X染色体倾斜失活人胚胎干细胞的拷贝数变异

背景：倾斜性与随机X染色体失活的人胚胎干细胞拷贝数变异是否存在差异不清楚。目的：在全基因组水平分析倾斜性X染色体失活的人胚胎干细胞的拷贝数变异情况,分析其涵盖基因及其对细胞功能产生的影响。方法：3株倾斜性X染色体失活细胞为研究组,两株随机X染色体失活细胞为对照组。运用美国Affymetrix公司Cytogenetics Whole-Genome2.7M芯片对其进行全基因组拷贝数变异分析,数据经ChAS软件、OMIM等工具分析,在3株倾斜性X染色体失活细胞中寻找相同拷贝数变异区域及其涵盖基因。结果与结论：①研究组中大于50kb的拷贝数变异数均超过130个,高于对照组的平均36个,两组中拷贝数变异改变均以重复为主（〉70%）。②研究组中共发现9个共同拷贝数变异区域,分布于1q22、1p34.1、6q16.3、7q31.32、11q13.1、16q12.2、19p13.12、Xp22.33及Xq26.2,均为3个拷贝的重复,总共涵盖19个基因。对照组中这些区域及基因均为正常2个拷贝。③拷贝数变异涵盖基因多与DNA及核苷酸结合等功能相关,Xq26.2区域的GPC3基因突变与倾斜性X染色体失活可能有关联。结果表明倾斜性X染色体失活细胞相对随机失活细胞具有更多的微小基因组改变,拷贝数变异涵盖的重要基因可能对人胚胎干细胞功能产生不利影响。

Copy number variation in human embryonic stem cells with skewed X chromosome inactivation

BACKGROUND： Human embryonic stem cells have two different X chromosome inactivation patterns： skewed X chromosome inactivation and random X chromosome inactivation. Whether there is any difference in copy number variation between those cells is not clear. OBJECTIVE： To analyze the copy number variation in human embryonic stem cells with skewed X chromosome inactivation at whole genome level, and to analyze the effect of copy number variation on the function of human embryonic stem cells with skewed X chromosome inactivation.METHODS： Three skewed X chromosome inactivation cell strains were included in the research group, and two random skewed X chromosome inactivation cell strains were included in the control group. The copy number variation was analyzed with Cytogenetics Whole-Genome 2.7M array produced by Affymetrix, USA. The data were analyzed using ChAS software and OMIM software. The same copy number variation regions and genes were found in the three skewed X chromosome inactivation cell strains. RESULTS AND CONCLUSION： More than 130 copy number variation （＆gt;50 kb） were found in the research group, which was higher than that of 36 copy number variation in the control group, the changes of copy number variation in the two groups were mainly repeated （＆gt;70%）. Nine gain copy number variation regions were found in the research group, distributed on 1q22, 1p34.1, 6q16.3, 7q31.32, 11q13.1, 16q12.2, 19p13.12, Xp22.33 and Xq26.2, respectively, all were repeated for three copy number variation. Nineteen genes were found within those copy number variation. All of those above copy number variation regions and genes in the control group were normal two copies. Genes within the copy number variation were closely related to the function of binding of DNA and nucleotide. GPC3 gene mutation on the Xq26.2 was found to be correlated with the skewed X chromosome inactivation. Micro-genomic variation in human embryonic stem cells with skewed X chromosome inactivation was higher than that in the random skewed X chromosome inactivation human embryonic stem cells. Key genes within copy number variation may have disadvantage to the function of human embryonic stem cells.