The LEPR Gene Is Associated with Reproductive Seasonality Traits in Rasa Aragonesa Sheep

SIMPLE SUMMARY: Seasonality of reproduction is one of the limiting factor of sheep production, with the leptin receptor (LEPR) gene associated with some reproductive traits in different species. Thereby, we searched for polymorphisms in the ovine LEPR gene and associated them with three reproductive seasonality traits: the total days of anoestrous (TDA) and the progesterone cycling months (P4CM), both based on blood progesterone level and related to seasonal ovarian function; and the oestrous cycling months (OCM) as an indicator of oestrous behaviour. Two non-synonymous and non-linked single nucleotide polymorphisms (SNPs) in the LEPR gene were involved in the OCM trait (rs403578195 and rs405459906). These findings show for the first time the involvement of LEPR gene in seasonality reproduction in sheep and will help to improve genetic selection programs by implementing the genotyping of reproducers, which might increase the productivity of meat sheep. ABSTRACT: The aim of this study was to characterize and identify causative polymorphisms in the leptin receptor (LEPR) gene responsible for the seasonal variation of reproductive traits in sheep. Three reproductive seasonality traits were studied: the total days of anoestrous (TDA), the progesterone cycling months (P4CM) and the oestrous cycling months (OCM). In total, 18 SNPs were detected in 33 ewes with extreme values for TDA and OCM. Six SNPs were non-synonymous substitutions and two of them were predicted in silico as deleterious: rs596133197 and rs403578195. These polymorphisms were then validated in 239 ewes. The SNP rs403578195, located in exon 8 and leading to a change of alanine to glycine (Ala284Gly) in the extracellular domain of the protein, was associated with the OCM trait, being the G allele associated with a decrease of 12 percent of the OCM trait. Haplotype analyses also suggested the involvement of other non-synonymous SNP located in exon 20 (rs405459906). This SNP also produces an amino acid change (Lys1069Glu) in the intracellular domain of the protein and segregates independently of rs403578195. These results confirm for the first time the role of the LEPR gene in sheep reproductive seasonality.