Coxiella burnetii causes Q fever in small ruminants and in humans, and small ruminants are believed to be the primary source of transmission to humans. The current costs to small ruminant agriculture are estimated in the millions of dollars per year in North America, primarily due to abortions and lost offspring sale value. However, these costs are dwarfed by potential costs if large‐scale outbreaks of human disease occur. Such costs are estimated in the hundreds of millions of dollars, and these costs would be borne disproportionately by small ruminant industry. Current interventions include vaccination of small ruminants and humans. However, no fully efficacious vaccine exists for ruminants, and human vaccines are not recommended for seropositive individuals, who comprise a large fraction of the highest risk population. A retrospective study suggested the largest single source of transmission to humans in the U.S. has been from sheep, and an epidemiological study in a large human Q fever outbreak found a significant increase in risk (3‐fold) when farm exposure included the Blessumer breed of sheep. The latter result suggests meaningful genetic variation for C. burnetii shedding exists in domestic sheep and shows promise for selective breeding for reduced shedding of C. burnetii as another approach to risk mitigation. We propose to investigate the genetic basis of such differences in C. burnetii shedding. Specifically, we will collect shedding data from 600 sheep from multiple U.S. states and breeds. Then, we will select 210 age‐ and breed‐matched sheep for no, low, and high C. burnetii shedding groups and perform genome‐wide association scans to identify genetic regions associated with
C. burnetii shedding. These data will inform the potential of future work on marker‐assisted selective breeding in domestic sheep and form the foundation of future efforts to dissect genetics of C. burnetii shedding in mammalian systems.

Update 2015

The investigators thank the National Sheep Industry Improvement Center for funding our research project on “Identification of Genetic Regions Associated with Shedding of Coxiella burnetii (Q Fever) in Sheep.”  We began this work by testing a dozen published Coxiella burnetii quantitation methods for performance in a lab setting.  Further, we also leveraged many newly released Coxiella burnetii genome sequences to examine how well these methods would quantify diverse isolates of Coxiella burnetii from around the world.  We identified a robust quantification method, and we are moving forward with sampling for the primary genetic experiments.  At this time, we request a no-cost extension for this project.  The expanded time will add an additional lambing season to sample collection, and a short interval for final cumulative analysis of the results.  Expanding total samples will increase the statistical power of the project to identify genetic regions associated with shedding of Coxiella burnetii.