猪8号染色体影响肌内脂肪含量QTL的遗传解析

Intramuscular fat (IMF) content is an important indicator that affect the meat color, taste and process of pork. Understanding the molecular mechanism underlying IMF deposition is critical for genetic improvement of pork quality. Recently, using genome-wide association analysis (GWAS) and linkage disequilibrium (LD) analysis, we mapped a major quantitative trait loci (QTL) for IMF on chromosome 8 in a Duroc population (P<1E-7). This QTL explained about 8.1% of the phenotypic variance in this population, with a confidence interval of 3.37 Mb. Based on these results, we attempted to perform a further integrative systems biology approach to identify the causal variant underlying the QTL. This project will be carried out in the following steps: first, refine the QTL via the increase in marker density and linkage and linkage disequilibrium assays; then, with RNA sequencing (RNA-seq) in muscle from this population with extreme phenotypes, expression QTL (eQTL) and quantitative trait transcript (QTT) as well as the gene network would be analyzed; next, integrative systems biology analyses will be performed to identify critical genes for IMF; finally, the causal mutations in the target genes will be identified by the functional assay in cells. The expected findings will not only provide new insights our understanding of the genetic architecture of IMF but also greatly contribute to the genetic improvement of meat quality in Duroc related pigs.

猪肌内脂肪(IMF)含量是影响猪肉色泽、口感及加工的重要因素，揭示IMF沉积的分子机制对猪肉品质遗传改良具有重要意义。通过前期全基因组关联性分析及连锁不平衡分析,本项目组在猪8号染色体上发现一个显著影响IMF含量的QTL（P<1E-7）,其QTL置信区间为3.37Mb，解释了杜洛克群体8.1%的表型变异。本项目拟在此基础上，通过增加标记密度和基于连锁不平衡的关联分析精细定位该QTL；进一步利用极端表型个体肌肉组织的转录组数据，开展肌肉表达 QTL定位及基因表达量与表型关联的QTT分析，并构建与IMF含量相关的基因调控网络；进而通过整合系统生物学方法，鉴别8号染色上影响IMF 含量的因果基因；最后，通过细胞功能验证确定关键基因中的因果突变位点。结果不仅将为IMF的复杂遗传本质提供新的视角，而且有益于杜洛克及其合成系的肉质性状遗传改良。

猪肌内脂肪(IMF)含量是影响猪肉品质的关键因素，鉴别影响IMF沉积的关键基因及突变对猪肉品质遗传改良至关重要。采用全基因组关联分析，本项目首次将猪8号染色体上影响肌内脂肪含量的QTL的置信区间由3.27Mb缩小至1.24Mb，并鉴别到ZDHHC16、 LOC102162218 及 PCDH7三个基因极可能是猪8号染色体上影响肌内脂肪含量的关键基因。进一步通过扩大群体规模及新增3种不同的多标记统计分析模型（MrMLM、FASmrEMMA和ISIS EM-BLASSO），本研究最终在整个基因组上鉴别到28个显著的SNPs与肌内脂肪含量相关，并推测出BDKRB2、GTF2IRD1、UTRN、TMEM138、DPYD、CASQ2、ZNF518B、S1PR1、GPC6和GLI1这10个基因可能是影响肌内脂肪的候选基因。本项目不仅为肌内脂肪的复杂遗传本质提供新的视角，而且获得了2项具备潜在育种价值的分子标记（已获国家发明专利授权），上述标记可直接应用于杜洛克及其合成系的肉质性状遗传改良。