Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases^1–4, yet remain under-characterized in population-scale cohorts⁵. Here we conducted long-read sequencing⁶ in 1,019 humans to construct an intermediate-coverage resource covering 26 populations from the 1000 Genomes Project. Integrating linear and graph genome-based analyses, we uncover over 100,000 sequence-resolved biallelic SVs and we genotype 300,000 multiallelic variable number of tandem repeats⁷, advancing SV characterization over short-read-based population-scale surveys^3,4. We characterize deletions, duplications, insertions and inversions in distinct populations. Long interspersed nuclear element-1 (L1) and SINE-VNTR-Alu (SVA) retrotransposition activities mediate the transduction^8,9 of unique sequence stretches in 5′ or 3′, depending on source mobile element class and locus. SV breakpoint analyses point to a spectrum of homology-mediated processes contributing to SV formation and recurrent deletion events. Our open-access resource underscores the value of long-read sequencing in advancing SV characterization and enables guiding variant prioritization in patient genomes.

Genetic syndromes often involve craniofacial malformations. We have investigated whether a computer can recognize disease-specific facial patterns in unrelated individuals. For this, 55 photographs (256 × 256 pixel) of patients with mucopolysaccharidosis type III (n=6), Cornelia de Lange (n=12), fragile X (n=12), Prader–Willi (n=12), and Williams–Beuren (n=13) syndromes were preprocessed by a Gabor wavelet transformation. By comparing the feature vectors at 32 facial nodes, 42/55 (76%) of the patients were correctly classified. In another four patients (7%), the correct and an incorrect diagnosis scored equally well. Clinical geneticists who were shown the same photographs achieved a recognition rate of 62%. Our results prove that certain syndromes are associated with a specific facial pattern and that this pattern can be described in mathematical terms.

Mutations affecting the transcriptional regulator Ankyrin Repeat Domain 11 (ANKRD11) are mainly associated with the multisystem developmental disorder known as KBG syndrome, but have also been identified in individuals with Cornelia de Lange syndrome (CdLS) and other developmental disorders caused by variants affecting different chromatin regulators. The extensive functional overlap of these proteins results in shared phenotypical features, which complicate the assessment of the clinical diagnosis. Additionally, re‐evaluation of individuals at a later age occasionally reveals that the initial phenotype has evolved toward clinical features more reminiscent of a developmental disorder different from the one that was initially diagnosed. For this reason, variants in ANKRD11 can be ascribed to a broader class of disorders that fall within the category of the so‐called chromatinopathies. In this work, we report on the clinical characterization of 23 individuals with variants in ANKRD11. The subjects present primarily with developmental delay, intellectual disability and dysmorphic features, and all but two received an initial clinical diagnosis of either KBG syndrome or CdLS. The number and the severity of the clinical signs are overlapping but variable and result in a broad spectrum of phenotypes, which could be partially accounted for by the presence of additional molecular diagnoses and distinct pathogenic mechanisms.