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Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice
Excel Que1,2, Kristen L James2, Alisha R Coffey3
1Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, California 95616.
Genetics
|August 9, 2020
Summary
Genetic regulation of gene expression (eQTL) and microRNA (mirQTL) differs, with more trans-acting factors influencing miRNAs. Diet impacts this genetic architecture, revealing complex regulation of RNA classes vital for health.
Area of Science:
- Genomics and Systems Biology
- Molecular Genetics
- Quantitative Trait Loci Analysis
Background:
- Genetic regulation influences molecular traits like gene expression, similar to clinical traits.
- Expression quantitative trait loci (eQTL) studies have advanced understanding of genetic regulation.
- Extending these analyses to other molecular traits, including microRNA (miRNA) expression, is crucial.
Purpose of the Study:
- To perform global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in Diversity Outbred mice.
- To compare the genetic regulation (cis vs. trans) of mRNA and miRNA expression.
- To investigate the influence of diet on the genetic architecture of eQTL and mirQTL.
Main Methods:
- Global hepatic eQTL and mirQTL analysis in Diversity Outbred mice.
- Comparison of cis- and trans-acting regulatory mechanisms for mRNA and miRNA.
- Assessment of heritability and variance explained by eQTL and mirQTL.
- Investigation of dietary effects on the genetic architecture of RNA expression.
Main Results:
- Approximately 50% of mirQTL are regulated by trans-acting factors, compared to ~25% of eQTL.
- Cis-acting variants generally explain more phenotypic variance for both mRNA and miRNA expression than trans-acting variants.
- Diet significantly impacts the genetic architecture of both eQTL and mirQTL.
Conclusions:
- mRNA and miRNA expression exhibit distinct modes of genetic regulation (cis/trans).
- Environmental factors, such as diet, play a critical role in shaping the genetic architecture of RNA expression.
- These findings highlight the complex genetic regulation of mRNA and miRNA, essential for understanding clinical traits and disease susceptibility.
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