Carcass length is very important for body size and meat production for swine, thus understanding the genetic mechanisms that underly this trait is of great significance in genetic improvement programs for pigs. Although many quantitative trait loci (QTL) have been detected in pigs, very few have been fine-mapped to the level of the causal mutations. The aim of this study was to identify potential causal single nucleotide polymorphisms (SNPs) for carcass length by integrating a genome-wide association study (GWAS) and functional assays. Here, we present a GWAS in a commercial Duroc × (Landrace × Yorkshire) (DLY) population that reveals a prominent association signal (P = 4.49E−07) on pig chromosome 17 for carcass length, which was further validated in two other DLY populations. Within the detected 1 Mb region, the BMP2 gene stood out as the most likely causal candidate because of its functions in bone growth and development. Whole-genome gene expression studies showed that the BMP2 gene was differentially expressed in the cartilage tissues of pigs with extreme carcass length. Then, we genotyped an additional 267 SNPs in 500 selected DLY pigs, followed by further whole-genome SNP imputation, combined with deep genome resequencing data on multiple pig breeds. Reassociation analyses using genotyped and imputed SNP data revealed that the rs320706814 SNP, located approximately 123 kb upstream of the BMP2 gene, was the strongest candidate causal mutation, with a large association with carcass length, with a ~ 4.2 cm difference in length across all three DLY populations (N = 1501; P = 3.66E−29). This SNP segregated in all parental lines of the DLY (Duroc, Large White and Landrace) and was also associated with a significant effect on body length in 299 pure Yorkshire pigs (P = 9.2E−4), which indicates that it has a major value for commercial breeding. Functional assays showed that this SNP is likely located within an enhancer and may affect the binding affinity of transcription factors, thereby regulating BMP2 gene expression. Taken together, these results suggest that the rs320706814 SNP on pig chromosome 17 is a putative causal mutation for carcass length in the widely used DLY pigs and has great value in breeding for body size in pigs.

中文翻译：

---

鉴定和验证与猪胴体长度相关的 BMP2 基因上游调控突变

胴体长度对猪的体型和产肉量非常重要，因此了解这种性状背后的遗传机制对于猪的遗传改良计划具有重要意义。尽管已在猪中检测到许多数量性状基因座 (QTL)，但很少有人能精确定位到因果突变的水平。本研究的目的是通过整合全基因组关联研究 (GWAS) 和功能测定来确定胴体长度的潜在因果单核苷酸多态性 (SNP)。在这里，我们在商业杜洛克×（长白×约克郡）（DLY）种群中展示了一个 GWAS，它揭示了猪 17 号染色体上关于胴体长度的显着关联信号（P = 4.49E-07），这在另外两个 DLY 中得到了进一步验证人口。在检测到的 1 Mb 区域内，BMP2 基因因其在骨骼生长和发育中的功能而成为最有可能的候选基因。全基因组基因表达研究表明，BMP2基因在具有极长胴体长度的猪的软骨组织中存在差异表达。然后，我们在 500 头选定的 DLY 猪中对另外 267 个 SNP 进行了基因分型，然后进一步进行全基因组 SNP 插补，并结合多个猪品种的深度基因组重测序数据。使用基因分型和估算的 SNP 数据进行的重新关联分析显示，位于 BMP2 基因上游约 123 kb 的 rs320706814 SNP 是最强的候选因果突变，与胴体长度有很大关联，所有三个的长度差异约为 4.2 cm DLY 种群（N = 1501；P = 3.66E-29）。该 SNP 在 DLY 的所有亲本系中分离（Duroc，大白猪和长白猪），并且对 299 只纯约克夏猪的体长有显着影响（P = 9.2E-4），这表明它对商业育种具有重要价值。功能分析表明，该 SNP 可能位于增强子内，并可能影响转录因子的结合亲和力，从而调节 BMP2 基因表达。总之，这些结果表明，猪17号染色​​体上的rs320706814 SNP是广泛使用的DLY猪胴体长度的推定因果突变，在猪体型育种中具有重要价值。功能分析表明，该 SNP 可能位于增强子内，并可能影响转录因子的结合亲和力，从而调节 BMP2 基因表达。总之，这些结果表明，猪17号染色​​体上的rs320706814 SNP是广泛使用的DLY猪胴体长度的推定因果突变，在猪体型育种中具有重要价值。功能分析表明，该 SNP 可能位于增强子内，并可能影响转录因子的结合亲和力，从而调节 BMP2 基因表达。总之，这些结果表明，猪17号染色​​体上的rs320706814 SNP是广泛使用的DLY猪胴体长度的推定因果突变，在猪体型育种中具有重要价值。