Genetic Diversity and Population Structure of Haemonchus contortus

Gilleard, John S.; Redman, Elizabeth

doi:10.1016/bs.apar.2016.02.009

Cited by 80 publications

(60 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, the MPL-R isolate remains viable in the presence of many mutations to the monepantel receptor gene, indicating that the Hco- MPTL-1 protein is most likely not essential for the worm. Given that H. contortus is known to be highly polymorphic (reviewed in Gilleard and Redman, 2016), it is perhaps not unexpected that many mutations will exist in a gene that codes for a non-essential protein as the mutations will have very little or no negative impact on the fitness of the worm. Hence, these mutations which confer drug resistance through the loss of a functional receptor will be rapidly selected for by drug exposure.…”

Section: Resultsmentioning

confidence: 99%

Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus

Bagnall

Ruffell

Raza

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

Resistance to the anthelmintic drug monepantel (Zolvix®) has emerged in parasitic worms infecting sheep and goats. The mechanism of resistance in these cases is unknown. The drug targets nicotinic acetylcholine receptors belonging to the nematode-specific DEG-3 subfamily. We examined the receptor gene, Hco-mptl-1, in a highly Zolvix®-resistant and a -susceptible isolate of the parasitic nematode Haemonchus contortus. cDNA coding for the full length receptor protein (Hco-MPTL-1) was present in all clones prepared from a pool of susceptible larvae (21/21 clones) and approximately 50% of those from the resistant isolate (17/33). On the other hand, the remaining clones from the resistant isolate showed various mutations that resulted in truncated predicted proteins, missing at least one transmembrane domain. The most common mutation (11/33 clones) resulted in the retention of intron 15, a premature stop codon, and a truncated protein. Sequencing of intron 15 genomic DNA showed very few SNPs in susceptible larvae and in 12/18 clones from resistant larvae, alongside the presence of at least 17 SNPs in the remaining resistant clones. The present study shows that the highly resistant isolate has a number of mutations in the drug target gene that would most-likely result in a non-functional receptor, thus rendering the larvae insensitive to the drug. The presence of many wild-type sequences in this highly-resistant population suggests that there was a significant presence of heterozygotes in the survivors of the field drench treatment from which the isolate was derived, and hence that at least some of the mutations may be dominant. Alternatively, their presence may be due to the additional influence of mutations at another locus contributing to the resistance phenotype. The presence of multiple separate mutations in the Hco-mptl-1 gene in this viable field-derived worm isolate may at least partly explain why resistance to Zolvix® has arisen rapidly in the field.

show abstract

Section: Resultsmentioning

confidence: 99%

Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus

Bagnall

Ruffell

Raza

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

show abstract

“…In this example, two differential splicing events are observed; (i) alternate splice donors of exon 8, and (ii) exon skipping of exon 9.Distribution of global genetic diversity throughout the chromosomesH. contortus is a globally distributed parasite, characterised by large population sizes and in turn, high genetic diversity[25][26][27]49] . We have characterised the distribution of genetic diversity throughout the V4 chromosomes by exploiting a recent large scale analysis of global genetic diversity[25] that we have extended by sequencing an additional 74 individual worms from previously unsampled regions including Pakistan, Switzerland, USA, and the United Kingdom ( Figure 6 A ; https://microreact.org/project/hcontortus_global_diversity ).…”

mentioning

confidence: 99%

Extensive genomic and transcriptomic variation defines the chromosome-scale assembly ofHaemonchus contortus, a model gastrointestinal worm

Doyle

Tracey

Laing

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants, and has become the key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Two draft genome assemblies for H. contortus were reported in 2013, however, both were highly fragmented, incomplete, and differed from one another in important respects. While the introduction of long-read sequencing has significantly increased the rate of production and contiguity of de novo genome assemblies broadly, achieving high quality genome assemblies for small, genetically diverse, outcrossing eukaryotic organisms such as H. contortus remains a significant challenge. ResultsHere, we report using PacBio long read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome. We show a remarkable pattern of almost complete conservation of chromosome content (synteny) with Caenorhabditis elegans , but almost no conservation of gene order. Long-read transcriptome sequence data has allowed us to define coordinated transcriptional regulation throughout the life cycle of the parasite, and refine our understanding of cisand trans -splicing relative to that observed in C. elegans .Finally, we use this assembly to give a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. ConclusionsThe H. contortus MHco3(ISE).N1 genome assembly presented here represents the most contiguous and resolved nematode assembly outside of the Caenorhabditis genus to date, together with one of the highest-quality set of predicted gene features. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes, and extends the experimental tractability of this model parasitic nematode in understanding pathogen biology, drug discovery and vaccine development, and important adaptive traits such as drug resistance.

show abstract

“…Our estimates indicate a high female fertility of 1295.9 ± 280.4 eggs/female/day on average, which outperforms other trichostrongylids [82]. It is usually postulated that this high female fertility will result in a huge population size showing a high degree of genetic variability [83]. However, our estimates also suggest that larval establishment constitutes a strong bottleneck as only a quarter of the ingested larvae will have an opportunity to mate and pass on their genetic material to subsequent generations.…”

Section: Discussionmentioning

confidence: 85%

Meta-analysis of the parasitic phase traits of Haemonchus contortus infection in sheep

et al. 2017

View full text Add to dashboard Cite

BackgroundThe parasitic nematode Haemonchus contortus shows highly variable life history traits. This highlights the need to have an average estimate and a quantification of the variation around it to calibrate epidemiological models.MethodsThis paper aimed to quantify the main life history traits of H. contortus and to identify explanatory factors affecting these traits using a powerful method based on a systematic review and meta-analysis of current literature. The life history traits considered are: (i) the establishment rate of ingested larvae; (ii) the adult mortality rate; (iii) the fertility (i.e. the number of eggs laid/female/day); and (iv) fecundity of female worms (i.e. the number of eggs per gram of faeces).ResultsA total of 37 papers that report single experimental infection with H. contortus in sheep and published from 1960 to 2015, were reviewed and collated in this meta-analysis. This encompassed 115 experiments on 982 animals. Each trait was analysed using a linear model weighted by its inverse variance. The average (± SE) larval establishment rate was 0.24 ± 0.02, which decreased as a function of the infection dose and host age. An average adult mortality rate of 0.021 ± 0.002) was estimated from the literature. This trait varied as a function of animal age, breed and protective response due to prior exposure to the parasite. Average female fertility was 1295.9 ± 280.4 eggs/female/day and decreased in resistant breeds and previously infected hosts. Average faecal egg count at necropsy was 908.5 ± 487.1 eggs per gram of faeces and varied as a function of infection duration and host resistance. The average sex ratio of H. contortus was 0.51 ± 0.006.ConclusionThis work is the first systematic review to summarise the available information on the parasitic phase of H. contortus in sheep. The results of the meta-analysis provide robust estimates of life history traits for parametrization of epidemiological models, their expected variation according to experimental factors, and provides correlations between these.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2131-7) contains supplementary material, which is available to authorized users.

show abstract

Genetic Diversity and Population Structure of Haemonchus contortus

Cited by 80 publications

References 96 publications

Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus

Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus

Extensive genomic and transcriptomic variation defines the chromosome-scale assembly ofHaemonchus contortus, a model gastrointestinal worm

Meta-analysis of the parasitic phase traits of Haemonchus contortus infection in sheep

Contact Info

Product

Resources

About