Abstract
Blood values of calcium (Ca), inorganic phosphorus (IP), and alkaline phosphatase activity (ALP) are valuable indicators for mineral status and bone mineralization. The mineral homeostasis is maintained by absorption, retention, and excretion processes employing a number of known and unknown sensing and regulating factors with implications on immunity. Due to the high inter-individual variation of Ca and P levels in the blood of pigs and to clarify molecular contributions to this variation, the genetics of hematological traits related to the Ca and P balance were investigated in a German Landrace population, integrating both single-locus and multi-locus genome-wide association study (GWAS) approaches. Genomic heritability estimates suggest a moderate genetic contribution to the variation of hematological Ca (N = 456), IP (N = 1049), ALP (N = 439), and the Ca/P ratio (N = 455), with values ranging from 0.27 to 0.54. The genome-wide analysis of markers adds a number of genomic regions to the list of quantitative trait loci, some of which overlap with previous results. Despite the gaps in knowledge of genes involved in Ca and P metabolism, genes like THBS2, SHH, PTPRT, PTGS1, and FRAS1 with reported connections to bone metabolism were derived from the significantly associated genomic regions. Additionally, genomic regions included TRAFD1 and genes coding for phosphate transporters (SLC17A1–SLC17A4), which are linked to Ca and P homeostasis. The study calls for improved functional annotation of the proposed candidate genes to derive features involved in maintaining Ca and P balance. This gene information can be exploited to diagnose and predict characteristics of micronutrient utilization, bone development, and a well-functioning musculoskeletal system in pig husbandry and breeding.
Highlights
In the body, the homeostasis of calcium (Ca) and phosphorus (P) is maintained to ensure appropriate conditions for bone mineralization, energy utilization, nucleic acid synthesis, and signal transduction of each individual cell and the entire organism
Other transcription factors like MafB have been identified as involved in the regulation of mineral homeostasis by orchestrating intracellular signaling (Morito et al, 2018)
The highest significant association of this particular study was identified for ALPL, an alkaline phosphatase that hydrolyzes phosphate compounds at alkaline pH and is involved in bone mineralization (Kestenbaum et al, 2010)
Summary
The homeostasis of calcium (Ca) and phosphorus (P) is maintained to ensure appropriate conditions for bone mineralization, energy utilization, nucleic acid synthesis, and signal transduction of each individual cell and the entire organism. Other transcription factors like MafB have been identified as involved in the regulation of mineral homeostasis by orchestrating intracellular signaling (Morito et al, 2018). A GWAS for humans with European ancestry revealed several QTL regions containing functional candidate genes such as FGF23, SLC34A1, and CAST, whereby the most prominent SNPs are located in nearby regions representing other genes (Kestenbaum et al, 2010). The highest significant association of this particular study was identified for ALPL, an alkaline phosphatase that hydrolyzes phosphate compounds at alkaline pH and is involved in bone mineralization (Kestenbaum et al, 2010)
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