title: Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways.
abstract: Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Kapil Dev
authors.initials: KD
authors.lastname: Singh
authors.affiliation: Functional Genomics Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Roschitzki
authors.affiliation: Laboratory of Nematology, Wageningen University, Wageningen, The Netherlands.
authors.forename: L Basten
authors.initials: LB
authors.lastname: Snoek
authors.affiliation: Functional Genomics Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grossmann
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Xue
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Elvin
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Polina
authors.initials: P
authors.lastname: Kamkina
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Sabine P
authors.initials: SP
authors.lastname: Schrimpf
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Gino B
authors.initials: GB
authors.lastname: Poulin
authors.affiliation: Laboratory of Nematology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Kammenga
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D040641:Quantitative Trait Loci; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D029742:Caenorhabditis elegans Proteins