Identification of suppressors of mbk-2/DYRK by whole-genome sequencing

Yuemeng Wang, Jennifer T. Wang, Dominique Rasoloson, Michael L. Stitzel, Kevin F. O'Connell, Harold E. Smith, Geraldine Seydoux

Research output: Contribution to journalArticlepeer-review

Abstract

Screening for suppressor mutations is a powerful method to isolate genes that function in a common pathway or process. Because suppressor mutations often do not have phenotypes on their own, cloning of suppressor loci can be challenging. A method combining whole-genome sequencing (WGS) and single nucleotide polymorphism (SNP) mapping (WGS/SNP mapping) was developed to identify mutations with visible phenotypes in C. elegans. We show here that WGS/SNP mapping is an efficient method to map suppressor mutations without the need for previous phenotypic characterization. Using RNA-mediated interference to test candidate loci identified by WGS/SNP mapping, we identified 10 extragenic and six intragenic suppressors of mbk-2, a DYRK family kinase required for the transition from oocyte to zygote. Remarkably, seven suppressors are mutations in cell-cycle regulators that extend the timing of the oocyteto- zygote transition.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalG3: Genes, Genomes, Genetics
Volume4
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • C. elegans
  • DYRK kinase
  • MBK-2
  • Single nucleotide polymorphism mapping
  • Suppressors
  • Whole-genome sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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