Improving the reference genome assembly for the dengue fever vector Aedes aegypti

 描述(申请人提供)：埃及伊蚊传播多种虫媒病毒疾病，包括威胁到几乎一半人口的登革热。最近的物理和遗传作图工作将原始草稿基因组组合的71%分配给蚊子的染色体。然而，Ae.埃及伊蚊的基因组组装仍然高度分散。此外，这两种作图方法都确定了现有基因组超重叠群中的高错组率。缺乏高质量的基因组组装阻碍了种群和进化基因组学的研究。两个亚种，Ae.埃及伊蚊Aegypti Aegypti和Ae.Aegypti formosus，已根据身体着色进行了描述。这些亚种在全球分布、与人类的联系以及传播病原体的能力方面存在显著差异。根据我们的初步数据，我们假设染色体倒位有助于建立和维持伊蚊的基因组和表型差异。在按蚊群体中，多态倒位通常是流行病学上重要的表型，但从未在伊蚊中直接观察到。我们的长期目标是了解Ae在流行病学上重要的表型和行为差异的潜在基因组决定因素。埃及伊蚊亚种。为此，我们提出了该项目的三个具体目标：1)改进Ae的基因组组装和基因注释。基于太平洋生物科学遥感测序数据的埃及埃及；2)开发高分辨率的Ae物理地图。3)以新的基因组组合为参照，检测Ae亚种2个亚种的倒位。Aegypti和一个姊妹分类群Ae.睫毛膏。将强大的第三代测序技术与物理染色体图谱相结合的创新战略将创建改进的高质量基因组组装，从而使在Ae中发现染色体倒置成为可能。埃及伊蚊并将推动未来旨在防止蚊媒疾病传播的基因研究。

 DESCRIPTION (provided by applicant): Aedes aegypti transmits a number of arboviral diseases including dengue fever, which threatens virtually one half of the human population. Recent physical and genetic mapping efforts assigned 71% of the original draft genome assembly to the mosquito chromosomes. However, the Ae. aegypti genome assembly still remains highly fragmented. Moreover, both mapping approaches determined high rates of misassembly in the existing genomic supercontigs. The lack of a high-quality genome assembly has hindered population and evolutionary genomics studies. Two subspecies, Ae. aegypti aegypti and Ae. aegypti formosus, have been described based on body coloration. These subspecies remarkably differ from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. Based on our preliminary data, we hypothesize that chromosomal inversions contribute to the establishment and maintenance of genomic and phenotypic divergence in aedini mosquitoes. Polymorphic inversions are often responsible for epidemiologically important phenotypes in Anopheles populations but they have never been directly observed in Aedes. Our long-term goal is to understand the underlying genomic determinants of epidemiologically important phenotypic and behavioral differences of the Ae. aegypti subspecies. Toward this end, we propose three specific aims for this project: 1) improve the genome assembly and gene annotation of Ae. aegypti based on Pacific Biosciences RS sequencing data; 2) develop a high- resolution physical map for the Ae. aegypti genome; 3) use the new genome assembly as a reference to detect inversions in 2 subspecies of Ae. aegypti and in a sister taxon, Ae. mascarensis. The innovative strategy of integrating a powerful 3rd generation sequencing technology with physical chromosome mapping will create an improved high-quality genome assembly that will make possible the discovery of chromosomal inversions in Ae. aegypti and will stimulate future genetic studies aimed at preventing mosquito- borne disease transmission.