Genetic association of tolerance to Johne's disease

Ricardo Zanella

Johne’s disease is a contagious disease caused by Mycobacterium avium subspecies paratuberculosis (Map). This disease may potentially be zoonotic because of its association with Crohn’s disease. To estimate the heritability of tolerance to Johne’s disease, a definition of tolerance was determined by an index calculated by the average colony forming units (cfu)/gram of fecal and tissues values for Map at slaughter(average fecal culture + 100/average of tissue culture + 100). Ninety-four animals were tissue positive and used for the basis of the simulated data of 2500 offspring, 25 sires and 2500 dams. The estimated heritability of tolerance from the simulated data was h 2 = 0.09 ± 0.03 using the MTDFREML program and Restricted Maximum Likelihood test. To identify the loci associated with tolerance, a whole genome association analysis was conducted with the Illumina Bovine SNP50 Bead array. Average tolerance and peak tolerance, using the highest fecal and tissue cfus/g for each animal instead of average value were used as phenotypes. After quality control filtering, 45,789 SNPs and 90 animals remained. The statistical analysis was conducted using the R statistical environment and PLINK (version 1.04). There was no evidence of genetic variation between animals after evaluation of the genomic inflation factor, Q-Q or MDS plots. Strong evidence for association was identified with peak tolerance and a locus on BTA 15 (p = 1.1x10−7 , after Bonferroni correction p = 0.005), while moderate evidence for association (p = 3.0x10−5 ) was identified on two adjacent SNPs on BTA 6. The same SNP on BTA 15 showed moderate evidence for association (p = 2.1x10−6 ) with average tolerance. Two additional SNPs showed moderate evidence for association on BTA 2 (p = 3.3x10−5 ) and BTA 1 (p = 3.3x10−5 ). The estimation of the heritability of tolerance and the identification of loci associated with tolerance provides necessary information in the development of tools for selecting animals that are tolerant to Johne’s disease. Selecting animals that are tolerant to Johne’s disease may minimize animal and economic losses and reduce risks to human health.

Genetic association of tolerance to Johne's disease

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