利用微卫星标记对中国恒河猴MHC基因遗传同质性分群的研究

【作者】 闫熙；

【导师】 魏强； 李万波； 张连峰；

【作者基本信息】 中国协和医科大学 ， 动物学， 2009， 硕士

【摘要】 恒河猴是医学生物学研究中重要的非人灵长类模式动物,广泛应用于传染性疾病模型制作、疫苗开发、干细胞研究以及器官移植,尤其在模拟艾滋病感染人体的实验中,是不可代替的猴艾滋病模型。由于恒河猴地理分布广泛,而且驯化程度有限、无法建立近交系,所以在同一个实验分组中参与实验的恒河猴个体往往是遗传背景异质性,但是医学实验中需要参与实验的动物尽量保持遗传背景的同质性从而使实验结果便于分析,这样的客观矛盾导致实验中往往会出现个体差异。相同地理来源的恒河猴往往由于地理隔离,个体差异比较小,而主要组织相容性复合物分子是免疫遗传学中最重要的基因,所以选取相同地域来源和相同主要组织相容性复合物分子基因型的恒河猴实验动物参与实验将有利于缩小个体差异。本文试图根据已知地域性微卫星遗传标记与特定MHC基因高度连锁的微卫星遗传标记,建立一套恒河猴免疫遗传学同质性分类方法。实验结果表明,中国恒河猴的遗传背景复杂,地理来源遗传标记需要进一步完善。特定MHC基因高度连锁的微卫星遗传标记则可以替代连锁的MHC基因,将恒河猴区分为若干个不同的群体。本方法的建立和进一步完善,在对中国恒河猴遗传背景缺乏详细了解的情况下,将为中国恒河猴参与实验分组提供参考,也可以指导恒河猴繁育管理,长远可用于对相对封闭地区中国恒河猴进行遗传调查并逐步建立遗传同质性群体。更多还原

【Abstract】 Macaca mulatta is an important non-human primate model in biomedical research. They are widely used in numbers of infectious diseases, vaccine development, stem cell research, organ transplants and especially as an essential AIDS model in a simulated human body of HIV infection experiments. Due to its wide geographical distribution and domestication of a limited degree, it is very difficult to establish the inbred strains. Researcher made great efforts to maintain the homogeneity of genetic background of experimental results to decrease the results error in medical experiments. However, macaca mulatta participated in the same experiment are almost with heterogeneous genetic background. So, the individual differences results in the actual experimental more complicated.Macaca mulatta with the same geographical origin are close in genetic relationship and relatively small individual differences. The major histocompatibility complex molecular (MHC) genes are the most important immunogenetic genes. So animals with the same geographical origin and the same MHC genotype will be beneficial to reduce individual differences in the experiment.In this paper, we established a macaca mulatta immunogenetic homogeneity classification based on the known regional micro-satellite genetic markers and micro-satellite linked definitude MHC genes. Our results indicated that the genetic background of Chinese macaca mulatta was complicated. So the genetic marker of demographic origin should be further studied. We could replace the linked MHC genes with micro-satellite linked definitude MHC genes to divide the animals into numbers of subgroups.As the lack of detailed understanding about the genetic background of Chinese macaca mulatta, our methods will provide the basic research reference for the macaca mulatta medical experiments and the management for the animals’ propagation. It could be applied in genetic investigation on macaca mulatta from closed region to established the homogeneous genetic background subgroups in the future.更多还原