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

 描述（由申请人提供）：埃及伊蚊传播包括登革热在内的多种虫媒病毒疾病，登革热威胁着几乎一半的人口。最近的物理和遗传作图工作将71%的原始基因组草图分配给蚊子染色体。然而，Ae。埃及人的基因组组合仍然高度分散。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误组装率。缺乏高质量的基因组组装阻碍了人口和进化基因组学研究。两个亚种，Ae.埃及伊蚊Aegypti aegypti和埃及伊蚊Ae.台湾埃及伊蚊（Aegypti formosus），已经基于身体颜色进行了描述。这些亚种在世界范围内的分布、与人类的关系以及传播病原体的能力方面彼此显着不同。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基因组和表型分歧的伊蚊。多态倒位往往是负责流行病学上重要的表型在按蚊种群，但他们从来没有直接观察到伊蚊。我们的长期目标是了解流行病学上重要的表型和行为差异的Ae的潜在基因组决定因素。埃及亚种为此，我们提出了本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RS测序数据的埃及伊蚊; 2）开发埃及伊蚊的高分辨率物理图。埃及伊蚊基因组; 3）使用新的基因组组装作为参考，以检测倒位在2亚种的Ae。aegypti和姐妹分类群Ae.马斯卡伦西斯将强大的第三代测序技术与物理染色体作图相结合的创新策略将创建一个改进的高质量基因组组装，这将使发现Ae染色体倒位成为可能。并将促进未来旨在预防蚊子传播疾病的遗传学研究。

 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.