Resource development for a new model of social threat response

社会威胁应对新模式的资源开发

基本信息

批准号：
8771140
负责人：
DONNA L MANEY
金额：
$ 23.76万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8771140
关键词：
Affect Aggressive behavior American Amygdaloid structure Anger Animal Model Animals Anxiety Attention deficit hyperactivity disorder Autistic Disorder Behavior Behavior Control Behavioral Behavioral Mechanisms Biological Models Bipolar Disorder Birds Borderline Personality Disorder Brain Brain region Candidate Disease Gene Cataloging Catalogs Chromosomal Rearrangement Chromosomes Chromosomes, Human, Pair 2 Code Complex DNA Sequence Rearrangement Environment Etiology Evolution Face Female Future Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Genetic Drift Genetic Polymorphism Genome Genomics Goals Habitats Haplotypes Health Homozygote Human Hypothalamic structure Impulsivity Individual Knowledge Lead Link Mammals Maps Medial Mental Depression Mental disorders Messenger RNA Modeling Molecular Molecular Genetics Neuroendocrinology Pathway Analysis Pathway interactions Phenotype Population Postdoctoral Fellow Public Health Reading Research Resource Development Resources Risk-Taking Schizophrenia Sexually Transmitted Diseases Single Nucleotide Polymorphism Social Behavior Songbirds Sparrows Stimulus Substance abuse problem System Techniques Testing Tissues Variant Vertebrates Weight Work base behavior measurement comparative genomics criminal behavior experience innovation interest male next generation novel programs protein function public health relevance response social social attachment social model trait

项目摘要

DESCRIPTION (provided by applicant): The underlying genetic basis of variation in social behavior is of intense interest, yet only a handful of genes have been linked to specific social behaviors in vertebrates. Thus, there is a strong need to identify populations, human or otherwise, in which there is clear linkage between genes and social behavior. In the proposed project, resources will be developed to take advantage of a uniquely suited model, the white-throated sparrow. Males and females of this abundant North American songbird occur in two plumage morphs that differ with respect to the presence of a chromosomal rearrangement (ZAL2m) that predicts responses to social threat. Birds of the white-striped (WS) plumage morph (ZAL2m/ZAL2) respond to a territorial intrusion with high levels of vocal aggression, whereas birds of the tan-striped (TS) morph (ZAL2/ZAL2) respond with relatively little or no vocal aggression. The morphs also differ with respect to the formation of social attachments and parental provisioning rates; the phenotypes are thus characterized by a suite of correlated complex traits with a discrete genetic basis. The long-term goal of this research program is to fully exploit this unique model organism, which resembles humans with respect to many aspects of social behavior, to link gene expression and complex behavior in ways never before possible. Limited gene flow between the ZAL2 and ZAL2m haplotypes has led to the genetic differentiation of the rearranged chromosomal region, resulting in the accumulation of single nucleotide polymorphisms and other changes. The primary objective of this proposal is to assess the impact of these genetic forces on the genome and brain transcriptome, thus laying the groundwork to identify molecular mechanisms of behavioral dysregulation in future studies. We will combine the experience of two PIs: one with expertise in the behavioral neuroendocrinology of wild sparrows and the other in genome evolution. In Aim 1, we will identify and evaluate sequence differences between the two haplotypes, which will reveal a large number of potential functional polymorphisms that can then be explored experimentally. In Aim 2, we will use Next Generation techniques to sequence total mRNA from individuals for whom reactive aggression was quantified in a natural setting. We will then use weighted gene coexpression network analysis (WGCNA) of the mapped and quantified reads to identify modules of highly correlated genes associated with morph and reactive aggression. Together, the two aims will reveal candidate mechanisms underlying social strategies. This exploratory project will focus on responses to social threat, which are difficult to study in humans in a naturalistic setting. All behavioral manipulations and measurement will be conducted in the animals' natural habitat, making this project highly innovative. The project is significant because many mental disorders-including autism, depression, bipolar disorder and schizophrenia are characterized by dysregulated responses to social threat and because reactive aggression is often comorbid with risk-taking, substance abuse, and criminal behavior. Thus an understanding of the mechanisms underlying response to social threat is important for human health.

描述（由申请人提供）：社会行为差异的基本遗传基础引起了人们的强烈关注，但只有少数基因与脊椎动物中的特定社会行为有关。因此，迫切需要识别人类或其他人的人群，其中基因与社会行为之间存在明确的联系。在拟议的项目中，将开发资源来利用独特的模型，即白喉的麻雀。这种丰富的北美鸣禽的男性和女性发生在两个羽毛形态中，这些形态在存在染色体重排（ZAL2M）方面有所不同，该染色体会预测对社会威胁的反应。白色条纹（WS）羽毛变体的鸟类（ZAL2M/ZAL2）对领土侵入的反应具有高水平的声音侵略性，而棕褐色（TS）的鸟类（ZAL2/ZAL2）的鸟类的反应相对较少或没有声音攻击。在社会依恋和父母供应率的形成方面，形态也有所不同；因此，表型的特征是与离散遗传基础的一组相关的复杂性状。该研究计划的长期目标是充分利用这种独特的模型生物，类似于人类在社会行为的许多方面，以将基因表达和复杂行为联系起来，以前所未有的方式将其联系起来。 ZAL2和ZAL2M单倍型之间的基因流量有限，导致重排的染色体区域的遗传分化，导致单核苷酸多态性和其他变化的积累。该提案的主要目的是评估这些遗传力对基因组和脑转录组的影响，从而在未来的研究中为鉴定行为失调的分子机制奠定了基础。我们将结合两个PI的经验：一个在野麻雀的行为神经内分泌学方面具有专业知识，另一个在基因组进化中。在AIM 1中，我们将识别和评估两种单倍型之间的序列差异，这将揭示大量潜在的功能多态性，然后可以通过实验探索。在AIM 2中，我们将使用下一代技术来对自然环境中反应性攻击的个体进行总mRNA。然后，我们将使用映射和量化读取的加权基因共表达网络分析（WGCNA）来识别与变形和反应性攻击相关的高度相关基因的模块。这两个目标将共同揭示社会策略的候选机制。这个探索性项目将集中于对社会威胁的反应，社会威胁在自然主义环境中很难在人类中进行研究。所有行为操纵和测量都将在动物的自然栖息地中进行，这使该项目具有很高的创新性。该项目很重要，因为许多精神障碍，包括自闭症，抑郁症，躁郁症和精神分裂症的特征是对社会威胁的反应失调，因为反应性侵略通常与冒险，滥用药物和犯罪行为合并。因此，了解对社会威胁反应的机制对人类健康至关重要。