Evolutionary genomic and bacteria GWAS analysis of Mycobacterium avium subsp. paratuberculosis and dairy cattle Johne's disease phenotypes

Vincent P Richards; Annette Nigsch; Paulina Pavinski Bitar; Qi Sun; Tod Stuber; Kristina Ceres; Rebecca L Smith; Suelee Robbe Austerman; Ynte Schukken; Yrjo T Grohn; Michael J Stanhope

doi:10.1128/AEM.02570-20

Evolutionary genomic and bacteria GWAS analysis of Mycobacterium avium subsp. paratuberculosis and dairy cattle Johne's disease phenotypes

Appl Environ Microbiol. 2021 Apr 15;87(8):e02570-20. doi: 10.1128/AEM.02570-20. Epub 2021 Feb 5.

Authors

Affiliations

¹ Department of Biological Sciences, Clemson University, Clemson, SC 29634.
² Department of Animal Sciences, Wageningen University, Wageningen, the Netherlands.
³ Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853.
⁴ Cornell Institute of Biotechnology, Cornell University, Ithaca, NY, 14853.
⁵ National Veterinary Services Laboratories, United States Department of Agriculture, Animal and Plant Health Inspection Service, Ames, IA, USA.
⁶ Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, IL 61801.
⁷ Royal GD, Deventer, the Netherlands.
⁸ Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853 mjs297@cornell.edu.

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease in ruminants, which has important health consequences for dairy cattle. The Regional Dairy Quality Management Alliance (RDQMA) project is a multistate research program involving MAP isolates taken from three intensively studied commercial dairy farms in the northeastern United States, which emphasized longitudinal data collection of both MAP isolates and animal health in three regional dairy herds for a period of about 7 years. This paper reports the results of a pan-GWAS analysis involving 318 MAP isolates and dairy cow Johne's disease phenotypes, taken from these three farms. Based on our highly curated accessory gene count the pan-GWAS analysis identified several MAP genes associated with bovine Johne's disease phenotypes scored from these three farms, with some of the genes having functions suggestive of possible cause/effect relationships to these phenotypes. This paper reports a pan-genomic comparative analysis between MAP and Mycobacterium tuberculosis, assessing functional Gene Ontology category enrichments between these taxa. Finally, we also provide a population genomic perspective on the effectiveness of herd isolation, involving closed dairy farms, in preventing MAP inter-farm cross infection on a micro-geographic scale.IMPORTANCE Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease in ruminants, which has important health consequences for dairy cattle, and enormous economic consequences for the dairy industry. Understanding which genes in this bacterium are correlated with key disease phenotypes can lead to functional experiments targeting these genes and ultimately lead to improved control strategies. This study represents a rare example of a prolonged longitudinal study of dairy cattle where the disease was measured and the bacteria were isolated from the same cows. The genome sequences of over 300 MAP isolates were analyzed for genes that were correlated with a wide range of Johne's disease phenotypes. A number of genes were identified that were significantly associated with several aspects of the disease and suggestive of further experimental follow-up.