基因定位方法的创新与DNA自动机硬件的研究
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摘要
基因分型,统计分析和基因功能研究是现代遗传学研究中的三个核心组成部分。这三个部分顺序衔接,成为揭开遗传疾病致病机制的重要手段。本文对这三个部分的研究方法做出细致的分析并针对存在的问题提出改进方法。首先,应用纳米金粒子对基于等位基因特异性PCR方法的SNP基因分型作出改进,增强了等位基因特异性PCR方法的基因分型能力。由于纳米金的成本很低,且不需要对原有的实验方法作出大的改动,所以这种方法有望发展成为高性价比的基因分型方法。其次,基于Haseman-Elston模型对受累同胞对法作出改进,使其可以应用到顺序性状的研究中。数据模拟的结果表明新的方法更加适合小样本,及存在较强连锁关系的标记位点的情况。最后,在实验结果的基础上探讨了DNA自动机硬件对连接酶的依赖性。而DNA自动机已经可以根据一定的逻辑在体外调控基因的表达,为基因功能的研究提供了一种新的方法。从实验结果可以看出,FokI是本文涉及的几种限制性内切酶中最适合的无连接酶DNA自动机的硬件,而其他几种酶则各具特色。这项研究给向无酶DNA自动机的跨越提供了有力支持。
Genotyping, statistical analysis and gene function research are the three key parts of modern genetics. This three parts linking in turn becomes an important method for discovering the mechanism of genetic dieases. In this thesis, the research methods in these three parts were analyzed and improvement was presented to solve the existing problems. At first, a novel AuNP assisted allele specific PCR was presented to enhance the genotyping ability of ASPCR. Because AuNP is cheap and the original protocol is changed little, this method is hopeful to become a new cost-efficient genotyping method. At second, the sib-pair linkage analysis method is improved based on the Haseman-Elston model to be applied to ordinal trait loci mapping. The data simulation results showed that the new linkage analysis method is optimal for small sample with strong linkage. At last, the ligase dependency of type II restriction enzymes when performing DNA automaton computing was investigated based on the experiment result. Moreover, DNA automaton could also be used to regulate gene expression in vitro logically. This provided a novel method for gene function analysis. From the result, we can see that FokI is the most suitable DNA automaton hardware, but other enzymes have their advantages. This investigation supported the development to enzyme-free DNA automaton.
Genotyping, statistical analysis and gene function research are the three key parts of modern genetics. This three parts linking in turn becomes an important method for discovering the mechanism of genetic dieases. In this thesis, the research methods in these three parts were analyzed and improvement was presented to solve the existing problems. At first, a novel AuNP assisted allele specific PCR was presented to enhance the genotyping ability of ASPCR. Because AuNP is cheap and the original protocol is changed little, this method is hopeful to become a new cost-efficient genotyping method. At second, the sib-pair linkage analysis method is improved based on the Haseman-Elston model to be applied to ordinal trait loci mapping. The data simulation results showed that the new linkage analysis method is optimal for small sample with strong linkage. At last, the ligase dependency of type II restriction enzymes when performing DNA automaton computing was investigated based on the experiment result. Moreover, DNA automaton could also be used to regulate gene expression in vitro logically. This provided a novel method for gene function analysis. From the result, we can see that FokI is the most suitable DNA automaton hardware, but other enzymes have their advantages. This investigation supported the development to enzyme-free DNA automaton.
引文
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[9] NEWTON-CHEH C, HIRSCHHORN J N. Genetic association studies of complex traits: Design and analysis issues [J]. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2005, 573(1-2): 54-69.
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