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

测量：动物体型的多组学评估——猪体型的遗传结构

• 批准号: 438575335
• 负责人: Professorin Dr. Julia Metzger
• 金额: --
• 依托单位: Institut für Tierzucht und Vererbungsforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/438575335?language=en
• 关键词: MEASURE; Multi; omics; Evaluation; Animals

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.

本研究的目的是利用多组学方法，以猪为模型，对猪体型的遗传结构进行评价。它特别旨在深入调查的相互关系的大小决定的变体，转录变异之间的小型和大型的大小，以及识别的拓扑相关结构域（TADs）和假定的增强子参与身体大小的决定。本研究特别侧重于阐明猪的监管格局及其在决定体型大小方面的重要作用，对小型猪与标准体型猪的全基因组测序数据进行初步分析，以确定潜在的选择特征，反映出小型猪和大型猪两个方向上的高选择压力，这些选择特征包含导致小型化的变异体。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与长骨生长板中ChIP-seq的活性增强子（H3 K27 ac和H3 K4 me 1）相关的高组蛋白修饰水平，检测这些变体区域中的染色质相互作用（定义为TAD）和推定的增强子元件。这些活跃DNA序列的标记将与小型猪和大型猪之间的转录变异相关联。将建立一个体外模型进行进一步的功能验证。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大小的影响的研究。基于这些数据，我们的目标是增加哺乳动物调节生长和确定身体大小的生物过程的知识。这种对体型发育的深刻理解不仅对牲畜育种具有重要意义，而且还将更好地了解生长生物学，发育遗传学和生长过程中的干扰。