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

Area of Science:

• Genomics
• Molecular Biology
• Genetics

Background:

• Genomic rearrangements are implicated in human diseases but remain understudied in rare conditions due to detection challenges.
• Short-read whole genome sequencing (srWGS) is economical and accurate, yet long-read approaches are often recommended for genomic rearrangements.
• Caenorhabditis elegans (C. elegans) balancer strains utilize chromosomal rearrangements but lack molecular characterization.

Purpose of the Study:

• To evaluate the capability of srWGS in detecting diverse complex genomic rearrangements.
• To assess the utility of srWGS for characterizing molecular-level chromosomal variations in model organisms.

Main Methods:

• Sequencing of three C. elegans balancer strains using short-read Illumina technology.
• Bioinformatic analysis to identify genomic rearrangement breakpoints.
• Experimental validation of srWGS-identified breakpoints.

Main Results:

• srWGS successfully detected a reciprocal translocation (eT1), a free duplication (sDp3), a large deletion (sC4), and chromoanagenesis events.
• Experimental validation confirmed the accuracy of breakpoints identified by srWGS.
• Combined analyses enabled comprehensive detection of complex genomic rearrangements.

Conclusions:

• srWGS is a viable and effective method for detecting complex genomic rearrangements.
• Applying srWGS in model organisms can inform the development of bioinformatics pipelines for human genome analysis.
• This approach facilitates systematic detection of complex rearrangements in human genomes, advancing rare disease research.