Identification of Suppressors of mbk-2/DYRK by Whole-Genome Sequencing

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...

Full description

Saved in:
Bibliographic Details
Published in:G3 : genes - genomes - genetics 2014-02, Vol.4 (2), p.231-241
Main Authors: Wang, Yuemeng, Wang, Jennifer T, Rasoloson, Dominique, Stitzel, Michael L, O’ Connell, Kevin F, Smith, Harold E, Seydoux, Geraldine
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Caenorhabditis elegans - embryology
Caenorhabditis elegans - genetics
Caenorhabditis elegans Proteins - chemistry
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Catalytic Domain
Epistasis, Genetic
Gene Expression Regulation, Developmental
Genome, Helminth
Investigations
Molecular Sequence Data
Polymorphism, Single Nucleotide
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
RNA Interference
Sequence Analysis, DNA
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 oocyte-to-zygote transition.
ISSN:2160-1836
2160-1836
DOI:10.1534/g3.113.009126