Characterizing the landscape of gene expression variance in humans

PLoS Genetics, Journal Year: 2023, Volume and Issue: 19(7), P. e1010833 - e1010833

Published: July 6, 2023

Gene expression variance has been linked to organismal function and fitness but remains a commonly neglected aspect of molecular research. As result, we lack comprehensive understanding the patterns transcriptional across genes, how this is context-specific gene regulation function. Here, use 57 large publicly available RNA-seq data sets investigate landscape variance. These studies cover wide range tissues allowed us assess if there are consistently more or less variable genes what mechanisms drive these patterns. We show that broadly similar studies, indicating pattern consistent. similarity create both global within-tissue rankings variation, which function, sequence regulatory signatures contribute Low-variance associated with fundamental cell processes have lower levels genetic polymorphisms, higher gene-gene connectivity, tend be chromatin states transcription. In contrast, high-variance enriched for involved in immune response, environmentally responsive immediate early polymorphisms. results not noise. Instead, it consistent trait seems functionally constrained human populations. Furthermore, phenotypic variation harbors important information understand complex traits disease.

Language: Английский

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Genetic Variants Contribute to Gene Expression Variability in Humans

Genetics, Journal Year: 2012, Volume and Issue: 193(1), P. 95 - 108

Published: Nov. 14, 2012

Abstract Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these focused on the mean expression level, but not variance level (i.e., variability). In present study, we systematically explore genome-wide association variability in humans. We adapt double generalized linear model (dglm) to simultaneously fit means variances among three possible genotypes a biallelic SNP. The genomic showing significant are termed QTL (evQTL). Using data set lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, identify cis-acting evQTL involving 218 distinct genes, which 8 ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, TNFRSF11B, cross-validated using an extra same LCLs. also ∼300 trans-acting >13,000 common SNPs 500 randomly selected representative genes. employ two scenarios, emphasizing single-SNP multiple-SNP effects variability, explain formation evQTL. argue that detecting may represent novel method for effectively screening interactions, especially when influence is implied. implication our results revealing mechanisms discussed.

Language: Английский

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Epigenetic and Transcriptional Variability Shape Phenotypic Plasticity

BioEssays, Journal Year: 2017, Volume and Issue: 40(2)

Published: Dec. 18, 2017

Epigenetic and transcriptional variability contribute to the vast diversity of cellular organismal phenotypes are key in human health disease. In this review, we describe different types, sources, determinants epigenetic variability, enabling cells organisms adapt evolve a changing environment. We highlight latest research hypotheses on how chromatin structure epigenome influence gene expression variability. Further, provide an overview challenges analysis biological An improved understanding molecular mechanisms underlying at both intra‐ inter‐individual level, provides great opportunity for disease prevention, better therapeutic approaches, personalized medicine.

Language: Английский

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Feedback Control of Gene Expression Variability in the Caenorhabditis elegans Wnt Pathway

Cell, Journal Year: 2013, Volume and Issue: 155(4), P. 869 - 880

Published: Nov. 1, 2013

Language: Английский

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Transcriptomic responses to seawater acidification among sea urchin populations inhabiting a natural pH mosaic

Molecular Ecology, Journal Year: 2017, Volume and Issue: 26(8), P. 2257 - 2275

Published: Jan. 31, 2017

Increasing awareness of spatial and temporal variation in ocean pH suggests some marine populations may be adapted to local regimes will therefore respond differently present-day long-term acidification. In the Northeast Pacific Ocean, differences strength coastal upwelling cause latitudinal prevailing that are hypothesized promote adaptation unequal tolerance among resident populations. this study, responses experimental seawater acidification were compared embryos larvae from six purple sea urchins (Strongylocentrotus purpuratus) inhabiting areas differ their frequency low exposure prior research locally pH. Transcriptomic analyses demonstrate urchin most frequently exposed responded by expressing genes within major ATP-producing pathways at greater levels than encountering less often. Multiple tricarboxylic acid cycle, electron transport chain fatty beta oxidation upregulated experiencing conditions frequently. These same metabolic significantly over-represented both expressed a population-specific manner putatively under selection enhance tolerance. Collectively, these data suggest natural is acting on gene networks redirect ATP toward maintaining acid-base homeostasis As trade-off, more tolerant have energy put towards other aspects fitness additional change.

Language: Английский

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