Argentine ants: A system a study genes involved in human behavioral disease

阿根廷蚂蚁：研究与人类行为疾病相关的基因的系统

• 批准号: 7687388
• 负责人: Christopher David Smith
• 金额: $ 11.51万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-16 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687388
• 关键词: Affect; Animal Model; Ants; Bees; Behavior; Behavior Disorders; Behavioral; Biochemical; Bioinformatics; Biological Assay; Biological Markers; Biological Models; Cardiopulmonary; Characteristics; Chromosomes, Human, Pair 7; Complementary DNA; Complex; Coupled; Development; Disease; Educational process of instructing; Exhibits; Exons; Gene Targeting; Genes; Genetic; Genome; Genomics; Goals; Health; Hostility; Human; Hymenoptera; Individual; Insecta; Language; Learning; Link; Literature; Maps; Mentors; Methods; Methylation; Molecular; Molecular Biology; Music; Nature; Neurologic; Orthologous Gene; Personal Satisfaction; Phenotype; Principal Investigator; Proteins; Psyche structure; Public Health; RNA Interference; Regulator Genes; Regulatory Element; Research; Resources; Reverse Transcriptase Polymerase Chain Reaction; Social Behavior; Social Interaction; Symptoms; System; Testing; Therapeutic Intervention; Vertebrates; Williams Syndrome; Work; comparative; depression; experience; improved; in vivo; nervous system disorder; novel; prevent; promoter; skills; social; social integration

DESCRIPTION (provided by applicant): Increasingly, human neurological diseases are being mapped to genome regions shared between affected individuals, however current methods generally identify large genomic regions containing many genes. For example, Williams-Beuren Syndrome (WBS), results in learning deficits and cardiopulmonary phenotypes and is associated with deletion of at least 25 genes in the 1.5 Mb WBS critical region (WBSCR). Interestingly, those affected with WBS often have a 'hyper-gregarious' nature and enhanced language or music skills. Despite the small number of genes implicated, the lack of a social animal model has limited the study of how WBSCR genes affect social interaction and little is known about the WBSCR genes or how they contribute to the characteristic WBS symptoms. Social insects, including ants and bees, are a tractable experimental system to test the in vivo effects of WBSCR genes on complex social behaviors. We propose to perturb the expression level of genes from the WBSCR in the social insect, Linepithema humile (Argentine ant). We will: 1) Use comparative genomics to identify WBSCR gene orthologs in several genomes and annotate their exons, regulatory elements, and repeats. 2) Develop L. humile cDNA and fosmid resources to clone, sequence, and assess the methylation state of WBSCR gene regions. 3) Use RNA interference constructs to perturb expression of WBSCR genes in ants and observe changes in individual and group behaviors. In addition to these research objectives, the principal investigator will pursue the following developmental goals with the guidance of his mentor, Dr. Gary Karpen 4) establish an independent research group 5) enhance personal mentoring and teaching skills 6) improve the quality of research. Relevance to Public Health: Social interaction is a complex behavior that profoundly affects human health and well-being. Experimentation with behavior genes in humans is not feasible, making the development of a 'social behavior' animal model system desirable. The proposed studies will elucidate the conserved protein, cis-DNA regulatory features, and gene networks involved in Williams-Beuren Syndrome and will develop a social animal model system to test other gene-behavior interactions. This study of WBSCR genes promises to identify novel biomarkers and gene targets for therapeutic intervention of behavioral disorders.

描述（由申请人提供）：越来越多的人类神经系统疾病正在映射到受影响个体之间共享的基因组区域，但是当前的方法通常鉴定出包含许多基因的大基因组区域。例如，Williams-Beuren综合征（WBS）导致学习缺陷和心肺表型，并与1.5 MB WBS关键区域（WBSCR）中至少25个基因删除有关。有趣的是，受WBS影响的人通常具有“过度弥补”的性质和增强的语言或音乐技能。尽管涉及少数基因，但缺乏社交动物模型限制了对WBSCR基因如何影响社会相互作用的研究，对WBSCR基因或它们如何对特征性WBS症状做出贡献知之甚少。包括蚂蚁和蜜蜂在内的社交昆虫是一个可进行的实验系统，用于测试WBSCR基因对复杂社会行为的体内影响。 我们建议在社交昆虫，linepithema humile（阿根廷蚂蚁）中扰动WBSCR的基因表达水平。我们将：1）使用比较基因组学鉴定几种基因组中的WBSCR基因直系同源物并注释其外显子，调节元素和重复序列。 2）开发humile cDNA和FOSMID资源以克隆，序列和评估WBSCR基因区域的甲基化状态。 3）使用RNA干扰构建体来驱动蚂蚁中WBSCR基因的表达，并观察到个体和群体行为的变化。除了这些研究目标外，首席研究者还将在其导师的指导下追求以下发展目标。 与公共卫生的相关性：社会互动是一种复杂的行为，对人类健康和福祉产生深远的影响。在人类中对行为基因进行实验是不可行的，这使得“社会行为”动物模型系统的发展令人期待。拟议的研究将阐明涉及威廉姆斯 - 布伦综合征的保守蛋白，顺式-DNA调节特征和基因网络，并将开发一种社交动物模型系统来测试其他基因行为相互作用。 WBSCR基因的这项研究有望鉴定出新型的生物标志物和基因靶标，以进行行为障碍的治疗干预。