Bovine pituitary homeobox 2 (PITX2): mRNA expression profiles of different alternatively spliced variants and association analyses with growth traits

Pituitary homeobox 2 (PITX2) plays crucial roles in embryogenesis, ontogenesis, growth, and development via the Wnt/beta-catenin and POU1F1 pathways. To better understand the characteristics and genetic effects of the cattle PITX2 gene, we identified alternative PITX2 splicings, examined the effects of the spliced variants on mRNA expression levels in tissues, and then used association analyses to explore the relationships between a PITX2 deletion genetic variant and growth traits in 750 native Chinese cattle. An unreported spliced variant of PITX2, designated here as PITX2-V1, was identified in cattle using in silico cloning and RT-PCR. The entire coding sequence of PITX2 is 978 bp, encoding 325 amino acids, whereas that of PITX2-V1 is 357 bp encoding 118 amino acids. Cattle PITX2 exhibited both a perfect homeodomain and an OAR domain, but PITX2-V1 lacked the homeodomain. Analyses with qRT-PCR showed that the expression level of PITX2 in cattle testis was very low, and PITX2-V1 was only very slightly expressed in the brain and testis. Furthermore, a 24 bp deletion was detected within PITX2 intron, and the different genotypes were significantly associated with growth traits (e.g., body height, body length, heart girth) in four cattle breeds (P < 0.05). These results are of direct benefit to future cattle breeding, and provide new insights into the characteristics and functions of cattle PITX2 gene.