Linked-Read Sequencing to Resolve Complex Structural Variants. Linked-Read Sequencing to Resolve Complex Structural Variants

Large structural variants (SVs) are important contributors to disease yet remain one of the most difficult types of variation to accurately ascertain, in part because they cluster in duplicated/repetitive regions, but also because the signals for these events can be challenging to detect with short reads. Clinically, array comparative genome hybridization and karyotype remain the most commonly used assays for genome-wide SV detection, though there is clear potential benefit to an NGS-based assay that accurately detects both SVs and single nucleotide variants. Linked-Read sequencing is a simple, fast, and cost-effective method that is applicable to both genome and targeted assays. Linked-Reads are generated by performing haplotype-level dilution of long input DNA molecules into >1 million barcoded partitions, generating barcoded short reads within those partitions, and performing short read sequencing in bulk. We performed 30x Linked-Read genome sequencing... (for more see dbGaP study page.)