A New Foundation for Leishmaniasis Vector Research and Control Through Generation of High-quality Sand Fly Genome Assemblies.

项目摘要 利什曼病是仅次于疟疾的第二大寄生虫杀手。据估计， 据估计，每年有240万残疾调整生命年（DIFFERS）。利什曼 当雌性白蛉叮咬人类以获取所需的血液时，寄生虫会传播给人类 用于繁殖。更好地了解白蛉生物学和种群对于控制和 监测这种疾病的传播媒介。这一建议将产生高质量的基因组参考，以支持未来 沙蝇和利什曼原虫控制工作。 通过基因组分析改进了新的和正在进行的病媒综合控制方法。的描述 物种复合体，估计有效种群规模，监测农药抗性等位基因的出现， 以及对种群结构变化的评估都可以通过遗传分析来完成。新向量 基于CRISPR-Cas9操作的控制方法，以创建基因驱动来防止传播疟疾， 用沃尔巴克氏体操纵微生物组以防止登革热传播的试验正在蚊子身上进行。 不幸的是，我们早期为白蛉创建高质量基因组参考资源的尝试并没有成功。 成功这项研究将产生新的，非常高质量的参考基因组序列的两个关键白蛉 种：Lutzomyia longipalpis，发现于新大陆，是美国内脏利什曼病的主要媒介 和Phlebotomus papatasi，发现于旧世界，包括北方非洲，中东和印度，是一种 皮肤利什曼病的传播媒介。 新的DNA测序和基因组组装技术提高了质量，降低了成本， 产生新的参考基因组。这项研究将产生多个高质量的DNA序列信息 新的高质量基因组组装的数据集。一级序列信息将是长读段（10-15 使用新的DNA测序平台，从一个单一的DNA序列中获得1000个碱基）的高准确度（> 99.8%）DNA序列。 每个物种的个体。将生成HiC染色质序列数据，以了解相对的 序列的染色体位置。光学测绘数据将能够更好地搭建和验证 最后的组装。基于脊椎动物基因组组装流水线的基因组组装软件流水线 目前生成的最高质量的参考基因组组装将被用于组装数据， 尽可能分离单倍型。将生成长读高准确度转录组数据，以支持 高质量的基因组注释，以及白蛉的微生物组，以充分表征 利什曼原虫在这些载体。最终产品将成为未来高质量的基因组参考基础 努力监测和控制这种毁灭性疾病的媒介。

Project Summary Leishmaniasis is the second biggest parasitic killer after malaria. It is estimated to kill an estimated 40,000 people every year, and accounts for an estimated 2.4 million disability-adjusted life-years (DALYs). The Leishmania parasite is transmitted to humans when female sand flies bite humans to obtain blood meals that they require for reproduction. A better understanding of sand fly biology and populations is important for the control and monitoring of this disease vector. This proposal will generate a high-quality genome references to support future sand fly and Leishmania control efforts. New and ongoing methods of integrated vector control are improved by genomic analysis. Descriptions of species complexes, estimation of effective population sizes, monitoring of pesticide resistance allele emergence, and assessment of changes in population structure can all be accomplished using genetic analyses. New vector control methods based on CRISPR-Cas9 manipulation to create gene drives to prevent transmitting malaria and microbiome manipulation with Wolbachia to prevent transmission of dengue are being trialed in mosquitoes. Unfortunately, our early attempts to create high-quality genome reference resources for sand flies were not successful. This study will generate new, very high-quality reference genome sequences for two critical sand fly species: Lutzomyia longipalpis, found in the New World, is the primary vector of American visceral leishmaniasis and Phlebotomus papatasi, found in the Old World, including northern Africa, the Middle East and India, is a vector of cutaneous leishmaniasis. New DNA sequencing and genome assembly techniques have improved the quality and reduced the cost to generate new reference genomes. This study will generate multiple high-quality DNA sequence information datasets for new high-quality genome assemblies. The primary sequence information will be long read (10-15 thousand bases) high accuracy (> 99.8%) DNA sequences using new DNA sequencing platforms from a single individual of each species. HiC chromatin sequence data will be generated to understand the relative chromosome position of the sequences. Optical mapping data will enable better scaffolding and validation of the final assembly. A genome assembly software pipeline based on the vertebrate genome assembly pipeline currently generating the highest quality reference genome assemblies will be used to assemble the data as much as possible separating haplotypes. Long read high accuracy transcriptome data will be generated to support a high-quality genome annotation, and the sand flies' microbiomes to fully characterize the environment of Leishmania in these vectors. The final product will be a high-quality genome reference foundation for future efforts to monitor and control the vector of this devastating disease.