Neville et al. combine trio whole-genome sequencing with ultra-accurate sperm sequencing to quantify how de novo mutation timing and selection shape transmittable disease risk. Early embryonic mosaicism can create an uncommon elevated transmission risk, whereas universal age-associated mutation accumulation and spermatogonial selection account for most paternal pathogenic de novo mutations.

Over the course of a lifetime, somatic mutations accrue in normal human cells, causing variation in cell phenotype and engendering somatic evolution with outcomes ranging from the adaptive immune syst...

Garcia-Salinas et al. detect early parental postzygotic mutations from standard-depth trio WGS across 12,015 rare disease trios, identifying 1,015 high-confidence events. Their catalog reveals distinc...

Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilit...

Abstract. Somatic mosaicism is pervasively observed in human aging, with clonal expansions of cells harboring mutations in recurrently mutated driver genes. Bulk sequencing of tissues captures mutatio...

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Environmental stresses, such as a high-fat diet, disrupt liver cell balance by promoting pro-survival, developmental, and regenerative programs while impairing key tissue functions. These stress respo...

The classic theory of mutation-selection balance predicts the equilibrium frequency of genetic variation under negative selection. The model predicts a simple relationship between the total frequency ...

Artificial intelligence agents may have a transformative effect on how biological research is performed.

Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

Some children have already died and only a minority who inherit the mutation will escape cancer in their lifetimes.

Researchers reveal how certain harmful DNA variations become more common in sperm as men age, raising genetic disease risk for offspring.

De novo structural variants are an important cause of rare disorders but remain poorly understood. Here, the authors analyse over 12,000 families and reveal the prevalence, diversity, and clinical imp...

Spatial omics has empowered the discovery of developmental and disease-associated molecular signatures, cell states and multicellular niches, as well as the evaluation of disease heterogeneity within ...

Scientists are testing whether GLP-1 drugs can help to cut cravings for cigarettes, alcohol and opioids — as well as food.

We can now better inform anti-TNF prescribing through HLA testing! Huge thanks to Tauseef Sharip, Chris Roberts, Eathar Shakweh MBBS BSc MRCP, Miles Parks, Tariq Ahmad, as well as Laura Fachal and Ca...

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Scientists reveal that mutation order influences tumour growth in the intestine.

Scientists reveal that mutation order influences tumour growth in the intestine.

Do you want to help us improve human health and understand life on Earth? Make your mark by shaping the future to enable or deliver life-changing science to solve some of humanity’s greatest challenge...

Whole-genome and transcriptome analysis of 1,364 cases of breast cancer from South Korea broadens our understanding of breast cancer biology and reveals genomic features that connect tumour ...

The impact of transcription on germline mutagenesis remains poorly understood. Here, the authors identify a mutational hotspot at transcription start sites in the human germline that is significantly ...

A new study led by researchers at the MRC Molecular Haematology Unit has shown that resistance to a targeted treatment for acute myeloid leukaemia (AML) can develop much earlier than expected.

Postzygotic mutations (PZMs) arising post-fertilisation, prior to primordial germ cell specification, may be subsequently inherited by both somatic and germ cells, causing somatic mosaicism in the par...

A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

A systematic statistical genetics approach discovers CES drivers as hotspots of human de novo mutation and shows that clonal expansions in germline may both modulate the prevalence of disorders and lead to false-positive disease associations.

Sex bias and association with smoking history identified in the landscape of driver mutations and clonal expansions in normal human bladder tissue may explain the higher bladder cancer risk in men and smokers.

Nature Communications - Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that...

Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that common genetic variants likely c...

Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) ...

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...

Do you want to help us improve human health and understand life on Earth? Make your mark by shaping the future to enable or deliver life-changing science to solve some of humanity’s greatest challenge...

A platform for mRNA lipid nanoparticle delivery to the placenta to treat pre-eclampsia is shown to improve fetal and maternal health in mice and has potential clinical applications in obstetric disorders and women's health.

Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, w...