Genetic influence of a STAU2 frameshift mutation and RELN regulatory elements on performance in Icelandic horses

Selection for performance in horse breeding benefits from precise genetic insights at a molecular level, but knowledge remains limited. This study used whole-genome sequences of 39 elite and non-elite Icelandic horses to identify candidate causal variants linked to previously identified haplotypes in the STAU2 and RELN genes affecting pace and other gaits. A frameshift variant in linkage disequilibrium with the previously identified haplotypes in the STAU2 gene (r² = 0.85) was identified within a predicted STAU2 transcript. This variant alters the amino acid sequence and introduces a premature stop codon but does not appear harmful or disease-causing and is potentially unique to equine biology. A large portion of the RELN haplotype overlapped with an H3K27me3 modification mark, suggesting a regulatory role of this region. Despite the small sample size, the RELN haplotype's effects were validated for tölt, trot, and canter/gallop. Additionally, the RELN haplotype significantly influenced the age at which horses were presented for breeding field tests, indicating a potential role of the region in precocity and trainability. Functional experiments are needed to further investigate the regions' influences on biological processes and their potential impact on horse performance.