Submitted to: Medical Mycology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/15/2008
Publication Date: 3/24/2009
Citation: Fedorova, N.D., Harris, S., Chen, D., Denning, D., Yu, J., Cotty, P.J., Nierman, W.C. 2009. Using aCGH to study intraspecific genetic variability in two pathogenic molds, Aspergillus fumigatus and Aspergillus flavus. Medical Mycology. 47(S1):S34-S41. Interpretive Summary: A. fumigatus is the most common invasive mold infection in immunocompromised individuals. After A. fumigatus, A. flavus is the second leading cause of both invasive and non-invasive aspergillosis. It can also attack wounded plants and is the major producer of aflatoxin, which has been linked to many human and animal diseases. The availability of the genomic sequences of two A. fumigatus isolates, Af293 and A1163, A. oryzae ATCC 42149 and A. flavus NRRL3357 provided an opportunity to examine genetic diversity within the two species at the whole genome level. Studies through comparative genomic hybridization (CGH) technique using microarray are effective strategy to identify the genetic features that are in common or difference among those related species. This information could be helpful in genetically engineering commercial crop cultivar with antifungal property to reduce aflatoxin contamination of agricultural commodity.
Technical Abstract: Intraspecific molecular divergence is the basis of all sequence-based typing methods employed in many clinical laboratories to differentiate strains of pathogenic fungi. We have examined the feasibility of using array comparative genomic hybridization (aCGH) approaches to explore the extent of genetic variability in two opportunistic pathogenic molds, Aspergillus fumigatus and Aspergillus flavus. On average, 2% of genes from the reference genome are not detected in target isolates from different vegetative (heterokaryon) compatibility groups (VCGs). In contrast, two A. flavus isolates from widely separated regions, but with the same VCG affiliations, have almost identical gene content. Based on aCGH patterns, we predicted eight new candidate het genes in A. fumigatus. A PCR survey of nine A. flavus isolates and three A. fumigatus isolate showed that VCGs may be significantly associated with either alpha or HMG mating type (Chi-square test, P = 0.05). Our analysis showed that CGH can be used to effectively identify isolate-specific and variable genes and that gene flow in these two species is constrained by VCG boundaries, although further VCG sampling is required to confirm the latter observation.