蠕蟲是一類重要的寄生蟲,對全世界的公共衛(wèi)生、獸醫(yī)、農(nóng)業(yè)和社會經(jīng)濟部門產(chǎn)生重大影響。迄今為止,用于控制寄生蟲的最重要且廣譜的藥物是伊維菌素(IVM)。但是,在寄生蟲中已經(jīng)出現(xiàn)了對IVM的抵抗力,且保持IVM的功效正成為一個嚴重的問題。從經(jīng)濟上講,寄生線蟲Haemonchus contortus是全球小型反芻動物的重要寄生蟲。許多資料報道該寄生蟲對IVM產(chǎn)生了抗藥性。解決IVM抗性的遺傳基礎(chǔ)受到越來越多的關(guān)注。關(guān)于IVM抗性涉及多基因的證據(jù)越來越多。盡管已經(jīng)提出了使用較低基因組倍數(shù)數(shù)據(jù)來篩選IVM抗藥性候選基因,但IVM抗藥性的遺傳基礎(chǔ)仍然難以解決。在本文中,我們應用種群基因組學方法,來篩選和鑒定捻轉(zhuǎn)血矛線蟲中與IVM抗性相關(guān)的基因,為闡明線蟲抗藥性的分子基礎(chǔ)及其機制提供新的途徑。為了解線蟲地理株系的遺傳變異情況,我們分析了從不同地理區(qū)域(第2章和第3章)中分離出的Haemonchus contortus。首先,我們對來自中國(西藏,TB;湖北,HB;內(nèi)蒙古,IM;四川,SC)、英國(UK)和澳大利亞(AS)等三個全球不同地理區(qū)域的蟲株進行了全基因組的2b-RAD測序,鑒定了所有蟲株中的單...

【文章頁數(shù)】：103 頁

【學位級別】：博士

【文章目錄】：
摘要
Abstract
CHAPTER 1 INTRODUCTION
    1.1 Parasitic infections
    1.2 The helminths
    1.3 Control of helminths
    1.4 Piperazine
    1.5 Benzimidazoles
    1.6 Imidazothiazole,and tetrahydropyrimidines
    1.7 Macrocyclic lactones
    1.8 IVM resistance
    1.9 Haemonchus contortus
    1.10 Problem
    1.11 Solution
CHAPTER 2 ANALYSIS OF THE BACKGROUND GENETIC VARIATION OF VARIOUS POPULATIONS OF HAEMONCHUS CONTORTUS FROM FIELD,LABORATORY,AND RESISTANT STRAINS USING GENOME-WIDE DATA
    2.1 Abstract
    2.2 Introduction
    2.3 Methods
        2.3.1 Collection of worms
        2.3.2 DNA extraction,library construction and pool sequencing
        2.3.3 SNP calling
        2.3.4 Characterization of genetic variability
        2.3.5 Selective sweep analysis
        2.3.6 Statistical analysis
    2.4 Results
        2.4.1 SNP description and characterization
        2.4.2 Nucleotide diversity and population differentiation
        2.4.3 Identification of selective sweeps
        2.4.4 Functional annotation of private selective sweeps
    2.5 Discussion
    2.6 Conclusions
CHAPTER 3 MICROSATELLITE ANALYSIS REVEALS EXTENSIVE GENE FLOW,AND LACK OF POPULATION STRUCTURE IN THE FARM POPULATIONS OF HAEMONCHUS CONTORTUS IN NORTHERN CHINA
    3.1 Abstract
    3.2 Introduction
    3.3 Methods
        3.3.1 Worm collection,identification,and DNA extraction
        3.3.2 Microsatellite genotyping
        3.3.3 Data analysis
    3.4 Results
        3.4.1 Allele frequency analysis
        3.4.2 Genetic diversity and Hardy-Weinberg equilibrium
        3.4.3 Genetic differentiation,population structure and clustering
    3.5 Discussion
    3.6 Conclusions
CHAPTER 4 WHOLE GENOME RE-SEQUENCING REVEALS THE CANDIDATE GENES ASSOCIATED WITH IVERMECTIN RESISTANCE IN HAEMONCHUS CONTORTUS
    4.1 Abstract
    4.2 Introduction
    4.3 Methods
        4.3.1 Background of strains,worm collection and identification
        4.3.2 DNA isolation,library construction,and whole genome re-sequencing
        4.3.3 Mapping reads,and variant calling
        4.3.4 Characterization of genetic variability/and tracing selection
    4.4 Results
        4.4.1 Results of whole genome re-sequencing
        4.4.2 Results of population genomics analyses
    4.5 Discussion
    4.6 Conclusions
CHAPTER 5 FUNCTIONAL VALIDATION OF CANDIDATE GENES ASSOCIATED WITH IVERMECTIN RESISTANCE IN HAEMONCHUS CONTORTUS BY RNAI BASED GENE SILENCING
    5.1 Abstract
    5.2 Introduction
    5.3 Methods
        5.3.1 Egg extraction
        5.3.2 Culturing eggs into larvae
        5.3.3 RNAi based silencing of candidate genes
        5.3.4 Larval feeding inhibition assay(LFIA)
        5.3.5 RNA extraction and q PCR
        5.3.6 Statistical analysis
    5.4 Results
        5.4.1 Results of egg extraction and larvae culture
        5.4.2 Results of si RNA uptake
        5.4.3 Results of RNAi and LFI assays
    5.5 Discussion
    5.6 Conclusions
CONCLUSIONS
REFERENCES
ACKNOWLEDGEMENTS
CURRICULUM VITAE



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