Spatial Chromatin Architecture Alteration by Structural Variations in Human Genomes at Population Scale

This genome-wide study is focused on the impact of structural variants identified in individuals from 26 human populations onto three-dimensional structures of their genomes. We assess the tendency of structural variants to accumulate in spatially interacting genomic segments and design a high-resolution computational algorithm to model the 3D conformational changes resulted by structural variations. We show that differential gene transcription is closely linked to variation in chromatin interaction networks mediated by RNA polymerase II. We also demonstrate that CTCF-mediated interactions are well conserved across population, but enriched with disease-associated SNPs. Altogether, this study assesses the critical impact of structural variants on the higher order organization of chromatin folding and provides unique insight into the mechanisms regulating gene transcription at the population scale, among which the local arrangement of chromatin loops seems to be the leading one. It is the first insight into the variability of the human 3D genome at the population scale.