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确定猪的生长、屠体和肉质数量性状的因果突变所在的短染色体区域，并测试这些片段内的多态结构因果关系。四个现有的和表型特征非常好的猪F2杂交组合被汇集成一个强大的关节设计，由3466个F2个体组成。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。该项目包括通过重新测序对创始人动物进行完整的SNP基因分型，基于芯片的F1和F2个体的SNP基因分型，以及F1和F2个体的序列归属。具有最强特征关联证据的染色体区域被识别，并随后对单倍型和突变进行筛选。这些都经过了结构性因果关系的检验。特别关注分离在皮耶特兰方正品种中的基因变异，因为从育种的角度来看，这是最重要的群体，而皮耶特兰相关突变的图谱分辨率最高。考虑了加性和非加性基因效应和配子印迹，并利用已识别的因果多态研究了这些基因效应之间的相互关系。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，并为探索分离群体中类似的性状复合体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.