Abstract
BackgroundBovine paratuberculosis (ParaTB) also known as Johne's disease, is a contagious fatal disease resulting from infection by Mycobacterium avium subspecies paratuberculosis (MAP). Previous studies have identified loci associated with ParaTB using different measurements to define cases and controls. The objective of this study was to combine the data from two recent studies to identify genetic loci associated with MAP tissue infection and humoral immune response, defined by MAP ELISA-positive cattle, by comparing cases and control animals for one or both measures of infection.Methodology/Principal FindingsThe two populations used for the association analyses were a cohort of MAP tissue infected animals and control Holstein cows from the USA and the second cohort composed of ELISA-positive and ELISA-negative Holstein cows from Italy. Altogether 1190 cattle were genotyped with the Illumina BovineSNP50 BeadChip. SNP markers were removed if the minor allele frequency <0.01 or genotyping failure was >5%. Animals were removed with >5% genotyping failure. Whole genome association analyses were conducted with the GRAMMAR-CG method using two different definitions of control populations.Conclusion/SignificanceThe analyses identified several loci (P<5 e-05) associated with ParaTB, defined by positive ELISA and presence of bacteria in tissue compared to ELISA and tissue negative animals, on chromosomes 1, 12 and 15 and one unassigned SNP. These results confirmed associations on chromosome 12 and the unassigned SNP with ParaTB which had been found in the Italian population alone. Furthermore, several additional genomic regions were found associated with ParaTB when ELISA and tissue positive animals were compared with tissue negative samples. These loci were on chromosomes 1, 6, 7, 13, 16, 21,23 and 25 (P<5 e-05). The results clearly indicate the importance of the phenotype definition when seeking to identify markers associated with different disease responses.
Highlights
Control of major infectious disease in livestock remains difficult, despite the detailed characterisation of the infectious agents associated with common diseases and the deciphering of their genome sequences [1]
Paratuberculosis (ParaTB) or Johne’s disease, caused by Mycobacterium avium subspecies paratuberculosis commonly known as MAP in cattle, is a chronic gastroenteritis characterized by diarrhoea, weight loss, decreased milk production and death [3]
The joint analysis of the combined data, from the two independent genome-wide studies of ParaTB, identified SNPs associated with MAP ELISA positive or MAP tissue infection positive samples, compared to controls that were either MAP ELISA or MAP tissue negative
Summary
Control of major infectious disease in livestock remains difficult, despite the detailed characterisation of the infectious agents associated with common diseases and the deciphering of their genome sequences [1]. Previous studies to estimate heritability were based on serology [4,5], while recent genome wide association studies GWAS have used tissue and faecal culture of the bacterium as well as serology as the phenotypes to define infected and control individuals [6,7,8,9,10,11]. These different definitions of infected status may explain the different genetic loci identified as involved in the susceptibility to ParaTB. The objective of this study was to combine the data from two recent studies to identify genetic loci associated with MAP tissue infection and humoral immune response, defined by MAP ELISA-positive cattle, by comparing cases and control animals for one or both measures of infection
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