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从结构上鉴定携带猪生长、胴体和肉质数量性状因果突变的短染色体区域，并测试片段内的多态性以确定结构因果关系。四个现有的和表型非常好的特点猪F2杂交合并成一个强大的联合设计组成的3466 F2个体。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联合分析杂交。该项目包括通过重新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，以及对F1和F2个体进行序列插补。染色体区域与最强的证据性状协会被确定，随后筛选单倍型和突变。这些都是测试结构的因果关系。特别关注的是在皮特兰创始人品种中分离的基因变异，因为从育种的角度来看，它是最重要的群体，并且皮特兰相关突变的定位分辨率最高。添加剂以及非添加剂的基因效应和配子印记被认为是这些基因效应之间的相互关系进行了研究，使用确定的因果多态性。功能随访研究的设计是该项目的最后一步。该项目的结果有助于杂交设计中数量性状的遗传解剖，并为分离群体中相似性状复合体的探索提供了有价值的贡献。

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.