Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans

J.E. Kammenga, J. Fisher, Y. Li, M.A. Swertz, M. Elvin, G. Poulin, L.B. Snoek, M. Rodriguez Sanchez, A. Beyer, S. Schrimpf, J. van de Velde, J. Escobar, T. Schmid, C. Zheng, A. Hajnal, M. Hengartner, R. Jansen

Research output: Chapter in Book/Report/Conference proceedingAbstract

Abstract

The nematode worm C. elegans has intensively been studied for complex human disease pathways. Within the EU FP7 funded PANACEA consortium we perform a quantitative pathway analysis of natural variation in complex disease signalling in C. elegans. Here, we present a robust approach for selecting candidate genes associated with the Notch, Wnt and RAS pathway using a combination of recombinant inbred lines (RILs), derived from a cross of the wildtypes N2 and CB4856, and RNAi. The consortium focuses on the transcriptome, proteome and cellular development. We tested 180 different RNAi’s targeted against genes within these three pathways in a set of 50 RILs. We highlight a case of this cryptic genetic variation in genome wide gene expression levels underlying a gld-1 knock-down (a gene involved in germline development) This revealed new candidate regulators of gld-1 affected gene expression. Furthermore we will show how mutations of the RAS pathway in different genetic backgrounds lead to the discovery of hidden modifiers affecting vulva-development, an important readout of cancer signalling pathways. All this (transcriptomics, proteomics and phenotypic) data will feed into a predictive model of vulva development which can be used to investigate the relative contributions of various recombinants.
Original languageEnglish
Title of host publicationAbstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011
Place of PublicationHeidelberg
PublisherIBM System Storage Solutions
Pages116-116
Publication statusPublished - 2011
EventICSB 2011, Heidelberg/Mannheim, Germany -
Duration: 28 Aug 20111 Sep 2011

Conference

ConferenceICSB 2011, Heidelberg/Mannheim, Germany
Period28/08/111/09/11

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Gene Regulatory Networks
RNA Interference
Genes
Gene Knockdown Techniques
Vulva
Proteome
Proteomics
Genome
Gene Expression
Mutation

Cite this

Kammenga, J. E., Fisher, J., Li, Y., Swertz, M. A., Elvin, M., Poulin, G., ... Jansen, R. (2011). Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans. In Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011 (pp. 116-116). Heidelberg: IBM System Storage Solutions.
Kammenga, J.E. ; Fisher, J. ; Li, Y. ; Swertz, M.A. ; Elvin, M. ; Poulin, G. ; Snoek, L.B. ; Rodriguez Sanchez, M. ; Beyer, A. ; Schrimpf, S. ; van de Velde, J. ; Escobar, J. ; Schmid, T. ; Zheng, C. ; Hajnal, A. ; Hengartner, M. ; Jansen, R. / Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans. Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011. Heidelberg : IBM System Storage Solutions, 2011. pp. 116-116
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abstract = "The nematode worm C. elegans has intensively been studied for complex human disease pathways. Within the EU FP7 funded PANACEA consortium we perform a quantitative pathway analysis of natural variation in complex disease signalling in C. elegans. Here, we present a robust approach for selecting candidate genes associated with the Notch, Wnt and RAS pathway using a combination of recombinant inbred lines (RILs), derived from a cross of the wildtypes N2 and CB4856, and RNAi. The consortium focuses on the transcriptome, proteome and cellular development. We tested 180 different RNAi’s targeted against genes within these three pathways in a set of 50 RILs. We highlight a case of this cryptic genetic variation in genome wide gene expression levels underlying a gld-1 knock-down (a gene involved in germline development) This revealed new candidate regulators of gld-1 affected gene expression. Furthermore we will show how mutations of the RAS pathway in different genetic backgrounds lead to the discovery of hidden modifiers affecting vulva-development, an important readout of cancer signalling pathways. All this (transcriptomics, proteomics and phenotypic) data will feed into a predictive model of vulva development which can be used to investigate the relative contributions of various recombinants.",
author = "J.E. Kammenga and J. Fisher and Y. Li and M.A. Swertz and M. Elvin and G. Poulin and L.B. Snoek and {Rodriguez Sanchez}, M. and A. Beyer and S. Schrimpf and {van de Velde}, J. and J. Escobar and T. Schmid and C. Zheng and A. Hajnal and M. Hengartner and R. Jansen",
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Kammenga, JE, Fisher, J, Li, Y, Swertz, MA, Elvin, M, Poulin, G, Snoek, LB, Rodriguez Sanchez, M, Beyer, A, Schrimpf, S, van de Velde, J, Escobar, J, Schmid, T, Zheng, C, Hajnal, A, Hengartner, M & Jansen, R 2011, Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans. in Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011. IBM System Storage Solutions, Heidelberg, pp. 116-116, ICSB 2011, Heidelberg/Mannheim, Germany, 28/08/11.

Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans. / Kammenga, J.E.; Fisher, J.; Li, Y.; Swertz, M.A.; Elvin, M.; Poulin, G.; Snoek, L.B.; Rodriguez Sanchez, M.; Beyer, A.; Schrimpf, S.; van de Velde, J.; Escobar, J.; Schmid, T.; Zheng, C.; Hajnal, A.; Hengartner, M.; Jansen, R.

Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011. Heidelberg : IBM System Storage Solutions, 2011. p. 116-116.

Research output: Chapter in Book/Report/Conference proceedingAbstract

TY - CHAP

T1 - Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans

AU - Kammenga, J.E.

AU - Fisher, J.

AU - Li, Y.

AU - Swertz, M.A.

AU - Elvin, M.

AU - Poulin, G.

AU - Snoek, L.B.

AU - Rodriguez Sanchez, M.

AU - Beyer, A.

AU - Schrimpf, S.

AU - van de Velde, J.

AU - Escobar, J.

AU - Schmid, T.

AU - Zheng, C.

AU - Hajnal, A.

AU - Hengartner, M.

AU - Jansen, R.

PY - 2011

Y1 - 2011

N2 - The nematode worm C. elegans has intensively been studied for complex human disease pathways. Within the EU FP7 funded PANACEA consortium we perform a quantitative pathway analysis of natural variation in complex disease signalling in C. elegans. Here, we present a robust approach for selecting candidate genes associated with the Notch, Wnt and RAS pathway using a combination of recombinant inbred lines (RILs), derived from a cross of the wildtypes N2 and CB4856, and RNAi. The consortium focuses on the transcriptome, proteome and cellular development. We tested 180 different RNAi’s targeted against genes within these three pathways in a set of 50 RILs. We highlight a case of this cryptic genetic variation in genome wide gene expression levels underlying a gld-1 knock-down (a gene involved in germline development) This revealed new candidate regulators of gld-1 affected gene expression. Furthermore we will show how mutations of the RAS pathway in different genetic backgrounds lead to the discovery of hidden modifiers affecting vulva-development, an important readout of cancer signalling pathways. All this (transcriptomics, proteomics and phenotypic) data will feed into a predictive model of vulva development which can be used to investigate the relative contributions of various recombinants.

AB - The nematode worm C. elegans has intensively been studied for complex human disease pathways. Within the EU FP7 funded PANACEA consortium we perform a quantitative pathway analysis of natural variation in complex disease signalling in C. elegans. Here, we present a robust approach for selecting candidate genes associated with the Notch, Wnt and RAS pathway using a combination of recombinant inbred lines (RILs), derived from a cross of the wildtypes N2 and CB4856, and RNAi. The consortium focuses on the transcriptome, proteome and cellular development. We tested 180 different RNAi’s targeted against genes within these three pathways in a set of 50 RILs. We highlight a case of this cryptic genetic variation in genome wide gene expression levels underlying a gld-1 knock-down (a gene involved in germline development) This revealed new candidate regulators of gld-1 affected gene expression. Furthermore we will show how mutations of the RAS pathway in different genetic backgrounds lead to the discovery of hidden modifiers affecting vulva-development, an important readout of cancer signalling pathways. All this (transcriptomics, proteomics and phenotypic) data will feed into a predictive model of vulva development which can be used to investigate the relative contributions of various recombinants.

M3 - Abstract

SP - 116

EP - 116

BT - Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011

PB - IBM System Storage Solutions

CY - Heidelberg

ER -

Kammenga JE, Fisher J, Li Y, Swertz MA, Elvin M, Poulin G et al. Combining Genetic Variation with Targeted Knock-downs to Construct Gene Networks of Complex Human Diseases in C. elegans. In Abstract Book of the 12th International Conference on Systems Biology, Heidelberg/Mannheim, Germany, 28 August - 1 September 2011. Heidelberg: IBM System Storage Solutions. 2011. p. 116-116