The human genome encodes millions of enhancers (tangled balls) that quantitatively tune the expression of 21,000 genes (arrows). The regulatory wiring connecting enhancers to their target genes has remained elusive. In this issue, Fulco, Nasser and colleagues develop new experimental and computational approaches to map this complex wiring, and demonstrate their utility in interpreting the functions of genetic variants associated with human diseases.

See Fulco et al.

There is a genetic contribution that influences brain-region volumes and brain structure. GWAS in large-scale, deeply phenotyped cohorts have uncovered loci associated with these complex neurological traits.

See Satizabal et al. Zhao et al.

Red pineapple (Ananas comosus var. bracteatus) was cultivated for fiber or fruit juice, and as a living hedge, and it is now a pantropical ornamental. The bracteatus plant is conspicuous for its bright pink-to-red fruit. The sequenced pineapple genomes partly validated ‘one-step operation’ for domestication of clonally propagated crops and revealed candidate genes for self-incompatibility. The photograph was taken 1 month after flowering.

See Chen et al.

The genome sequence of the pea Pisum sativum, the original model used by Johan Gregor Mendel to determine his law of inheritance, links the dawn of the genetics field to the modern sequencing era.

See Kreplak et al.

The mountains represent wild-type topologically associating domains (TADs), and the reflection in the water below depicts the rearranged TADs present on Drosophila balancer chromosomes. Although there are many changes in topology (the landscape), these have little effect on gene expression.

See Ghavi-Helm et al.

Analysis of the evolutionary dynamics of colorectal cancer metastasis through a novel analytic approach provides quantitative in vivo evidence that early disseminated cancer cells can seed distant metastases before the carcinoma is clinically detectable. By delineation of the timing of metastasis, drivers of this lethal process and potential biomarkers to guide patient stratification can be identified. The dandelion seeds represent the early cancer cells that can seed metastases.

See Hu et al.

This artistic rendering depicts a role for folate metabolism in BRD4-mediated transcription. The folate metabolic enzyme MTHFD1 is recruited to chromatin through physical interaction with BRD4. Through its enzymatic activity, MTHFD1 provides one-carbon intermediates, which form the building blocks for several important metabolite classes in the nucleus, including purines, which are incorporated into RNA during transcription.

See Sdelci et al.

Chromatin is folded dynamically inside the nucleus, changing its conformation as cells divide and differentiate. The spheres in this image represent topologically associating domains (TADs), which can interact to form cliques (highlighted by darker colors) that seem to stabilize heterochromatin at the nuclear periphery.

See Paulsen et al.

This image depicts a key step in the discovery of a repeat expansion in RFC1 as a common cause of a late-onset ataxia syndrome known as CANVAS. A visual break in the sequence alignment, depicted here as a torn canvas, is produced by unjoined reads originating on each side of the expansion, disrupting the otherwise continuous tiling pattern.

See Cortese et al.

The cultivated garden strawberry emerged as a hybrid between two wild octoploid species in the gardens of Versailles approximately 250 years ago. Analysis of its assembled genome provides new insights into the origin and evolutionary processes that shaped this complex allopolyploid.

See Edger et al.

Analysis of genomic data for the entire barley collection of the German Federal ex situ Genebank provides insights into the population structure of domesticated barley and helps link natural variation to human selection during crop evolution.

See Milner et al.

Genetic variation from many thousands of individuals is needed to confidently detect regions depleted of variation. This cover image draws an analogy between genetic variation and rain falling on a sidewalk. We think of rainfall as being random. But what if it isn’t? We only begin to see non-random patterns with many raindrops.

See Havrilla et al.