title: Spectrum of variations in dog-1/FANCJ and mdf-1/MAD1 defective Caenorhabditis elegans strains after long-term propagation.
abstract: BACKGROUND
  Whole and partial chromosome losses or gains and structural chromosome changes are hallmarks of human tumors. Guanine-rich DNA, which has a potential to form a G-quadruplex (G4) structure, is particularly vulnerable to changes. In Caenorhabditis elegans, faithful transmission of G-rich DNA is ensured by the DOG-1/FANCJ deadbox helicase.
  
  
  RESULTS
  To identify a spectrum of mutations, after long-term propagation, we combined whole genome sequencing (WGS) and oligonucleotide array Comparative Genomic Hybridization (oaCGH) analysis of a C. elegans strain that was propagated, in the absence of DOG-1 and MDF-1/MAD1, for a total of 470 generations, with samples taken for long term storage (by freezing) in generations 170 and 270. We compared the genomes of F170 and F470 strains and identified 94 substitutions, 17 InDels, 3 duplications, and 139 deletions larger than 20 bp. These homozygous variants were predicted to impact 101 protein-coding genes. Phenotypic analysis of this strain revealed remarkable fitness recovery indicating that mutations, which have accumulated in the strain, are not only tolerated but also cooperate to achieve long-term population survival in the absence of DOG-1 and MDF-1. Furthermore, deletions larger than 20 bp were the only variants that frequently occurred in G-rich DNA. We showed that 126 of the possible 954 predicted monoG/C tracts, larger than 14 bp, were deleted in unc-46 mdf-1 such-4; dog-1 F470 (JNC170).
  
  
  CONCLUSIONS
  Here, we identified variants that accumulated in C. elegans' genome after long-term propagation in the absence of DOG-1 and MDF-1. We showed that DNA sequences, with G4-forming potential, are vulnerable to deletion-formation in this genetic background.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, V5A 1S6, Burnaby, BC, Canada. maja@cmmt.ubc.ca.|Department of Medical Genetics, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada. maja@cmmt.ubc.ca.|Current affiliation: Centre for Molecular Medicine and Therapeutics; Child and Family Research Institute, Vancouver, BC, Canada. maja@cmmt.ubc.ca.|Current affiliation: Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, BC, Canada. maja@cmmt.ubc.ca.
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo-Graovac
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, V5A 1S6, Burnaby, BC, Canada. tammywong112@gmail.com.
authors.forename: Tammy
authors.initials: T
authors.lastname: Wong
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, V5A 1S6, Burnaby, BC, Canada. qzhaozhao@gmail.com.
authors.forename: Zhaozhao
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Zoology, University of British Columbia, V6T 1Z4, Vancouver, BC, Canada. sflibotte@gmail.com.
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.affiliation: Department of Zoology, University of British Columbia, V6T 1Z4, Vancouver, BC, Canada. jon.cr.taylor@gmail.com.
authors.forename: Jon
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Department of Zoology, University of British Columbia, V6T 1Z4, Vancouver, BC, Canada. moerman@zoology.ubc.ca.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.affiliation: Department of Medical Genetics, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada. annroseubc@gmail.com.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rose
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, V5A 1S6, Burnaby, BC, Canada. chenn@sfu.ca.
authors.forename: Nansheng
authors.initials: N
authors.lastname: Chen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004265:DNA Helicases / Q000235:genetics*; D054856:G-Quadruplexes; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C412839:MDF-1 protein, C elegans; D004265:DNA Helicases; C464789:Dog-1 protein, C elegans