Data_Sheet_1_Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs.pdf

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.

血液中钙（Calcium, Ca）、无机磷（Inorganic phosphorus, IP）与碱性磷酸酶活性（Alkaline phosphatase activity, ALP）的检测值，是评估机体矿物质营养状态与骨骼矿化程度的重要指标。矿物质稳态通过吸收、留存与排泄过程维持，该过程涉及诸多已知与未知的感知及调控因子，且这些因子对免疫功能具有潜在影响。鉴于猪血液中钙与磷水平存在显著的个体间差异，为阐明该差异的分子调控机制，本研究针对德国长白猪（German Landrace）群体中与钙磷平衡相关的血液学性状遗传学展开探究，整合了单座位与多座位全基因组关联分析（Genome-Wide Association Study, GWAS）两种研究策略。基因组遗传力估计结果显示，血液钙（样本量N=456）、无机磷（N=1049）、碱性磷酸酶活性（N=439）以及钙磷比（N=455）的个体差异均受到中等程度的遗传调控，遗传力值介于0.27至0.54之间。全基因组标记分析共鉴定出多个与上述性状相关的基因组区域，即数量性状基因座（Quantitative Trait Locus, QTL），其中部分区域与既往研究结果存在重叠。尽管目前对于参与钙磷代谢的基因认知仍存在不足，但本研究从显著关联的基因组区域中筛选出了THBS2、SHH、PTPRT、PTGS1及FRAS1等已被报道与骨骼代谢相关的基因。此外，关联区域中还包含TRAFD1基因以及编码磷转运蛋白（Phosphate Transporters, SLC17A1–SLC17A4）的基因家族，这类基因均与钙磷稳态密切相关。本研究呼吁对所提出的候选基因开展更完善的功能注释，以解析参与维持钙磷平衡的关键分子特征。上述基因信息可应用于养猪生产与育种工作中，用于诊断和预测生猪的微量营养素利用效率、骨骼发育状况以及肌肉骨骼系统的正常功能状态。