MEASURE: Multi-omics Evaluation of Animals for body StatURE – the genetic architecture of body size in pigs

这项研究工作的目的是用多组学的方法使用猪模型来评估身体大小的遗传结构。它特别旨在深入研究大小决定变异体之间的相互关系，小体型和大体型之间的转录差异，以及与体型决定有关的拓扑相关结构域(TADS)和可能的增强子的鉴定。这项研究特别关注于阐明猪的调控环境及其在决定体型大小方面的重要作用。对小型和标准大小品种/群体的全基因组测序数据的初步分析被认为是识别潜在的选择特征，反映了在两个方向上的高选择压力-微型和大尺寸-包含导致品种间小型化的变异。随后，我的目标是通过靶向Hi-C分析中染色质相互作用的高强度峰以及长骨生长板中与活性增强剂(H3K27ac和H3K4me1)相关的高组蛋白修饰水平，在参与大小决定的这些变体区域检测染色质相互作用和可能的增强子元件。然后，这些活性DNA序列的标记将与小型猪和大型猪之间的转录变异联系在一起。将建立一个体外模型用于进一步的功能验证。这将是第一次研究基因组和功能对体型的影响，特别是针对猪的生长板。基于这些数据，我们的目标是增加对哺乳动物调节生长和确定身体大小的生物学过程的了解。这种对体型发育的深刻理解不仅对家畜育种具有高度的重要性，而且还将提供对生长生物学、发育遗传学和生长过程中的干扰的更好的理解。

The objective of this research work is to evaluate the genetic architecture of body size using a pig model in a multi-omics approach. It particularly aims at in-depth investigations of interrelations of size determining variants, transcriptional variation among miniature and large size as well as the identification of topologically associated domains (TADs) and putative enhancers involved in body size determination. This study is particularly focusing on the elucidation of the regulatory landscape in pigs and its essential role in the determination of body size.Initial analyses of whole genome sequencing data of miniature versus standard sized breeds/populations are supposed to identify potential signatures of selection reflecting high selection pressures in both directions- miniature and large size- harboring variants causative for the miniaturization across-breeds. Subsequently, I aim at detecting chromatin interactions defined as TADs and putative enhancer elements in the region of these variants involved in size-determination by targeting high intensity peaks of chromatin interactions from Hi-C analysis as well as high histone modification levels associated with active enhancers (H3K27ac and H3K4me1) from ChIP-seq in the growth plates of the long bones. These marks of active DNA sequences will then be linked to transcriptional variation in-between miniature and large pigs. An in vitro model will be established for further functional validation.This will be the first study investigating genomic and functional effects on body size specifically targeting growth plates in pigs. Based on these data, we aim at increasing the knowledge of biological processes in mammals regulating growth and determining the size of a body. This profound understanding of body size development will not only be of high importance for livestock breeding but will also provide better understanding of growth biology, developmental genetics and disturbances in growth processes.