The intracellular pathogen resistance 1 (Ipr1) gene has been reported to play a role in mediating innate immunity in a mouse model of Mycobacterium tuberculosis
infection, and polymorphisms of its human ortholog, SP110 nuclear body protein, have been suggested to be associated with tuberculosis. Thus, the bovine SP110
gene was considered to be a promising candidate for a genetic association study of bovine paratuberculosis, or Johne’s disease, a chronic granulomatous enteritis caused by Mycobacterium avium ssp. paratuberculosis
(MAP). Initially, single nucleotide polymorphisms (SNP) within the bovine SP110 gene were identified, and subsequently a population-based genetic association
study was carried out. Seventeen new SNP along the SP110 gene were identified in Holstein-Friesian cattle, and 6 more were compiled from public databases.
A total of 14 SNP were included in the association study of 2 independent populations. The SNP c.587A>G was found to be significantly associated with MAP infection, with the major allele A appearing
to confer greater disease susceptibility in one of the analyzed populations. In addition, 2 haplotypes containing this SNP were also found to be associated with
infection in the same population. The SNP c.587A>G is a nonsynonymous mutation that causes an amino acid change in codon 196 from asparagine to serine.
In silico analyses point to SNP c.587A>G as a putative causal variant for susceptibility to MAP infection.
The elucidation of the precise mechanism by which this SNP can exert its effect in the protein and, as a result, in the risk of infection, requires future functional
analyses. Likewise, the absence of genetic association in one of the analyzed populations renders it necessary to
carry out this study in other independent populations, with the aim of substantiating the repeatability of the present results. Nevertheless, the present results deepen
our understanding of the genetic basis of susceptibility and resistance mechanisms related to MAP infection in cattle and, in turn, constitute a step forward toward the
implementation of marker-assisted selection in breeding programs aimed at controlling paratuberculosis.