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）：靶向负责载体能力的基因是控制传染病的一种新方法。为了更好地了解媒介能力的遗传决定因素，在媒介生物学家和疟疾界成员的支持下，NHGRI 和 NIAID 资助了 16 个按蚊物种的基因组和转录组测序 (http://www.broadinstitute.org) /注释/基因组/按蚊）。随着基因组序列的出现，研究人员现在拥有独特的机会进行比较分析，以推断与载体能力相关的进化变化。然而，如果研究人员处理大量测序支架而不是基于染色体的基因组组装，这些比较基因组分析的成功将是有限的，并且关于矢量容量特征进化的推断将缺乏信息。该 R21 项目的主要目标是为三种主要疟疾载体开发基于染色体的参考基因组组件：An。阿拉伯树，An.斯蒂芬西和安.白马努斯。这些物种的基因组组装草案可供使用 (https://olive.broadinstitute.org/comparisons/anopheles.1)。我们的项目是及时的，因为它将为新测序的按蚊物种创建重要的基因组工具。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）和自动显微分析。我们将首次通过全基因组基因顺序分析对按蚊进行系统发育分析，并获得对染色体重排的模式和机制的重要见解。最先进的设备以及 PI 在细胞遗传学和比较基因组分析方面的专业知识将确保项目目标的成功实现。该提案有三个具体目标。具体目标 1. 将测序支架物理映射到 An 染色体。阿拉伯树，An.斯蒂芬西和安.白马努斯。我们将通过 AM-FISH 将支架放置并定向到多线染色体，从而为属于 Pyretophorus 系列（Cellia 亚属）、Neocellia 系列（Cellia 亚属）和 Albimanus 系列（Nyssorhynchus 亚属）的物种创建基于染色体的参考基因组组件， 分别。具体目标 2. 重建按蚊属基因组规模的重排系统发育。我们将识别 An 中所有固定反转的断点。 arabiensis 并将完善 An 的染色体系统发育。冈比亚复合体使用 An.斯蒂芬西和安. albimanus 作为外群种。具体目标 3. 确定按蚊属染色体进化的模式和机制。我们将测试以下假设：(i) 尽管倒位多态性很少，但 X 染色体具有最高的倒位固定率；(ii) 倒位具有染色体特异性和物种特异性的起源机制和固定率。 ！