Genome-Wide Association Study Demonstrates the Role Played by the Gene in Rasa Aragonesa Sheep Reproductive Seasonality.

A genome-wide association study (GWAS) was used to identify genomic regions influencing seasonality reproduction traits in Rasa Aragonesa sheep. Three traits associated with either ovarian function based on blood progesterone levels (total days of anoestrus and progesterone cycling months) or behavioral signs of oestrous (oestrous cycling months) were studied. The GWAS included 205 ewes genotyped using the 50k and 680k Illumina Ovine Beadchips. Only one SNP associated with the progesterone cycling months overcame the genome-wide significance level (rs404991855). Nine SNPs exhibited significant associations at the chromosome level, being the SNPs rs404991855 and rs418191944, that are located in the () gene, associated with the three traits. This gene is related to reproductive diseases. Two other SNPs were located close to the () gene, which is involved in circadian rhythms. To validate the GWAS, partial characterization of both genes by Sanger sequencing, and genotyping of two synonymous and two nonsynonymous SNPs in the and genes, respectively, were performed. SNP association analysis showed that only SNP rs404360094 in the exon 3 of the gene, which produces an amino acid substitution from asparagine (uncharged polar) to aspartic acid (acidic), was associated with the three seasonality traits. Our results suggest that the gene may be involved in the reproductive seasonality in Rasa Aragonesa.