猕猴（Macaca mulatta）衰老过程中凝血功能变化规律及基因表达调控机制研究

衰老是复杂的生物学过程，在人类中的一个特殊表型为凝血功能随年龄增长而增强，容易提高脑卒中、血栓等的发病率。尚不明确凝血功能增强过程中相关基因的表达变化和调控机制，也不清楚其它非人灵长类是否有与人类相似的表型以及其演化意义。猕猴(Macaca mulatta)是非人灵长类中分布最广泛的物种，并且与人类亲缘关系较近，是研究灵长类进化和衰老机制的极佳素材。本项目以猕猴为研究对象，对不同年龄的圈养个体进行凝血时间和凝血因子活性的检测、血液转录组和DNA甲基化组的测序分析，明确猕猴在衰老过程中凝血功能的变化规律，阐明凝血相关基因的表达变化和DNA甲基化调控机制。与人类研究结果进行比较，并在已经完成基因组拼装的所有灵长类物种中对凝血相关差异表达基因进行正选择分析，揭示猕猴和人类在凝血功能变化方面的异同，扩展对凝血相关基因在灵长类物种中适应性进化的认识，必将为灵长类物种的进化生物学研究提供宝贵的资源。

Aging is a very complicated biological process. One of the special phenotypes is human's blood coagulation function would be enhanced with age, which might increase the risk of cardiovascular diseases, such as thrombosis and stroke. However, little is known about the gene expression changes and the gene regulation during the enhanced blood coagulation process. We also do not know whether other nonhuman primates have the similar phenotype. The rhesus macaque (Macaca mulatta) is the most wide-spread nonhuman primate, which is widely used in evolutionary studies. It is also used in aging-related studies due to its close relationship with human. In this study, we are going to test the blood coagulation time and the activities of coagulation factors in rhesus macaques with different ages, which could allow us to analyze the phenotype changes of the blood coagulation during aging. We are also going to sequence the blood transcriptomes and DNA methylomes, to detect the gene expression changes and epigenetic changes of blood coagulation-related genes. We will analyze the association between gene expression level and the differential methylation regions to discuss the influence of methylation on the gene expression. Therefore, the genetic mechanisms of gene expression and regulation of blood coagulation function will be discussed based on blood transcriptomes, DNA methylomes, and phenotype measurements. We will compare the results between rhesus macaque and human to better understand the changes of blood coagulation function and its genetic mechanisms of gene expression and regulation in primates during aging. In the end, we will test the positive selection on the blood coagulation-related genes that showed differentially expressed in rhesus macaques within all the primates that have complete genome sequences.