Empowering sheep breeding by identifying variants associated with growth traits using allele-specific expression

绵羊是全球粮食生产中至关重要的动物，是肉、奶和纤维的来源。英国是欧洲最大的羔羊和羊肉生产国，也是最大的羊产品出口国。目前，英国饲养了大约1310万只繁殖母羊，每年生产30万吨肉。该项目将使用基因组学来揭示绵羊特征（或“性状”）的复杂遗传控制，这些特征对绵羊生产行业来说是可取的。我们将在这个项目中关注的性状是生长，因为了解遗传如何驱动生长性状可以为农民和动物育种者提供关键信息，他们可以利用这些信息制定遗传改良策略，以提高羊产品的质量和数量。绵羊基因组的大小约为26亿个碱基（或字母）。我们才刚刚开始了解绵羊基因组的哪些部分是功能性的，在发育的哪个阶段，以及它们在产生健康和多产的动物方面所起的作用。基因表达是利用基因信息合成功能性基因产物的过程。遗传变异是指种群中个体之间DNA序列的差异。影响基因表达的遗传变异已被证明会影响牲畜的“性状”（例如生长）。因此，测量任何给定组织或细胞类型中的基因表达可以提供对遗传变异的深入了解。我们知道，在特塞尔羊中，基因组特定区域的遗传变异会影响肌肉特征，但只有当它从父系遗传而不是从母系遗传时才会如此。这被称为“父源效应”。多年来，通过使用经典遗传学技术关注基因组的特定区域，发现了特塞尔羊的父母起源效应。在这个提议中，我们将使用新的测序技术来测量整个基因组的基因表达。在项目的第一阶段，我们将测量杂交特塞尔与苏格兰黑脸羊在相关发育阶段对生长重要的组织中的基因表达。这将使我们能够测量基因组中每个碱基的基因表达，并识别在父系或母系方向上表达不平衡的变异。在该项目的第二阶段，我们将使用统计预测模型将这些表现出不平衡表达的变异与绵羊生长性状相关的基因组区域联系起来。这将使我们能够预测这些变异对绵羊中观察到的某些生长特征有多大的影响。该项目的结果将是一组与绵羊生长性状相关的变异。其中一些将具有类似于特塞尔羊的肌肉变异的亲本起源效应。在英国，这些变体将具有特别的经济重要性，因为它们将奠定从Texel继承所需肌肉性状的基础，Texel通常被用作英国商业羔羊生产的终端父系。我们在这个项目中发现的变异可以纳入羊的遗传改良计划。该项目产生的信息将对绵羊育种者和生产者具有巨大价值，他们可以优先考虑特定的重要变种，以加强其育种计划。遗传改良被广泛应用于绵羊和基因组学育种计划，如在新西兰建立的那些，在英国和全球越来越普遍。我们以羊和生长性状为例，但该项目的成果可以应用于其他牲畜和其他感兴趣的性状，以提高动物生产效率。

Sheep are a vitally important animal for global food production, providing a source of meat, milk and fibre. The UK is the largest producer of lamb and mutton and the largest exporter of sheep products in Europe. There are approximately 13.1 million breeding ewes currently being raised in the UK producing 300,000 tonnes of meat annually.This project will use genomics to unravel the complex genetic control of characteristics (or 'traits') in sheep that are desirable to the sheep production industry. The trait that we will focus on for this project is growth because understanding how genetics can drive growth traits can provide farmers and animal breeders with crucial information they can use in genetic improvement strategies designed to enhance the quality and quantity of sheep products.The sheep genome is ~2.6 billion bases (or letters) in size. We are only beginning to understand which parts of the sheep genome are functional, at what time during development, and the role that they play in generating healthy and productive animals. Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. Genetic variation is the difference in DNA sequences between individuals within a population. Genetic variation that affects gene expression has been shown to influence 'traits' (e.g. growth) in livestock. Therefore, measuring gene expression in any given tissue or cell type can provide insight into genetic variation. We know that in Texel sheep genetic variation in a specific region of the genome affects muscling characteristics, but only when it is inherited from the sire and not from the dam. This is called a 'parent-of-origin' effect. This parent-of-origin effect in Texel sheep was discovered over many years by focusing on specific regions of the genome using classical genetics techniques. In this proposal we will use new sequencing technologies to measure gene expression across the whole genome. In the first stage of the project we will measure gene expression in tissues that are important for growth at relevant developmental stages in crossbred Texel x Scottish Blackface sheep. This will allow us to measure gene expression at each base in the genome and identify variants where the expression is unbalanced in the direction of the sire or the dam.In the second stage of the project we will use statistical prediction models to associate these variants exhibiting unbalanced expression with regions of the genome that are associated with growth traits in sheep. This will allow to predict how likely these variants are to be contributing to some of the growth characteristics observed in sheep.The outcome of the project will be a set of variants associated with growth traits in sheep. Some of these will have parent-of-origin effects similar to the muscling variants in Texel sheep. In the UK these variants will be of particular economic importance as they will underlie inheritance of the desired muscling traits from the Texel which is commonly used as terminal sire in British commercial lamb production.The variants we discover in this project can be incorporated in genetic improvement programs for sheep. The information generated by this project will be of huge value to sheep breeders and producers, who can priortise particular important variants, to enhance their breeding programmes. Genetic improvement is widely used in sheep and genomics enabled breeding schemes such as those, which have been established in New Zealand are increasingly common in the UK and across the globe. We have focused on sheep and growth traits as an example but the outcomes of the project could be applied to other livestock and other traits of interest to improve the efficiency of animal production.