Abstract

Background Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic enteritis in a wide range of animal species. In cattle, MAP causes a chronic disease called Johne's disease, or paratuberculosis, that is not treatable and the efficacy of vaccine control is controversial. The clinical phase of the disease is characterised by diarrhoea, weight loss, drop in milk production and eventually death. Susceptibility to MAP infection is heritable with heritability estimates ranging from 0.06 to 0.10. There have been several studies over the last few years that have identified genetic loci putatively associated with MAP susceptibility, however, with the availability of genome-wide high density SNP maker panels it is now possible to carry out association studies that have higher precision.Methodology/Principal FindingsThe objective of the current study was to localize genes having an impact on Johne's disease susceptibility using the latest bovine genome information and a high density SNP panel (Illumina BovineSNP50 BeadChip) to perform a case/control, genome-wide association analysis. Samples from MAP case and negative controls were selected from field samples collected in 2007 and 2008 in the province of Lombardy, Italy. Cases were defined as animals serologically positive for MAP by ELISA. In total 966 samples were genotyped: 483 MAP ELISA positive and 483 ELISA negative. Samples were selected randomly among those collected from 119 farms which had at least one positive animal.Conclusion/SignificanceThe analysis of the genotype data identified several chromosomal regions associated with disease status: a region on chromosome 12 with high significance (P<5×10−6), while regions on chromosome 9, 11, and 12 had moderate significance (P<5×10−5). These results provide evidence for genetic loci involved in the humoral response to MAP. Knowledge of genetic variations related to susceptibility will facilitate the incorporation of this information into breeding programmes for the improvement of health status.

Highlights

  • Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis or Johne’s disease in cattle, a chronic granulomatous gastroenteritis [1,2]

  • The current study presents evidence for loci associated with Mycobacterium avium subsp. paratuberculosis (MAP) susceptibility that were identified using a high density single nucleotide polymorphism (SNP) panel in a case-control study with a sample size of about 900 Holstein cattle using the presence of antibody against the bacterium as the definition of susceptibility

  • No outliers were identified by Classical Multi Dimension Scaling (MDS), the final data set that passed the quality controls and was used in the association analysis contained 46350 Genome wide SNPs and 925 samples

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Summary

Introduction

Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis or Johne’s disease in cattle, a chronic granulomatous gastroenteritis [1,2]. Several studies have suggested a link between MAP and Crohn’s disease in man [8,9,10]. The evidence for a link between Johne’s and Crohn’s diseases remains controversial and the causal role of MAP has not been proven [11,12,13]. Paratuberculosis (MAP) causes chronic enteritis in a wide range of animal species. MAP causes a chronic disease called Johne’s disease, or paratuberculosis, that is not treatable and the efficacy of vaccine control is controversial. There have been several studies over the last few years that have identified genetic loci putatively associated with MAP susceptibility, with the availability of genome-wide high density SNP maker panels it is possible to carry out association studies that have higher precision

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