Browse Articles

Using laser-capture microdissection and whole-genome sequencing of individual crypts, we characterized the landscape of somatic mutations in human small intestinal epithelium. Mutational signatures of APOBEC mutagenesis were found frequently and are probably due to the activity of APOBEC1, which is expressed at high levels in the small intestine.

Using a series of mouse mutants, we found that the Sox2 promoter does not require CTCF–cohesin loops to interact with distal enhancers. Surprisingly, mice with varying numbers of CTCF motifs in different positions showed that some distal enhancers can bypass boundaries that are created by CTCF–cohesin loops to ensure robust Sox2 expression.

Genetic manipulation of the Sox2 locus in mice shows that gene activation by distal enhancers does not require CTCF-mediated loops and can occur across ectopic CTCF-mediated boundaries. The ability to bypass CTCF boundaries varies with their insulation strength and the tissue-specific enhancers responsible for activation.

Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.

A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

Current methods of chromatin analysis focus mainly on the most abundant cell types in a sample. We present a workflow that combines enrichment of rare cell types with high-resolution mapping of histone modifications, which enables us to study chromatin dynamics in rare stem and progenitor cell populations.

Genome-wide analyses in BioBank Japan and populations of European ancestry identify new risk loci for atrial fibrillation. A polygenic risk score constructed from the cross-ancestry meta-analysis is associated with increased risk of long-term cardiovascular mortality.

A high-quality Ixodes scapularis genome contributes to improved annotations, expansion of gene families, development of proteome catalogs and the deciphering of genetic variation in wild ticks.

Notch1 mutations have opposing effects on clonal growth in normal and tumor cells of the mouse esophagus. In a mouse model of squamous esophageal tumorigenesis, Notch1 blockade reduced premalignant tumor growth, suggesting that it might be an effective prevention strategy for the disease.

This Perspective article discusses Singapore’s efforts to implement a National Precision Medicine Strategy through the integration of genomic, clinical and lifestyle data of up to one million Singaporean individuals.

In aging mouse livers, 40% of elongating RNA polymerases are stalled, biasing transcriptional output dependent on gene length. This transcriptional stress appears to be caused by endogenous DNA damage.

Genome-wide association analyses identify 93 risk loci for venous thromboembolism (VTE). A polygenic score derived from these results identifies individuals at increased VTE risk equivalent to monogenic forms of the disease.

Endometriosis affects around 10% of individuals born with a uterus, yet we know remarkably little about its underlying biology. Our single-cell transcriptional profiling of endometrial-type epithelial and stromal cells is shedding light on the cells and processes that contribute to endometriosis, which opens up new avenues for diagnostics and therapeutics.

De novo genome assembly and analyses of 12 maize FILs provide insights into genomic and phenotypic differentiation of various heterotic groups and the molecular basis of heterosis in maize.