Genetic Studies of Dengue Vectors in Brazil

 描述（由申请人提供）：我们提出了三个相关的项目，都集中在控制的主要载体，埃及伊蚊，登革热在巴西。 我们已经开发了一种强大的新工具来进行这种蚊子的遗传分析，这是一种具有约30，000个经过充分验证的SNP的SNP芯片，将应用于所有三个项目。第一个项目是分析一个 释放计划使用转基因蚊子来抑制种群数量，即所谓的RIDL技术。 任何此类计划都有一个悬而未决的问题，那就是释放这种蚊子是否会对自然目标种群的遗传构成产生持久的影响。我们已经基因分型（使用我们的SNP芯片）样品从一个网站之前释放开始，以及释放菌株的样品。 我们将在释放后6个月和12个月对现场进行采样，以检查释放菌株的遗传物质是否转移到目标人群中。如果是这样的话，这对任何此类未来版本都有巨大的影响。 第二个项目的重点是研究雌性Ae能力变异的遗传基础。埃及人传播登革热病毒，DENV。 我们的SNP芯片加上最近在基因组组装方面的重大进展，使这成为进行此类研究的特别有利的时机。 在这些工作中从未解决的一个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。 我们还将讨论DENV能力的时间遗传稳定性问题。第三个项目是关于Ae中杀虫剂抗性的演变。埃及在巴西 里约热内卢Fiocruz的同事正在进行的研究揭示了kdr基因座上负责对拟除虫菊酯杀虫剂抗性的等位基因频率的非常有趣的模式。 这包括世界范围的模式以及巴西的详细模式。 我们建议继续这些研究，增加来自相同样本的30K SNP数据的重要辅助，用于研究kdr等位基因。这将提供有关抗性进化的前所未有的信息，并解决诸如Ae起源等问题。巴西的埃及人种群以及杀虫剂抗药性的时间和起源。

 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.