Behavioral genetics of monoamine-regulatory genes

描述(申请人提供)：本研究项目将调查一种假设，即候选单胺调节基因的变异与优势食蟹猴和从属食蟹猴之间的行为和单胺能代谢物差异显著相关。此外，该项目旨在通过对来自主要灵长类家族的代表性物种的序列差异进行系统发育分析，来检查这些基因的进化变化。DNA样本可以从大约1000个束状分支杆菌中获得，这些分支杆菌的社会地位是已知的。这些人中大约有800人可以获得脑脊液单胺代谢物浓度。新的单核苷酸多态(SNPs)跨越多巴胺能和5-羟色胺能途径的候选基因将被识别。这些变异将在所有个体中进行检查，并接受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的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系统发育比较，以评估这些基因进化变化的程度和方向，识别祖先灵长类的基因类型，并确定每个谱系的分歧。目前对基因组与行为和神经递质活性等复杂表型特征之间的关系知之甚少。研究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起的作用，以及行为选择对灵长类基因组进化的影响。对非人类灵长类动物等表现出与人类相似的复杂社会互动的动物的这些过程的理解，可能有助于揭示我们自己物种的社会性和个性特征的进化，如外向、攻击性、冲动、恐惧和焦虑。

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.