13 Genome scanning reveals regions with increased homozygosity negatively affecting fertility in Pura Raza Español mares

Mares are known to be individuals with moderate fertility and reduced conception rate compared with other livestock species. Several factors have been described as potential causes, including reproductive and productive management and the stress caused by training programs on competition animals, but this is also due to differences in their genetic background. In addition, an increase in the average inbreeding value, which is largely associated with fertility decreases, has been described in several horse breeds. However, no previous studies have been conducted to elucidate the relationship between inbreeding and fertility in mares from a genomic viewpoint. Hereby, we performed a whole-genome scanning to determine regions with increased homozygosity ratios associated with changes in fertility in a large Pura Raza Español population. We first estimated the breeding values for the reproductive efficiency (RE) parameter using a large pedigree database (n = 340 000) and a mixed model in BLUPF90 software. Then, we selected two groups of individuals showing 10% high (HFert, n = 86) and low (LFert; n = 86) fertility estimated breeding values. These individuals were genotyped using the Axiom HD SNP genotyping array (≈670 000 markers per individual; ThermoFisher Scientific). Then, we determined the genomic regions in which the homozygosity levels were significantly increased by performing a “runs of homozygosity” analysis, retaining only the regions in which the increase in homozygosity was 1000×, at least in comparison with random occurrence probability (permutation test). Our results showed a significant increase in inbreeding in LFert individuals (vs. HFert) in 13 regions (located in eight chromosomes). The most affected region was located in ECA7 (49 515 421 to 49 632 127), encompassing several genes previously related to female fertility, including prostaglandin E receptor 1 (PTGER1), protein kinase cAMP-activated catalytic subunit alpha (PRKACA), and anti-silencing function 1B histone chaperone (ASFB1). Those genes were related to oocyte developmental processes. An additional genomic region located in ECA3 (40 269 277 to 41 449 687) showed a significant increase in homozygosity. It included the eukaryotic translation initiation factor 4E (EIF4E), which plays a key role in the oocyte to zygote transition in mammals. Hereby, we demonstrated the existence of specific regions that could be involved in the depression of fertility performance due to inbreeding in the horse. However, further studies including a large population of genotyped animals and additional breeds are necessary to validate our findings.