Dataset Information

Defining the effects of genetic variation on a proteome-wide scale

ABSTRACT: Genetic variation governs protein expression through both transcriptional and post-transcriptional processes. To investigate this relationship, we combined a multiplexed, mass spectrometry-based method for protein quantification with an emerging mouse model harboring extensive genetic variation from 8 founder strains. We collected genome-wide mRNA and protein profiling measurements to link genetic variation to protein expression differences in livers from 192 diversity outcross mice. We observed nearly 3,700 protein-level quantitative trait loci (pQTL) with an equal proportion of proteins regulated directly by their cognate mRNA as uncoupled from their transcript. Our analysis reveals an extensive array of at least five models for genetic variant control of protein abundance including direct protein-to-protein associations that act to achieve stoichiometric balance of functionally related enzymes and subunits of multimeric complexes.

OTHER RELATED OMICS DATASETS IN: MSV000081696PRJNA295057

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

SUBMITTER: Joel Chick

LAB HEAD: Steven Gygi

PROVIDER: PXD002801 | Pride | 2016-06-15

REPOSITORIES: Pride

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			Action	DRS
	f01564_MDP_liver_fusion_tmt10_Set2_F01.raw	Raw
	f01564_MDP_liver_fusion_tmt10_Set2_F01.tgz	Other
	f01565_MDP_liver_fusion_tmt10_Set2_F02.raw	Raw
	f01565_MDP_liver_fusion_tmt10_Set2_F02.tgz	Other
	f01566_MDP_liver_fusion_tmt10_Set2_F03.raw	Raw

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Defining the consequences of genetic variation on a proteome-wide scale.

Chick Joel M JM Munger Steven C SC Simecek Petr P Huttlin Edward L EL Choi Kwangbom K Gatti Daniel M DM Raghupathy Narayanan N Svenson Karen L KL Churchill Gary A GA Gygi Steven P SP

Nature 20160615 7608

Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, here we combine a multiplexed, mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in livers from 192 Diversity outbred mice, we ide ...[more]

PMID: 27309819

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