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

摘要

Johne’s disease is a chronic enteritis caused byMycobacterium avium ssp. paratuberculosis (MAP)that causes substantial financial losses for the cattleindustry. Susceptibility to MAP infection is reportedto be determined in part by genetic factors, so markerassistedselection could help to obtain bovine populationsthat are increasingly resistant to MAP infection.Solute carrier family 11 member 1 (SLC11A1) wasadjudged to be a potential candidate gene because ofits role in innate immunity, its involvement in susceptibilityto numerous intracellular infections, and itsprevious association with bovine MAP infection. Theobjectives of this study were to carry out an exhaustiveprocess of discovery and compilation of polymorphismsin SLC11A1 gene, and to perform a population-basedgenetic association study to test its implication in susceptibilityto MAP infection in cattle. In all, 57 singlenucleotide polymorphisms (SNP) were detected, 25 ofwhich are newly described in Bos taurus. Twenty-fourSNP and two 3′-untranslated region polymorphisms,previously analyzed, were selected for a subsequent associationstudy in 558 European Holstein-Friesian animals.The SNP c.1067C > G and c.1157–91A > T anda haplotype formed by these 2 SNP yielded significantassociation with susceptibility to MAP infection. Thec.1067C > G is a nonsynonymous SNP that causes anamino acid change in codon 356 from proline to alanine(P356A) that could alter SLC11A1 protein function.This association study supports the involvement ofSLC11A1 gene in susceptibility to MAP infection incattle. Our results suggest that SNP c.1067C > G may be a potential causal variant, although functional studiesare needed to assure this point.