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Title: Genome-wide scan of gastrointestinal nematode resistance in closed Angus population selected for minimized influence of MHC

item BENAVIDES, MAGDA VIEIRA - Embrapa-Labex
item Sonstegard, Tad
item KEMP, STEPHEN - International Livestock Research Institute (ILRI) - Kenya
item MUGAMBI, JOHN - Veterinary Research Laboratory - Kenya
item GIBSON, JOHN - University Of New England
item BAKER, R. LEYDEN - Collaborator
item HANOTTTE, OLIVIER - University Of Nottingham
item MARSHALL, KAREN - International Livestock Research Institute (ILRI) - Kenya
item Van Tassell, Curtis - Curt

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/21/2015
Publication Date: 4/13/2015
Citation: Benavides, M., Sonstegard, T.S., Kemp, S., Mugambi, J.M., Gibson, J., Baker, R., Hanottte, O., Marshall, K., Van Tassell, C.P. 2015. Genome-wide scan of gastrointestinal nematode resistance in closed Angus population selected for minimized influence of MHC. PLoS One. doi: 10.1371/journal.pone.0122797.eCollection2015.

Interpretive Summary: This report is a continuation of a previous study in a backcross resource population derived from an indigenous breed of sheep from Kenya. This breed was included in the experimental design in an attempt to map the genomic locations of parasite resistance derived from centuries of adaptive selective pressure from the grazing environment. In the first study, the regions were mapped using older DNA marker technology at a much lower resolution of about 200 markers. In this study, a SNP assay bead chip with DNA markers for 50,000 locations across the genome were analyzed using the phenotypic data collected from grazing plots in Kenya. The genome wide association analysis identified 5 locations of significance revealing the complex nature of host resistance to parasites. These results will lead to further studies to test DNA markers for immune variants that can be used to guide selection of animals for resistance to parasitic infection, while simulataneously improving production for meat.

Technical Abstract: Gastrointestinal (GI) parasitic infection is the main health constraint for small ruminant production, causing loss of weight and/or death. Red Maasai sheep have adapted to a tropical environment where extreme parasite exposure, especially with highly pathogenic Haemonchus contortus, is a constant. This breed has been reported to be resistant to gastrointestinal parasite infection, hence it is considered an invaluable resource to study associations between host genetics and resistance. The aim of this study was to identify polymorphisms strongly associated with host resistance in a double backcross population derived from Red Maasai and Dorper sheep on a single nucleotide polymorphism (SNP)-based genome-wide association study (GWAS) analysis. The animals that were genotyped represented the most resistant and susceptible individuals based on the tails of phenotypic distribution (10% each) for average faecal egg counts (AVFEC). AVFEC, packed cell volume (AVPCV), and live weight (AVLWT) were adjusted for fixed effects and co-variables, and an association analysis was run using EMMAX. Revised significance levels were calculated using 100,000 permutation tests. The top five significant SNP markers with -log10 p-values >3.794 were observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results confirmed EMMAX significant regions for this trait. One of these regions included a cluster of significant SNP on chromosome (Chr) 6 not in linkage disequilibrium to each other. This genomic location contains annotated genes involved in cytokine signalling, haemostasis and mucus biosynthesis. Only one association detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated here reveal candidate immune variants for genes involved in differential response to infection and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep of a similar genetic background to the double backcross population.