鼠疫耶尔森氏菌与假结核耶尔森氏菌比较基因组学研究

发布时间：2018-06-09 21:19

本文选题：鼠疫耶尔森氏菌 + 假结核耶尔森氏菌　；参考：《中国人民解放军军事医学科学院》2005年博士论文

【摘要】：鼠疫是由鼠疫菌引起的烈性传染病,同时鼠疫菌也是一种生物战剂。鼠疫的流行曾给人类带来巨大的灾难。目前,鼠疫虽得到有效控制,但世界卫生组织已将鼠疫列为重新抬头的传染病,并且鼠疫菌生物剂用于生物战和生物恐怖的可能性依然存在。因此,对鼠疫菌进行深入研究具有重要意义。耶尔森氏菌属包括11个耶尔森氏菌种,其中鼠疫菌、假结核菌和小肠结肠炎耶尔森氏菌对人致病,其它种对人不致病。鼠疫菌与假结核菌非常近缘,它可能是在1,500-20,000年前由假结核菌株0∶1b进化而来。然而,鼠疫菌引起令人恐怖的鼠疫,而假结核菌仅引起肠道疾病。鼠疫菌比假结核菌多两个毒力质粒,这在一定程度上能解释它与假结核菌之间传播方式的不同。然而,两个毒力质粒的存在不足以解释鼠疫菌的特殊毒力。比较基因组学的方法有望阐明二者之间不同表型的分子机制。目前细菌比较基因组学的方法主要包括全基因组序列测定、全基因组芯片和抑制消减杂交等技术。利用全基因组序列进行比较基因组学研究无疑是最佳选择,但是,测定全基因组序列需要投入大量的人力和物力。细菌的不同生物型和不同分离株基因组之间存在着一定的差异。为比较它们之间的差异,不可能对每一株菌都进行全基因组序列测定,只能选择一些具有代表性的菌株进行。测定,因此这个方法显然不现实。目前已有三株鼠疫菌和一株假结核菌的全基因组序列测定完成,这为我们比较二者之间的差别提供了丰富的信息。另一个比较理想的比较细菌基因组的方法就是全基因组芯片。全基因组芯片要求包括基因组内所有编码序列,这样的工作量和花费的才力也是相当巨大的。抑制消减杂交技术是近几年发展起来的一种比较基因组的方法。它通过对两组基因组DNA进行比较筛选出差异序列,有效抑制相同序列的检出,主要检出差异序列,而且花费的人力和物力相对较低。因此,本研究主要目的是通过抑制削减杂交技术,筛选出假结核菌相对于鼠疫菌的差异序列,制备差异片段DNA芯片,用制备的芯片筛选多株鼠疫菌和假结核菌,希望找到二者之间具有代表性的差异片段,为正确认
[Abstract]:Yersinia pestis is a severe infectious disease caused by Yersinia pestis, and Yersinia pestis is also a biological warfare agent. The plague once brought great disaster to mankind. At present, although plague is under effective control, the World Health Organization has listed plague as a newly rising infectious disease, and the possibility of using biological agents of Yersinia pestis in biological warfare and bioterror still exists. Therefore, it is of great significance to study Yersinia. Yersinia includes 11 Yersinia strains, including Yersinia pestis, pseudotuberculum and Yersinia enterocolitica. Yersinia pestis is closely related to pseudotuberculum, which probably evolved from Pseudotuberculosis strain 0: 1b between 1500 and 20, 000 years ago. Yersinia pestis, however, cause horrific plague, while pseudotuberculosis causes only intestinal disease. Yersinia pestis has two more virulent plasmids than pseudotuberculous bacillus, which can explain the different transmission modes between Yersinia pestis and pseudotuberculosis to some extent. However, the existence of two virulent plasmids is not sufficient to explain the specific virulence of Yersinia pestis. Comparative genomics is expected to clarify the molecular mechanisms of different phenotypes between them. At present, the methods of bacterial comparative genomics mainly include whole genome sequencing, whole genome chip and suppression subtractive hybridization. It is undoubtedly the best choice to use the whole genome sequence for comparative genomics research, but it takes a lot of manpower and material resources to determine the whole genome sequence. There are some differences between the genomes of different biotypes and isolates of bacteria. In order to compare the differences between them, it is impossible to sequence the whole genome of each strain, only some representative strains can be selected. Determination, therefore, this method is obviously unrealistic. Three strains of Yersinia pestis and one strain of pseudotuberculosis have been sequenced, which provides abundant information for comparing the differences between the two strains. Another ideal way to compare bacterial genomes is the whole genome chip. The entire genome chip requires all the coding sequences in the genome, and the workload and talent involved are enormous. Suppression subtractive hybridization is a relatively genomic method developed in recent years. By comparing the two groups of genomic DNA, it can effectively inhibit the detection of the same sequence, mainly detect the differential sequence, and spend relatively low manpower and material resources. Therefore, the main purpose of this study was to screen out the differential sequences of pseudotuberculous bacteria relative to Yersinia pestis by suppression and reduction hybridization, and to prepare the DNA microarray of differential fragments, and to screen several strains of Yersinia pestis and pseudotuberculous bacilli by using the microarray. Hope to find the representative difference between the two pieces, for the correct recognition
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R378

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