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Eukaryotic Cell, January 2005, p. 156-165, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.156-165.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Demonstration of Loss of Heterozygosity by Single-Nucleotide Polymorphism Microarray Analysis and Alterations in Strain Morphology in Candida albicans Strains during Infection

Anja Forche,1,2 Georgiana May,2 and P. T. Magee1*

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis,1 Department of Ecology, Evolution and Behavior, University of Minnesota, St. Paul, Minnesota2

Received 30 September 2004/ Accepted 11 November 2004

Candida albicans is a diploid yeast with a predominantly clonal mode of reproduction, and no complete sexual cycle is known. As a commensal organism, it inhabits a variety of niches in humans. It becomes an opportunistic pathogen in immunocompromised patients and can cause both superficial and disseminated infections. It has been demonstrated that genome rearrangement and genetic variation in isolates of C. albicans are quite common. One possible mechanism for generating genome-level variation among individuals of this primarily clonal fungus is mutation and mitotic recombination leading to loss of heterozygosity (LOH). Taking advantage of a recently published genome-wide single-nucleotide polymorphism (SNP) map (A. Forche, P. T. Magee, B. B. Magee, and G. May, Eukaryot. Cell 3:705-714, 2004), an SNP microarray was developed for 23 SNP loci residing on chromosomes 5, 6, and 7. It was used to examine 21 strains previously shown to have undergone mitotic recombination at the GAL1 locus on chromosome 1 during infection in mice. In addition, karyotypes and morphological properties of these strains were evaluated. Our results show that during in vivo passaging, LOH events occur at observable frequencies, that such mitotic recombination events occur independently in different loci across the genome, and that changes in karyotypes and alterations of phenotypic characteristics can be observed alone, in combination, or together with LOH.

* Corresponding author. Mailing address: Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455. Phone: (612) 624-7280. Fax: (612) 626-6140. E-mail: ptm{at}biosci.cbs.umn.edu.

Eukaryotic Cell, January 2005, p. 156-165, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.156-165.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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