G-protein-coupled receptor genes of Dirofilaria immitis
| Autor: | Thangadurai Mani, Catherine Bourguinat, Roger K. Prichard |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dirofilaria immitis Single-nucleotide polymorphism Biology Genome Polymorphism Single Nucleotide G Protein-Coupled Receptor Gene Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine medicine Animals Molecular Biology Gene G protein-coupled receptor Genetics Whole genome sequencing Genome Helminth Helminth Proteins biology.organism_classification 3. Good health 030104 developmental biology Multigene Family Parasitology Emodepside 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Molecular and biochemical parasitology. 222 |
| ISSN: | 1872-9428 |
| Popis: | The diversity and uniqueness of nematode heterotrimeric G-protein-coupled receptors (GPCRs) provides impetus for identifying ligands that can be used as therapeutics for treating diseases caused by parasitic nematode infections. In human medicine, GPCRs have represented the largest group of 'drugable' targets exploited in the market today. In the filarial nematode Dirofilaria immitis, which causes heartworm disease, the macrocyclic lactones (ML) have been used as the sole preventatives for more than 25 years and now there is confirmed ML resistance in this parasite. A novel anthelmintic emodepside, with antifilarial activity, can act on a GPCR. In view of the ML resistance, there is an urgent need to identify new drug targets and GPCRs of D. immitis may be promising receptors. Knowledge of polymorphism within the GPCR superfamily is of interest. A total of 127 GPCR genes have been identified, so far, in the genome of D. immitis. Whole genome sequencing data from four ML susceptible and four ML loss of efficacy populations was used to identify 393 polymorphic loci in 35 D. immitis GPCR genes. Out of 57 SNPs in exonic regions, 36 of them caused a change in an amino acid, out of which 2 changed the predicted secondary structure of the protein. Knowledge about GPCR genes and their polymorphism is valuable information for drug design processes. Further studies need to be carried out to more fully understand the implications of each of the SNPs identified by this study. |
| Databáze: | OpenAIRE |
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