Molecular characterization and evidencing of the porcine CRH gene as a functional-positional candidate for growth and body composition

Abstract

Corticotropin-releasing hormone (CRH), a major regulator of neuroendocrine response to stress, is involved in the control of energy balance and thus may affect body composition and growth. The porcine CRH (pCRH) gene was studied as a comparative-positional candidate for QTL for longissimus muscle area, average backfat thickness, carcass length, and average daily gain on test on porcine chromosome 4. Sequence of the complete transcriptional unit of pCRH gene spanning 2068bp was determined along with 582bp of the 5'-flanking region. Cross-species sequence comparison revealed a number of potential regulatory regions including an intronic evolutionary conserved region and an adjacent CpG island that may control cell-type specific expression of the CRH gene. A SNP in exon 2 (c.+83G>A) leading to a non-conservative amino acid exchange (p.28Arg>Gln) in the prohormone was identified that is segregating in the DUMI resource population. Linkage and association analysis based on this SNP revealed that for all four traits the pCRH gene falls in the QTL peak area and that the c.+83G>A SNP shows a highly significant additive effect (p<0.0001). Physical mapping using the IMpRH panel assigned the pCRH gene to interval SW724-S0107, promoting the gene as a positional candidate also for QTL identified in other porcine resource populations. Additional four variable sites were identified that segregate in commercial pig breeds. Particularly interesting is a SNP (g.233C>T) in the 5'-flanking region that occurred in an evolutionary conserved motif. The knowledge of the DNA-variation of pCRH gene will facilitate follow-up studies necessary to provide definite genetic evidence of the effect of pCRH gene on body composition and growth.