English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Given the central metabolic role of the liver, hepatic metabolites and transcripts reflect the organismal physiological state. Biochemical-clinical plasma biomarkers, hepatic metabolites, transcripts, and single nucleotide polymorphism (SNP) genotypes of some 300 pigs were integrated by weighted correlation networks and genome-wide association analyses. Network-based approaches of transcriptomic and metabolomics data revealed linked of transcripts and metabolites of the pentose phosphate pathway (PPP). This finding was evidenced by using a NADP/NADPH assay and  HDAC4  and  G6PD  transcript quantification with the latter coding for first limiting enzyme of this pathway and by RNAi knockdown experiments of  HDAC4 . Other transcripts including  ARG2  and  SLC22A7  showed link to amino acids and biomarkers. The amino acid metabolites were linked with transcripts of immune or acute phase response signaling, whereas the carbohydrate metabolites were highly enrich in cholesterol biosynthesis transcripts. Genome-wide association analyses revealed 180 metabolic quantitative trait loci (mQTL) ( p  < 10 -4 ). Trans-4-hydroxy- L -proline ( p  = 6 × 10 -9 ), being strongly correlated with plasma creatinine (CREA), showed strongest association with SNPs on chromosome 6 that had pleiotropic effects on  PRODH2  expression as revealed by multivariate analysis. Consideration of shared marker association with biomarkers, metabolites, and transcripts revealed 144 SNPs associated with 44 metabolites and 69 transcripts that are correlated with each other, representing 176 mQTL and expression quantitative trait loci (eQTL). This is the first work to report genetic variants associated with liver metabolite and transcript levels as well as blood biochemical-clinical parameters in a healthy porcine model. The identified associations provide links between variation at the genome, transcriptome, and metabolome level molecules with clinically relevant phenotypes. This approach has the potential to detect novel biomarkers displaying individual variation and promoting predictive biology in medicine and animal breeding.

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters