Genome-Wide Association Analysis and Genomic Prediction of Mycobacterium avium Subspecies paratuberculosis Infection in US Jersey Cattle

Yalda Zare,Brian W Kirkpatrick,Michael T Collins,George E Shook,Dipshikha Chakravortty

doi:10.1371/journal.pone.0088380

Abstract

Paratuberculosis (Johne’s disease), an enteric disorder in ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), causes economic losses in excess of $200 million annually to the US dairy industry. To identify genomic regions underlying susceptibility to MAP infection in Jersey cattle, a case-control genome-wide association study (GWAS) was performed. Blood and fecal samples were collected from ∼5,000 mature cows in 30 commercial Jersey herds from across the US. Discovery data consisted of 450 cases and 439 controls genotyped with the Illumina BovineSNP50 BeadChip. Cases were animals with positive ELISA and fecal culture (FC) results. Controls were animals negative to both ELISA and FC tests that matched cases on birth date and herd. Validation data consisted of 180 animals including 90 cases (positive to FC) and 90 controls (negative to ELISA and FC), selected from discovery herds and genotyped by Illumina BovineLD BeadChip (∼7K SNPs). Two analytical approaches were used: single-marker GWAS using the GRAMMAR-GC method and Bayesian variable selection (Bayes C) using GenSel software. GRAMMAR-GC identified one SNP on BTA7 at 68 megabases (Mb) surpassing a significance threshold of 5×10−5. ARS-BFGL-NGS-11887 on BTA23 (27.7 Mb) accounted for the highest percentage of genetic variance (3.3%) in the Bayes C analysis. SNPs identified in common by GRAMMAR-GC and Bayes C in both discovery and combined data were mapped to BTA23 (27, 29 and 44 Mb), 3 (100, 101, 106 and 107 Mb) and 17 (57 Mb). Correspondence between results of GRAMMAR-GC and Bayes C was high (70–80% of most significant SNPs in common). These SNPs could potentially be associated with causal variants underlying susceptibility to MAP infection in Jersey cattle. Predictive performance of the model developed by Bayes C for prediction of infection status of animals in validation set was low (55% probability of correct ranking of paired case and control samples).

Highlights

Paratuberculosis or Johne’s disease (JD) is a chronic bacterial infection of the gastrointestinal tract caused by Mycobacterium avium subspecies paratuberculosis (MAP)
Our objectives were to identify genomic regions that underlie susceptibility to infection with MAP as well as development of a multi-marker model to be used in genomic selection against susceptibility to MAP infection in Jersey cattle
In a previous study [32] using a temporal clustering approach, we showed that MAP-infected animals were significantly clustered by birth date within dairy herds

Summary

Introduction

Paratuberculosis or Johne’s disease (JD) is a chronic bacterial infection of the gastrointestinal tract caused by Mycobacterium avium subspecies paratuberculosis (MAP). MAP is contagious; infected animals expose their cohorts to the pathogen by shedding bacterium into their colostrum, milk or feces [1]. Clinical signs of JD in MAP-infected dairy cattle usually appear after 2nd or 3rd lactation and include poor nutrient uptake, severe diarrhea, progressive weight loss, low milk production and eventually death [4]. The NAHMS Dairy 2007 study estimated the apparent herd-level prevalence of MAP-infected herds in the top 17 US dairy states to be at least 68% based on recovery of viable MAP in environmental fecal samples [5]. The true herd-level prevalence of MAP infection in these herds was estimated to be 91.1% [6]. JD is a common disease in countries with a significant dairy industry [7] and causes a negative impact on the global economy [8,9]

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