High-Resolution SNP/CGH Microarrays Reveal the Accumulation of Loss of Heterozygosity in Commonly Used Candida albicans Strains

G3: Genes, Genomes, Genetics

Meleah Hickman³  Judith Berman²  Darren Abbey³  David Gresham¹ 

[1] Center for Genomics and Systems BiologyDepartment of Biology, New York University, New York, New York 10003Center for Genomics and Systems BiologyCenter for Genomics and Systems BiologyDepartment of Biology, New York University, New York, New York 10003Department of Biology, New York University, New York, New York 10003Center for Genomics and Systems BiologyDepartment of Biology, New York University, New York, New York 10003;Department of Genetics, Cell Biology and DevelopmentDepartment of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455Department of Genetics, Cell Biology and DevelopmentDepartment of Genetics, Cell Biology and DevelopmentDepartment of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455Department of Genetics, Cell Biology and DevelopmentDepartment of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455;Department of Genetics, Cell Biology and DevelopmentDepartment of Genetics, Cell Biology and DevelopmentDepartment of Genetics, Cell Biology and Development

关键词: comparative genome hybridization;    single nucleotide polymorphisms;    loss of heterozygosity;    aneuploidy;    genome profiling;    haplotype mapping;   

DOI  :  10.1534/g3.111.000885

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Phenotypic diversity can arise rapidly through loss of heterozygosity (LOH) or by the acquisition of copy number variations (CNV) spanning whole chromosomes or shorter contiguous chromosome segments. In Candida albicans, a heterozygous diploid yeast pathogen with no known meiotic cycle, homozygosis and aneuploidy alter clinical characteristics, including drug resistance. Here, we developed a high-resolution microarray that simultaneously detects ∼39,000 single nucleotide polymorphism (SNP) alleles and ∼20,000 copy number variation loci across the C. albicans genome. An important feature of the array analysis is a computational pipeline that determines SNP allele ratios based upon chromosome copy number. Using the array and analysis tools, we constructed a haplotype map (hapmap) of strain SC5314 to assign SNP alleles to specific homologs, and we used it to follow the acquisition of loss of heterozygosity (LOH) and copy number changes in a series of derived laboratory strains. This high-resolution SNP/CGH microarray and the associated hapmap facilitated the phasing of alleles in lab strains and revealed detrimental genome changes that arose frequently during molecular manipulations of laboratory strains. Furthermore, it provided a useful tool for rapid, high-resolution, and cost-effective characterization of changes in allele diversity as well as changes in chromosome copy number in new C. albicans isolates.

【 授权许可】

Unknown