Supplemental datasets for 'Distinct mechanisms of CNV formation at the human 15q13.3 locus'

Supplementary data for Höps et al. (2026), “Distinct mechanisms of CNV formation at the human 15q13.3 locus” (preprint: https://doi.org/10.64898/2026.03.03.709017). Contents: Raw sequencing data and derived assemblies for the 15q13.3 region: raw reads (sequencing/fastq) aligned reads (sequencing/bam) local assemblies (assembly/fasta) assembly visualizations (assembly/plots) Abstract: Human chromosome 15q13.3 is a hotspot for recurrent pathogenic copy number variants (CNVs) associated with schizophrenia, developmental delay and epilepsy. We generated long-read genome assemblies for 10 patient-parent trios and compared them to 581 population controls from diverse ancestry where this complex region is fully resolved. We find that both the long (“BP4-BP5”) and short (“CHRNA7”) forms of 15q13.3 CNVs arise predominantly by non-allelic homologous recombination (NAHR) whose susceptibility has been promoted by large inversion polymorphisms. While three BP4-BP5 breakpoints cluster in a 2 kbp PRDM9-enriched recombination hotspot, most CNVs are structurally distinct and affect the disease-relevant genes ARHGAP11B and CHRFAM7A differentially. Population analyses reveal at least 18 distinct structural haplotypes in 15q13.3 and show that the BP4-BP5 CNV is stratified more than 10-fold depending on ancestry, with 68.4% of Europeans but only 5.1% of East Asians predisposed. Comparison to six ape species indicates that the duplication architecture promoting instability expanded recently and is largely human-specific.