Abstract
BackgroundBovine paratuberculosis is a contagious disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences. Published results on host genetic resistance to MAP are inconsistent, mainly because of difficulties in characterizing the infection status of cows. The objectives of this study were to identify quantitative trait loci (QTL) for resistance to MAP in Holstein and Normande cows with an accurately defined status for MAP.ResultsFrom MAP-infected herds, cows without clinical signs of disease were subjected to at least four repeated serum ELISA and fecal PCR tests over time to determine both infected and non-infected statuses. Clinical cases were confirmed using PCR. Only cows that had concordant results for all tests were included in further analyses. Positive and control cows were matched within herd according to their birth date to ensure a same level of exposure to MAP. Cows with accurate phenotypes, i.e. unaffected (control) or affected (clinical or non-clinical cases), were genotyped with the Illumina BovineSNP50 BeadChip. Genotypes were imputed to whole-genome sequences using the 1000 Bull Genomes reference population (run6). A genome-wide association study (GWAS) of MAP status of 1644 Holstein and 649 Normande cows, using either two (controls versus cases) or three classes of phenotype (controls, non-clinical and clinical cases), revealed three regions, on Bos taurus (BTA) chromosomes 12, 13, and 23, presenting significant effects in Holstein cows, while only one of those was identified in Normande cows (BTA23). The most significant effect was found on BTA13, in a short 8.5-kb region. Conditional analyses revealed that only one causal variant may be responsible for the effects observed on each chromosome with the ABCC4 (BTA12), CBFA2T2 (BTA13), and IER3 (BTA23) genes as good functional candidates.ConclusionsA sequence-based GWAS on cows for which resistance to MAP was accurately defined, was able to identify candidate variants located in genes that were functionally related to resistance to MAP; these explained up to 28% of the genetic variance of the trait. These results are very encouraging for efforts towards implementation of a breeding strategy aimed at improving resistance to paratuberculosis in Holstein cows.
Highlights
Bovine paratuberculosis is a contagious disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences
Paratuberculosis, referred to as Johne’s disease (JD), is an infectious, contagious, and incurable disease caused by Mycobacterium avium subsp. paratuberculosis (MAP)
A large number of genes was located on BTA23, we identified a limited number of positional candidate genes within the confidence intervals of all of the quantitative trait loci (QTL) that we detected: 31, 42, and 38 in the Normande 0/1, Holstein 0/1, and Holstein 0/1/2 analyses, respectively
Summary
Bovine paratuberculosis is a contagious disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences. There are no effective treatment protocols and vaccination (which provides only partial protection) is limited because it can induce a false positive reaction at the intradermal test used for tuberculosis detection [3] For this reason, several countries have initiated programs for the control of JD with the objective of reducing MAP contamination, mainly by testing animals, culling seropositive animals and preventing the exposure of calves, which are the most susceptible animals in infected farms [4]. Several countries have initiated programs for the control of JD with the objective of reducing MAP contamination, mainly by testing animals, culling seropositive animals and preventing the exposure of calves, which are the most susceptible animals in infected farms [4] These programs have a high cost and a limited efficiency in clearing MAP mainly because of the disease’s long periods of latency (from infection to seropositive conversion or fecal shedding) and incubation (from infection to clinical symptoms) [5]. These periods vary greatly among individuals, as does the amount of bacteria shed by infected cattle, which suggests the existence of individual variability in resistance to MAP
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