Fine-Scale Recombination Rate Variation in Anopheles gambiae

描述(申请人提供)：尽管通过以杀虫剂为基础的病媒控制在减少疟疾传播方面取得了进展，但该疾病继续每年夺走500,000多人的生命，其中大多数是非洲儿童。非洲控制的一个重大障碍是冈比亚按蚊的存在，这是该大陆特有的一种独特有效的蚊子媒介。虽然在分子生物学和遗传学方面已经取得了很大的进展。冈比亚在过去十年中，关于该物种重组率的数据不足，阻碍了新的和传统的媒介控制策略的最大有效部署。重组是一个具有深刻进化意义的基本生物学过程。在蚊子和其他有性真核生物中，同源染色体之间的重组是从二倍体生殖细胞正确形成单倍体配子和产生新的等位基因组合所必需的。然而，重组发生的速度随基因组位置、性别和染色体倒置的存在而不同。重组率的这种变化影响了无数的进化过程，包括自然选择的效率、站立多样性的水平和有害突变的消除。利用高通量的下一代测序技术，本项目的目标是：1)建立高分辨率的雌蚊重组率图谱。冈比亚亚纲，2)构建雄性冈比亚按蚊的高分辨率重组率图谱。冈比亚，以及3)系统地确定倒置对重组的影响。我们关于重组的定量数据将有助于针对AN的控制策略的设计、实施和评估。冈比亚，同时也极大地提高了该物种的种群遗传学和全基因组关联研究的能力。归根结底，该项目为防治疟疾提供了一个关键工具。

DESCRIPTION (provided by applicant): Despite progress in reducing malaria transmission with insecticide-based vector control, the disease continues to claim over 500,000 lives per year, most of which are African children. A significant impediment to control in Africa is the presence of Anopheles gambiae - a uniquely efficient mosquito vector endemic to the continent. While great advancements have been made in the molecular biology and genetics of An. gambiae over the past decade, inadequate data on recombination rate in this species prevents novel and traditional vector control strategies from being deployed with maximum effectiveness. Recombination is a fundamental biological process with profound evolutionary implications. In mosquitoes and other sexual eukaryotes, recombination between homologous chromosomes is required for both the proper formation of haploid gametes from diploid germ cells and the production of new combinations of alleles. However, the rate at which recombination occurs varies with genomic position, sex, and the presence of chromosomal inversions. Such variation in recombination rate influences a myriad of evolutionary processes including the efficacy of natural selection, levels of standing diversity, and the elimination of deleterious mutations. Usin high-throughput next generation sequencing techniques, this project aims to: 1) create a high-resolution recombination rate map for female An. gambiae, 2) create a high-resolution recombination rate map for male An. gambiae, and 3) systematically determine the effect of inversions on recombination. Our quantitative data on recombination will aid in the design, implementation, and evaluation of control strategies targeting An. gambiae, while also greatly improving the power of population genetics and whole-genome association studies in this species. Ultimately, this project provides a critical tool in the fight against malaria.