Resolution of trisomic mosaicism in prenatal diagnosis: estimated performance of a 50K SNP microarray
Resolution of trisomic mosaicism in prenatal diagnosis: estimated performance of a 50K SNP microarray
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DOI：
10.1002/pd.1884
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发表时间：
2007-12-01
影响因子：
3
通讯作者：
Hannan, Garry N.
中科院分区：
文献类型：
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作者：
Cross, Jillian;Peters, Greg;Hannan, Garry N.
目的评价DNA单核苷酸多态性（SNP）微阵列检测产前三体染色体嵌合现象的能力，并与常规细胞遗传学进行比较。方法通过将含有8号三体的男性成纤维细胞与等量的正常女性核型细胞混合，制备了一系列稀释的模拟马赛克样品。从这些马赛克混合物中提取dna，然后在Affymetrix 50K Xba SNP芯片上进行分析。使用间期FISH对每个马赛克样本的重复等分进行探测，对X、Y和8号染色体使用着丝粒探针，以独立估计每个样本中雄性8号三体的比例。来自阵列的数据使用公开可用的分析工具进行分析。然后使用学生t检验进行统计计算，以确定每个染色体的拷贝数之间是否存在显著差异。结果使用Affymetrix 50K Xba SNP微阵列进行的实验显示，嵌合现象在20%时明显，加上额外的统计计算，检测下限约为10%。结论所测试的SNP微阵列平台可以检测出产前样本中三体嵌合现象，其水平与常规细胞遗传学技术相当。版权所有(c) 2007约翰威利父子有限公司
Objective To evaluate the ability of a DNA single nucleotide polymorphism (SNP) microarray to detect chromosome mosaicism for trisomy in prenatal samples in order to compare this with conventional cytogenetics.Method We created a dilution series of mock mosaic samples, by mixing measured amounts of fibroblast cells containing trisomy 8 from a male with aliquots of cells with a normal female karyotype. DNAs were extracted from these mosaic mixtures, then analysed on the Affymetrix 50K Xba SNP chip. Duplicate aliquots of each mosaic sample were probed using interphase FISH, with centromeric probes for chromosomes X, Y and 8, to estimate independently the proportion of male trisomy 8 in each sample. Data from the arrays were analysed using publicly available analysis tools. Statistical calculations were then performed using a Student's t-test to determine if there was a significant difference between the copy numbers of each chromosome.Results These experiments using the Affymetrix 50K Xba SNP microarray showed mosaicism to be obvious at 20% and with additional statistical calculations, the lower limit for detection is about 10%.Conclusion The SNP microarray platform tested can detect mosaicism for trisomy in prenatal samples at levels comparable with conventional cytogenetic techniques in routine use. Copyright (c) 2007 John Wiley & Sons, Ltd.