Christopher Grochowski, Baylor College of Medicine

Conference: AGBT 2020
Abstract Title: Deciphering genomic inversion events using optical mapping

Methods for inversions, such as fosmid clone sequencing (PMID: 18451855, 17901297) and paired-end (PE) sequencing (15895083), are limited in resolving breakpoints. Optical mapping (OM) involves tagging sequence motifs along unbroken DNA strands preserving the architecture of SVs. Given the evidence for inversion rearrangements contributing to disease, we sought to compare SV detection methods. We performed OM on a lymphoblastoid line (NA15510) using Bionano direct label stain (DSL) technology. As inversions can be mediated by repeats, we incorporated a custom database, Highly Similar Intrachromosomal Repeats (HSIRs), for the visualization of inverted repeats. For a comparison of OM versus fosmid/PE sequencing the genomic location of inversions detected by these methods were also considered. In total, 90 inversions were detected by OM and/or other methods. Of the 46 inversions detected by OM, 36% were not detected by other methods while 15% were detected by at least one other technique. Only 1% of inversions were detected by both OM and all other methods analyzed. Only 19% of inversions studied involved HSIRs while 35% involved segmental duplications. The precise location of previously documented inversions were further refined due to the uncertainty inherent to previous methods versus OM. Visualization of unbroken DNA is critical in studying an SV with two breakpoints in cis. As the role of SVs in disease becomes more clear new methods like OM may be required to study a structural aberration in its totality.