發(fā)布時間：2018-01-29 21:07

  本文關鍵詞： 鼠疫耶爾森菌 鼠疫自然疫源地 序列分析 編碼序列　出處：《中國疾病預防控制中心》2009年碩士論文　論文類型：學位論文

【摘要】： 鼠疫是由鼠疫耶爾森菌引起的一種危害嚴重的烈性傳染病。鼠疫自然疫源地在世界范圍內(nèi)的分布相當廣泛,在時間跨度上也有1500年的歷史,生化表型上都非單一群體,同時鼠疫菌的染色體又在不斷的發(fā)生基因水平上的改變,是一類進化比較活躍的細菌。目前已有近10株鼠疫菌的全基因組已被測序,為進行相關的研究提供了豐富的資料。 2005年,在云南省玉龍縣鹿子自然村先后發(fā)現(xiàn)高熱、咳嗽、咳痰、痰中帶血、呼吸困難病人5例,初步診斷為“不明原因重癥肺炎”,后確診為“肺鼠疫”。 衛(wèi)生部及云南省衛(wèi)生廳決定由云南省地方病防治所、中國疾控中心傳染病預防控制所等5個專業(yè)技術部門組成聯(lián)合調(diào)查隊對玉龍縣是否存在著鼠疫疫源地進行自然生態(tài)、宿主、媒介、血清學及病原學的系統(tǒng)調(diào)查。重點以玉龍縣黃山鎮(zhèn)鹿子村為中心,向周圍的村莊進行放射性調(diào)查。調(diào)查結(jié)果顯示,該地區(qū)的大絨鼠和齊氏姬鼠是優(yōu)勢鼠種,特新蚤指名亞種、方葉櫛眼蚤為主要媒介,指示動物犬和貓血清中鼠疫F1抗體的陽性率分別達到23.5%和26.4%,并且在自斃鼠和蚤中分離到5株鼠疫菌。根據(jù)此調(diào)查結(jié)果,判定了玉龍縣存在著鼠疫自然疫源地。 我們對此次調(diào)查中分離到的鼠疫菌(D106004)提取了DNA,并選擇來自滇西山地齊氏姬鼠-大絨鼠疫源地(劍川菌株D182038)和青藏高原喜馬拉雅旱獺疫源地(西藏那曲菌株Z176003)的鼠疫菌作為對照菌株,進行了全基因組序列測定和編碼序列(CDS)預測。 通過對D182038,D106004,CO92,KIM,91001,Nepal516,Antiqua,Pestoides F等8株鼠疫菌基因組上CDS的兩兩比較,建立了默認編碼序列(Default)數(shù)據(jù)庫,在此基礎上,對玉龍和劍川鼠疫菌的CDS進行了比較分析。結(jié)果顯示:劍川菌株和玉龍菌株的CDS在總體COG分類的構(gòu)成上無明顯差別,但在結(jié)合其他菌株形成的Default數(shù)據(jù)庫中,可以看到兩株鼠疫菌的CDS在COG簇的構(gòu)成上存在著具體的差別。 同時,我們用鼠疫疫苗EV76的高表達蛋白序列與玉龍、劍川鼠疫菌的基因組進行了比較。云南玉龍菌株D106004和劍川菌株D182038的“高表達基因”比較接近,但玉龍菌株和劍川菌株在部分高表達基因上有著具體的差異。在有差別的56條蛋白序列中,玉龍菌株有24條蛋白序列可能被大量表達,劍川菌株有16條蛋白序列可能被大量表達。這些均提示,玉龍和劍川鼠疫菌在高表達基因上有一定的差異,這些差異可能是玉龍和劍川菌株在進化過程中獨自進化造成的。 通過對玉龍與劍川鼠疫菌CDS和高表達蛋白序列遺傳學特征的比較,發(fā)現(xiàn)它們可能來自于同一個祖先,但是在進化過程中兩者又各自有獨特的特征。玉龍與劍川鼠疫自然疫源地屬于同一種類型,但又相對獨立活動的鼠疫自然疫源地,這種獨立性是由于兩片疫源地在地理上的阻隔形成的。且這種獨立性的存在已經(jīng)相當久遠,因而表現(xiàn)為鼠疫菌株間多位點的差異。
[Abstract]:Yersinia pestis is a severe infectious disease caused by Yersinia pestis. Plague natural foci are widely distributed in the world and have a history of 1500 in the time span. Biochemical phenotype is not a single population, at the same time, Yersinia pestis chromosomes are constantly occurring gene level changes. The whole genome of nearly 10 strains of Yersinia pestis has been sequenced. In 2005, 5 patients with high fever, cough, expectoration, blood in sputum and dyspnea were found in Luzi Natural Village, Yulong County, Yunnan Province. Later diagnosed as "pneumonic plague." The Ministry of Health and the Department of Health of Yunnan Province decided by the Yunnan Provincial endemic Disease Prevention and Control Institute. Five professional and technical departments such as the Institute of Infectious Diseases Prevention and Control of the China Center for Disease Control and Prevention formed a joint investigation team to conduct natural ecology, host and media for the existence of plague foci in Yulong County. The systematic investigation of serology and etiology was carried out, focusing on Luzi Village, Huangshan Town, Yulong County, and radioactivity investigation was carried out to the surrounding villages. The results showed that Apodemus chrysoides and Apodemus chizyzae were the dominant species in this area. The positive rates of Yersinia pestis F1 antibody in the sera of dogs and cats were 23.5% and 26.4% respectively. Five strains of Yersinia pestis were isolated from dead rats and fleas. We extracted DNA from Yersinia pestis D106004 isolated in this investigation. The foci of Apodemus chrysodii (strain D182038) and Himalayan marmot (strain Z176003) were selected from western Yunnan mountainous region. Of Yersinia pestis as a control strain. The whole genome sequencing and coding sequence prediction were carried out. The antiqua of D182038 / D106004 / KIMM 91001 / Nepal516 was studied. Based on the pairwise comparison of CDS on the genome of 8 strains of Yersinia pestis, Pestoides F, a default coding sequence (Default) database was established. The CDS of Yulong and Jianchuan Yersinia pestis were compared and analyzed. The results showed that there was no significant difference in the composition of the total COG classification between the CDS of Jianchuan strain and that of Yulong strain. However, in the Default database combined with other strains, it can be seen that the CDS of the two strains of Yersinia pestis has a specific difference in the composition of COG cluster. At the same time, we used the Yersinia pestis vaccine EV76 high expression protein sequence and Yulong. The genomes of Yersinia pestis in Jianchuan were compared. The "high expression genes" of Yulong strain D106004 and strain D182038 were similar. However, there were specific differences between Yulong strain and Jianchuan strain on some high expression genes. Among the 56 protein sequences, 24 protein sequences of Yulong strain could be expressed in large quantities. The 16 protein sequences of Jianchuan strain may be expressed in a large amount, which suggests that Yulong and Yersinia pestis have some differences in high expression genes. These differences may be caused by the evolution of Yulong and Jianchuan strains alone. By comparing the genetic characteristics of Yulong and Yersinia pestis CDS and high expression protein sequences, it was found that they may have originated from the same ancestor. Yulong and Jianchuan plague natural foci belong to the same type, but relatively independent activities of plague natural foci. This independence is due to the geographical barrier between the two foci, and this independence has existed for a long time, thus showing the difference of multiple loci between the strains of Yersinia pestis (Yersinia pestis).
【學位授予單位】：中國疾病預防控制中心
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R181.3

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本文編號：1474364