鉴别猪13号染色体影响悬蹄过度生长的目的基因及其关键突变

由悬蹄过度生长导致的能繁母猪被提前淘汰，是造成我国能繁母猪生产效率低下的重要原因。然而，尽管这一现象普遍存在于瘦肉型猪种中，但国际上尚无有效的早期选育方法，迫切需要建立高效精准的分子育种技术。申请人前期通过全基因组关联分析，首次在猪13号染色体上发现一个显著影响悬蹄长度的基因座（QTL，P<8E-9），其置信区间为1.2Mb。本研究拟在此基础上，通过深度重测序、基因型填充及共享单倍型分析，精细定位该QTL；进一步利用实验群体的转录组数据，开展表达QTL定位和基因表达量与表型关联的QTT分析，并构建与目标性状相关的基因调控网络；进一步结合非编码RNA及染色质开放区定位等结果，初步鉴别影响悬蹄长度的目的基因及其关键突变；最后，通过细胞水平实验对关键突变进行验证。预期结果不仅将深入揭示趾蹄疾患的遗传本质，还将为能繁母猪提供悬蹄过度生长的早期分子育种手段，从而有效地提升我国能繁母猪的生产效率。

Overgrowth of dewclaws leads to the early elimination of fertile sows, which is an important reason for the low productivity of sows in China. However, although this phenomenon is prevalent in commercial pigs, there is no effective method for early culling of affected individuals. Therefore, it is urgent to establish molecular diagnostic tool to eradicate this genetic defect. Recently, using genome-wide association analysis (GWAS), we mapped a major quantitative trait loci (QTL) for the length of dewclaws on chromosome 13 in a Large White population(P < 8E-9). We have defined this QTL into a confidence interval of 1.2 Mb. Based on these results, this project will first refine the location of this QTL via an integrative analysis including deep resequencing, genotype imputation and identical-by-decent (IBD) mapping.Then, RNA sequencing (RNA-seq), expression QTL (eQTL), quantitative trait transcript (QTT) and the gene network analysis would be conducted. Next, the non-coding RNA and ATAC-seq data will be incorporated to identify the responsible genes and critical mutations for the length of dewclaws in pigs. Finally, the biological function of the causative mutations will be verified at cell levels. This project will not only reveal the genetic architecture of overgrowth of dewclaws in pigs, but also provide molecular diagnostic tool for early culling of individuals with overgrowth of dewclaws, thus improving sow production efficiency in China.