Break-induced replication underlies formation of inverted triplications and generates unexpected diversity in haplotype structures
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ABSTRACT: The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a type of complex genomic rearrangement (CGR). Although it has been identified as an important mutation signature of pathogenicity for genomic disorders and cancer genomes, its architecture remains unresolved. Here we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping and StrandSeq the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ~2.2-5.5 kb of 100% nucleotide similarity. These data provide experimental evidence supporting the hypothesis that inverted LCRs act as a recombinant substrate. This type of CGR can result in multiple conformers which contributes to generate diverse SV haplotypes in susceptible loci.
ORGANISM(S): Homo sapiens
PROVIDER: GSE250451 | GEO | 2023/12/18
REPOSITORIES: GEO
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