Identification of single nucleotide polymorphisms in the bovine solute carrier family 11 member 1 (SLC11A1) gene and their association with infection by Mycobacterium avium subspecies paratuberculosis

Abstract

Johne's disease is a chronic enteritis caused by Mycobacterium avium ssp. paratuberculosis (MAP) that causes substantial financial losses for the cattle industry. Susceptibility to MAP infection is reported to be determined in part by genetic factors, so markerassisted selection could help to obtain bovine populations that are increasingly resistant to MAP infection. Solute carrier family 11 member 1 (SLC11A1) was adjudged to be a potential candidate gene because of its role in innate immunity, its involvement in susceptibility to numerous intracellular infections, and its previous association with bovine MAP infection. The objectives of this study were to carry out an exhaustive process of discovery and compilation of polymorphisms in SLC11A1 gene, and to perform a population-based genetic association study to test its implication in susceptibility to MAP infection in cattle. In all, 57 single nucleotide polymorphisms (SNP) were detected, 25 of which are newly described in Bos taurus. Twenty-four SNP and two 3′-untranslated region polymorphisms, previously analyzed, were selected for a subsequent association study in 558 European Holstein-Friesian animals. The SNP c.1067C > G and c.1157-91A > T and a haplotype formed by these 2 SNP yielded significant association with susceptibility to MAP infection. The c.1067C > G is a nonsynonymous SNP that causes an amino acid change in codon 356 from proline to alanine (P356A) that could alter SLC11A1 protein function. This association study supports the involvement of SLC11A1 gene in susceptibility to MAP infection in cattle. Our results suggest that SNP c.1067C > G may be a potential causal variant, although functional studies are needed to assure this point.

Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

“…Susceptibility to mycobacterial diseases, leprosy, and Buruli’s ulcer were also associated with polymorphism of the SLC11A1 gene (70). Similar polymorphisms have been associated with Johne’s disease (paratuberculosis) in cattle (71), goats (72), and sheep (73). A SLC11A1 defect mouse was created by researchers at the Belgium Pasteur Institute to develop a murine model for MAP infection (74).…”

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

“…However, for Jersey with smaller population size and higher inbreeding the extent of LD may be even higher. Association of SNPs in SLC11A1 (another member of SLC family) with MAP infection has been reported [58]. SLC11A1 and SLC17A1 both encode membrane transport proteins and mutations in these genes have been associated with inflammatory diseases such as Crohn’s and Gout diseases [59], [60].…”

Phenotype definition is a main point in genome-wide association studies for bovine Mycobacterium avium ssp. paratuberculosis infection status

“…A genome wide linkage analysis identified a quantitative trait locus associated with MAP susceptibility on Bos taurus chromosome 20 (BTA 20) (Gonda et al, 2007). Polymorphisms with significant associations to MAP susceptibility were found in the following candidate genes: CARD15 (Pinedo et al, 2009a;Ruiz-Larranaga et al, 2010a), IL10 , TLR1, TLR2, TLR4 (Mucha et al, 2009;Purdie et al, 2011) and SLC11A1 (Pinedo et al, 2009b;Ruiz-Larranaga et al, 2010b). The first genome-wide association (GWA) study using the Illumina Bovine SNP50 BeadChip related to MAP susceptibility was published by Settles et al (2009).…”