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A flexible and compact database containing rare variant genotypes and phenotypes of 77,539 participants sequenced by the 100,000 Genomes Project enables the identification of new disease-causing genes.

Non-coding cancer driver mutations that induce splicing variants exist, but are largely unexplored. Here, the authors find these non-coding mutations in known pan-cancer driver genes and show that they create new exons and might interact with pre-existing potential splice sites.

A combination of genetics and calcium imaging is used to detail the neuronal circuitry in Caenorhabditis elegans that allows odour-sensing neurons to activate or inhibit downstream interneurons controlling crawling and turning behaviours. The nerve cell connectivity and molecules used by this nematode to process olfactory information shows striking homologies with those used to sense light in mammalian retina

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

In animals with complex life cycles, selection on one life phase may constrain adaptation in another phase. Here the authors find that, during the adaptive radiation of mantellid frogs, the evolution of tadpole and adult morphologies has been uncoupled through phase-specific gene expression.

Salmonella mutants with reduced ability to colonize the mouse gut and cause disease are selected for by vaccine-induced intestinal antibody responses in mice.

Here, using metagenomic profiling in 180 individuals from the Democratic Republic of the Congo, the authors find associations between the gut microbiome and konzo, a neurodegenerative disease that mostly affects children and is caused by the consumption improperly processed cassava.

Atrial fibrillation (AF) is accompanied by a detrimental loss of functional cardiomyocytes. Here, Zhang et al. show that AF-induced cardiomyocyte dysfunction is a consequence of DNA damage-mediated PARP1 activation, which leads to depletion of NAD⁺ and further oxidative stress and DNA damage, and identify PARP1 inhibition as a potential therapeutic strategy in the treatment of AF.

Toxoplasma gondii is a parasite that causes zoonotic infections in humans. Here, the authors identify tandem amplification and diversification of secretory pathogenesis determinants in the T. gondiigenome and show that clade-specific inheritance of conserved haploblocks enriched for these determinants shapes population structure.

Clapes et al. show that chemotherapy leads to chromatin reorganization and increased expression of transposable elements, which promote an MDA5-driven inflammatory response that enhances haematopoietic regeneration.

The mutations underlying sexually selected traits like the red fins on a male medaka fish can be hard to pinpoint. Using a new genome, transcriptomics and gene editing, Ansai et al. find that the gene csf1 causes male fins to be red, which attracts females and, surprisingly, is less attractive to predators.

Enhancer variants associated with red blood cell traits alter signaling transcription factor motifs, leading to changes in expression of genes that are upregulated during erythroid differentiation.

The understanding of pathogenicity in quantitative plant pathosystems remains limited. This study reveals the genetic architecture of quantitative pathogenicity traits in a significant fungal plant pathogen, shedding light on potential evolutionary mechanisms involved in host adaptation.

Completion of genome sequences for the diploid Setaria italica reveals features of C₄ photosynthesis that could enable improvement of the polyploid biofuel crop switchgrass (Panicum virgatum). The genetic basis of biotechnologically relevant traits, including drought tolerance, photosynthetic efficiency and flowering control, is also highlighted.

Regeneration capable flatworms have emerged as powerful models for studying stem cell biology and patterning, however their study has been hindered by the lack of transgenesis methods. Here, the authors describe a transgenesis method for Macrostomum lignano, as well as a new annotated genome sequence.

Whole genome sequencing (WGS) data on non-European and admixed individuals remains scarce. Here, the authors analyse WGS data from 1,171 admixed elderly Brazilians from a census cohort, characterising population-specific genetic variation and exploring the clinical utility of this expanded dataset.

Host immune responses exert selective pressure on Plasmodium falciparum. Here, the authors show that allele-specific immunity impacts the antigenic diversity of individual malaria infections. This process partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines should account for allele-specific immunity.

Sequencing and genomic diversification of five allopolyploid cotton species provide insights into polyploid genome evolution and epigenetic landscapes for cotton improvement.

Asexual vertebrates are extremely rare. Here, the authors sequence the genome of the Amazon molly, an asexual fish, and find few signs of genetic degeneration but clonal polymorphism and high heterozygosity, which might explain the success of this species.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.

Cancer-associated mutations in isocitrate dehydrogenase are proposed to impair TET2-dependent DNA demethylation. By comparing the methylomes of IDH-mutant cancers, the authors identify the transcription factor EBF1 as a partner of TET2, suggesting a possible means for targeting TET2 to specific DNA sequences.

Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Martin Farrall and colleagues report the results of a large genome-wide association meta-analysis of coronary artery disease based on 1000 Genomes imputation. They identify ten new risk loci and show that susceptibility to this disease is largely determined by common SNPs with small effect sizes.

