Deciphering complex genome rearrangements in C. elegans using short-read whole genome sequencing

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

doi:10.1038/s41598-021-97764-9

Tatiana Maroilley, Francesca Jean + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-97764-9

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Abstract

Genomic rearrangements cause congenital disorders, cancer, and complex diseases in human. Yet, they are still understudied in rare diseases because their detection is challenging, despite the advent of whole genome sequencing (WGS) technologies. Short-read (srWGS) and long-read WGS approaches are regularly compared, and the latter is commonly recommended in studies focusing on genomic rearrangements. However, srWGS is currently the most economical, accurate, and widely supported technology. In Caenorhabditis elegans (C. elegans), such variants, induced by various mutagenesis processes, have been used for decades to balance large genomic regions by preventing chromosomal crossover events and allowing the maintenance of lethal mutations. Interestingly, those chromosomal rearrangements have rarely been characterized on a molecular level. To evaluate the ability of srWGS to detect various types of complex genomic rearrangements, we sequenced three balancer strains using short-read Illumina technology. As we experimentally validated the breakpoints uncovered by srWGS, we showed that, by combining several types of analyses, srWGS enables the detection of a reciprocal translocation (eT1), a free duplication (sDp3), a large deletion (sC4), and chromoanagenesis events. Thus, applying srWGS to decipher real complex genomic rearrangements in model organisms may help designing efficient bioinformatics pipelines with systematic detection of complex rearrangements in human genomes.

Highlights

Genomic rearrangements cause congenital disorders, cancer, and complex diseases in human
C. elegans balancers constitute an interesting source of various genomes and complex genomic rearrangements to assess the ability of short-read PCR-free whole genome sequencing (WGS) Illumina technologies and tailored bioinformatics workflows to detect and characterize complex structural variants
We found that short-read WGS datasets can be used to detect, identify, and characterize SVs and complex genomic rearrangements in C. elegans genomes

Summary

Introduction

Genomic rearrangements cause congenital disorders, cancer, and complex diseases in human. In Caenorhabditis elegans (C. elegans), such variants, induced by various mutagenesis processes, have been used for decades to balance large genomic regions by preventing chromosomal crossover events and allowing the maintenance of lethal mutations Those chromosomal rearrangements have rarely been characterized on a molecular level. In C. elegans, SVs and complex rearrangements have been used for decades to balance large parts of the genome by suppressing crossover events and maintaining heterozygosity It facilitates the investigation of lethal mutations, the construction of new strains, and the screening of m utations[28]. C. elegans balancers constitute an interesting source of various genomes and complex genomic rearrangements to assess the ability of short-read PCR-free WGS Illumina technologies and tailored bioinformatics workflows to detect and characterize complex structural variants. The knowledge gained from the analytical methods used on C. elegans balancers may help optimize detection and characterization of complex variants in humans using short-read WGS

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