A missense mutation in the PROP1 (prophet of Pit 1) gene affects male fertility and milk production traits in the US Holstein population

In previous studies, we reported significant associations of the POU1F1 pathway genes with reproduction and production traits in several dairy cattle populations. Polymorphisms in genes of this pathway were found to be associated with both female and male fertility traits in dairy cattle. The POU1F1 gene is a direct downstream target for the regulation of the prophet of Pit1 (PROP1) gene, also known as PROP paired-like homeobox 1. Interestingly, the position of PROP1 coincides with a quantitative trait locus affecting ovulation rate in cattle. Therefore, the objective of this study was to investigate whether PROP1 affects fertility and milk production traits in Holstein cattle. Using the DNA pooling sequencing approach, a missense single nucleotide polymorphism that replaces a histidine amino acid with an arginine was detected in exon 3 of PROP1. The arginine allele was found to be associated with a decrease in sire conception rate and an increase in productive life, protein yield, and net merit index in a population of 1,951 Holstein bulls. The transcription factors produced from the histidine and arginine isoforms are known to have different transcription, DNA binding, and regulation activities. As such, we propose that the association of the arginine isoform with decreased bull fertility is likely caused by reduced activity of this allele in male functions. The findings of this study suggest PROP1 polymorphisms as candidates in selection programs for fertility, health, and milk production traits in dairy cattle.