Glycopeptide antibiotics (GPAs) are microbial natural products synthesized by multiple enzymes, including a nonribosomal peptide synthetase for assembly of the peptide core. Here, the authors use computational techniques to infer a gene set for biosynthesis of an ancestral GPA, produce the peptide in a microbial host, and provide insights into the evolution of key enzymatic domains.

When applied in large scale to electronic medical record data, the PheWAS approach replicates GWAS associations and reveals potentially new pleiotropic associations.

The molecular genetic landscape of leiomyosarcoma (LMS) is largely unknown. Here, the authors identify frequent DNA copy number alterations, whole-genome duplication, TP53 and RB1 inactivation, alternative telomere lengthening, and genomic imprints of defective DNA repair via homologous recombination as a potential therapeutic target in LMS patients.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions.

AAV-mediated CRISPR/Cas9 therapy extends life span and ameliorates disease-related phenotypes in a mouse model of Hutchinson–Gilford progeria syndrome.

Vascular dysfunction is associated with ageing and chronic diseases, but its role in lung repair and fibrosis is unclear. Here, the authors show that the endothelial transcription factor ERG is a mediator of vascular repair whose function declines in aged lungs resulting in sustained fibrosis

Integrating methods that assess allele-specific regulatory activity and chromatin accessibility in T cells identifies putative causal variants for five autoimmune diseases.

A rare variant burden analytical framework for Mendelian diseases was developed and applied to data from the 100,000 Genomes Project, identifying 69 probable new disease–gene associations.

Androgen receptor (AR) mediated transcription is critical to prostate tumorigenesis and development. Here, utilising clinical whole genome sequencing data, the authors show that the non-coding AR binding sites on DNA are frequently mutated in prostate cancer potentially due to faulty base excision repair mechanisms

Adaptation in diploids is poorly understood. Here, the authors show a slower rate of adaptation and a shift towards adaptive dominant mutations in long-term experimental evolution of diploid strains of the yeast Saccharomyces cerevisiae.

The authors assemble and analyse previously generated mycobiome data linked to geographical locations across the world. They describe the distribution of fungal taxa and show that climate is an important driver of fungal biogeography and that fungal diversity appears to be concentrated at high latitudes.

Joshua Bis, Christopher O'Donnell and colleagues report a meta-analysis of genome-wide association studies from the CHARGE Consortium that identifies loci associated with carotid intima media thickness and plaque. These are established measures of subclinical atherosclerosis that predict future cardiovascular disease events.

This is an issue edsumm for ng1935. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. It shows that sea surface temperatures near the North Pole increased from roughly 18 degrees Celsius to over 23 degrees Celsius — such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming.

An in vivo RNAi dropout screen identifies Mapk14 as a new mediator of sorafenib resistance in hepatocellular carcinoma, and Mapk14 inhibition both improves sorafenib therapy and restores sensitivity to sorafenib-resistant tumors.

Metastatic cancer cells are shown to have a tendency towards forming a bulky glycocalyx owing to the production of large glycoproteins, and this cancer-associated glycocalyx has a mechanical effect on the spatial organization of integrins — by funnelling integrins into adhesions, integrin clustering and signalling is promoted, which leads to enhanced cell survival and proliferation.

Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.

Small cell lung cancer (SCLC) patients frequently relapse and become resistant to chemotherapy. Here, the authors analyse the genomic and transcriptomic landscape of primary and relapsed SCLC patients as well as in vitro models, and discover that activation of WNT signalling can drive chemotherapy resistance.

Priming of the adult mouse heart with Tβ4 activates dormant epicardium-derived cells to aid repair of injured myocardium. Here, Vieiraet al. explain this process and show that Tβ4 binds a chromatin remodeller BRG1 and activates Wt1, the key regulator of epicardial epithelial-to-mesenchymal transformation, by altering the epigenetic landscape of the Wt1 locus.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

The auditory response of song premotor HVC neurons in sleeping birds, and HVC activity in singing birds, is synchronized with particular moments of vocal motor movements as defined by a dynamical systems model of song production; this HVC activity could be used as a ‘forward’ model to predict behaviour and evaluate feedback.

The Salkhit skull from Mongolia was initially suggested to have archaic hominin characters. Here, Devièse and colleagues date the skull to approximately 34–35 thousand years ago and reconstruct its mitochondrial genome, finding that it falls within modern human haplogroup N found across Eurasia.

The Microfluidic-based Ligand Enrichment (SMiLE) sequencing strategy probes DNA binding of single and heterodimeric transcription factors over a wide affinity range.

Like all terrestrial mammals, humans emit body odors that subtly communicate emotions. This study suggests that adults with autism may be misreading these chemical signals and that this may explain a portion of their social difficulties.