C. albicans, one of the most important fungal pathogens of humans, is remarkable in the plasticity of its genome. The ability to assess the role of specific chromosomal changes in important cellular processes would be greatly enhanced by a detailed physical and genetic map. Recent advances in molecular genetics have greatly facilitated the ability to produce such maps. The investigators will begin their studies with the development of a physical map of the C. albicans genome based on a set of overlapping clones. Previously identified genes and others isolated during the course of the work will be assigned to the emerging map, eventually locating them to a resolution of 25-50 kb. They plan to use sequence data obtained as part of the mapping effort to identify about 150 additional genes. The investigators will apply their map to two key problems in C. albicans biology: the nature of centromeres and the effects on phenotype of variation in karyotype. The structure of the centromeres will be explored and the cloned centromeres will be used to build a new generation of improved cloning vectors. The investigators will focus on the consequences of being aneuploid for small regions of the genome. The ability to examine efficiently many chromosome rearrangements should provide insight into the role of subtle karyotypic changes in infection. These efforts could potentially be of great assistance to the entire Candida community. The investigators specifically include plans to make available their mapping and sequence data via the Internet throughout the project period and to distribute their materials while the work is in progress.
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