The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
The New York Stem Cell Foundation Research Institute, New York, New York 10032, USA.
Nat Commun. 2016 Jul 7;7:12144. doi: 10.1038/ncomms12144.
Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations.
基因组不稳定性对细胞表型有深远的影响。研究表明，具有异常核型的多能细胞可能生长更快、分化更少，对细胞凋亡的抵抗性更强。此前，我们通过比较正常和非整倍体样本之间的基因表达水平，利用微阵列基因表达谱来分析染色体异常。在这里，我们采用这种方法对 RNA-Seq 数据进行分析，并提出了 eSNP-Karyotyping，用于检测染色体异常，其原理是测量两个等位基因之间的表达比值。我们证明了该方法能够检测多能细胞及其衍生物中的染色体增益和丢失，以及减数分裂重组模式。这种方法的优点是不需要配对的二倍体样本进行比较，对由异常引起的全局表达变化的敏感性较低，并利用已有的基因表达谱来确定染色体异常。
