Fine-Scale Recombination Rate Variation in Anopheles gambiae

描述（由申请人提供）：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，但该疾病每年继续夺去50多万人的生命，其中大多数是非洲儿童。在非洲控制疟疾的一个重大障碍是冈比亚按蚊的存在——冈比亚按蚊是非洲大陆特有的一种独特有效的病媒。虽然在安的分子生物学和遗传学方面已经取得了很大的进展。在过去十年中，关于该物种重组率的数据不足，妨碍了以最大效果部署新的和传统的病媒控制策略。重组是一个具有深远进化意义的基本生物学过程。在蚊子和其他性真核生物中，同源染色体之间的重组是由二倍体生殖细胞形成单倍体配子和产生新的等位基因组合所必需的。然而，重组发生的速率因基因组位置、性别和染色体倒位的存在而异。这种重组率的变化影响着无数的进化过程，包括自然选择的有效性、生存多样性的水平和有害突变的消除。利用高通量新一代测序技术，本项目旨在：1)建立一个高分辨率的重组率图谱。冈比亚（gambiae）， 2)创建了男性An的高分辨率重组率图。3)系统地确定反转对重组的影响。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。同时也大大提高了种群遗传学和该物种全基因组关联研究的能力。最终，这个项目为抗击疟疾提供了一个关键的工具。

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.