Behavioral genetics of monoamine-regulatory genes

描述（由申请人提供）：本研究项目将研究候选单胺调节基因的变异与显性和从属食蟹猕猴（Macaca fascicularis）的行为和单胺代谢差异之间的显著相关。此外，本项目旨在通过对主要灵长类科中具有代表性的物种序列变异的系统发育分析来研究这些基因的进化变化。大约有1000只束状斑蝶的DNA样本，它们的社会等级是已知的。其中约800人的脑脊液单胺代谢物浓度可用。新的单核苷酸多态性（snp）跨越候选基因的多巴胺能和血清素能途径将被确定。这些变异将在所有个体中进行检查，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灵长类主要家族的代表中进行系统发育比较，以评估这些基因进化变化的程度和方向，确定灵长类祖先的基因型，并确定每个谱系的差异。目前对基因组与复杂表型性状（如行为和神经递质活性）之间的关系知之甚少。研究基因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的作用，以及行为选择对灵长类基因组进化的影响。对动物（如非人类灵长类动物）的这些过程的理解，可能会揭示我们自己物种的社会性和性格特征的进化，如外向性、攻击性、冲动性、恐惧和焦虑。灵长类动物表现出与人类相似的复杂的社会互动。

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.