Gilleard J S, Beech R N
Division of Infection and Immunity, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow, UK G61 1QH.
Parasitology. 2007;134(Pt 8):1133-47. doi: 10.1017/S0031182007000066.
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.
抗蠕虫药耐药性研究的一个关键目标是识别能够作为灵敏且准确诊断测试基础的分子标记。这些标记将为研究抗蠕虫药耐药性在野外的起源和传播以及监测旨在预防和管理耐药性的策略提供有力工具。分子标记还可作为用于监测和临床兽医实践的常规诊断测试的基础。迄今为止进行的许多研究都集中在调查特定候选基因与耐药表型之间可能存在的关联。未来，随着完整的寄生虫基因组序列可用，将有机会应用全基因组方法来识别抗蠕虫药耐药性的潜在遗传位点。对候选基因研究的解读以及全基因组方法的应用都需要深入了解相关寄生虫的遗传学和群体生物学，以及耐药突变如何在群体中产生和被选择的知识。不幸的是，寄生线虫在这方面的许多信息都很匮乏。本综述探讨了与这些问题相关的遗传学和群体生物学的多个方面。我们讨论了耐药突变的可能起源以及后续选择对赋予耐药性位点的遗传变异可能产生的影响。我们还回顾了一些用于测试候选基因与抗蠕虫药耐药表型之间关联的实验方法，并强调了对未来全基因组研究的启示。
