Dataset Information

Genome-wide single-nucleotide polymorphism map for Candida albicans.

ABSTRACT: Single-nucleotide polymorphisms (SNPs) are essential tools for studying a variety of organismal properties and processes, such as recombination, chromosomal dynamics, and genome rearrangement. This paper describes the development of a genome-wide SNP map for Candida albicans to study mitotic recombination and chromosome loss. C. albicans is a diploid yeast which propagates primarily by clonal mitotic division. It is the leading fungal pathogen that causes infections in humans, ranging from mild superficial lesions in healthy individuals to severe, life-threatening diseases in patients with suppressed immune systems. The SNP map contains 150 marker sequences comprising 561 SNPs and 9 insertions-deletions. Of the 561 SNPs, 437 were transition events while 126 were transversion events, yielding a transition-to-transversion ratio of 3:1, as expected for a neutral accumulation of mutations. The average SNP frequency for our data set was 1 SNP per 83 bp. The map has one marker placed every 111 kb, on average, across the 16-Mb genome. For marker sequences located partially or completely within coding regions, most contained one or more nonsynonymous substitutions. Using the SNP markers, we identified a loss of heterozygosity over large chromosomal fragments in strains of C. albicans that are frequently used for gene manipulation experiments. The SNP map will be useful for understanding the role of heterozygosity and genome rearrangement in the response of C. albicans to host environments.

SUBMITTER: Forche A

PROVIDER: S-EPMC420121 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

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Genome-wide single-nucleotide polymorphism map for Candida albicans.

Forche Anja A Magee P T PT Magee B B BB May Georgiana G

Eukaryotic cell 20040601 3

Single-nucleotide polymorphisms (SNPs) are essential tools for studying a variety of organismal properties and processes, such as recombination, chromosomal dynamics, and genome rearrangement. This paper describes the development of a genome-wide SNP map for Candida albicans to study mitotic recombination and chromosome loss. C. albicans is a diploid yeast which propagates primarily by clonal mitotic division. It is the leading fungal pathogen that causes infections in humans, ranging from mild ...[more]

PMID: 15189991

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Project description:BACKGROUND: This paper introduces and applies a genome wide predictive study to learn a model that predicts whether a new subject will develop breast cancer or not, based on her SNP profile. RESULTS: We first genotyped 696 female subjects (348 breast cancer cases and 348 apparently healthy controls), predominantly of Caucasian origin from Alberta, Canada using Affymetrix Human SNP 6.0 arrays. Then, we applied EIGENSTRAT population stratification correction method to remove 73 subjects not belonging to the Caucasian population. Then, we filtered any SNP that had any missing calls, whose genotype frequency was deviated from Hardy-Weinberg equilibrium, or whose minor allele frequency was less than 5%. Finally, we applied a combination of MeanDiff feature selection method and KNN learning method to this filtered dataset to produce a breast cancer prediction model. LOOCV accuracy of this classifier is 59.55%. Random permutation tests show that this result is significantly better than the baseline accuracy of 51.52%. Sensitivity analysis shows that the classifier is fairly robust to the number of MeanDiff-selected SNPs. External validation on the CGEMS breast cancer dataset, the only other publicly available breast cancer dataset, shows that this combination of MeanDiff and KNN leads to a LOOCV accuracy of 60.25%, which is significantly better than its baseline of 50.06%. We then considered a dozen different combinations of feature selection and learning method, but found that none of these combinations produces a better predictive model than our model. We also considered various biological feature selection methods like selecting SNPs reported in recent genome wide association studies to be associated with breast cancer, selecting SNPs in genes associated with KEGG cancer pathways, or selecting SNPs associated with breast cancer in the F-SNP database to produce predictive models, but again found that none of these models achieved accuracy better than baseline. CONCLUSIONS: We anticipate producing more accurate breast cancer prediction models by recruiting more study subjects, providing more accurate labelling of phenotypes (to accommodate the heterogeneity of breast cancer), measuring other genomic alterations such as point mutations and copy number variations, and incorporating non-genetic information about subjects such as environmental and lifestyle factors.

Project description:Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages.

Dataset Information

Genome-wide single-nucleotide polymorphism map for Candida albicans.

Publications

Genome-wide single-nucleotide polymorphism map for Candida albicans.

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