THE ASPERGILLUS FUMIGATUS GENETIC VARIANT AND ISOLATE REPOSITORY (FUMIGATUSGVIR): A COMMUNITY RESOURCE TO FACILITATE ASSOCIATION MAPPING OF PATHOGENICITY ASSOCIATED TRAITS

Project SummaryNearly 600 fungal species are capable of causing human infections, affecting ~300 million people worldwide.Though most fungal infections are non-life threatening, mortality rates from several species can exceed 50%.Aspergillus fumigatus is the most prominent opportunistic fungal pathogen and is responsible for the deaths of~100,000 people annually. Over the last several decades, a tremendous collection of work has been devoted touncovering the mechanisms, molecules, and genes involved in A. fumigatus pathogenicity. Despite these efforts,treating and controlling A. fumigatus infections is more challenging than ever, largely due to the emergence ofdrug resistance and the increased usage of immunosuppressive treatments. New resources, tools, andapproaches are needed to decipher the genes and polymorphisms underlying the complex nature of A. fumigatuspathogenicity. To date, A. fumigatus genomic research has lagged behind the pace at which DNA-sequencingtechnologies and computational biology methodologies have advanced. The ultimate goal of this proposal is toestablish a community resource of A. fumigatus isolates and their associated genetic variant data in an effort tofacilitate quantitative genetic and population genomic research. In Aim 1, we will create a publicly availablecollection of 230 genetically and phenotypically diverse A. fumigatus isolates that will be used as a referencepanel for trait measurements. In Aim 2, we will sequence the genomes of each isolate and comprehensivelycatalogue genetic variation for use in A. fumigatus association mapping. In Aim 3, we will conduct a proof-of-concept genome-wide association analysis of virulence in the well-established wax moth larvae model systemof invasive aspergillosis. At the conclusion of these studies we will have (i) created an invaluable tool that willallow for rapid, economical, and reliable association mapping of pathogenicity-associated traits, (ii) applied novelapproaches to address and expand our knowledge of the genetic basis of A. fumigatus pathogenicity, and (iii)identified novel candidate genes to functionally examine in future studies. The results of this proposal have thepotential to positively impact the hundreds of thousands of people burdened by A. fumigatus infection.