29 Conditional GWAS using sequence-based genotypes for susceptibility to Mycobacterium avium subsp paratuberculosis infection in Canadian Holstein

Abstract

Abstract Paratuberculosis is an incurable disease caused by Mycobacterium avium spp. paratuberculosis (MAP). Variability in the definition of a true infection could explain the lack of consensus in published results on host genetic susceptibility to MAP. The objective of this study was to identify quantitative trait loci (QTL) for susceptibility to paratuberculosis in Canadian Holstein with an accurately defined status. Cows with known parentage were recruited from 23 Canadian dairy herds and enrolled in a longitudinal study. Blood and feces were collected semi-annually over a 3-5-yr period. Serum samples were analyzed by ELISA (IDEXX) and feces by qPCR. Cows were labelled based on positive ELISA (> 45%) and on at least two consecutive fecal excretion of MAP (n = 382). Control cows (n = 669) did not excrete MAP nor have MAP antibodies (< 10%) over the 3–5 year period. Their genotypes (GGP Bovine 50K chip) were imputed to HD-SNP (within-breed), then to WGS using FImpute software and Run6 of 1,000 Bulls’ genome project as a multi-breed reference. Using GCTA software, heritability (h2) was estimated and conditional GWAS was performed to define multiple true causal mutations in QTL regions from those caused by linkage disequilibrium. The h2(se) was 0.52 (0.01) and after FDR correction, 1,357 variants presented significant effects (-log10 P > 6), grouped within 7 QTL located on chromosome BTA7, BTA16, BTA20, and BTA23. The most significant variant was on BTA20 (-log10 P =12.39). Functional annotation showed that 76% of all the variants of the QTL were intergenic, with the rest being mostly intronic. Of interest was variant located on BTA7 with effect size (se) of -0.77 (0.02). In conclusion, using accurate phenotypes, chromosomal regions and candidate genes that could be functionally related to MAP infection were uncovered. The significant variants found in this study could contribute to the enhancement of genomic evaluation for MAP resistance.