A 20 Bp Indel of HNF4A Is Associated with Piglet Growth Partially by Regulating Its Transcription

Hepatocyte nuclear factor 4α (HNF4A) is a critical transcription factor that regulates the differentiation and metabolism of intestinal epithelial cells. However, its role in piglet growth remains unclear. In this study, the tissue expression of HNF4A was examined using RT-qPCR, and the putative functional SNPs were analyzed by integrating bioinformatics and DNA sequencing. Association analysis was performed in 156 Min pigs and 160 Landraces, and the biological function of the identified genetic variant was explored using a dual-luciferase reporter assay. The results showed that HNF4A was widely expressed in liver, kidney and gastrointestinal tissues, with significantly higher expression in the liver of adult pigs than in newborn piglets (p < 0.05). A 20 bp InDel was identified in the first intron of porcine HNF4A. Allele frequency analysis showed that the Del allele (20 bp deletion) was dominant in Landrace and Duroc pigs, while the In allele (20 bp insertion) was dominant in Min and Jinhua pigs. Association analysis revealed that Min pigs with the In/Del genotype had significantly higher body weights at 14, 21, 28 and 35 days and higher average daily gain (ADG) than those of the In/In animals (p < 0.05). Landrace piglets with the Del/Del genotype exhibited significantly higher body weight at 21 and 28 days than those of the In/Del genotype (p < 0.05). The dual-luciferase reporter assay suggested that the plasmid carrying the In allele exhibited higher transcriptional activity than the Del allele (p < 0.05). Notably, the genotype associated with superior growth performance differed between the two breeds. Collectively, a 20 bp InDel within HNF4A was identified, which might affect piglet growth partially by modulating its transcription, and further study in other populations with different genetic backgrounds is needed before its application in pig breeding.