Variants in the pregnancy-associated plasma protein-A2 gene on Bos taurus autosome 16 are associated with daughter calving ease and productive life in Holstein cattle

Reproductive disorders in dairy herds have a negative effect on farm profitability and sustainability of milk production. Given the substantial evidence of the role of the pregnancy-associated plasma protein (PAPP) gene family in the regulation of reproduction in humans and mice, its role in insulin-like growth factor metabolism, quantitative trait loci effects in the mouse, and location of a calving ease QTL on bovine chromosome 16, the PAPP-A2 gene was chosen as a candidate gene to perform an association study for reproductive health in cattle. Single nucleotide polymorphisms (SNP) were identified in coding and conserved noncoding regions of the PAPP-A2 gene in 3 dairy breeds. A total of 7 tag SNP were genotyped in 662 Holstein bulls (UCD-bulls) to perform marker trait association analysis. Three SNP (SNP 13, 15, and 16) were in strong linkage disequilibrium in Holsteins, showing significant positive associations with daughter calving ease, productive life, milk yield, and protein yield. These results were validated by genotyping SNP15 in a larger population of 992 bulls from the cooperative dairy DNA repository (CDDR-bulls). Our results demonstrate that the PAPP-A2 gene is associated with reproductive health in Holstein cattle and that the identified SNP can be used as genetic markers in dairy breeding due to their positive association with reproductive and productive traits. Functional studies need to be conducted to identify the mechanisms for the association of SNP with these traits.