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Loss of function of the minor spliceosome component ZRSR2 enhances hematopoietic stem cell self-renewal through minor intron retention of its target LZTR1, which is a regulator of RAS-related GTPases. Minor intron retention of LZTR1 was also identified in Noonan syndrome and diverse solid tumor types.

Freezing of gait is a debilitating motor symptom that commonly occurs in Parkinson disease, atypical parkinsonism and other neurodegenerative conditions, the management of which is complex. This Expert Recommendation provides updated, state-of-the-art recommendations for the management of freezing of gait, based on the latest insights into the pathophysiology of the condition.

The hydroclimatic variations of the Amazon River basin can exert profound impacts on the marine ecosystem in the Amazon plume region. Here the authors show that an amplified seasonal cycle of Amazonia precipitation during 1979–2018 leads to enhanced seasonality in both Amazon river discharge and ocean salinity.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Nitrogen isotopic measurements from fossilized cycad leaves and ancestral state reconstructions suggest that N₂-fixing symbiosis arose independently in the lineages leading to extant cycads at some point during or after the Jurassic.

It has been thought that the evolution of mammals similar to modern grass-eating horses in South America ∼38 million years ago was a response to the spread of grasslands. This study uses microscopic plant silica fossils from southern Argentina to show that these presumed grass-eating mammals evolved in forests, not grasslands.

A multi-omic atlas of breast cancers, integrating single-cell RNA sequencing, spatial transcriptomics and immunophenotyping, identifies nine ecotypes associated with cellular heterogeneity and prognosis.

Globins are best known for their role in respiration, but recent studies suggest they might contribute to redox signalling as well. Here, the authors present biochemical, structural and in vivoevidence that the roundworm globin Glb-12 acts as a superoxide generator necessary for germline development.

Crop wild relatives’ genetic diversity is usually not considered in conservation planning. Here, the authors introduce an approach to identify conservation areas based on evolutionary and threat processes, by developing proxies of genetic differentiation, and including taxa’s habitat preferences.

A new GWAS of schizophrenia (11,260 cases and 24,542 controls) and meta-analysis identifies 50 new associated loci and 145 loci in total. The common variant association signal is highly enriched in mutation-intolerant genes and in regions under strong background selection.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

In this study, the authors use ATAC-seq and promoter capture Hi-C data from human adipocytes treated with fatty acids to identify gene–environment (G×E) interactions that influence body-mass index in humans. They report 154 genes that respond to saturated fat and discover 38 new G×E variants for body-mass index in data from the UK Biobank.

The authors show that the Martian crust, ~4300 km from the InSight landing site, has a subsurface interface similar to that beneath the lander, suggesting it is a regional or global feature that may be related to the closure of pore spaces at depth.

Tractor is a statistical framework that facilitates the inclusion of admixed individuals in association studies by leveraging local ancestry. Tractor generates accurate ancestry-specific effect-size estimates and improves the resolution of association signals.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Non-coding RNAs are widely expressed, yet their functions remain poorly understood. Here, Leong et al. identify a set of antisense RNAs elevated during the yeast stress response that directly correlate with reduced protein levels, indicating a general regulatory effect of antisense expression.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

Rett syndrome (RTT) is caused by mutations in MeCP2. This study describes a new line of knock-in mutant mice that mimics a MeCP2 mutation found in individuals with RTT and recapitulates RTT-like phenotypes, including motor and cognitive impairments. These MeCP2 knock-in mice also have age-dependent abnormalities in audiogenic event-related neuronal information processing.

IFN-γ is central in inflammatory pathogenesis, response to infection and autoimmune diseases. Here the authors show that MMP12 expression is reduced in patients with SLE and that MMP12 post-translationally truncates IFN-y, inhibiting its function and affecting pathogenesis of mouse models of peritonitis, SLE and rheumatoid arthritis.

Mass spectrometry (MS) has furthered our understanding of MHC class I-associated peptides (MIPs), but the technique is inadequate for studying MIP-associated polymorphisms. Here, the authors combine high-throughput MS with exome and transcriptome sequencing to identify polymorphic MIPs from two female siblings.

