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Cell-to-cell stochastic variation in gene expression is a complex genetic trait.

ABSTRACT: The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or 'noise'). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits.

SUBMITTER: Ansel J

PROVIDER: S-EPMC2289839 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Cell-to-cell stochastic variation in gene expression is a complex genetic trait.

Ansel Juliet J Bottin Hélène H Rodriguez-Beltran Camilo C Damon Christelle C Nagarajan Muniyandi M Fehrmann Steffen S François Jean J Yvert Gaël G

PLoS genetics 20080411 4

The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitat ...[more]

PMID: 18404214

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Project description:BackgroundEconomically important growth and meat quality traits in pigs are controlled by cascading molecular events occurring during development and continuing throughout the conversion of muscle to meat. However, little is known about the genes and molecular mechanisms involved in this process. Evaluating transcriptomic profiles of skeletal muscle during the initial steps leading to the conversion of muscle to meat can identify key regulators of polygenic phenotypes. In addition, mapping transcript abundance through genome-wide association analysis using high-density marker genotypes allows identification of genomic regions that control gene expression, referred to as expression quantitative trait loci (eQTL). In this study, we perform eQTL analyses to identify potential candidate genes and molecular markers regulating growth and meat quality traits in pigs.ResultsMessenger RNA transcripts obtained with RNA-seq of longissimus dorsi muscle from 168 F2 animals from a Duroc x Pietrain pig resource population were used to estimate gene expression variation subject to genetic control by mapping eQTL. A total of 339 eQTL were mapped (FDR ≤ 0.01) with 191 exhibiting local-acting regulation. Joint analysis of eQTL with phenotypic QTL (pQTL) segregating in our population revealed 16 genes significantly associated with 21 pQTL for meat quality, carcass composition and growth traits. Ten of these pQTL were for meat quality phenotypes that co-localized with one eQTL on SSC2 (8.8-Mb region) and 11 eQTL on SSC15 (121-Mb region). Biological processes identified for co-localized eQTL genes include calcium signaling (FERM, MRLN, PKP2 and CHRNA9), energy metabolism (SUCLG2 and PFKFB3) and redox hemostasis (NQO1 and CEP128), and results support an important role for activation of the PI3K-Akt-mTOR signaling pathway during the initial conversion of muscle to meat.ConclusionCo-localization of eQTL with pQTL identified molecular markers significantly associated with both economically important phenotypes and gene transcript abundance. This study reveals candidate genes contributing to variation in pig production traits, and provides new knowledge regarding the genetic architecture of meat quality phenotypes.

Dataset Information

Cell-to-cell stochastic variation in gene expression is a complex genetic trait.

Publications

Cell-to-cell stochastic variation in gene expression is a complex genetic trait.

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