Population genetics of anthelmintic resistance in parasitic nematodes

Population genetics of anthelmintic resistance in parasitic nematodes
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DOI:
10.1017/s0031182007000066
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发表时间:
2007-01-01
期刊:
影响因子:
2.4
通讯作者:
Beech, R. N.
Beech, R. N.
中科院分区:
医学2区
文献类型:
--
作者:
Gilleard, J. S.;Beech, R. N.

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抗蠕虫药耐药性研究的一个关键目标是确定分子标记,这些标记可以形成敏感和准确的诊断测试的基础。这些将提供强有力的工具来研究驱虫药耐药性的起源和传播,并监测旨在预防和管理耐药性的战略。分子标记物还可以构成用于监测和临床兽医实践的常规诊断测试的基础。迄今为止进行的大部分研究都集中在调查特定候选基因与抗性表型的可能关联。将来,随着寄生虫全基因组序列的获得,将有机会应用全基因组方法来确定驱虫药抗性的遗传位点。候选基因研究的解释和全基因组方法的应用都需要很好地理解相关寄生虫的遗传学和种群生物学,以及抗性突变如何在种群中产生和选择的知识。不幸的是,这方面的信息很多是缺乏寄生线虫。这篇评论涉及遗传学和种群生物学的一些方面,是有关这些问题。我们讨论了抗性突变的可能起源和随后的选择对抗性基因座遗传变异的可能影响。我们还回顾了一些已被用来测试候选基因和驱虫药抗性表型之间的关联的实验方法,并强调对未来全基因组研究的影响。
A key aim of anthelmintic resistance research is to identify molecular markers that could form the basis of sensitive and accurate diagnostic tests. These would provide powerful tools to study the origin and spread of anthelmintic resistance in the field and to monitor strategies aimed at preventing and managing resistance. Molecular markers could also form the basis of routine diagnostic tests for use in surveillance and clinical veterinary practice. Much of the research conducted to date has focused on the investigation of possible associations of particular candidate genes with the resistance phenotype. In the future, as full parasite genome sequences become available, there will be an opportunity to apply genome-wide approaches to identify the genetic loci that underlie anthelmintic resistance. Both the interpretation of candidate gene studies and the application of genome-wide approaches require a good understanding of the genetics and population biology of the relevant parasites as well as knowledge of how resistance mutations arise and are selected in populations. Unfortunately, much of this information is lacking for parasitic nematodes. This review deals with a number of aspects of genetics and population biology that are pertinent to these issues. We discuss the possible origins of resistance mutations and the likely effects of subsequent selection on the genetic variation at the resistance-conferring locus. We also review some of the experimental approaches that have been used to test associations between candidate genes and anthelmintic resistance phenotypes and highlight implications for future genome-wide studies.