Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice.

Tytuł:: Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice.
Autorzy:: Que E; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, California 95616.; Department of Nutrition, University of California, Davis, California.
James KL; Department of Nutrition, University of California, Davis, California.
Coffey AR; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina.
Smallwood TL; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina.
Albright J; Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina.
Huda MN; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, California 95616.; Department of Nutrition, University of California, Davis, California.
Pomp D; Department of Genetics, University of North Carolina at Chapel Hill, North Carolina.
Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York .
Bennett BJ; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, California 95616 .; Department of Nutrition, University of California, Davis, California.
Źródło:: Genetics [Genetics] 2020 Sep; Vol. 216 (1), pp. 241-259. Date of Electronic Publication: 2020 Aug 06.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Retracted Publication
Język:: English
Imprint Name(s):: Publication: 2021- : [Oxford] : Oxford University Press
Original Publication: Austin, Tex. [etc.]
MeSH Terms:: Diet*
Genetic Variation*
Hybridization, Genetic*
Liver/*metabolism
MicroRNAs/*genetics
RNA, Messenger/*genetics
Animals ; Biological Variation, Population ; Mice ; MicroRNAs/metabolism ; Phenotype ; Quantitative Trait Loci ; RNA, Messenger/metabolism ; Transcriptome
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Grant Information:: P30 DK056350 United States DK NIDDK NIH HHS; R01 DK105965 United States DK NIDDK NIH HHS; R01 HL128572 United States HL NHLBI NIH HHS
Contributed Indexing:: Keywords: Multiparental models; Quantitative trait loci; eQTL; mirQTL
Substance Nomenclature:: 0 (MicroRNAs)
0 (RNA, Messenger)
Entry Date(s):: Date Created: 20200809 Date Completed: 20210714 Latest Revision: 20240229
Update Code:: 20240229
PubMed Central ID:: PMC7463293
DOI:: 10.1534/genetics.120.303481
PMID:: 32763908
: Czasopismo naukowe

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation ( cis or trans ) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a trans -acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general, cis -acting variants affecting mRNA or miRNA expression explain more phenotypic variance than trans -acting variants. Lastly, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility.
(Copyright © 2020 Que et al.)

Retraction in: Genetics. 2021 Jul 14;218(3):. (PMID: 34849861)

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