M. avium subsp. paratuberculosis (MAP) is an emerging pathogen of livestock and other mammals, in which it causes inflammatory bowel disease. Transmission from farmed animals, usually from cows, to wildlife or other "unusual" hosts has been well documented through the use of genotyping methods. However some strains seem to cluster with specific hosts. For instance sheep (S) strains, and some strains infecting bison (B), appear to be distinct from classical cattle (C) strains both phenotypically (more difficult to culture) and by molecular typing methods (IS1311-based). The basis for these genotypic and phenotypic differences is poorly understood.From whole genome DNA microarray-based comparative genomic studies, we have determined that there is extensive genomic diversity among the subspecies of the M. avium complex, with large sequence polymorphisms (LSPs) differentiating between MAP and other members of the complex. Since analysis of a restricted set of strains has revealed that MAP strains form a relatively homogeneous group, we hypothesised that LSPs may be a source of genetic diversity among phenotypically and genotypically distinct strains. To that end, we performed DNA comparisons of 3 S strains, 3 C strains, and one bison isolate, using M. avium subsp. avium (MAA, strain 104) as the referent. In addition to previously described LSPs, we found that a 16kb sequence, present in MAA 104 and in S strains, appears to be missing from the C strains and the bison isolate tested. Conversely, a 7kb sequence present in MAA 104 and C strains appears to be missing from the S strains tested. These results suggest that some LSPs may discriminate between different MAP strains. Confirmation and testing across a larger number of isolates is underway.