Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes.

ABSTRACT: Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than ex

SUBMITTER: Schopflin R 

PROVIDER: S-EPMC9617858 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature