THE ANOPHELES GAMBIAE GENOME PROJECT

疟疾、结核病和艾滋病是世界上人类死亡的三大主要病原体。世界上90%以上的疟疾发生在非洲，冈比亚按蚊是主要的传播媒介。人类和疟疾寄生虫基因组计划目前正在进行中，预计将在未来一两年内完成。本提案旨在启动冈比亚疟基因组计划，期望冈比亚疟寄生虫、人类宿主和媒介基因组的可用性将导致新的疟疾控制策略的发展。这项建议的直接目的如下：(1)对5种不同的蚊子组织（唾液腺、中肠、脂肪体、头部和免疫应答细胞系）的标准化cDNA文库中的10000条ESTs进行测序；(2)对蚊子的多烯染色体进行2000个基因组DNA细菌人工染色体（BACs）的物理映射；(3)对25000个基因组DNA BACs的两端进行测序。(4)选取与黑腹果蝇Adh区同源的3兆碱基序列进行测序，评估蚊子与黑腹果蝇的局部尺度同源性。这4个目标将为直接基因发现，基因表达分析（通过微阵列技术），以及确定D和D之间广泛（多染色体水平）和局部（兆碱基序列水平）的一致性提供序列。黑腹虫和冈比亚虫。它们还将促进后续的全基因组测序项目，无论是通过序列标记连接器策略还是通过霰弹枪策略。该项目的结构涉及美国和欧洲机构的参与，使其成为一项国际努力。长远的目标是鼓励更多的资助机构加入到对这种蚊子全基因组测序的支持中来。

Malaria, tuberculosis, and AIDS are three major pathogen-specific causes of human mortality in the world. More than 90% of the world's malaria is in Africa, where the mosquito Anopheles gambiae is the primary vector. Human and malaria parasite genome projects are now underway and expected to be complete within the next year or two. This proposal seeks to initiate an A.gambiae genome project, with the expectation that the availability of the genomes of the parasite, human host, and the vector will lead to the development of novel malaria control strategies. The immediate aims of this proposal are the following: (1)to sequence 10,000 ESTs from normalized cDNA libraries made from each of five different mosquito tissues (salivary gland, midgut, fatbody, head, and immune- responsive cell lines), (2) to physically map to the mosquito's polytene chromosomes 2,000 genomic DNA Bacterial Artificial Chromosomes (BACs), (3) to sequence both ends of 25,000 genomic DNA BACs, and (4) to assess local scale synteny between the mosquito and Drosophila melanogaster by sequencing 3 megabases of sequence selected to be homologous with the well studied D. melanogaster Adh region. These 4 aims will provide sequences for direct gene discovery, for gene expression analysis (by microarray techniques), and for the determination of broad (polytene chromosome level) and local (megabase sequence level) synteny between D .melanogaster and A. gambiae. They will also facilitate a subsequent full genome sequencing project, either by a Sequence Tagged Connector strategy or by a shotgun strategy. The project is structured to involve the participation of both US and European institutions so as to make this an international effort. The long range is to encourage a broad range of funding agencies to join in supporting an effort to sequence the entire genome of this mosquito.