Fine-Scale Recombination Rate Variation in Anopheles gambiae

描述（由申请人提供）：尽管通过基于杀虫剂的病媒控制在减少疟疾传播方面取得了进展，但该疾病每年仍夺去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，这是非洲大陆特有的一种高效蚊子媒介。虽然在分子生物学和遗传学方面已经取得了很大的进展。冈比亚过去十年来，由于关于该物种重组率的数据不足，无法最有效地采用新的和传统的病媒控制战略。进化是一个基本的生物学过程，具有深远的进化意义。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，重组发生的速率随基因组位置、性别和染色体倒位的存在而变化。这种重组率的变化影响了无数的进化过程，包括自然选择的效力，站立多样性的水平，以及有害突变的消除。本项目利用高通量的新一代测序技术，旨在：1）建立一个高分辨率的雌性安氏按蚊重组率图谱。gambiae，2）创建雄性An的高分辨率重组率图。冈比亚，和3）系统地确定转化对重组的影响。我们的重组的定量数据将有助于设计，实施和评估的控制策略，针对安。冈比亚，同时也大大提高了人口遗传学和全基因组关联研究在这个物种的力量。最终，该项目为防治疟疾提供了一个重要工具。

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.