The Nramp1AA genotype confers susceptibility to Brucella abortus in water buffalo

Abstract

The 3' untranslated region of the water buffalo Nramp1 (natural resistance-associated macrophage protein 1) gene contains two alleles (Nramp1A and Nramp1B), as detected by the denaturing gradient gel electrophoresis (DGGE) technique. The Nramp1BB genotype is associated with resistance of water buffalo to the intracellular pathogen Brucella abortus. This article provides evidence that the Nramp1AA genotype is associated with susceptibility to the same pathogen. Susceptibility or resistance of water buffalo to B. abortus was established by agglutination, complement fixation, and skin tests. The Nramp1 genotype was established by DGGE analysis. The association between the Nramp1AA genotype and susceptibility to B. abortus was demonstrated in two independent population samples (152 cases and 281 controls; 87 cases and 124 controls, respectively). Macrophages from Nramp1AA subjects displayed a lower Nramp1 mRNA level when compared with macrophages from Nramp1BB subjects. Also, monocytes and macrophages from Nramp1AA subjects displayed a higher number of viable intracellular bacteria in comparison with monocytes and macrophages from Nramp1BB animals, providing biological significance to the results from association studies.

Effect of polymorphisms in the Slc11a1 coding region on resistance to brucellosis by macrophages in vitro and after challenge in two Bos breeds (Blanco Orejinegro and Zebu)

“…The SLC11A1 gene has been implicated in the modulation of certain diseases (Blackwell and Searle, 1999; Blackwell et al , 2000), and is associated with resistance to brucellosis in buffalo (Borriello et al , 2006, Capparelli et al , 2007a,b). In this study, we examined the relationship between bacterial survival (rSOB24h) and animal phenotype by crossing individuals resistant or susceptible to brucellosis and then examining the resistance of their progeny to infection.…”

“…Significant genetic variability for resistance/susceptibility to brucellosis has been detected in cattle (Feng et al , 1996; Barthel et al , 2001) and buffalo (Borriello et al , 2006; Capparelli et al , 2007a,b). In cattle, part of this resistance has been associated with a 3' untranslated polymorphism in the Slc11a1 gene (microsatellite 3'UTR) (GT)n (Adams and Templeton, 1998; Horin et al , 1999; Barthel et al , 2001) that apparently does not affect the function of Nramp1 protein.…”

0309 Systematic profiling of short tandem repeats in the cattle genome

“…This is a highly conserved gene across mammals and is associated with resistance and susceptibility to various intracellular pathogens in humans as well as in livestock species (Blackwell et al 2001;Thomas and Joseph 2012). Previous studies have shown that microsatellite alleles localized in the 3 0 UTR of the SLC11A1 are involved in macrophage function and resistance to Brucella abortus infections in both cattle and buffalo (Kumar et al 2005;Borriello et al 2006;Capparelli et al 2007;Ganguly et al 2008;Martinez et al 2008;Kumar et al 2011). Another gene ATP8B2 contains STR in its exon.…”

Novel variants within the coding regions of the Slc11A1 gene identified in Bos taurus and Bos indicus breeds

“…Interestingly, Borriello et al. (2006) and Capparelli et al. (2006) studying the two Nramp1 alleles located in the 3′UTR of the water buffalo Nramp1 gene, found differences in the number of GT repeats (33 in the A allele and 36 in B) and detected that the Nramp1AA genotype confers susceptibility to Brucella abortus in water buffalo.…”