title: Genome-wide association study of tick resistance in South African Nguni cattle.
abstract: Ticks and tick-borne diseases are among the main causes of economic loss in the South African cattle industry through high morbidity and mortality rates. Concerns of the general public regarding chemical residues may tarnish their perceptions of food safety and environmental health when the husbandry of cattle includes frequent use of acaricides to manage ticks. The primary objective of this study was to identify single nucleotide polymorphism (SNP) markers associated with host resistance to ticks in South African Nguni cattle. Tick count data were collected monthly from 586 Nguni cattle reared in four herds under natural grazing conditions over a period of two years. The counts were recorded for six species of ticks attached in eight anatomical locations on the animals and were summed by species and anatomical location. This gave rise to 63 measured phenotypes or traits, with results for 12 of these traits being reported here. Tick count (x) data were transformed using log10(x+1) and the resulting values were examined for normality. DNA was extracted from hair and blood samples and was genotyped using the Illumina BovineSNP50 assay. After quality control (call rate >90%, minor allele frequency >0.02), 40,436 SNPs were retained for analysis. Genetic parameters were estimated and association analysis for tick resistance was carried out using two approaches: a genome-wide association (GWA) analysis using the GenABEL package and a regional heritability mapping (RHM) analysis. The Bonferroni genome-wide (P<0.05) corrected significance threshold was 1.24×10(-6), with 2.47×10(-5) as the suggestive significance threshold (P<0.10) (i.e., one false positive per genome scan) in the GWA analysis. Likelihood ratio test (LRT) thresholds for genome-wide and suggestive significance were 13.5 and 9.15 for the RHM analysis. Six ixodid tick species were identified, with Amblyomma hebraeum (the vector for Heartwater disease) being the dominant species. Heritability estimates (h(2)) from the fitted animal and sire models ranged from 0.02±0.00 to 0.17±0.04 for the transformed tick count data. Several genomic regions harbouring quantitative trait loci (QTL) were identified for different tick count traits by both the GWA and RHM approaches. Three genome-wide significant regions on chromosomes 7, 10 and 19 were identified for total tick count on the head, total body A. hebraeum tick count and total A. hebraeum on the perineum region, respectively. Additional regions significant at the suggestive level were identified on chromosomes 1, 3, 6, 7, 8, 10, 11, 12, 14, 15, 17, 19 and 26 for several of the traits. The GWA approach identified more genomic regions than did the RHM approach. The chromosomal regions identified here as harbouring QTL underlying variation in tick burden form the basis for further analyses to identify specific candidate genes and polymorphisms related to cattle tick resistance and provide the potential for marker-assisted selection in Nguni cattle.
authors.affiliation: Agricultural Research Council, Private Bag X2, Irene 0062, South Africa; Department of Animal Sciences, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa. Electronic address: ntanga@arc.agric.za.
authors.forename: N O
authors.initials: NO
authors.lastname: Mapholi
authors.affiliation: Agricultural Research Council, Private Bag X2, Irene 0062, South Africa; University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Maiwashe
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, UK.
authors.forename: O
authors.initials: O
authors.lastname: Matika
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, UK.
authors.forename: V
authors.initials: V
authors.lastname: Riggio
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Bishop
authors.affiliation: Agricultural Research Council, Private Bag X2, Irene 0062, South Africa; University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa; Delta G, 145 Ice Cave Road, Miles City, MT 59301, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: MacNeil
authors.affiliation: Agricultural Research Council, Private Bag X2, Irene 0062, South Africa.
authors.forename: C
authors.initials: C
authors.lastname: Banga
authors.affiliation: Division of Animal Sciences, University of Missouri, 920 East Campus Drive, Columbia, MO 65211-5300, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Taylor
authors.affiliation: Department of Animal Sciences, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa. Electronic address: kdzama@sun.ac.za.
authors.forename: K
authors.initials: K
authors.lastname: Dzama
mesh_terms: D000483:Alleles; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000737:chemistry; D004247:DNA / Q000235:genetics / Q000276:immunology; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D008297:Male; D059208:Parasite Load; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D048494:Rhipicephalus / Q000145:classification / Q000235:genetics; D013019:South Africa; D013984:Tick Infestations / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000662:veterinary*
chemical_list: D004247:DNA
keywords: Genomic analyses; Indigenous cattle; SNP markers; Tick count