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Category: Clinical Microbiology; Fungi and Fungal Pathogenesis
The Cryptococcus Genomes: Tools for Comparative Genomics and Expression Analysis, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap09-1.gif /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap09-2.gifAbstract:
This chapter describes the genomic resources available for Cryptococcus neoformans and C. gattii and discusses selected examples of the application of the resources to address questions relevant to virulence. It appears that in C. neoformans, natural selection is gradually lengthening short introns and shortening longer introns toward a modal size, which presumably provides an increased level of evolutionary fitness. The current picture, however, may be refined in light of future sequencing of related genomes. Although several studies employed subtractive hybridization methods and differential display to identify genes with specific patterns of regulation, the chapter focuses on experiments with microarrays and serial analysis of gene expression (SAGE) methods. The influence of temperature on gene expression with a shotgun genomic DNA microarray containing 6,274 elements is described in the chapter. The shotgun microarray was used in additional transcriptome profiling experiments to identify targets of Mga2, and these included genes for fatty acid biosynthesis. This study serves to focus attention on fatty acid and sterol metabolism as important aspects of the response to temperature and other stresses. The genome sequences have enabled a series of transcriptome analyses with oligonucleotide microarrays and serial analysis of gene expression. The studies on genome sequences are becoming standard in the analysis of complex traits and the impact of mutations and drug treatments. There is a clear need for a central, curated database for the cryptococcal genome sequences and related resources such as mutant phenotypes, transcriptome and proteome data, protein interaction data, literature, and community information.
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Hybridization of the genomes of the progenitor strains NIH12 (MAT α) and NIH433 (MAT a) to the tiling array of the reference strain JEC21. Regions with higher variability in log2 ratios in the NIH12 and NIH433 genomes are more divergent from the JEC21 sequence; regions with log2 ratios close to zero have greater similarity. A reciprocal pattern of similar and divergent segments is found upon hybridization of genomes of NIH12 and NIH433 to the JEC21 array. The scale of chromosome coordinates for the JEC21 genome is indicated at the top of the figure, and gaps in the chromosomes represent putative centromeric regions ( 40 ). The borders of segments are likely sites of recombination events that occurred during the cross between strains NIH12 and NIH433 and the subsequent backcrossing to obtain JEC21 ( 22 ). Reproduced from Hu et al. ( 23 ).
C. neoformans and C. gattii strains with sequenced genomes