The influence of selective breeding on MHC diversity.

选择性育种对 MHC 多样性的影响。

• 批准号: BB/L004070/1
• 负责人: Louise Matthews
• 金额: $ 56.23万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL004070%2F1
• 关键词: influence; selective; breeding; MHC; diversity.

Individuals differ in susceptibility to disease and much of the variation is genetic in origin. The collection of all the genes in an individual is known as the genome. Many different regions of the genome influence susceptibility to disease. One of the most important genetic regions is the major histocompatibility complex (MHC). This region contains genes that determine how the immune system recognises and responds to disease-causing foreign organisms.Animal breeders want to identify genetically resistant animals and use these individuals to produce offspring with enhanced resistance to disease. This is difficult but could become easier if we could use the MHC. Evolution has produced a wide range of different genetic variants at the MHC and we want to manage this diversity to optimise disease resistance in livestock populations.The purpose of this proposal is to identify the selective forces that maintain variation at the MHC using infection with parasitic roundworms in sheep as our test system. Parasitic roundworms are an important disease of livestock. The infection and disease process in sheep is one of the best understood of all diseases. We already know that the MHC plays an important role in resistance to roundworms and this system is therefore ideal to study how MHC variation influences resistance to disease.We plan to quantify the selective forces that maintain the high variation at the MHC. We will use a population of sheep that has been selected for high levels of resistance to roundworm infections. We will compare the resistance to roundworms of individuals with different MHC genes using advanced statistical programs that remove all background variation and test whether the differences between individuals with different MHC alleles could have arisen by chance. We have already tested a Scottish population and know that there are two different effects involved. There are differences among genes. In addition most individuals have two different genes but some inherit two identical copies. Individuals with two different genes are more resistant than individuals with two identical copies of the same gene. We want to extend this analysis. We predict that some individuals with two different copies (say A and B) will be more resistant than individuals with another set of two genes (say C and D). In particular, an individual with a pair of similar genes will recognise fewer parasite molecules than an individual with a pair of dissimilar genes. Individuals that recognise more parasite molecules will more resistant to infection.We then plan to examine the influence on MHC diversity of the selective breeding for disease resistance and production traits. There are many different ways to measure diversity but we plan to use a recently developed method that uses a mathematical formula to aggregate many different measures into a single diversity profile. We predict that overall, there will be no marked loss of MHC diversity as a consequence of selection for resistance to nematodes as well as increased meat and wool production. As individuals with two different alleles are more resistant, selection is expected to maintain diversity. In particular, we expect the frequency of heterozygotes to be maintained and we expect selection to increase diversity by favouring divergent alleles.Finally we will mathematically model the process of selection to reproduce the effect of selection on MHC diversity. Once we understand how selection affects MHC diversity and how MHC diversity affects disease resistance we can create selection schemes to optimise the contribution of the MHC for resistance to disease.

个体对疾病的易感性不同，大部分变异是遗传的。个体中所有基因的集合被称为基因组。基因组的许多不同区域影响对疾病的易感性。最重要的遗传区域之一是主要组织相容性复合体（MHC）。该区域包含决定免疫系统如何识别和应对致病外来生物的基因。动物育种家希望识别出具有遗传抗性的动物，并利用这些个体培育出对疾病具有更强抵抗力的后代。这是困难的，但如果我们可以使用MHC，可能会变得更容易。进化已经产生了广泛的不同的遗传变异的MHC，我们希望管理这种多样性，以优化疾病的抵抗力在牲畜population.This建议的目的是确定选择力，保持在MHC变异使用感染寄生蛔虫在绵羊作为我们的测试系统。寄生性蛔虫病是家畜的一种重要疾病。绵羊的感染和疾病过程是所有疾病中最好理解的疾病之一。我们已经知道MHC在抵抗蛔虫中起着重要作用，因此该系统是研究MHC变异如何影响抗病性的理想方法。我们计划量化维持MHC高变异的选择力。我们将使用对蛔虫感染具有高度抵抗力的绵羊种群。我们将使用先进的统计程序来比较具有不同MHC基因的个体对蛔虫的抗性，该程序消除了所有背景变异，并测试具有不同MHC等位基因的个体之间的差异是否可能是偶然出现的。我们已经测试了苏格兰人口，知道有两种不同的影响。基因之间存在差异。此外，大多数人有两个不同的基因，但有些人继承了两个相同的副本。具有两个不同基因的个体比具有相同基因的两个相同拷贝的个体更具抗性。我们想扩展这个分析。我们预测，一些具有两个不同拷贝的个体（比如A和B）将比具有另一组两个基因的个体（比如C和D）更具抗性。特别是，具有一对相似基因的个体识别的寄生虫分子比具有一对不同基因的个体识别的寄生虫分子少。识别寄生虫分子越多的个体对感染的抵抗力越强，我们计划研究抗病性和生产性状的选择性育种对MHC多样性的影响。有许多不同的方法来衡量多样性，但我们计划使用最近开发的方法，使用数学公式将许多不同的措施汇总为一个单一的多样性概况。我们预测，总体而言，将不会有显着的损失MHC多样性的结果，选择抗线虫以及增加肉和羊毛产量。由于具有两个不同等位基因的个体更具抵抗力，选择有望保持多样性。特别是，我们希望杂合子的频率保持不变，我们希望选择增加多样性，有利于不同的等位基因。最后，我们将数学模型的选择过程中重现选择对MHC多样性的影响。一旦我们了解选择如何影响MHC多样性以及MHC多样性如何影响抗病性，我们就可以创建选择方案来优化MHC对抗病性的贡献。

项目成果

MOESM1 of Analysis of pooled genome sequences from Djallonke and Sahelian sheep of Ghana reveals co-localisation of regions of reduced heterozygosity with candidate genes for disease resistance and adaptation to a tropical environment

MOESM1 对加纳贾隆克羊和萨赫勒羊的基因组序列进行分析，揭示了杂合性降低的区域与抗病和适应热带环境的候选基因的共定位

• DOI: 10.6084/m9.figshare.10270478
• 发表时间: 2019
• 作者: M. Yaro

Multitrait indices to predict worm length and number in sheep with natural, mixed predominantly Teladorsagia circumcincta infection.

• DOI: 10.1017/s0031182014001905
• 发表时间: 2015-05
• 期刊: Parasitology
• 影响因子: 2.4
• 作者: Mair C;Matthews L;De Cisneros JP;Stefan T;Stear MJ
• 通讯作者: Stear MJ

Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models

使用贝叶斯多元自回归模型估计病原体动态的时间协方差

• DOI: 10.48550/arxiv.1611.09063
• 发表时间: 2016
• 作者: Mair C

Implementation of an extended ZINB model in the study of low levels of natural gastrointestinal nematode infections in adult sheep.

• DOI: 10.1186/s12917-016-0723-7
• 发表时间: 2016-06-10
• 期刊: BMC veterinary research
• 影响因子: 2.6
• 作者: Atlija M;Prada JM;Gutiérrez-Gil B;Rojo-Vázquez FA;Stear MJ;Arranz JJ;Martínez-Valladares M
• 通讯作者: Martínez-Valladares M

The genetic architecture of the MHC class II region in British Texel sheep.

• DOI: 10.1007/s00251-016-0962-6
• 发表时间: 2017-03
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Ali AO;Stear A;Fairlie-Clarke K;Brujeni GN;Isa NM;Salisi MS;Donskow-Łysoniewska K;Groth D;Buitkamp J;Stear MJ
• 通讯作者: Stear MJ