De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.

ABSTRACT: Three-dimensional genome organization plays a critical role in gene regulation, and disruptions can lead to developmental disorders by altering the contact between genes and their distal regulatory elements. Structural variants (SVs) can disturb local genome organization, such as the merging of topologically associating domains upon boundary deletion. Testing large numbers of SVs experimentally for their effects on chromatin structure and gene expression is time and cost prohibitive. To address this, we propose a computational approach to predict SV impacts on genome folding, which can help prioritize causal hypotheses for functional testing. We developed a weighted scoring method that measures chromatin contact changes specifically affecting regions of interest, such as regulatory element

SUBMITTER: Gjoni K 

PROVIDER: S-EPMC11580890 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature