Association of microsatellite polymorphisms with immune responses to a killed Mycobacterium avium subsp paratuberculosis vaccine in Merino sheep

作者：Dukkipati V S R; Blair H T^*; Garrick D J; Lopez Villalobos N; Whittington R J; Reddacliff L A; Eppleston J; Windsor P; Murray A

来源：New Zealand Veterinary Journal, 2010, 58(5): 237-245.

DOI：10.1080/00480169.2010.69154

• Paratuberculosis
• OJD
• Johne's disease
• sheep
• vaccination
• immune responses
• genetic markers
• gene polymorphisms
• MHC
• SLC11A1
• IFN-gamma

AIM: To study the association of polymorphisms at five microsatellite loci with immune responses to a killed Mycobacterium avium subsp. paratuberculosis (Map) vaccine.
METHODS: Merino sheep (504 vaccinates and 430 unvaccinated controls) from a long-term Johne's vaccine trial undertaken on three different properties in the Central Tablelands of New South Wales, Australia, were genotyped for five microsatellite markers located in three immunologically significant chromosome regions. The marker loci included three from the major histocompatibility complex (MHC), namely DYMS1, OLADRB and SMHCC1; and one each from the solute carrier family 11 member 1 (SLC11A1), OVINRA1, and the interferon-gamma (IFN-gamma), o(IFN)-gamma, gene regions. Associations between immune responses and genetic polymorphisms at the marker loci were examined by analysing both allelic and genotypic effects.
RESULTS: The o(IFN)-gamma locus had only two alleles, whereas the other four loci exhibited extensive polymorphism, with the number of alleles ranging from 10 (OVINRA1) to 21 (DYMS1), resulting in 30-92 genotypes per locus. Heterozygosities varied between 37% (o(IFN)-gamma) and 87% (SMHCC1), while information on polymorphic contents ranged from 0.31 (o(IFN)-gamma) to 0.87 (DYMS1). Each of the three properties exhibited unique allelic and genotypic frequencies. Analysis of immune response data revealed strong antibody and IFN-gamma responses as early as 2 months post-vaccination. Immune responses in control animals on all three properties remained consistently low, except for slightly elevated IFN-gamma responses at a few time-points on two properties, concomitant with exposure to natural infection. Genotype-phenotype association analyses revealed a number of marker geno types/alleles to be significantly associated with anti body and IFN-gamma responses. However, the effects of only five geno types (one each at DYMS1, OLADRB, SMHCC1, OVINRA1 and o(IFN)-gamma) and three alleles (one each at o(IFN)-gamma, DYMS1 and OLADRB) on IFN-gamma responses were consistent across the three properties.
CONCLUSION: Considering the significance of IFN-gamma responses in protection against Map, it is possible that the genotypes/alleles identified might have a role in protective immune responses to natural Map infections, and further studies are warranted to confirm this.

• 出版日期2010