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

绵羊是一种对全球粮食生产至关重要的动物，提供肉类、牛奶和纤维。英国是欧洲最大的羊肉和羊肉生产国，也是最大的羊肉产品出口国。目前英国大约有1310万只种羊，每年生产30万吨肉。该项目将利用基因组学来揭开绵羊特征(或特征)的复杂基因控制，这些特征是绵羊生产行业所希望的。这个项目的重点是生长，因为了解遗传如何驱动生长特性可以为农民和动物饲养者提供关键信息，他们可以使用这些信息来制定遗传改进策略，以提高绵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有功能的，在发育的什么时候，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基因产物的过程。遗传变异是指种群内不同个体之间的DNA序列差异。影响基因表达的遗传变异已被证明会影响家畜的“特征”(例如生长)。因此，测量任何特定组织或细胞类型的基因表达可以提供对遗传变异的洞察。我们知道，在德克赛尔绵羊中，基因组特定区域的遗传变异会影响肌肉特征，但只有在这种变异是从父系而不是从母羊遗传的时候才会影响。这就是所谓的“原产地父母”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，特克塞尔绵羊的这种亲本效应被发现。在这项提案中，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，我们将测量在杂交的特克塞尔×苏格兰黑脸绵羊中对相关发育阶段的生长至关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，并识别在公羊或母羊方向上表达不平衡的变异。在项目的第二阶段，我们将使用统计预测模型将这些表现不平衡表达的变异与基因组中与绵羊生长性状相关的区域联系起来。这将允许预测这些变异对绵羊观察到的某些生长特征有多大影响。该项目的结果将是一组与绵羊生长特征相关的变异。其中一些基因将具有类似于特克塞尔绵羊肌肉发达的变体的亲本效应。在英国，这些变异将具有特别重要的经济意义，因为它们将为从特克塞尔遗传所需肌肉特征奠定基础，特克塞尔在英国商业羊肉生产中通常被用作终端父系。我们在这个项目中发现的变异可以被纳入绵羊的遗传改良计划中。该项目产生的信息将对绵羊饲养者和生产者具有巨大的价值，他们可以优先考虑特定的重要变异，以加强他们的育种计划。基因改良被广泛应用于绵羊，基因组学支持的育种计划，如新西兰建立的计划，在英国和全球范围内越来越常见。我们将重点放在羊和生长性状上，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，以提高动物生产的效率。

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.