Structural identification of trait associated chromosomal segments and of causal mutations for quantitative traits in pooled F2 crosses using next-generation sequencing technologies and innovative statistical methods

该研究项目的目的是在结构上确定猪生长、胴体和肉质数量性状突变的短染色体区域，并测试片段内多态性的结构因果关系。4个现有且表型特征非常好的猪F2杂交组合汇集成一个由3466个F2个体组成的强大联合设计。使用下一代测序技术以及生物信息学、统计学和基因组学方法和模型对杂交进行联合分析。该项目包括通过重测序对创始动物进行完整的SNP基因分型，对F1和F2个体进行基于芯片的SNP基因分型，并对F1和F2个体进行序列代入。具有性状关联最强证据的染色体区域被确定并随后筛选单倍型和突变。这些都是为了检验结构性因果关系。特别关注的是在pisamain创始品种中分离的基因变异，因为从育种的角度来看，它是最重要的种群，并且与pisamain相关的突变的制图分辨率最高。考虑了加性和非加性基因效应和配子印记，并利用确定的因果多态性研究了这些基因效应之间的相互关系。功能跟踪研究的设计是项目的最后一步。该项目的结果有助于对杂交设计中数量性状的遗传解剖，并为在分离群体中探索相似性状复合体提供有价值的贡献。

The aim of the research project is to structurally identify short chromosomal regions harbouring causal mutations of quantitative traits for growth, carcass and meat quality in pigs and to test the polymorphisms within the segments for structural causality. Four existing and phenotypically very well characterised porcine F2 crosses are pooled into a powerful joint design consisting of 3 466 F2 individuals. The crosses are analysed jointly using next generation sequencing technologies as well as bioinformatic, statistical and genomic methods and models. The project includes complete SNP genotyping of founder animals by re-sequencing, a chip-based SNP-genotyping of F1 and F2 individuals, and the imputation of sequence in the F1 and F2 individuals. Chromosomal regions with strongest evidence for trait associations are indentified and subsequently screened for haplotypes and mutations. These are tested for structural causality. Special focus is set on gene variants that segregate within the Piétrain founder breed, because it is the most important population from a breeding perspective, and mapping resolution is highest for the Piétrain related mutations. Additive as well as non-additive gene effects and gametic imprinting are considered and the interrelationships between these gene effects are investigated using the identified causal polymorphisms. The design of functional follow-up studies is the last step of the project. The results of the project contribute to the genetic dissection of quantitative traits in crossbred designs and provide valuable contributions to the exploration of similar trait complexes in segregating populations.