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.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Proteomics ; quantitative trait loci ; TMT ; Quantitative
Principal Investigators: (in alphabetical order) |
Steven Gygi, harvard medical school, N/A |
Submitting User: | ccms |
Chick JM, Munger SC, Simecek P, Huttlin EL, Choi K, Gatti DM, Raghupathy N, Svenson KL, Churchill GA, Gygi SP.
Defining the consequences of genetic variation on a proteome-wide scale.
Nature. 2016 Jun 23;534(7608):500-5. Epub 2016 Jun 15.
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