Maroilley, Tatiana et al. (2021) International Worm Meeting "Characterizing complex genomic rearrangements in C. elegans using short-read Whole Genome Sequencing"

Maroilley, Tatiana, Tarailo-Graovac, Maja, Li, Xiao, Oldach, Matthew, Jean, Francesca, Stasiuk, Susan

[International Worm Meeting, 2021]

Structural variants (SVs) and complex rearrangements are a significant, but understudied, part of genomic natural diversity. They can also result in various phenotypes in Caenorhabditis elegans. Additionally, certain strains, known as balancers, carry various types of spontaneous or induced (X-rays, gamma irradiation, chemical mutagens, or more recently CRISPR-Cas9) chromosomal rearrangements. Because those rearrangements abolish or reduce crossover events between large portions of the C. elegans genome, balancers have been used for decades to maintain lethal mutations, facilitate strain construction, or capture mutations. However, despite the advent of sequencing technologies, detecting SVs and complex rearrangements is challenging and thus, in most mutagen-induced balancers, the chromosomal rearrangements have not been characterized at the molecular level. High-throughput WGS sequencing, based on short-reads (srWGS), is the most economical, accurate, and widely supported technology at this time. Yet, the length of short-reads is often reported as limiting the detection of complex genetic events. Long-read technologies are then recommended as an alternative despite their increased costs. Here, we applied srWGS alongside tailored bioinformatics approaches to unravel complex genomic rearrangements in several C. elegans balancer genomes. Our method successfully identified complex balancer rearrangements such as reciprocal translocation (eT1), large deletion (eDf43), chromosome fusion (sC4), and free duplication (sDp3). We were also able to identify and experimentally confirm several chromoanagenesis events. Therefore, our results show that we can maximize the possibilities of srWGS by implementing meticulous analytical approaches. Higher confidence in complex variant calls from srWGS will help to molecularly characterize C. elegans balancers and in the future, to decipher the full spectrum of natural genetic variation in C. elegans.