Downregulation of growth plate genes involved with the onset of femoral head separation in young broilers

Abstract

Femoral head separation (FHS) is characterized by the detachment of growth plate (GP) and articular cartilage, occurring in tibia and femur. However, the molecular mechanisms involved with this condition are not completely understood. Therefore, genes and biological processes (BP) involved with FHS were identified in 21-day-old broilers through RNA sequencing of the femoral GP. 13,487 genes were expressed in the chicken femoral head transcriptome of normal and FHS-affected broilers. From those, 34 were differentially expressed (DE; FDR ≤0.05) between groups, where all of them were downregulated in FHS-affected broilers. The main BP were enriched in receptor signaling pathways, ossification, bone mineralization and formation, skeletal morphogenesis, and vascularization. RNA-Seq datasets comparison of normal and FHS-affected broilers with 21, 35 and 42 days of age has shown three shared DE genes (FBN2, C1QTNF8, and XYLT1) in GP among ages. Twelve genes were exclusively DE at 21 days, where 10 have already been characterized (SHISA3, FNDC1, ANGPTL7, LEPR, ENSGALG00000049529, OXTR, ENSGALG00000045154, COL16A1, RASD2, BOC, GDF10, and THSD7B). Twelve SNPs were associated with FHS (p < 0.0001). Out of those, 5 were novel and 7 were existing variants located in 7 genes (RARS, TFPI2, TTI1, MAP4K3, LINK54, and AREL1). We have shown that genes related to chondrogenesis and bone differentiation were downregulated in the GP of FHS-affected young broilers. Therefore, these findings evince that candidate genes pointed out in our study are probably related to the onset of FHS in broilers.

Bone Metabolite Profile Differs between Normal and Femur Head Necrosis (FHN/BCO)-Affected Broilers: Implications for Dysregulated Metabolic Cascades in FHN Pathophysiology

“…The severity of disrupted cellular functions and overall bone homeostasis is becoming clearer as high-throughput omics studies are employed. Recent studies of the transcriptome and proteome revealed major alterations to bone development, cellular proliferation, and the immune response from normal bone [ 11 , 12 , 35 ]. Here, we found the differences between normal and FHN-affected bone to exist within the metabolome of these tissues as well.…”

“…However, a recent study found differentially expressed cytokine and chemokine profiles in the local bone and blood of FHN-affected broilers compared to normal, healthy broilers [ 10 ]. Other researchers have utilized high-throughput transcriptomics and proteomics and identified key cartilage and bone growth as well as lipid metabolism and immune-related factors in FHS and FHN [ 11 , 12 ].…”

Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age

“…They are predicted to affect the CUB2 domain, the second most common domain, followed by the serine protease domains, in which mutations causing 3MC syndrome have been frequently reported [37][38][39]. Although the mechanism of postnatal growth failure in 3MC syndrome is unclear, MASP1 has been indicated to play a role in extracellular biological processes, and its molecular function is related to calcium ion binding and ECM components [40].…”