Comparative genome mapping of the Anopheles species cluster

按蚊物种簇的比较基因组作图

• 批准号: 8637289
• 负责人: IGOR V SHARAKHOV
• 金额: $ 22.53万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8637289
• 关键词: Achievement; Aedes; Anopheles Genus; Bioinformatics; Chromosomal Rearrangement; Chromosome Mapping; Chromosomes; Communicable Diseases; Communities; Comparative Genomic Analysis; Complex; Confusion; Culicidae; Cytogenetic Map; Cytogenetics; DNA; DNA Resequencing; DNA Sequence Rearrangement; Data; Drosophila genus; Ensure; Equipment; Evolution; Fluorescent in Situ Hybridization; Funding; Gene Expression Profile; Gene Order; Gene Targeting; Genes; Genetic Determinism; Genetic Polymorphism; Genome; Genome Mappings; Genomics; Genotype; Goals; Haplotypes; In Situ; Institutes; Karyotype; Lead; Letters; Link; Malaria; Maps; Microscopic; National Human Genome Research Institute; National Institute of Allergy and Infectious Disease; Olives - dietary; Pattern; Personal Communication; Phenotype; Phylogenetic Analysis; Phylogeny; Population; Population Study; Research; Research Personnel; Series; Testing; Time; United States National Institutes of Health; X Chromosome; base; comparative; comparative genomics; genome annotation; genome sequencing; genome-wide; innovation; insight; member; novel strategies; paralogous gene; public health relevance; sample fixation; scaffold; success; tool; trait; vector

DESCRIPTION (provided by applicant): Targeting genes responsible for vectorial capacity is a novel approach to controlling infectious diseases. To develop a better understanding of genetic determinants of vectorial capacity and with support from vector biologists and members of the malaria community, NHGRI and NIAID have funded the sequencing of the genomes and transcriptomes of 16 Anopheles species (http://www.broadinstitute.org/annotation/genome/anopheles). With genome sequences becoming available, researchers now have the unique opportunity to perform comparative analysis for inferring evolutionary changes relevant to vector ability. However, success of these comparative genomic analyses will be limited, and inferences about evolution of the vectorial capacity traits will be less informative if researchers deal with numerous sequencing scaffolds rather than with chromosome-based genome assemblies. The major goal of this R21 project is to develop chromosome-based reference genome assemblies for three major malaria vectors: An. arabiensis, An. stephensi, and An. albimanus. Draft genome assemblies are available for these species (https://olive.broadinstitute.org/comparisons/anopheles.1). Our project is timely because it will create crucial genomic tools for the newly sequenced Anopheles species. The project is innovative because it will use the automated multicolor fluorescent in situ hybridizatio (AM-FISH) and automated microscopic analysis. We will, for the first time, perform phylogenetic analysis of anopheline mosquitoes by genome-wide gene order analysis and gain important insights into patterns and mechanisms of chromosomal rearrangements. The availability of state-of-the-art equipment and the expertise of the PI in cytogenetics and comparative genomic analysis will ensure successful achievement of the project's goal. The proposal has three specific aims. Specific Aim 1. Physically map sequencing scaffolds to chromosomes of An. arabiensis, An. stephensi, and An. albimanus. We will place and orient scaffolds to polytene chromosomes by AM-FISH, thus, creating chromosome-based reference genome assemblies for the species belonging to the series Pyretophorus (subgenus Cellia), series Neocellia (subgenus Cellia), and series Albimanus (subgenus Nyssorhynchus), respectively. Specific Aim 2. Reconstruct genome-scale rearrangement phylogeny of genus Anopheles. We will identify breakpoints of all fixed inversions in An. arabiensis and will refine the chromosomal phylogeny in the An. gambiae complex using An. stephensi and An. albimanus as outgroup species. Specific Aim 3. Determine the pattern and mechanisms of chromosome evolution in genus Anopheles. We will test the hypotheses that (i) the X chromosome has the highest rate of inversion fixation despite the paucity of inversion polymorphisms, and (ii) inversions have chromosome-specific and species-specific mechanisms of origin and rates of fixation. !

描述（由申请人提供）：靶向负责矢量能力的基因是控制传染病的一种新方法。为了更好地理解媒介能力的遗传决定因素，在媒介生物学家和疟疾社区成员的支持下，NHGRI和NIAID资助了16种肛门脉络物种的基因组和转录组的测序（http://wwwwwww.baradinstitute.org/annotatute.org/annotation/genome/genome/anomemophelephememememememephememememememememememememepheremememememememephes）。随着基因组序列的可用，研究人员现在有独特的机会来进行比较分析，以推断与向量能力相关的进化变化。但是，这些比较基因组分析的成功将受到限制，如果研究人员处理众多测序脚手架而不是基于染色体的基因组组件，则有关媒介物特征进化的推论将不那么信息。该R21项目的主要目标是开发三个主要疟疾媒介的基于染色体的参考基因组组件：An。阿拉伯语，一个。 Stephensi和An。阿尔比马努斯。这些物种可用于基因组组件草案（https://olive.broadinstitute.org/comparisons/anapheles.1）。我们的项目之所以及时，是因为它将为新测序的围绕物种创建至关重要的基因组工具。该项目具有创新性，因为它将使用自动多色荧光原位杂交（AM-FISH）和自动显微镜分析。我们将首次通过全基因组基因顺序分析对虫线蚊子进行系统发育分析，并获得对染色体重排的模式和机制的重要见解。最先进的设备的可用性以及PI在细胞遗传学和比较基因组分析中的专业知识将确保成功实现项目目标。该提案具有三个具体目标。特定的目标1。将测序支架物理映射到An的染色体。阿拉伯语，一个。 Stephensi和An。阿尔比马努斯。我们将通过AM-FISH将其放置在聚染色体上，因此，为属于植物体的基于染色体的参考基因组组件，分别为属于Pyretophorus系列的物种（亚属细胞），串联Neocellia（subgerus cellia）和serize albimanus（Subger of nyssorhyhynchus）。特定目标2。重建基因组尺度的重排系统发育。我们将确定AN中所有固定反转的断点。 Arabiensis，将在AN中完善染色体系统发育。冈比亚复合物使用An。 Stephensi和An。阿尔巴尼亚斯作为外部物种。特定目标3。确定围绕围绕菌群染色体演化的模式和机制。我们将测试（i）X染色体尽管倒置多态性稀少，但X染色体的反转固定速率最高，并且（ii）反转具有特异性和物种特异性的原点和固定速率。呢