Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans.

Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans.
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DOI:
10.1186/gb-2008-9-2-r41
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发表时间:
2008
期刊:
影响因子:
12.3
通讯作者:
Kronstad JW
Kronstad JW
中科院分区:
生物学1区
文献类型:
--
作者:
Hu G;Liu I;Sham A;Stajich JE;Dietrich FS;Kronstad JW

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通过不同交配型、分子亚型和倍性菌株之间的比较基因组杂交,揭示了艾滋病相关病原体新型隐球菌广泛的基因组变异。基因组变异性对病原微生物的毒力有着深远的影响。两株艾滋病相关真菌病原体新型隐球菌的基因组序列的可用性提供了一个机会,使用比较基因组杂交(CGH)来检查不同交配型,分子亚型和倍性菌株之间的基因组变异性。最初,使用CGH比较血清型A和D菌株中约100个内切酶MATa和MATα交配型区域,以确定杂交信号的Log2比值与序列同一性之间的关系。随后,我们将环境分离株NIH433(MATa)和临床分离株NIH12(MATα)的基因组与来自这些菌株的实验室菌株JEC21的基因组的平铺阵列进行了比较。在这种情况下,CGH确定了推定的重组位点和JEC21基因组特定片段的起源。类似地,CGH分析揭示了代表A血清型的VNI、VNII和VNB分子亚型的菌株的基因组的显著变异性,包括两种菌株中13号染色体的二体性。此外,CGH鉴定了具有杂合AD血清型的三种菌株之间的染色体含量差异,并揭示了来自血清型A基因组的1号染色体优先保留在所有三种菌株中。血清型A、D和AD菌株的基因组表现出广泛的变异,其范围从小的差异(例如分歧、缺失或扩增的区域)到单倍体菌株中染色体13的意外二体性和天然存在的二倍体中特定染色体的优先保留。
Extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans is revealed through comparative genome hybridization between strains of different mating type, molecular subtype and ploidy. Genome variability can have a profound influence on the virulence of pathogenic microbes. The availability of genome sequences for two strains of the AIDS-associated fungal pathogen Cryptococcus neoformans presented an opportunity to use comparative genome hybridization (CGH) to examine genome variability between strains of different mating type, molecular subtype, and ploidy. Initially, CGH was used to compare the approximately 100 kilobase MATa and MATα mating-type regions in serotype A and D strains to establish the relationship between the Log2 ratios of hybridization signals and sequence identity. Subsequently, we compared the genomes of the environmental isolate NIH433 (MATa) and the clinical isolate NIH12 (MATα) with a tiling array of the genome of the laboratory strain JEC21 derived from these strains. In this case, CGH identified putative recombination sites and the origins of specific segments of the JEC21 genome. Similarly, CGH analysis revealed marked variability in the genomes of strains representing the VNI, VNII, and VNB molecular subtypes of the A serotype, including disomy for chromosome 13 in two strains. Additionally, CGH identified differences in chromosome content between three strains with the hybrid AD serotype and revealed that chromosome 1 from the serotype A genome is preferentially retained in all three strains. The genomes of serotypes A, D, and AD strains exhibit extensive variation that spans the range from small differences (such as regions of divergence, deletion, or amplification) to the unexpected disomy for chromosome 13 in haploid strains and preferential retention of specific chromosomes in naturally occurring diploids.
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发表时间: 2000-04-01
期刊: MEDICAL MYCOLOGY
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