Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci

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dc.citation.articleNumber100590en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitleCell Genomicsen_US
dc.citation.volumeNumber4en_US
dc.contributor.authorGrochowski, Christopher M.en_US
dc.contributor.authorBengtsson, Jesse D.en_US
dc.contributor.authorDu, Haoweien_US
dc.contributor.authorGandhi, Miraen_US
dc.contributor.authorLun, Ming Yinen_US
dc.contributor.authorMehaffey, Michele G.en_US
dc.contributor.authorPark, KyungHeeen_US
dc.contributor.authorHöps, Wolframen_US
dc.contributor.authorBenito, Evaen_US
dc.contributor.authorHasenfeld, Patricken_US
dc.contributor.authorKorbel, Jan O.en_US
dc.contributor.authorMahmoud, Medhaten_US
dc.contributor.authorPaulin, Luis F.en_US
dc.contributor.authorJhangiani, Shalini N.en_US
dc.contributor.authorHwang, James Paulen_US
dc.contributor.authorBhamidipati, Sravya V.en_US
dc.contributor.authorMuzny, Donna M.en_US
dc.contributor.authorFatih, Jawid M.en_US
dc.contributor.authorGibbs, Richard A.en_US
dc.contributor.authorPendleton, Matthewen_US
dc.contributor.authorHarrington, Eoghanen_US
dc.contributor.authorJuul, Sisselen_US
dc.contributor.authorLindstrand, Annaen_US
dc.contributor.authorSedlazeck, Fritz J.en_US
dc.contributor.authorPehlivan, Davuten_US
dc.contributor.authorLupski, James R.en_US
dc.contributor.authorCarvalho, Claudia M. B.en_US
dc.date.accessioned2024-08-09T16:25:25Zen_US
dc.date.available2024-08-09T16:25:25Zen_US
dc.date.issued2024en_US
dc.description.abstractThe duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in 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 single-cell DNA template strand sequencing (strand-seq), 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 within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.en_US
dc.identifier.citationGrochowski, C. M., Bengtsson, J. D., Du, H., Gandhi, M., Lun, M. Y., Mehaffey, M. G., Park, K., Höps, W., Benito, E., Hasenfeld, P., Korbel, J. O., Mahmoud, M., Paulin, L. F., Jhangiani, S. N., Hwang, J. P., Bhamidipati, S. V., Muzny, D. M., Fatih, J. M., Gibbs, R. A., … Carvalho, C. M. B. (2024). Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci. Cell Genomics, 4(7). https://doi.org/10.1016/j.xgen.2024.100590en_US
dc.identifier.digitalPIIS2666979X24001745en_US
dc.identifier.doihttps://doi.org/10.1016/j.xgen.2024.100590en_US
dc.identifier.urihttps://hdl.handle.net/1911/117630en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleInverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder locien_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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