Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs

Abstract

Background Short tandem repeats (STRs) were recently found to have significant impacts on gene expression and diseases in humans, but their roles on gene expression and complex traits in pigs remain unexplored. This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds. Results We identified 5203 and 5868 significantly expression STRs (eSTRs, FDR < 1%) in the F6 and F7 populations, respectively, most of which could be reciprocally validated (π1 = 0.92). The eSTRs explained 27.5% of the cis-heritability of gene expression traits on average. We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs, respectively, which were significantly enriched in intron, ATAC peak, compartment A and H3K4me3 regions. We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs, which colocalized with epigenetic markers such as H3K27ac and ATAC peaks. These included eSTR of the CLPB, PGLS, PSMD6 and DHDH genes, which are linked with genome-wide association study (GWAS) SNPs for blood-related traits, leg conformation, growth-related traits, and meat quality traits, respectively. Conclusions This study provides insights into the effects of STRs on gene expression traits. The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.

A primate-specific (GCC) repeat in SMAD9 undergoes natural selection in humans and harbors unambiguous genotypes in late-onset neurocognitive disorder.

“…An increasing wealth of research supports the vast implications of short tandem repeats (STRs) (also known as microsatellites/simple sequence repeats) in evolutionary, biological, and pathological terms [1][2][3][4][5][6][7][8][9][10]. However, STRs remain underappreciated in comparison to single nucleotide substitutions [11,12], partly because of their repetitive nature and the hardship of accurate allele calling with the currently available methods.…”