Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status.
BACKGROUND
Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.


METHODS
The bovine candidate genes, interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1), TGFB receptor class I/II (TGFBR1/2), and natural resistance-associated macrophage protein 1 (SLC11A1) were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.


RESULTS
A total of 13 SNPs were identified. Four SNPs in IL10RA (984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs IL10RA 633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.


CONCLUSIONS
SNPs in IL10RA are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.
Verschoor
Chris P
CP
Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, 50 Stone Rd East, Guelph, Ontario, N1G2W1, Canada.
Pant
Sameer D
SD
You
Qiumei
Q
Schenkel
Flavio S
FS
Kelton
David F
DF
Karrow
Niel A
NA
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D010283:Paratuberculosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D053709:Interleukin-10 Receptor alpha Subunit
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