Characterization & Organization of Transposable Elements

描述（由申请方提供）：冈比亚按蚊种属复合体包括： 严格意义上的恶性疟原虫是疟疾的最重要媒介，这种疾病每年造成100多万人死亡。有效的疟疾控制需要多方面的努力，包括更好地了解病媒。我们的长期目标是1）了解的多样性，丰富性，稳定性，种群动态，进化，以及在一个转座因子（TE）的影响。冈比亚和2）发展人口基因组方法的基础上散布的TE研究的遗传异质性的An。冈比亚有限公司人口。我们提出了一个合作的努力，探索预期的一个。冈比亚基因组序列与一个跨学科的团队，已经证明了在基因组，生物信息学，分子和蚊子TE的进化分析，并在人口遗传学的一个。冈比亚湾S.及其物种复合体。我们将集中在DNA转座子和微型反向重复TE（MITE），它们共享基本结构和可能相似的转座机制。我们将追求以下具体目标：1）进行第一轮检查的多样性，丰度和分子特征的TE在一个。冈比亚。S.S. 2)研究了微孢子虫MITE和DNA转座子的进化历史和扩增方式。冈比亚。S.S.和它的兄弟物种 3)检查MITE和DNA转座子对An的影响。冈比亚。S.S.基因组结构和进化4)确定野生型安氏按蚊MITE和DNA转座子的拷贝数变异和插入位点多态性。冈比亚。S.S. 5)开发新的群体基因组工具。gambiae s.s.，使用来自DNA和RNA介导的TE的插入多态性标记。这项工作将在三个不同层面上促进改进病媒控制和监测以及制定疟疾控制替代战略，这两项工作都是迫切需要的。首先，为研究安氏按蚊的遗传异质性提供了强有力的群体基因组学工具。冈比亚湾S.这可能影响疾病传播和控制措施的效率。第二，拟议的工作将产生新的见解内源性TE在一个。这将有助于通过基于TE的遗传修饰控制蚊媒疾病的战略。最后，这项工作将加强我们对An的基本遗传学的理解。冈比亚通过系统地调查TE， 它们是基因组的重要和潜在的有效成分。

DESCRIPTION (provided by the applicant): The Anopheles gambiae species complex includes An: garnbiae sensu stricto, the most important vector of malaria, a disease that causes more than a million deaths every year. Effective malaria control requires multi-front efforts including a better understanding of its vectors. Our long-term goals are to 1) understand the diversity, abundance, stability, population dynamics, evolution, and impacts of transposable elements (TEs) in An. gambiae and 2) develop population genomic approaches based on interspersed TEs to study the genetic heterogeneity of An. gambiae s.s. populations. We propose a collaborative effort to explore the anticipated An. gambiae genome sequence with an interdisciplinary team that have demonstrated expertise in genomic, bioinformatic, molecular, and evolutionary analysis of mosquito TEs, and in population genetics of An. gambiae s. s. and its species complex. We will focus on DNA transposons and miniature inverted-repeats TEs (MITEs), which share essential structures and probably similar transposition mechanisms. We will pursue the following Specific Aims: 1) Make the first-round examination of the diversity, abundance, and molecular characteristics of TEs in An. gambiae. s.s. 2) Study the evolutionary history and mode of amplification of MITEs and DNA transposons in An. gambiae. s.s. and its sibling species. 3) Examine the impacts of MITEs and DNA transposons on An. gambiae. s.s. genome structure and evolution. 4) Determine copy number variation and insertion site polymorphism of MITEs and DNA transposons in wild populations of An. gambiae. s.s. 5) Develop novel population genomic tools for An. gambiae s.s.,using insertion polymorphism markers derived from both DNA and RNA-mediated TEs. This work will contribute, at three different levels, to the improvement of vector control and surveillance and the development of alternative malaria control strategies, both of which are urgently needed. First, powerful population genomic tools will be provided to study genetic heterogeneity in An. gambiae s. s. populations, which can affect disease transmission and the efficiency of control measures. Second, the proposed work will yield new insights into endogenous TEs in An. gambiae, which will contribute to the strategy to control mosquito-borne diseases by TE-based genetic modifications. Finally, this work will enhance our understanding of the basic genetics of An. gambiae by systematically investigating TEs, which are substantial and potentially potent components of the genome.