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

本研究工作的目的是利用猪模型的多组学方法来评估体型的遗传结构。它特别旨在深入研究大小决定变异的相互关系，小尺寸和大尺寸之间的转录变异，以及确定拓扑相关结构域（TADs）和参与体型决定的推定增强子。本研究特别侧重于阐明猪的调节景观及其在确定体型中的重要作用。对微型品种/群体与标准尺寸品种/群体的全基因组测序数据进行初步分析，旨在确定潜在的选择特征，反映在两个方向上的高选择压力——微型和大型——包含导致跨品种小型化的变异。随后，我的目标是检测染色质相互作用，定义为TADs和推测的增强子元件，在这些涉及大小确定的变异区域，通过靶向高强度峰的染色质相互作用从Hi-C分析，以及高组蛋白修饰水平相关的活性增强子（H3K27ac和H3K4me1）从ChIP-seq长骨生长板。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起来。将建立体外模型以进一步进行功能验证。这将是第一个专门针对猪生长板研究基因组和功能对体型影响的研究。基于这些数据，我们的目标是增加对哺乳动物调节生长和决定身体大小的生物过程的了解。这种对体型发育的深刻理解不仅对家畜育种具有重要意义，而且有助于更好地理解生长生物学、发育遗传学和生长过程中的干扰。

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.