title: Functional investigation of a QTL affecting resistance to Haemonchus contortus in sheep.
abstract: This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 associated with resistance to the abomasal nematode Haemonchus contortus. The first objective was to validate the identified QTL through the comparison of genetically susceptible (N) and resistant (R) sheep produced from Martinik × Romane back-cross sheep. The R and N genotype groups were then experimentally infected with 10 000 H. contortus larvae and measured for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences in FEC and haematocrit drop were found between R and N sheep. In addition, the female worms recovered from R sheep were less fecund. The second step of the characterization was to investigate functional mechanisms associated with the QTL, thanks to a gene expression analysis performed on the abomasal mucosa and the abomasal lymph node. The gene expression level of a candidate gene lying within the QTL region (PAPP-A2) was measured. In addition, putative interactions between the chromosome segment under study and the top ten differentially expressed genes between resistant MBB and susceptible RMN sheep highlighted in a previous microarray experiment were investigated. We found an induction of Th-2 related cytokine genes expression in the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression was observed between naïve and challenged sheep although no differential expression was recorded between challenged R and N sheep. The genotyping of this limited region should contribute to the ability to predict the intrinsic resistance level of sheep.
authors.affiliation: INRA, UMR1282, Infectiologie et Santé Publique, F-37380 Nouzilly, France. Guillaume.Salle@tours.inra.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sallé
authors.forename: Carole
authors.initials: C
authors.lastname: Moreno
authors.forename: Simon
authors.initials: S
authors.lastname: Boitard
authors.forename: Julien
authors.initials: J
authors.lastname: Ruesche
authors.forename: Aurélie
authors.initials: A
authors.lastname: Tircazes-Secula
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bouvier
authors.forename: Mathias
authors.initials: M
authors.lastname: Aletru
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Weisbecker
authors.forename: Françoise
authors.initials: F
authors.lastname: Prévot
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bergeaud
authors.forename: Cathy
authors.initials: C
authors.lastname: Trumel
authors.forename: Christelle
authors.initials: C
authors.lastname: Grisez
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Liénard
authors.forename: Philippe
authors.initials: P
authors.lastname: Jacquiet
mesh_terms: D000018:Abomasum / Q000469:parasitology; D000818:Animals; D060467:Disease Resistance; D005260:Female; D005786:Gene Expression Regulation; D006188:Haemonchiasis / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D006189:Haemonchus / Q000502:physiology*; D008198:Lymph Nodes / Q000469:parasitology; D008297:Male; D016133:Polymerase Chain Reaction / Q000662:veterinary; D040641:Quantitative Trait Loci; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics* / Q000276:immunology / Q000469:parasitology