{Reference Type}: Journal Article
{Title}: Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.
{Author}: Grochowski CM;Bengtsson JD;Du H;Gandhi M;Lun MY;Mehaffey MG;Park K;Höps W;Benito E;Hasenfeld P;Korbel JO;Mahmoud M;Paulin LF;Jhangiani SN;Hwang JP;Bhamidipati SV;Muzny DM;Fatih JM;Gibbs RA;Pendleton M;Harrington E;Juul S;Lindstrand A;Sedlazeck FJ;Pehlivan D;Lupski JR;Carvalho CMB;
{Journal}: Cell Genom
{Volume}: 4
{Issue}: 7
{Year}: 2024 Jul 10
暂无{DOI}: 10.1016/j.xgen.2024.100590
{Abstract}: The 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.