Genome-wide regulatory effects of STRs stabilized by elevated expression of antioxidant genes in C. elegans

Abstract

Genetic variation can cause significant differences in gene expression among individuals. Although quantitative genetic mapping techniques provide ways to identify genome-wide regulatory loci, they almost entirely focus on single nucleotide variants (SNVs). Short tandem repeats (STRs) represent a large source of genetic variation with potential regulatory effects. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes might affect STR variation systematically. Overall, we reveal the interplay between STRs and gene expression variation in a tractable model system to ultimately associate STR variation with differences in complex traits.