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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/17883

Title: 日本大垣市1992~2003年A型肝炎病毒結構基因的遺傳變異
Genetic Variability of the Structural (Capsid-related) Gene of Hepatitis A Virus during the Years 1992-2003 in Ogaki, Japan
Authors: Bai-Cheng Hsiao
蕭百成
Contributors: NTOU:Institute of Bioscience and Biotechnology
國立臺灣海洋大學:生物科技研究所
Keywords: A型肝炎病毒;殼蛋白;基因型;演化
hepatitis A virus;capsid;genotype;evolution
Date: 2010
Issue Date: 2011-07-04
Abstract: A型肝炎 (以下簡稱為HAV) 被發現至今已經快40年了,對於HAV所引發的臨床症狀、病毒學、流行病學、乃至演化學都有基礎的了解。目前對HAV基因型判別是以形成蛋白殼蛋白的結構基因中的VP1片段序列為基準,可將HAV分成6種基因型。過去有關HAV的基因變異研究多只侷限於VP1序列,然而有鑒於HAV在VP1上已有基因重組的例子被發現,因此這樣的基因型判別方式可能會存在錯誤。   本研究檢體採自日本大垣市立醫院1992到2003年之間的HAV,共分析了40個病毒株之完整結構基因,並利用鄰聚法以及最大概似法針對完整結構基因和其中的VP1、VP3、VP2,4片段分別來建構親緣關係樹。結果獲得一致的親緣關係樹拓墣學,而且皆可將參考株分成已知的基因群。本研究之樣本皆屬於IA型,而分別利用不同基因片段去分群和完整結構基因之分群結果並無顯著差異,然而以VP2,4的分群更接近完整結構基因之分群,這顯示VP2,4可能比較適合用於基因型鑑別。而從親緣演化樹中我們從過去文獻發表的序列歸納出一群顯著的次群,比對此群序列其相似性在97%以上,顯示可能為新基因亞型IC。 利用貝氏分析法推估得到完整結構基因之演化速率約為4.03x10-4 substitutions/site/year,而其中不同基因片段亦存在著演化速率上之差異,比對dN/dS速率後推論,VP1、VP3可能是構成蛋白殼較重要的基因片段,而相對的VP2,4比較能容許有較大的遺傳變異。依照演化速率推算出來的時間表顯示,大垣市的HAV的共同祖先大致是在1930年代左右分成兩個主要次群,之後再分成不同幾個小群。而經由SplitsTree的分析顯示,這些病毒之間極有可能存在著廣泛的基因重組現象。
  Hepatitis A virus (HAV) was identified about four decades ago. The clinical symptom, molecular virology, genetic diversity, and evolution of HAV have been studied extensively. HAV was classified into 6 genotpyes based on the VP1 region of its structural gene that coding for the capsid protein. So far, most publications concerning about the genetic diversity of HAV were focused on the VP1 region. However, gene recombination in VP1 region had been reported, raising the question for the reliability of HAV genotyping using VP1 solely.   Forty HAV isolates used in this study were collected form Ogaki, Japan during 1992~2003. The complete structural genes were amplified and sequenced then used for phylogenetic analysis. The results showed that all of the samples were classified as HAV type IA. The analysis based on the full-length of capsid gene gave better results than with shorter fragments. In addition, genotyping with VP2,4 was better than that of VP1. A novel group observed in phylogenetic trees reconstructed by different methods suggesting a putative genotype IC. Bayesian MCMC analysis of the complete structural genes showed an evolutionary rate of 4.03x10-4 nucleotide substitutions/site/year. By comparing the evolution rates and dN/dS ratio between different region of the capsid gene, VP1 and VP3 might be more important for the protein in contrast to the VP2,4 which might be more tolerant to sequence diversity. Furthermore, Bayesian Skyline Plot suggested that the ancestral HAV circulating in Ogaki evolved into 2 groups in 1930s and then continued to spread into other subgroups. SplitsTree analysis revealed that those viruses might have extensive gene recombination.
URI: http://ethesys.lib.ntou.edu.tw/cdrfb3/record/#G0M96360037
http://ntour.ntou.edu.tw/ir/handle/987654321/17883
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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