Genetic Studies of Dengue Vectors in Brazil

巴西登革热媒介的遗传学研究

• 批准号: 8819856
• 负责人: Jeffrey R POWELL
• 金额: $ 66.76万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-25 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8819856
• 关键词: Address; Adult; Aedes; Affect; Africa; African; Alleles; Area; Back; Brazil; Collection; Competence; Complex; Coupled; Culicidae; Data; Dengue; Evolution; Female; Freezing; Funding; Future; Gene Frequency; Genes; Genetic; Genetic Materials; Genetic Variation; Genetic study; Genome; Genomic Segment; Genomics; Genotype; Goals; Head; Home environment; Individual; Insecta; Insecticide Resistance; Insecticides; Larva; Location; Malaria; Methods; Mosquito Control; Pattern; Population; Population Control; Population Study; Process; Research; Resistance; Sampling; Site; Sorting - Cell Movement; Target Populations; Techniques; Time; Transgenic Organisms; Variant; Viral Genome; Virus; Work; disorder control; follow-up; genetic analysis; genetic makeup; genome wide association study; interest; knock-down; programs; public health relevance; pyrethroid; tool; trait; vector

 DESCRIPTION (provided by applicant): We propose three related projects all focused on control of the major vector, Aedes aegypti, of dengue fever in Brazil. We have developed a powerful new tool for genetic analysis of this species of mosquito, a SNP chip with ~30,000 well-validated SNPs, that will applied in all three projects. The first project is an analysis of a release program using transgenic mosquitoes to suppress population numbers, the so-called RIDL technique. One unanswered question for any such program of this sort is whether the release of such mosquitoes has a lasting impact on the genetic make-up of the natural target population. We have genotyped (using our SNP chip) samples from one site before releases began as well as a sample of the release strain. We will sample the field site 6 months and 12 months after release to examine whether genetic material from the release strain is being transferred to the target population. If so, this has enormous implications for any such future releases of this sort. The second project focuses on studying the genetic underpinning of variation in the ability of female Ae. aegypti to transmit the dengue fever virus, DENV. Our SNP chip coupled with very recent significant advances in genome assembly make this an especially propitious time to undertake such studies. One issue never before addressed in such work is the degree to which populations of mosquito vary geographically in the genes or gene regions responsible for DENV competence. We will also address issues of temporal genetic stability for DENV competence. The third project is on evolution of insecticide resistance in Ae. aegypti in Brazil. Ongoing studies by colleagues at Fiocruz in Rio de Janeiro have revealed very interesting patterns of allele frequencies at the kdr locus responsible for resistance to pyrethroi insecticides. This includes worldwide patterns as well as detailed patterns in Brazil. We propose to continue these studies adding the important adjunct of 30K SNP data from the same samples as studied for kdr alleles. This will provide unprecedented information on evolution of resistance as well as address issues such as the origin of Ae. aegypti populations in Brazil and the timing and origin of insecticide resistance.

 描述（由申请人提供）：我们提出了三个相关项目，全部侧重于控制巴西登革热的主要媒介埃及伊蚊。我们开发了一种强大的新工具，用于对该蚊子进行遗传分析，这是一种带有 SNP 芯片的工具。约 30,000 个经过充分验证的 SNP，将应用于所有三个项目。第一个项目是对一个项目的分析。 使用转基因蚊子来抑制种群数量的释放计划，即所谓的 RIDL 技术，此类计划的一个悬而未决的问题是，此类蚊子的释放是否会对自然目标种群的基因构成产生持久影响。我们在释放开始前对一个地点的样本以及释放菌株的样本进行了基因分型（使用我们的 SNP 芯片）。我们将在释放后 6 个月和 12 个月对现场进行采样，以检查来自释放菌株的遗传物质是否受到影响。转移到目标如果是这样，这对未来的此类释放具有巨大的影响。第二个项目的重点是研究雌性埃及伊蚊传播登革热病毒（DENV）能力的遗传基础。最近基因组组装方面取得了重大进展，这使得现在成为进行此类研究的一个特别有利的时机，这一问题是蚊子种群在负责 DENV 能力的基因或基因区域中的地理差异程度。也解决问题第三个项目是巴西伊蚊的杀虫剂抗性进化，里约热内卢 Fiocruz 的同事们正在进行的研究揭示了负责抗性的 kdr 位点的等位基因频率。这包括全球模式以及巴西的详细模式，我们建议继续这些研究，添加来自与 kdr 研究相同样本的 30K SNP 数据的重要辅助内容。这将提供有关抗性进化的前所未有的信息，并解决诸如巴西伊蚊种群的起源以及杀虫剂抗性的时间和起源等问题。