Genome sequencing of C. elegans balancer strains reveals previously unappreciated complex genomic rearrangements.

Autor:	Maroilley T; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Flibotte S; UBC/LSI Bioinformatics Facility, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Jean F; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Rodrigues Alves Barbosa V; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Galbraith A; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Chida AR; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Cotra F; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Li X; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Oncea L; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada., Edgley M; Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Moerman D; Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Tarailo-Graovac M; Departments of Biochemistry, Molecular Biology and Medical Genetics, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2023 Jan; Vol. 33 (1), pp. 154-167. Date of Electronic Publication: 2022 Dec 05.
DOI:	10.1101/gr.276988.122
Abstrakt:	Genetic balancers in Caenorhabditis elegans are complex variants that allow lethal or sterile mutations to be stably maintained in a heterozygous state by suppressing crossover events. Balancers constitute an invaluable tool in the C. elegans scientific community and have been widely used for decades. The first/traditional balancers were created by applying X-rays, UV, or gamma radiation on C. elegans strains, generating random genomic rearrangements. Their structures have been mostly explored with low-resolution genetic techniques (e.g., fluorescence in situ hybridization or PCR), before genomic mapping and molecular characterization through sequencing became feasible. As a result, the precise nature of most chromosomal rearrangements remains unknown, whereas, more recently, balancers have been engineered using the CRISPR-Cas9 technique for which the structure of the chromosomal rearrangement has been predesigned. Using short-read whole-genome sequencing (srWGS) and tailored bioinformatic analyses, we previously interpreted the structure of four chromosomal balancers randomly created by mutagenesis processes. Here, we have extended our analyses to five CRISPR-Cas9 balancers and 17 additional traditional balancing rearrangements. We detected and experimentally validated their breakpoints and have interpreted the balancer structures. Many of the balancers were found to be more intricate than previously described, being composed of complex genomic rearrangements (CGRs) such as chromoanagenesis-like events. Furthermore, srWGS revealed additional structural variants and CGRs not known to be part of the balancer genomes. Altogether, our study provides a comprehensive resource of complex genomic variations in C. elegans and highlights the power of srWGS to study the complexity of genomes by applying tailored analyses. (© 2023 Maroilley et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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