APOE on cognition.

Insecticide resistance in mosquitoes threatens the success of malaria control programmes. This study found that in different populations of a malaria mosquito species in West Africa, resistance is associated with different genes or different mutations in the same set of genes.

Polygenic Priority Score (PoPS) prioritizes candidate effector genes at complex trait loci by integrating genome-wide association summary statistics with other data types. Combining PoPS with methods that leverage local genetic signals further improves the performance.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

Shifts in species’ migration timing as a result of climate change can result in mismatched temporal overlap with their critical resources. Here the authors show that the magnitude and direction of shifts in juvenile Pacific salmon migration timing vary among species and populations, resulting in variable mismatch with marine productivity, which has implications for climate change vulnerability.

Injection of AAV–shRNA below the pial surface of the spinal cord prevents onset or ameliorates progression in a mouse model of ALS, and achieves widespread delivery to the spinal cord and brain motor centers in adult pigs and non-human primates.

Saloner et al. used large-scale cerebrospinal fluid proteomics to uncover molecular signatures in frontotemporal dementia, revealing RNA splicing and synaptic protein candidate markers for genetic and sporadic disease progression.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Here, the authors perform a large-scale meta-analysis of genome-wide association studies and cis-MR proteomics to identify protein biomarkers and drug targets for heart failure.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

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.

Researchers identify unique transcriptional regulation that controls photosynthetic response, growth and biochemical carbon storage in high light for two variants of the same algae species, offering a glimpse into diel control of plant and crop yields.

Although structural variation has been previously associated with autism spectrum disorders, this study reports a genome-wide significant association of common variants with susceptibility to this disorder group. The results implicate neuronal cell-adhesion molecules in the pathogenesis of this group of neurodevelopmental and neuropsychiatric disorders.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.