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Genetic mapping of vector competence in Culicoides sonorensis

库蠓载体能力的遗传图谱

基本信息

批准号：
BB/J016721/1
负责人：
Mark Fife
金额：
$ 84.22万
依托单位：
The Pirbright Institute
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ016721%2F1
关键词：
Genetic mapping vector competence Culicoides

项目摘要

Culicoides midges act as vectors of more than 50 arboviruses (viruses transmitted by arthropods vectors), including some of the most economically damaging diseases of livestock that are of international, economic and animal-welfare importance. These include Bluetongue virus (BTV) and African horse sickness virus (AHSV). In 2006 the first cases of BTV in Northern Europe in recorded history were detected in the Netherlands. The virus subsequently spread across a vast area of Europe, causing the most costly single outbreak of bluetongue (BT) in recorded history, with losses running into hundreds of millions of Euro's. The disease arrived in South-East England during August 2007, and only a rapid vaccination campaign prevented its re-emergence in the UK during 2008. This is estimated to have saved the UK ~£485 million. The whole of Europe must now be regarded as 'at risk' from further outbreaks of BT and other arboviral diseases including African horse sickness virus (AHSV). The latter is one of the most feared pathogens of horses with mortality rates in susceptible populations that can reach 95%. It is already known that variation in midge genes influences their ability to become infected by BTV and to subsequently infect animal hosts (this is termed their vector competence). This has a major impact on the distribution of BTV worldwide, as the virus can only survive for long periods where competent midges are present. We aim to discover what genes control this vector competence. To do this we will first generate the complete genetic map (genome) for this group using colonies of Culicoides sonorensis held at IAH. To date, similar genomes have been produced for three mosquitoes with additional projects underway for the tsetse fly, the sandfly, the blackfly, the housefly and additional mosquito vector species. Full genome sequencing has not yet been attempted for any Culicoides species although we have generated preliminary sequencing data that shows that this can be achieved relatively rapidly with recent technological advances. Once we have produced the genetic map of the midge we will then examine and catalogue all genetic differences between the individual midges in the population. This information will allow us to identify different versions of genes that influence the ability of the midge to become infected and transmit viruses (specifically BTV and AHSV). In addition to providing knowledge of how Culicoides and these viruses interact, our proposal will also generate the first annotated genome for this insect vector group. This will provide vast new opportunities in research on these important disease vectors. It will also allow us to compare the genes from C. sonorensis with other insect groups (e.g. mosquitoes) for which genome sequences are already available. The genome sequence of Culicoides generated in this study will also provide a long term fundamental tool for understanding the reasons which both BTV and AHSV are restricted in distribution and also why incursions such as that of BTV into northern Europe occur.

库蠓是50多种虫媒病毒（由节肢动物传播的病毒）的载体，包括一些具有国际、经济和动物福利重要性的最具经济破坏性的牲畜疾病。这些病毒包括蓝舌病毒（BTV）和非洲马瘟病毒（AHSV）。2006年，在荷兰发现了历史上北方的第一例BTV病例。该病毒随后在欧洲广大地区蔓延，造成有史以来最昂贵的蓝舌病（BT）单次爆发，损失高达数亿欧元。该疾病于2007年8月抵达英格兰东南部，只有快速疫苗接种运动才能防止其在2008年在英国再次出现。据估计，这为英国节省了约4.85亿英镑。整个欧洲现在必须被视为“处于危险之中”的进一步爆发的BT和其他虫媒病毒疾病，包括非洲马病病毒（AHSV）。后者是马最可怕的病原体之一，易感人群的死亡率可达95%。已经知道，蚊基因的变异影响它们被BTV感染并随后感染动物宿主的能力（这被称为它们的载体能力）。这对BTV的全球分布产生了重大影响，因为该病毒只能在有能力的蠓存在的地方长期存活。我们的目标是发现什么基因控制这种载体的能力。要做到这一点，我们将首先产生完整的遗传图谱（基因组），为这个群体使用殖民地库蠓sonorensis举行IAH。到目前为止，已经为三种蚊子制作了类似的基因组，并正在为采采蝇、白蛉、黑蝇、家蝇和其他蚊子媒介物种制作其他项目。全基因组测序尚未尝试任何库蠓物种，虽然我们已经产生的初步测序数据表明，这可以实现相对较快的技术进步。一旦我们绘制了摇蚊的遗传图谱，我们将检查并记录种群中单个摇蚊之间的所有遗传差异。这些信息将使我们能够识别影响蠓感染和传播病毒（特别是BTV和AHSV）能力的不同版本的基因。除了提供库蠓和这些病毒如何相互作用的知识外，我们的提议还将为这个昆虫载体群生成第一个注释的基因组。这将为研究这些重要的疾病媒介提供巨大的新机会。这也将使我们能够比较来自C. sonorensis与其他昆虫群体（如蚊子）的基因组序列已经可用。本研究中获得的库蠓基因组序列也将为了解BTV和AHSV在分布上受到限制的原因以及为什么会发生BTV入侵北方欧洲提供长期的基本工具。