Mutations in the STAT5A gene are associated with embryonic survival and milk composition in cattle.

The objective of this study was to investigate the association of the signal transducer and activator of transcription 5A (STAT5A) gene with fertilization rate, embryonic survival, and milk production and composition in cattle. The STAT proteins are transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. The STAT5A gene is a member of the interferon-tau (IFN-tau) and placental lactogen (PL) signaling pathway, which is involved in both milk production and initiation of pregnancy. Using the DNA-pooling sequencing approach, a total of 12 single nucleotide polymorphisms (SNP) were identified, 1 exonic and 11 intronic. For the study of association of these SNP with embryonic survival, 1,551 embryos were produced in vitro from 160 cows and 3 sires. Significant associations with embryonic survival were found for 7, 5, and 2 SNP for embryos produced from sires 1, 2, and 3 respectively. The association of fertilization rate with STAT5A polymorphisms was evaluated in more than 2,300 oocytes. Significant associations were found for 6, 2, and 2 SNP for sires 1, 2, and 3 respectively. For sire 1, 5 SNP showed significant associations with both embryonic survival and fertilization rate compared with 1 SNP for sires 2 and 3. To determine if embryonic losses had occurred before the blastocyst stage, 145 of the surviving embryos were harvested at d 7 of development and genotyped for the single exonic SNP12195. A significant segregation distortion was observed between oocytes produced from 2 sires carrying the same genotype. Thus, it is most likely that STAT5A is associated with 2 mechanisms of embryo death. One is a prefertilization mechanism involving sperm factors that cause low fertilization rate. The second is a postfertilization mechanism that causes incompatibility between the male pronucleus and the oocyte, which in turn leads to death of the embryo before the blastocyst stage. Association testing of SNP12195 (exon 8) and SNP14217 (intron 9) with milk composition revealed that allele G of SNP12195 was associated with a decrease in both protein and fat percentages. However, SNP14217 in intron 9 showed no significant association with milk production or health traits. The G allele of SNP12195 was also associated with low embryonic survival, making this SNP an attractive candidate for progeny testing programs in dairy cattle.