SNP rs403212791 in exon 2 of the MTNR1A gene is associated with reproductive seasonality in the Rasa aragonesa sheep breed

Abstract

The aim of this study was to characterize and identify causative SNPs in the MTNR1A gene responsible for the reproductive seasonality traits in the Rasa aragonesa sheep breed. A total of 290 ewes (155, 84 and 51 mature, young and ewe lambs, respectively) from one flock were controlled from January to August. The following three reproductive seasonality traits were considered: the total days of anoestrus (TDA) and the progesterone cycling months (P4CM); both ovarian function seasonality traits based on blood progesterone levels; and the oestrus cycling months (OCM) based on oestrous detection, which indicate behavioural signs of oestrous. We have sequenced the total coding region plus 733 and 251 bp from the promoter and 3'-UTR regions, respectively, from the gene in 268 ewes. We found 9 and 4 SNPs associated with seasonality traits in the promoter (for TDA and P4CM) and exon 2 (for the three traits), respectively. The SNPs located in the gene promoter modify the putative binding sites for various trans-acting factors. In exon 2, two synonymous SNPs affect RFLP sites, rs406779174/RsaI (for the three traits) and rs430181568/MnlI (for OCM), and they have been related with seasonal reproductive activity in previous association studies with other breeds. SNP rs400830807, which is located in the 3'-UTR, was associated with the three traits, but this did not modify the putative target sites for ovine miRNAs according to in silico predictions. Finally, the SNP rs403212791 (NW_014639035.1: g.15099004G > A), which is also associated with the three seasonality phenotypes, was the most significant SNP detected in this study and was a non-synonymous polymorphism, leading a change from an Arginine to a Cysteine (R336C). Haplotype analyses confirmed the association results and showed that the effects found for the seasonality traits were caused by the SNPs located in exon 2. We have demonstrated that the T allele in the SNP rs403212791 in the MNTR1A gene is associated with a lower TDA and higher P4CM and OCM values in the Rasa Aragonesa breed.

Polymorphisms of the melatonin receptor 1A gene that affects the reproductive seasonality and litter size in Small Tail Han sheep

“…In the present study, we firstly carried out polymorphism detection in exon 2, the most widely studied exon of MTNR1A , and found five SNPs in sheep, each locus contained three genotypes (Figure ), and both g.15118664G > T and g.15118683C > T loci were involved in amino acid changes (Figure b). Interestingly, three of the five loci had been detected in Altay sheep and Hu sheep (Wang, Shi, et al, ), and the other two loci were also found in the Rasa Aragonesa sheep (Calvo et al, ).…”

“…Polymorphisms of MTNR1A gene have a great influence on the reproduction of goat (Carcangiu, Vacca, et al, ; Chu et al, ), cattle (Elraey et al, ), pig (Ramírez et al, ), goose (Alsiddig et al, ), buffalo (Gunwant et al, ; Jiang et al, ), chicken (Sundaresan et al, ) and sheep (Pelletier et al, , Chu, Ji, & Chen, , Chu et al, , Chu et al, , Mateescu et al, , Wang, , Lei, Di, Liu, & Chu, , Giantsis et al, , Calvo et al, ). The earliest researchers found two polymorphic loci in the 824bp of exon 2 of the MTNR1A gene in many sheep breeds using restriction endonucleases MnlI and RsaI (Messer et al, ; Notter, Cockett, & Hadfield, ).…”

“…MTNR1A , a receptor of melatonin, plays important roles in regulating the physiological rhythm and reproductive seasonality of mammals (Lei et al, ). Many researches indicated that polymorphisms of MTNR1A gene had effects on the reproductive seasonality in sheep (Calvo et al, ; Carcangiu, Mura, et al, ; Chu et al, ; Giantsis et al, ; Mateescu et al, ; Pelletier et al, ), goat (Carcangiu, Vacca, et al, ; Chu et al, ) and buffalo (Gunwant et al, ; Luridiana et al, ). MTNR1A is one potential candidate gene involved in the control of ovine reproductive seasonality.…”

“…Interestingly, three of the five loci had been detected in Altay sheep and Hu sheep , and the other two loci were also found in the Rasa Aragonesa sheep (Calvo et al, 2018).…”

The effect of SNP rs400827589 in exon 2 of the MTNR1B gene on reproductive seasonality and litter size in sheep

“…Melatonin is a vital hormone that is secreted mainly by the pineal gland, and has a significant effect on several physiological functions including circadian rhythm and reproduction through binding its special receptors in mammals (Calvo et al., 2018; Chu et al., 2007; Chu, Ji, & Chen, 2003; Hardeland, 2017; Lei, Di, Liu, & Chu, 2015; Li et al., 2013; Ramírez et al., 2009) and birds (Alsiddig et al., 2016; Amit Kumar & Vinod, 2014; Feng et al., 2018; Rajesh & Chandana, 2011; Zhao et al., 2014). There are three melatonin receptor subtypes, melatonin receptor 1A (MTNR1A, MT1), melatonin receptor 1B (MTNR1B, MT2) and melatonin receptor 1C (MTNR1C), which belong to the superfamily of G protein‐coupled receptors (Dubocovich & Markowska, 2005; Reiter, 1980).…”