Function of Guy1, a Y-specific gene of Anopheles stephensi

史氏按蚊 Y 特异性基因 Guy1 的功能

• 批准号: 8492308
• 负责人: Zhijian Jake Tu
• 金额: $ 23.45万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492308
• 关键词: Anopheles Genus; Attention; Behavior; Bite; Blood; Chromosomes; Cloning; Communicable Diseases; Complement; Complementary DNA; Coupling; Culicidae; DNA; Data; Deposition; Development; Diagnosis; Disease; Drosophila melanogaster; Drug resistance; Embryo; Embryonic Development; Ensure; Evolution; Exposure to; Female; Fertility; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genomics; Human; Injection of therapeutic agent; Insecta; Insecticide Resistance; Insecticides; Investigation; Laboratories; Length; Malaria; Measures; Messenger RNA; Methods; Middle East; Modeling; Molecular; Monitor; Mosquito Control; Mosquito-borne infectious disease; Nature; Outcome; Parasites; Partner in relationship; Pharmaceutical Preparations; Phenotype; Phylogenetic Analysis; Physiology; Population; Recording of previous events; Regulation; Research; Reverse Transcriptase Polymerase Chain Reaction; Sex Behavior; Signal Transduction; Site; Spermatogenesis; System; Technology; Testing; Time; Transgenes; Transgenic Organisms; Vaccines; Work; Y Chromosome; base; combat; egg; experience; exposed human population; feeding; fly; gene function; genetic manipulation; improved; knock-down; male; next generation sequencing; novel; novel marker; novel strategies; paralogous gene; pathogen; promoter; public health relevance; research study; sex; sex determination; sexual dimorphism; transcriptome sequencing; vector

DESCRIPTION (provided by applicant): Anopheles mosquitoes are the primary vectors of malaria, one of the most deadly and costly diseases in human history. There is no effective vaccine against malaria, although promising candidates are being tested. Current control strategies rely on prompt diagnosis and drug treatment and the reduction of human exposure to infectious mosquito bites. These measures are becoming less effective as insecticide- and drug-resistance increases. Novel approaches to malaria control are urgently needed. Recent application of next-generation sequencing technologies to mosquito genomics offers exciting opportunities to enhance our understanding of mosquito genetics, physiology, and behavior, in ways that were previously unimaginable. This information will enable the development of new strategies to combat malaria and other mosquito-borne diseases. Only female mosquitoes feed on blood and transmit disease pathogens. Anopheles mosquitoes use the XX/XY sex-determination system. There is evidence that a dominant male-determining factor(s) on the Y chromosome initiates sexual differentiation in an Anopheles species. Genetic studies show that insect Y chromosomes are involved in the regulation of male fertility, mating behavior, and global gene expression. However, molecular characterizations of Y genes are rare outside of a few model species, mostly due to the repetitive nature of the Y chromosome and the difficulty of cloning repeat-rich heterochromatic sequences. We have recently discovered a few Y genes including a novel gene we call Guy1 (Gene Unique to Y). We choose to investigate the function of Guy1 in this R21 project because Guy1 is transcribed at the very onset of zygotic transcription in the early embryo and it is a single copy gene with no autosomal or X paralog. We will test the hypothesis that Guy1 is involved in sexual differentiation in the early embryo. We will investigate the effect of ectopic Guy1 expression (Aim 1) and Guy1 knockdown (Aim 2) on sex-related phenotypes as well as general changes in development and embryonic gene expression. This research will contribute to our long-term objective, which is to illuminate the genetic basis of sexual dimorphism in anopheline mosquitoes and develop relevant and new control strategies. The approach developed in this research will inform future work in other Anopheles species. We anticipate extending beyond this R21 to investigate the mechanism of Y gene function, develop mosquito control applications through the manipulation of Y genes, and establish Y genes as novel markers for phylogenetic, population and mating behavior studies.

描述（由申请人提供）：蚊子是疟疾的主要媒介，疟疾是人类历史上最致命，最昂贵的疾病之一。尽管正在测试有希望的候选人，但没有有效的疫苗针对疟疾。当前的控制策略依赖于迅速诊断和药物治疗以及减少人类接触感染性蚊子的叮咬。随着杀虫剂和抗药性的增加，这些措施变得越来越有效。迫切需要进行新颖的疟疾控制方法。下一代测序技术在蚊子基因组学上的最新应用提供了令人兴奋的机会，以以前难以想象的方式增强我们对蚊子遗传学，生理学和行为的理解。这些信息将使制定新策略来打击疟疾和其他蚊子传播疾病。只有雌性蚊子以血液和传递疾病病原体为食。 Anopheles蚊子使用XX/XY性别确定系统。有证据表明，Y染色体上的主要男性确定因子会引起肛门物种的性别分化。遗传研究表明，昆虫y染色体与男性生育能力，交配行为和全球基因表达有关。然而，Y基因的分子特征在几种模型物种之外很少见，这主要是由于Y染色体的重复性和克隆富含重复的异质序列的难度。最近，我们发现了一些Y基因，包括我们称为Guy1（Y独特的基因）的新基因。我们选择在此R21项目中研究Guy1的功能，因为Guy1是在早期胚胎中的Zygotic转录开始时转录的，它是一个没有常染色体或X paralog的单个副本基因。我们将检验以下假设：Guy1参与早期胚胎的性差异化。我们将研究异位GUY1表达（AIM 1）和GUY1敲低（AIM 2）对与性别相关的表型的影响以及发育和胚胎基因表达的一般变化。这项研究将有助于我们的长期目标，即阐明瞬时蚊子中性二态性的遗传基础，并制定相关和新的控制策略。这项研究中开发的方法将为其他止血物物种的未来工作提供信息。我们预计将延伸超出R21，以研究Y基因功能的机理，通过操纵Y基因来开发蚊子控制应用，并将Y基因作为系统发育，种群和交配行为研究的新颖标志。