Behavioral genetics of monoamine-regulatory genes

单胺调节基因的行为遗传学

• 批准号: 6956509
• 负责人: CASSANDRA M MILLER-BUTTERWORTH
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6956509
• 关键词: Macaca fascicularis; animal population study; behavior; behavioral /social science research tag; behavioral genetics; cerebrospinal fluid; dopamine; ethology; gene expression; genotype; linkage disequilibriums; neurotransmitters; postdoctoral investigator; regulatory gene; serotonin; single nucleotide polymorphism; social behavior

DESCRIPTION (provided by applicant): This research project will investigate the hypothesis that variation in candidate monoamine-regulatory genes is significantly associated with behavioral and monoaminergic metabolite differences identified between dominant and subordinate cynomolgus macaques, Macaca fascicularis. In addition, this project aims to examine evolutionary changes in these genes through a phylogenetic analysis of sequence variation across representative species from the major primate families. DNA samples are available from approximately 1000 M. fascicularis, for which social rank is known. Cerebrospinal fluid monoamine metabolite concentrations are available for approximately 800 of these individuals. Novel single nucleotide polymorphisms (SNPs) spanning candidate genes of the dopaminergic and serotonergic pathways will be identified. These variants will be examined in all individuals and subjected to haplotype association and linkage disequilibrium analyses to determine if they are associated significantly with social rank and related monoamine metabolite levels. Complete coding and regulatory sequences of these candidate genes will be compared phylogenetically in representatives from major primate families, to assess the extent and direction of evolutionary change of these genes, to identify the ancestral primate genotypes and to date the divergences of each lineage. Little is currently known about the relationship between the genome and complex phenotypic traits such as behavior and neurotransmitter activity. Examining the influence of genetic sequence variation on these phenotypes may help to explain the role the genome plays in determining human behavior patterns, as well as the effects of behavioral selection on evolution of the primate genome. Developing an understanding of these processes in animals such as the nonhuman primates, which display complex social interactions similar to those of humans, may shed light on the evolution of sociality and personality traits such as extraversion, aggression, impulsivity, fear and anxiety in our own species.

描述（由申请方提供）：本研究项目将研究以下假设：候选单胺调节基因的变异与显性和从属食蟹猴（Macaca fascicularis）之间确定的行为和单胺能代谢物差异显著相关。此外，该项目旨在通过对主要灵长类家族中代表性物种的序列变异进行系统发育分析来研究这些基因的进化变化。DNA样品可从约1000 M处获得。fascicularis，其中社会等级是已知的。脑脊液单胺代谢物浓度可用于约800人。新的单核苷酸多态性（SNP）跨越多巴胺能和多巴胺能途径的候选基因将被确定。将在所有个体中检查这些变体，并进行单倍型关联和连锁不平衡分析，以确定它们是否与社会等级和相关单胺代谢物水平显著相关。这些候选基因的完整编码和调控序列将在主要灵长类家族的代表中进行遗传学比较，以评估这些基因进化变化的程度和方向，确定祖先灵长类基因型，并确定每个谱系的分歧。目前对基因组和复杂的表型性状（如行为和神经递质活性）之间的关系知之甚少。检查遗传序列变异对这些表型的影响可能有助于解释基因组在决定人类行为模式中所发挥的作用，以及行为选择对灵长类动物基因组进化的影响。在非人类灵长类动物中发展对这些过程的理解，这些动物表现出与人类相似的复杂社会互动，可能会揭示我们自己物种中社会性和个性特征的进化，如外向性，侵略性，冲动性，恐惧和焦虑。