ArticlePLoS genetics2020
Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
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- Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Single-cell genomics meets human genetics.Nature reviews. Genetics · 2023Review
- Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.Genome research · 2023Article
- Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single cell resolution.bioRxiv : the preprint server for biology · 2022Article
- Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8Frontiers in immunology · 2022Review
- Where Are the Disease-Associated eQTLs?Trends in genetics : TIG · 2021Review
- Localization of RNA Pol II CTD (S5) and Transcriptome Analysis of Testis in Diploid and Tetraploid Hybrids of Red Crucian Carp (♀) × Common Carp (♂).Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis. However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans, with notably fewer variants acting in cis. Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans.
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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.