Whole Genome Sequencing Reveals the Role of NVCs in Insecticide Resistance in Malaria-carrying Mosquitoes



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LSTM researchers, along with colleagues from the Wellcome Sanger Institute of Cambridge and the Big Data Institute of Oxford University, used whole-genome sequencing to understand copy number variants (CNVs) in mosquitoes carrying malaria and their role in insecticide resistance.

Many diseases, such as malaria, zika and dengue, are transmitted by mosquitoes, making the fight against mosquito populations a cornerstone of efforts to control these diseases. This is usually achieved through the use of insecticides, traditionally very effective. Dr. Eric Lucas, first author of an article published in the newspaper Genome research, explained: "Malaria cases have been significantly reduced over the last 20 years, mainly due to improved vector control, but these efforts are threatened by the evolution of insecticide resistance. In many species of mosquitoes of medical importance.More understand and treat resistance insecticides, we must understand the genetic mutations that cause it, but only a few mutations have been discovered so far. "

To better understand the evolution of resistance, the LSTM, in collaboration with collaborators from Oxford University and the Wellcome Sanger Institute, is sequencing the genomes of thousands of individuals. of the main malaria mosquito, Anopheles gambiae, native to sub-Saharan Africa. from a project called the Year. Project gambiae 1000 genomes (Ag1000G).

One type of mutation that could lead to increased insecticide resistance is the gain in extra copies of genes that help break down the insecticide in the body of the mosquito. However, little research has been done on these copy number variants (CNVs) in mosquitoes that carry malaria. For this work, the team used the Ag1000G data to look for an increased copy number in An. Gambiae and found that CNV was much more likely to occur in genes that play a role in resistance to cancer. insecticides than in the rest of the genome. "These CNVs badociated with resistance were found in almost all populations in our study," Dr. Lucas continued, "and the copy number of some populations has increased by more than 90%. in the five genetic regions badociated with insecticide detoxification in An. gambiae, we found a total of 44 different CNVs.The repeated origins of increasing copy numbers in the same genes suggest that this type of mutation is relatively common and could provide a means of rapid evolutionary response to insecticide for mosquitoes. "

Professor Martin Donnelly, head of the vector biology department at LSTM, was the lead author of the document. He said:

This research demonstrates the importance of increasing the number of gene copies in the evolution of insecticide resistance and should prompt researchers to understand the exact effect of each of the NVCs and insecticides they are acting against. Once these effects are understood, testing the presence of these mutations and monitoring their spread between populations will help us predict the insecticides that a mosquito population can still be sensitive to. "

Genome-wide sequencing reveals a great complexity of copy number variation in insecticide-resistant loci in mosquitoes carrying malaria

Source:

Liverpool School of Tropical Medicine

Journal reference:

Lucas, E.R. et al. (2019) Whole genome sequencing reveals a great deal of complexity in copy number variation in insecticide-resistant loci in mosquitoes that carry malaria. Genome research. doi.org/10.1101/gr.245795.118.

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