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The Farm Animal Genotype-Tissue Expression (GTEx) consortium has just published a study on the effects of genetic variants on transcriptome regulation in pigs [1]. A similar study had already been carried out in cattle [2].

For this new study, researchers from all over the world (USA, China, Europe...), including INRAE, and coordinated by Lingzhao Fang from the Center for Quantitative Genetics and Genomics (University of Aarhus, Denmark), compiled publicly available RNA-seq data from 5457 samples, comprising 34 pig cell types and organs, as well as whole genome sequencing data from 1602 animals. Using these whole genome sequences, the researchers developed a porcine genotype imputation panel, which was then used to perform genome-wide association analyses for five "molecular transcriptomic" traits. The PigGTEx consortium mapped molecular quantitative trait loci (molQTLs) that act in cis (i.e. within 1 Mb of the transcription initiation site of the associated gene) for five transcriptomic traits: expression levels of coding genes (cis-eQTL), exons (cis-eeQTL ), long non-coding RNAs (cis-lncQTL) and enhancers (cis-enQTL), as well as alternative splicing events (cis-sQTL). The authors showed that 86% of expressed genes were affected by at least one regulatory variant in one or more tissues. The effects of molQTLs were more strongly correlated for tissues with similar function.

The team then functionally annotated molQTLs using other omics data (ATAC-seq, ChIP-seq ...) to better understand the mechanisms underlying these regulations. The researchers showed that molQTLs (particularly cis-eQTLs) were enriched for genome-wide association study (GWAS) signals for 207 complex traits measured in pigs, suggesting that regulatory variants are responsible for the variability of these phenotypes, such as backfat thickness. In fact, 80% of GWAS loci could be explained by at least one molQTL..

Given the biological similarities between pigs and humans, the resources produced by the PigGTEx consortium may have applications not only in animal husbandry but also in biomedicine.

Reference :

[1] Teng et al. (2024). A compendium of genetic regulatory effects across pig tissues. Nature Genetics 56(1):112-123. doi: 10.1038/s41588-023-01585-7.

[2] Liu et al. (2022). A multi-tissue atlas of regulatory variants in cattle. Nature Genetics 54(9):1438-1447. doi: 10.1038/s41588-022-01153-5.

Contact :

• Dominique Rocha : dominique.rocha@inrae.fr