Unidad de Tecnología en Producción Animal, CITA, Zaragoza, Spain.
Anim Reprod Sci. 2012 Aug;133(3-4):169-75. doi: 10.1016/j.anireprosci.2012.06.018. Epub 2012 Jul 3.
The ovine Melatonin Receptor 1A (MTNR1A) gene was structurally characterised and association between its variants and the reproductive seasonality was examined in a daughter design comprising three families of Rasa Aragonesa sheep breed. Sequencing of six Rasa Aragonesa ewes with extreme values for seasonality trait revealed 28 polymorphisms: 11 SNPs in the coding region (all in Exon 2), and 17 SNPs in the promoter region MTNR1A. All the substitutions in the coding region were found most likely lacking any phenotypic effect, because they are conservative mutations or were not part of the transmembrane domain. The silent mutations, which had shown association with reproductive seasonality in other breeds, were also found and genotyped in Rasa Aragonesa. The T allele of SNP606/RsaI of MNTR1A gene was associated with a greater percentage of oestrous cyclic ewes in the Rasa Aragonesa breed, indicating that this SNP may be in linkage disequilibrium with a mutation responsible for this trait close to MTNR1A, or in regulatory sequences of the gene. In this sense, several SNPs affecting a binding element for some transcription factors have been identified in the promoter region. The SNPs at 422 and 527 positions could constitute a binding element for some transcription factors (TFs), located in an EF2 and SRY consensus sites in the promoter region, respectively. Haplotype h(5) showed significant differences with the h(2) haplotype (66% compared to 49.2%) on oestrous cyclicity, thus these results are consistent with genotypic associations for each SNP. Haplotype with T, A and T alleles for SNPs 422, 677 (promoter region) and 612 (Exon 2) showed an increase of the percentage of oestrous cyclic ewes. Although some of these mutations have been associated with seasonal reproduction, further studies with a more appropriate animal design as well as functional studies of TF binding activity are needed.
绵羊褪黑素受体 1A（MTNR1A）基因的结构特征，并在由三个拉撒阿罗哈纳羊品种组成的女儿设计中检查其变体与生殖季节性之间的关联。对具有季节性特征值的六只拉撒阿罗哈纳母羊进行测序，揭示了 28 个多态性：编码区中的 11 个 SNP（全部在 2 号外显子中）和 MTNR1A 启动子区中的 17 个 SNP。编码区中的所有取代都最有可能缺乏任何表型效应，因为它们是保守突变或不是跨膜结构域的一部分。在其他品种中与生殖季节性相关的沉默突变也被发现并在拉撒阿罗哈纳中进行了基因分型。MTNR1A 基因的 SNP606/RsaI 的 T 等位基因与拉撒阿罗哈纳品种中发情周期母羊的百分比增加相关，表明该 SNP 可能与 MTNR1A 附近负责该特征的突变处于连锁不平衡状态，或在基因的调节序列中。在这种意义上，已经在启动子区域中鉴定出了影响某些转录因子结合元件的多个 SNP。位于启动子区域中的 422 和 527 位的 SNP 可以构成一些转录因子（TFs）的结合元件，分别位于 EF2 和 SRY 保守位点。单体型 h(5)与 h(2)单体型（66%比 49.2%）在发情周期方面存在显著差异，因此这些结果与每个 SNP 的基因型关联一致。单体型具有 SNP 422、677（启动子区域）和 612（外显子 2）的 T、A 和 T 等位基因显示发情周期母羊的百分比增加。尽管这些突变中的一些与季节性繁殖有关，但需要进一步进行具有更合适动物设计的研究以及 TF 结合活性的功能研究。