Magnetoencephalography (MEG) recordings are sensitive to movement and therefore are especially challenging with young participants. Here the authors develop a wearable MEG system based on a modified bicycle helmet, which enables reliable recordings in toddlers, children, teenagers and adults.

Crystallization processes are underpinned by an interplay between thermodynamics and kinetics, leading to complex energy landscapes spanned by polymorphs and metastable intermediates that are challenging to identify and characterize. In this Review, the authors highlight how recent progress in computational methods, and their augmentation with machine learning, have advanced our ability to predict crystal structures and simulate crystal nucleation.

A systematic analysis reveals that acidic or phosphorylated residues upstream of the PDZ-binding motif contribute to efficient recognition of cargos by the SNX27 PDZ domain, thus leading to the identification of hundreds of potential new SNX27 ligands.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Cephalopods are an enigmatic animal group with complex and adaptive behaviors such as camouflage; however the genetic basis for these traits is not well understood. Here the authors reveal a set of cephalopod-restricted rearranged genomic loci, involving known neuronal regulators but also unexpected gene families, that confer topological organization and gene regulation.

Glaucoma is the most common cause of irreversible blindness worldwide. Here, the authors carry out a large meta-analysis of genetic data from individuals of European and Asian ancestry and identify 10 new loci associated with vertical cup-disc ratio, a key factor in the clinical assessment of patients with glaucoma.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Fine scale mobile phone data is improving capacity to understand seasonal patterns in human movement. Here, the authors use multi-year movement data across three nations, as well as a model of pathogen spread, to understand the consequences of seasonal travel for disease dynamics.

The 501Y.V2 variant of SARS-CoV-2 in South Africa became dominant over other variants within weeks of its emergence, suggesting that this variant is linked to increased transmissibility or immune escape.

Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized by peripheral nerve myelination deficits. Here, the authors prevent the development of pathological features in a rat model of CMT1A through the local delivery of AAV2/9 expressing shRNAs against PMP22.

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

Analysis of rare de novo mutations in gene regulatory elements suggests that 1–3% of patients with neurodevelopmental disorders carry such mutations in elements that are active in the fetal brain.

Impaired somatostatin secretion owing to loss of β- to δ-cell electrical coupling underlies defective counter-regulatory glucagon secretion in type-1 diabetes.

Mark McCarthy and colleagues identify twelve new risk loci for type 2 diabetes through a large-scale genome-wide association and replication study in individuals of European ancestry. The identified loci affect both beta-cell function and insulin action and are enriched for genes involved in cell cycle regulation.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

Familial cortical myoclonic tremor (FAME) has so far been mapped to regions on chromosome 2, 3, 5 and 8 and pentameric repeat expansions in SAMD12 were identified as cause of FAME1. Here, Corbett et al. identify ATTTT/ATTTC repeat expansions in intron 1 of STARD7 in individuals with FAME2.”

Thousands of varieties of wine grapes have been recorded and described in historical accounts, some going back as far as the Middle Ages, but genetic relationships between ancient and modern varieties were unknown. Genomic sequencing of 28 seeds, dating back as far as the Iron Age, finds close relationships to today’s cultivars, including a genetic match to Savagnin Blanc from 1100 ce.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

Antigens encoded by var genes are major virulence factors of the human malaria parasite Plasmodium falciparum. Here, Larremore et al. identify var-like genes in distantly related Plasmodiumspecies infecting African apes, indicating that these genes already existed in an ancestral ape parasite many millions of years ago.

Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

The dynamics of chromatin and transcriptional changes underlying Huntington’s disease remain poorly understood. Here the authors use a Huntington’s mouse model to profile the striatal chromatin landscape, finding that the Huntington’s mutation accelerates age-dependent epigenetic and transcriptional changes, and locally affects 3D chromatin organization.

ATRX, a chromatin remodelling factor, is mutated in cancers that maintain telomere length by alternative lengthening of telomeres (ALT). Here, the authors show that ectopic expression of ATRX triggers telomere shortening, ALT suppression and reduced replication fork stalling.

Levels of the glycolytic intermediate metabolite dihydroxyacetone phosphate are shown to signal cellular glucose availability to the mTORC1 complex through an AMPK-independent route.