Novel Haplotype in the HHEX Gene Promoter Associated with Body Length in Pigs

Abstract

The screening of important candidate genes and the identification of genetic markers are important for molecular selection in the pig industry. The hematopoietically expressed homeobox (HHEX) gene plays an important role in embryonic development and organogenesis; however, the genetic variation and expression pattern of the porcine HHEX gene remains to be clarified. In this study, semiquantitative RT-PCR and immunohistochemistry results showed the specific expression of the HHEX gene in porcine cartilage tissues. A novel haplotype consisting of two SNPs rs80901185 (T > C) and rs80934526 (A > G) was detected in the promoter region of the HHEX gene. The expression of the HHEX gene was significantly higher in Yorkshire pigs (TA haplotype) than in Wuzhishan pigs (CG haplotype), and a population analysis showed that this haplotype was significantly associated with body length. An analysis subsequently revealed that the –586 to –1 bp region of the HHEX gene promoter showed the highest activity. Furthermore, we found that the activity of the TA haplotype was significantly higher than that of the CG haplotype by changing the potential binding of transcription factors YY1 and HDAC2. In summary, we conclude that the porcine HHEX gene may contribute to the breeding of pigs for body length traits.

Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326–NKX3.2-Regulated Porcine Chondrocyte Differentiation

“…Recent studies have shown that HHEX negatively regulates osteoclast differentiation [ 53 ]. Our recent study also found that a TA haplotype on the HHEX promoter was significantly associated with body length in pigs [ 54 ]. COL11A1 is normally found in cartilage, which is responsible for the formation of cartilage structures in the early stages of skeleton development.…”

“…A large number of DEGs that play essential roles in the regulation of bone development were identified. Key candidate genes were further identified through a combination of functional analysis with literature mining, including NKX3.2 [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ], WLS [ 41 , 42 , 43 ], GREM1 [ 44 , 45 , 46 ], FGFR3 [ 47 , 48 , 49 , 50 , 51 ], HHEX [ 52 , 53 , 54 ], COL11A1 [ 55 , 56 , 57 ], and WNT16 [ 58 , 59 ]. These genes were mainly enriched in the BMP, FGF, Wnt, and Notch signaling pathways, suggesting that they are involved in the development of the pig vertebral column.…”