Overexpression and nonsynonymous mutations of UDP-glycosyltransferases are potentially associated with pyrethroid resistance in Anopheles funestus

Al-Yazeedi, Talal, Muhammad, Abdullahi, Irving, Helen, Ahn, Seung-Joon, Hearn, Jack and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2024) 'Overexpression and nonsynonymous mutations of UDP-glycosyltransferases are potentially associated with pyrethroid resistance in Anopheles funestus'. Genomics, Vol 116, Issue 2, e110798.

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Abstract

UDP-glycosyltransferases (UGTs) enzymes are pivotal in insecticide resistance by transforming hydrophobic substrates into more hydrophilic forms for efficient cell elimination. This study provides the first comprehensive investigation of Anopheles funestus UGT genes, their evolution, and their association with pyrethroid resistance. We employed a genome-wide association study using pooled sequencing (GWAS-PoolSeq) and transcriptomics on pyrethroid-resistant An. funestus, along with deep-targeted sequencing of UGTs in 80 mosquitoes Africa-wide. UGT310B2 was consistently overexpressed Africa-wide and significant gene-wise F differentiation was observed between resistant and susceptible populations: UGT301C2 and UGT302A3 in Malawi, and UGT306C2 in Uganda. Additionally, nonsynonymous mutations in UGT genes were identified. Gene-wise Tajima's D density curves provide insights into population structures within populations across these countries, supporting previous observations. These findings have important implications for current An. funestus control strategies facilitating the prediction of cross-resistance to other UGT-metabolised polar insecticides, thereby guiding more effective and targeted insecticide resistance management efforts.

Item Type:	Article
Subjects:	QU Biochemistry > Enzymes > QU 135 Enzymes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.ygeno.2024.110798
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	08 Feb 2024 11:49
Last Modified:	08 Feb 2024 11:49
URI:	https://archive.lstmed.ac.uk/id/eprint/23984

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