Extreme-QTL mapping of monepantel resistance in Haemonchus contortus

Autor(es)

Meo Niciura, Simone Cristina ^[1] ; Tizioto, Polyana Cristine ^[2] ; Moraes, Caroline Valerio ^[3] ; Cruvinel, Giovanna Gabrielle ^[4] ; Alexandre de Albuquerque, Ana Claudia ^[5] ; Mascarenhas Santana, Raul Costa ^[1] ; de Souza Chagas, Ana Carolina ^[1] ; Esteves, Sergio Novita ^[1] ; Benavides, Magda Vieira ^[6] ; Talamini do Amarante, Alessandro Francisco ^[7]

Afiliação do(s) autor(es)

^[1] EMBRAPA Pecuaria Sudeste, Rodovia Washington Luiz, Km 234, BR-13560970 Sao Carlos, SP - Brazil

^[2] NGS Solucaes Genom, Rua Ajudante Albano 847, BR-13416030 Piracicaba, SP - Brazil

^[3] Univ Fed Sao Carlos, Rodovia Washington Luiz, Km 235, BR-13566905 Sao Carlos, SP - Brazil

^[4] Ctr Univ Cent Paulista, Rua Miguel Petroni 5111, BR-13563470 Sao Carlos, SP - Brazil

^[5] Univ Estadual Paulista UNESP, Fac Med Vet & Zootecnia, Rua Prof Doutor Walter Mauricio Correa S-N, BR-18618681 Botucatu, SP - Brazil

^[6] Embrapa Pecuaria, Rodovia BR 153, Km 632, 9 Vila Ind, BR-96401970 Bage, RS - Brazil

^[7] Univ Estadual Paulista UNESP, Inst Biociencias Botucatu, Rua Prof Dr Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PARASITES & VECTORS; v. 12, n. 1 AUG 14 2019.
• Citações Web of Science: 0

Resumo

Background Haemonchus contortus, a gastrointestinal nematode parasite of sheep, is mainly controlled by anthelmintics; the occurrence of anthelmintic resistance leads to treatment failures and increases economic burden. Because molecular mechanisms involved in drug resistance can be elucidated by genomic studies, an extreme quantitative trait locus (X-QTL) mapping approach was used to identify co-segregation of the resistance phenotype with genetic markers to detect the genome-wide variants associated with monepantel resistance in H. contortus. Methods A cross between H. contortus isolates using parental susceptible (Par-S) males and monepantel resistant (Par-R) females resulted in SR progeny, while reciprocal cross resulted in RS progeny. Pools (n = 30,000) of infective larvae (L3) recovered from Par-R, and from SR and RS populations in the F3 generation, collected both before (unselected group) and 7 days after (selected group) selection with monepantel treatment in sheep hosts, were subjected to genome sequencing (Pool-Seq). Pairwise comparisons of allele frequencies between unselected and selected groups were performed for each population by Fisher's exact test (FET) and for both populations combined by a Cochran-Mantel-Haenszel (CMH) test. Results Mapping rates varied from 80.29 to 81.77% at a 90.4X mean coverage of aligned reads. After correction for multiple testing, significant (P < 0.05) changes in allele frequencies were detected by FET for 6 and 57 single nucleotide polymorphisms (SNPs) in the SR and RS populations, respectively, and by the CMH test for 124 SNPs in both populations. The significant variants located on chromosome 2 generated a selection signal in a genomic region harboring the mptl-1, deg-3 and des-2 genes, previously reported as candidates for monepantel resistance. In addition, three new variants were identified in the mptl-1 gene. Conclusions This study expands knowledge on genome-wide molecular events underlying H. contortus resistance to monepantel. The identification of a genome region harboring major genes previously associated with monepantel resistance supports the results of the employed X-QTL approach. In addition, a deletion in exon 11 of the mptl-1 gene should be further investigated as the putative causal mutation leading to monepantel resistance. (AU)

• Processo FAPESP: 14/25821-0 - Genômica da resistência anti-helmíntica em Haemonchus contortus e investigação de metilação do DNA
• Beneficiário: Simone Cristina Méo Niciura
• Modalidade de apoio: Auxílio à Pesquisa - Regular