New insights into the genetic resistance to paratuberculosis in Holstein cattle via single-step genomic evaluation

Abstract

Background Bovine paratuberculosis, or Johne’s disease (JD), is a contagious and incurable disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has adverse effects on animal welfare and is very difficult to control, leading to serious economic consequences. An important line of defense to this disease is host genetic resistance to MAP, which, when it will be more fully understood, could be improved through selective breeding. Using a large dataset of Holstein cows (161,253 animals including 56,766 cows with ELISA serological phenotypes and 12,431 animals with genotypes), we applied a single-step single nucleotide polymorphism (SNP) best linear unbiased prediction approach to investigate the genetic determinism underlying resistance to this disease (heritability estimate and identification of relevant genomic regions) and estimated genetic trends, reliability, and relative risk factors associated with genomic predictions. Results Resistance to JD was moderately heritable (0.14) and 16 genomic regions were detected that accounted for at least 0.05% of the breeding values variance (GV) in resistance to JD, and were located on chromosomes 1, 3, 5, 6, 7, 19, 20, 21, 23, 25, and 27, with the highest percentage of variance explained by regions on chromosomes 23 (0.36% GV), 5 (0.22% GV), 1 (0.14% GV), and 3 (0.13% GV). When estimated for the whole chromosomes, the autosomes with the largest overall contributions were chromosomes 3 (5.3% GV), 10 (4.8%), 23 (4.7%), 1 (3.6%), 7 (3.4%), 5 (2.9%), 12 (2.5%), 11 (2.2%), and 13 (2%). We estimated a slightly favorable genetic trend in resistance to JD over the last two decades, which can be explained by a low positive genetic correlation between resistance to JD and total merit index (+ 0.06). Finally, in a validation population of 907 cows, relatively reliable genomic predictions (reliability = 0.55) were obtained, which allowed the identification of cows at high risk of infection. Conclusions This study provides new insights into the genetic determinism of resistance to JD and shows that this trait can be predicted from SNP genotypes. It has led to the implementation of a single-step genomic evaluation that should rapidly become an effective tool for controlling paratuberculosis on French Holstein farms.

Evaluation of Mycobacterium avium subsp. paratuberculosis isocitrate lyase (IcL) and ABC transporter (BacA) knockout mutants as vaccine candidates

“…It has proven difficult to establish a MAP infection through an oral route in mice or to generate clinical signs and intestinal lesions. Species-specific attenuation of mutant strains is consistent with previous literature (Scandurra et al, 2010;Bannantine et al, 2014b) where evaluation of MAP 1566 live-attenuated vaccine strain in mouse model indicated some level of protection against challenge, while the evaluation of same vaccine strains was unable to show promising results in goat model (Bannantine et al, 2014b). In present study, the opposite is observed where vaccine strains were not attenuated for colonization in mice tissue, while they were both attenuated for colonization in natural host.…”

“…Current control strategies focus on preventing the transmission of MAP through management practices ( Barkema et al., 2018 ) by testing and culling positive animals, decreasing the incidence of new infections, preventing spread, and protecting negative herds, and decreasing prevalence in bulk tank milk ( Wolf et al., 2014 ). Identifying and selectively breeding cattle with natural resistance to MAP infection is also an approach recently employed by Canada and some European countries ( Alonso-Hearn et al., 2022 ; Sanchez et al., 2022 ). Despite considerable efforts to control Johne's disease, their effectiveness has been limited mostly due to high costs, suboptimal diagnostics, and incomplete knowledge of MAP pathogenesis ( Nielsen and Toft, 2006 ; Nielsen and Toft, 2008 ).…”

Advances in understanding the genetic architecture of antibody response to paratuberculosis in sheep by heritability estimate and LDLA mapping analyses and investigation of candidate regions using sequence-based data

“…On the one hand, the significant region on OAR20 identified by LDLA analysis, maps close to a region that affects the resistance to gastro‐intestinal nematodes detected in the same experimental population [ 79 ]⁠. Moreover, the orthologous region on bovine chromosome 23 has been found to be significantly associated with resistance to PTB in most of the recent GWAS performed with high-density SNP genotypes or imputed whole-genome sequences [ 29 , 30 , 39 , 40 , 80 , 81 ]. In our population, this region explains a relevant portion of the genetic variance for both variables and could be exploited in selection schemes.…”

“…The role of host genetics in susceptibility to MAP infection has been largely studied in cattle. As reviewed by Brito et al [ 21 ], heritability estimates for this trait in this species ranged from 0.03 to 0.57 depending on the diagnostic tests, statistical models and populations [ 22 – 30 ]. Moreover, several genome-wide association studies (GWAS) have been carried out and numerous quantitative trait loci (QTL) have been mapped on nearly all the bovine chromosomes.…”

“…Indeed, to date, six and 601 QTL associated to “Johne’s disease tolerance” and “ M. paratuberculosis susceptibility”, respectively, have been listed in the CattleQTLdb (release 5.1). The variability in terms of number and locations of the QTL between different studies could be due to differences in the methods used to define infected and healthy cohorts [ 29 , 31 , 32 ], statistical methodologies ( i.e ., linear [ 29 ], threshold models [ 33 ], case–control studies [ 34 ]), genetic markers (microsatellites [ 35 ]; SNPchip: [ 30 , 31 , 36 – 39 ]; and whole‑genome sequence data [ 29 , 40 ]). Several positional candidate genes for MAP infection have been subsequently identified or suggested.…”