Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans

Mark G. Sterken, Linda van Bemmelen-van der Plaat, Joost A. Riksen, Miriam Rodriguez, Tobias Schmid, Alex Hajnal, Jan E. Kammenga, Basten L. Snoek

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6 Citations (Scopus)

Abstract

The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used a Caenorhabditis elegans RIL population containing a gain-of-function mutation in the Ras/MAPK pathway gene let-60 and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detected cis-eQTL were not specific for the let-60 mutation, whereas most (~76%) of the 898 detected trans-eQTL were associated with the let-60 mutation. We detected 6 eQTL trans-bands specific for the interaction between the genetic background and the mutation, one of which co-localized with the polymorphic Ras/MAPK modifier amx-2. Comparison between transgenic lines expressing allelic variants of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTL for genes mapping to this trans-band. Together, our results have revealed loci hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.
Original languageEnglish
Pages (from-to)3185-3193
JournalG3 : Genes Genomes Genetics
Volume7
Issue number9
DOIs
Publication statusPublished - 2017

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Caenorhabditis elegans
Mutation
Modifier Genes
Chromosome Mapping
Gene Expression Regulation
Genetic Background
Population
Genes

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Sterken, M. G., van Bemmelen-van der Plaat, L., Riksen, J. A., Rodriguez, M., Schmid, T., Hajnal, A., ... Snoek, B. L. (2017). Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans. G3 : Genes Genomes Genetics, 7(9), 3185-3193. https://doi.org/10.1534/g3.117.1120
Sterken, Mark G. ; van Bemmelen-van der Plaat, Linda ; Riksen, Joost A. ; Rodriguez, Miriam ; Schmid, Tobias ; Hajnal, Alex ; Kammenga, Jan E. ; Snoek, Basten L. / Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans. In: G3 : Genes Genomes Genetics. 2017 ; Vol. 7, No. 9. pp. 3185-3193.
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Sterken, MG, van Bemmelen-van der Plaat, L, Riksen, JA, Rodriguez, M, Schmid, T, Hajnal, A, Kammenga, JE & Snoek, BL 2017, 'Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans', G3 : Genes Genomes Genetics, vol. 7, no. 9, pp. 3185-3193. https://doi.org/10.1534/g3.117.1120

Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans. / Sterken, Mark G.; van Bemmelen-van der Plaat, Linda; Riksen, Joost A.; Rodriguez, Miriam; Schmid, Tobias; Hajnal, Alex; Kammenga, Jan E.; Snoek, Basten L.

In: G3 : Genes Genomes Genetics, Vol. 7, No. 9, 2017, p. 3185-3193.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Sterken, Mark G.

AU - van Bemmelen-van der Plaat, Linda

AU - Riksen, Joost A.

AU - Rodriguez, Miriam

AU - Schmid, Tobias

AU - Hajnal, Alex

AU - Kammenga, Jan E.

AU - Snoek, Basten L.

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AB - The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used a Caenorhabditis elegans RIL population containing a gain-of-function mutation in the Ras/MAPK pathway gene let-60 and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detected cis-eQTL were not specific for the let-60 mutation, whereas most (~76%) of the 898 detected trans-eQTL were associated with the let-60 mutation. We detected 6 eQTL trans-bands specific for the interaction between the genetic background and the mutation, one of which co-localized with the polymorphic Ras/MAPK modifier amx-2. Comparison between transgenic lines expressing allelic variants of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTL for genes mapping to this trans-band. Together, our results have revealed loci hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.

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DO - 10.1534/g3.117.1120

M3 - Article

VL - 7

SP - 3185

EP - 3193

JO - G3 : Genes Genomes Genetics

JF - G3 : Genes Genomes Genetics

SN - 2160-1836

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