Anaplasma marginale is an obligate intraerythrocytic parasite of cattle, causing cyclic anemia, decreased milk and meat production, and occasionally death. Epidemiological persistence requires mechanical or biological transmission. Biological transmission via ixodid ticks is the most significant means of transmission, with Dermacentor andersoni being the most common agent in the Pacific Northwest. Previous studies have found several strains that are not transmissible by D. andersoni; however, research to date has not linked this phenotype with a molecular cause. Because phenotype is encoded by genotype, we have undertaken a comparative genomic approach to identify genes involved in tick transmission. We have completed genome sequencing of the Florida strain, which is not transmissible by D. andersoni, and compared it to the previously sequenced St. Maries strain genome, to associate genetic differences with the observed phenotypic differences. DNA from three other strains (two tick-transmissible and one non-transmissible) were subjected to pyrosequencing and assembled, to increase our power of association. These studies show A. marginale has a closed-core genome with a high degree of polymorphisms between strains. While global comparisons are ongoing, we also tested the only A. marginale gene currently associated with tick transmission, to determine its role in determining this phenotype. Specifically, the repeat region of msp1a was implicated in adhesion to tick cells. Two strains were identified with the same msp1[alpha] genotype, but different transmission phenotypes. We tested the South Idaho and Mississippi strains, both with the msp1[alpha] genotype DDDDE, for transmission status with two tick species, D. andersoni and Rhipicephalus microplus. The Mississippi strain was not transmitted by either tick species, while the South Idaho strain was transmitted with D. andersoni but not R. microplus. South Idaho infection levels were significantly higher in D. andersoni ticks than in any other strain/tick combinations, implicating infection level as a factor in transmissibility. Our data suggests that the msp1a repeats do not play a role in the differential transmissibility of the South Idaho and Mississippi strains. Ongoing comparative analysis will produce a list of candidate genes involved in tick transmission for testing and development of transmission-blocking vaccines.