Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains

Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains
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DOI:
10.1111/j.1365-2958.2005.04492.x
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发表时间:
2005-03-01
影响因子:
3.6
通讯作者:
Berman, J
Berman, J
中科院分区:
生物学2区
文献类型:
--
作者:
Selmecki, A;Bergmann, S;Berman, J

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白色念珠菌临床菌株对非整倍体和其他基因组重排具有高度耐受性。我们利用比较基因组杂交技术(CGH),以阵列的形式,分析了6000多个开放阅读框(ORF)的拷贝数。携带1个(CAI-4)至3个(BWP 17)营养缺陷型的白色念珠菌实验室菌株。我们发现,在破坏的HIS 1基因座的所有基因端粒的HIS 1被删除和端粒重复序列被添加到一个9核苷酸序列内的转化DNA。这种缺失发生在类似于10%的分析转化体中,并且通过另外两轮转化和转化标记的反选择而稳定地保持。在一个实例中,缺失被修复,显然是通过断裂诱导的复制。此外,所有测试的CAI-4菌株都是2号染色体的三体,尽管这种三体似乎是不稳定的,因为在随后衍生自CAI-4的菌株中未检测到。我们的数据表明,CGH阵列可以用于检测单体和三体,预测染色体断裂的位点,并确定染色体畸变,没有检测到与其他方法在C。白色念珠菌菌株。此外,他们强调了C.白念珠菌实验室菌株暴露于5-氟-乳清酸的转化和反选择应激。
Clinical strains of Candida albicans are highly tolerant of aneuploidies and other genome rearrangements. We have used comparative genome hybridization (CGH), in an array format, to analyse the copy number of over 6000 open reading frames (ORFs) in the genomic DNA of C. albicans laboratory strains carrying one (CAI-4) to three (BWP17) auxotrophies. We find that during disruption of the HIS1 locus all genes telomeric to HIS1 were deleted and telomeric repeats were added to a 9 nt sequence within the transforming DNA. This deletion occurred in similar to10% of transformants analysed and was stably maintained through two additional rounds of transformation and counterselection of the transformation marker. In one example, the deletion was repaired, apparently via break-induced replication. Furthermore, all CAI-4 strains tested were trisomic for chromosome 2 although this trisomy appears to be unstable, as it is not detected in strains subsequently derived from CAI-4. Our data indicate CGH arrays can be used to detect monosomies and trisomies, to predict the sites of chromosome breaks, and to identify chromosomal aberrations that have not been detected with other approaches in C. albicans strains. Furthermore, they highlight the high level of genome instability in C. albicans laboratory strains exposed to the stress of transformation and counterselection on 5-fluoro-orotic acid.