ArticleGenome research2014
Heritability and genetic basis of protein level variation in an outbred population.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Protocol for mapping gene essentiality changes in yeast using inducible gene deletion mutants.STAR protocols · 2026Article
- A genome-to-proteome map reveals how natural variants drive proteome diversity and shape fitness.Science (New York, N.Y.) · 2025Article
- Gene-environment interactions modulate the phenotype severity in mouse models of congenital craniofacial syndromes.The Journal of clinical investigation · 2025Article
- A genome-to-proteome atlas charts natural variants controlling proteome diversity and forecasts their fitness effects.bioRxiv : the preprint server for biology · 2024Article
- Global analysis of suppressor mutations that rescue human genetic defects.Genome medicine · 2023Article
- Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth.Nature structural & molecular biology · 2023Article
- Article
- Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function.eLife · 2022Article
- Variation in upstream open reading frames contributes to allelic diversity in maize protein abundance.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size.Molecular cell · 2021Article
- Natural variants suppress mutations in hundreds of essential genes.Molecular systems biology · 2021Article
- Article
- DNA variants affecting the expression of numerous genes in trans have diverse mechanisms of action and evolutionary histories.PLoS genetics · 2019Article
- CompensatoryEvolution letters · 2019Article
- Characterization of Proteome Variation During Modern Maize Breeding.Molecular & cellular proteomics : MCP · 2019Article
- Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype.Frontiers in integrative neuroscience · 2019Article
- Identifying Multi-Omics Causers and Causal Pathways for Complex Traits.Frontiers in genetics · 2019Article
- Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance.PLoS genetics · 2018Article
- Accurate Classification of Protein Subcellular Localization from High-Throughput Microscopy Images Using Deep Learning.G3 (Bethesda, Md.) · 2017Article
- The genetic architecture of low-temperature adaptation in the wine yeast Saccharomyces cerevisiae.BMC genomics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
The genetic basis of heritable traits has been studied for decades. Although recent mapping efforts have elucidated genetic determinants of transcript levels, mapping of protein abundance has lagged. Here, we analyze levels of 4084 GFP-tagged yeast proteins in the progeny of a cross between a laboratory and a wild strain using flow cytometry and high-content microscopy. The genotype of trans variants contributed little to protein level variation between individual cells but explained >50% of the variance in the population's average protein abundance for half of the GFP fusions tested. To map trans-acting factors responsible, we performed flow sorting and bulk segregant analysis of 25 proteins, finding a median of five protein quantitative trait loci (pQTLs) per GFP fusion. Further, we find that cis-acting variants predominate; the genotype of a gene and its surrounding region had a large effect on protein level six times more frequently than the rest of the genome combined. We present evidence for both shared and independent genetic control of transcript and protein abundance: More than half of the expression QTLs (eQTLs) contribute to changes in protein levels of regulated genes, but several pQTLs do not affect their cognate transcript levels. Allele replacements of genes known to underlie trans eQTL hotspots confirmed the correlation of effects on mRNA and protein levels. This study represents the first genome-scale measurement of genetic contribution to protein levels in single cells and populations, identifies more than a hundred trans pQTLs, and validates the propagation of effects associated with transcript variation to protein abundance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.