Functional Genomics Tools for Haemonchus contortus and Lessons From Other Helminths

Britton, Collette; Roberts, Brett; Nd, Marks

doi:10.1016/bs.apar.2016.02.017

Cited by 45 publications

(32 citation statements)

References 88 publications

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“…Since this first experiment, RNAi has been successfully applied to a number of mammalian-parasitic nematode species, including Ascaris suum, B. malayi, Onchocerca volvulus, the ruminant parasite Haemonchus contortus and the filarial parasite of livestock Setaria digitata (Hagen et al, 2012;Luck et al, 2016;Maule et al, 2011;McCoy et al, 2015;Misra et al, 2017;Samarasinghe et al, 2011;Somarathne et al, 2018;Verma et al, 2017). However, results from RNAi experiments are often variable in terms of both the extent of gene knockdown and the resulting mutant phenotype (Britton et al, 2016;Hagen et al, 2012;Maule et al, 2011;McCoy et al, 2015). Moreover, in some species, RNAi has been attempted without success (Lendner et al, 2008).…”

Section: Rnai In Parasitic Nematodesmentioning

confidence: 99%

Recent advances in functional genomics for parasitic nematodes of mammals

Castelletto

Gang

Hallem

2020

Journal of Experimental Biology

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Human-parasitic nematodes infect over a quarter of the world's population and are a major cause of morbidity in low-resource settings. Currently available treatments have not been sufficient to eliminate infections in endemic areas, and drug resistance is an increasing concern, making new treatment options a priority. The development of new treatments requires an improved understanding of the basic biology of these nematodes. Specifically, a better understanding of parasitic nematode development, reproduction and behavior may yield novel drug targets or new opportunities for intervention such as repellents or traps. Until recently, our ability to study parasitic nematode biology was limited because few tools were available for their genetic manipulation. This is now changing as a result of recent advances in the large-scale sequencing of nematode genomes and the development of new techniques for their genetic manipulation. Notably, skin-penetrating gastrointestinal nematodes in the genus Strongyloides are now amenable to transgenesis, RNAi and CRISPR/Cas9-mediated targeted mutagenesis, positioning the Strongyloides species as model parasitic nematode systems. A number of other mammalian-parasitic nematodes, including the giant roundworm Ascaris suum and the tissue-dwelling filarial nematode Brugia malayi, are also now amenable to transgenesis and/or RNAi in some contexts. Using these tools, recent studies of Strongyloides species have already provided insight into the molecular pathways that control the developmental decision to form infective larvae and that drive the host-seeking behaviors of infective larvae. Ultimately, a mechanistic understanding of these processes could lead to the development of new avenues for nematode control.

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Section: Rnai In Parasitic Nematodesmentioning

confidence: 99%

Recent advances in functional genomics for parasitic nematodes of mammals

Castelletto

Gang

Hallem

2020

Journal of Experimental Biology

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“…A number of CRISPR/Cas9 genome editing protocols have been established in C. elegans (Friedland et al, 2013) opening new doors to studying the biology of closely related nematode parasites. Translation of CRISPR/Cas9 technology from C. elegans to Strongyloides spp ., Ascaris suum, Brugia malayi and Haemonchus contortus have been recently outlined (Ward, 2015; Britton et al, 2016; Zamanian and Andersen, 2016). Recent reports on topical application of dsRNA for resistance against viruses using layered double hydroxide clay nanosheets (Mitter et al, 2017) opens up possibilities to exploit such innovations for specific and combinatorial resistance against PPNs, insects and plant pathogenic fungi.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

RNA Interference: A Novel Source of Resistance to Combat Plant Parasitic Nematodes

Banerjee

Gill

et al. 2017

Front. Plant Sci.

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Plant parasitic nematodes cause severe damage and yield loss in major crops all over the world. Available control strategies include use of insecticides/nematicides but these have proved detrimental to the environment, while other strategies like crop rotation and resistant cultivars have serious limitations. This scenario provides an opportunity for the utilization of technological advances like RNA interference (RNAi) to engineer resistance against these devastating parasites. First demonstrated in the model free living nematode, Caenorhabtidis elegans; the phenomenon of RNAi has been successfully used to suppress essential genes of plant parasitic nematodes involved in parasitism, nematode development and mRNA metabolism. Synthetic neurotransmitants mixed with dsRNA solutions are used for in vitro RNAi in plant parasitic nematodes with significant success. However, host delivered in planta RNAi has proved to be a pioneering phenomenon to deliver dsRNAs to feeding nematodes and silence the target genes to achieve resistance. Highly enriched genomic databases are exploited to limit off target effects and ensure sequence specific silencing. Technological advances like gene stacking and use of nematode inducible and tissue specific promoters can further enhance the utility of RNAi based transgenics against plant parasitic nematodes.

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“…Partly for these reasons, H. contortus has emerged as a model parasitic nematode to characterise anthelmintic resistance, as well as drug and vaccine discovery research as alternate means of control [15][16][17] . Its utility as a model is largely due to a greater amenability to experimentation than most parasitic nematodes; it is possible to establish and maintain isolates in vivo in the natural host, perform genetic crosses in vivo , and undertake in vitro culture for part of its life cycle, allowing drug assays and genetic manipulation such as RNAi to be performed [18] . The ability to utilise these molecular approaches is complemented by extensive information about the structure of the genome and transcriptional differences between the major life stages [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus

Doyle

Illingworth

Laing

et al. 2018

Preprint

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Infections with helminths cause an enormous disease burden in humans, livestock, and companion animals. Helminth control is heavily dependent on anthelmintic drugs, but resistance to these drugs is widespread, and the genetic determinants of resistance remain unresolved. Here, we build on two previous genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus , an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. By combining genetic mapping and genome resequencing with population genetic modelling, we identify the first single genomic locus conclusively associated with ivermectin resistance in a parasitic nematode. This locus is common between two geographically and genetically divergent strains and does not include the leading candidate genes. This work is the first example of a major anthelmintic resistance locus to be identified by genetic mapping and represents the most comprehensive genetic analysis of this trait in a parasitic helminth to date.

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Functional Genomics Tools for Haemonchus contortus and Lessons From Other Helminths

Cited by 45 publications

References 88 publications

Recent advances in functional genomics for parasitic nematodes of mammals

Recent advances in functional genomics for parasitic nematodes of mammals

RNA Interference: A Novel Source of Resistance to Combat Plant Parasitic Nematodes

Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus

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