Functional confirmation of PLAG1 as the candidate causative gene underlying major pleiotropic effects on body weight and milk characteristics

A major pleiotropic quantitative trait locus (QTL) located at ~25 Mbp on bovine chromosome 14 affects a myriad of growth and developmental traits in Bos taurus and indicus breeds. These QTL have been attributed to two functional variants in the bidirectional promoter of PLAG1 and CHCHD7. Although PLAG1 is a good candidate for mediating these effects, its role remains uncertain given that these variants are also associated with expression of five additional genes at the broader locus. In the current study, we conducted expression QTL (eQTL) mapping of this region using a large, high depth mammary RNAseq dataset representing 375 lactating cows. Here we show that of the seven previously implicated genes, only PLAG1 and LYN are differentially expressed by QTL genotype, and only PLAG1 bears the same association signature of the growth and body weight QTLs. For the first time, we also report significant association of PLAG1 genotype with milk production traits, including milk fat, volume, and protein yield. Collectively, these data strongly suggest PLAG1 as the causative gene underlying this diverse range of traits, and demonstrate new effects for the locus on lactation phenotypes.