微阵列比较基因组杂交在临床细胞遗传诊断中的初步应用

Applying array-based comparative genomic hybridization analysis to clinical cytogenetic diagnosis

目的探讨微阵列比较基因组杂交（array—CGH）在临床细胞遗传诊断中应用的可行性和优越性。方法对G显带核型分析与array．CGH进行比对分析。同时采用G显带核型分析和array-CGH芯片对2008年4月至2010年4月到深圳市人民医院临床医学研究中心进行细胞遗传分析的10例病例进行核型分析，比较两种方法检测结果的差异。应用荧光定量PCR（FQ-PCR）和荧光原位杂交（FISH）对芯片结果进行验证。结果与G显带核型分析相比，除1例复杂染色体重排（CCR）外，array-CGH准确地确定了其余9例病例的核型。Array—CGH准确地确定了病例1和病例2的衍生染色体的来源和性质；未检测出病例3的CCR，但表明其CCR是平衡的；精确地确定了病例4畸变染色体区域的位置、大小和断裂点；准确地确定了病例10嵌合度约为50％的标记染色体的来源和性质；从10例病例中检测出了大量G显带核型分析难以发现的亚显微拷贝数变异（CNVs），其中包括6个可能的病理性CNVs。FQ—PCR和FISH表明array—CGH的检测结果是准确的。结论与G显带核型分析相比，array—CGH具有高分辨率、高敏感性、高通量、快速准确等优点，可作为G显带核型分析的有益补充应用于临床细胞遗传诊断中。

Objective To investigate the possibility and superiority of array-based comparative genomic hybridization （array-CGH） applied in clinical cytogenetic diagnosis. Methods Comparative analysis was performed between G-banding karyotype analysis and array-CGH. Both G-banding karyotype analysis and array-CGH were performed on 10 cases referred to the Clinical Medical Research Center Shenzhen People＇s Hospital for cytogenetic analysis between April 2008 and April 2010, the results of both methods were compared. Fluorescence quantitative polymerase chain reaction （FQ-PCR） and fluorescence in situ hybridization （FISH） were used to verify the results of G-banding karyotype analysis and array-CGH. Results Compared with G-banding karyotype analysis, 9 cases＇ karyotypes except one complex chromosomal rearrangement （CCR） , were detected by array-CGH accurately： the source and property of the derivative chromosomes in case 1 and case 2 were accurately determined; CCR in case 3 was indicated to be balanced; the regions, sizes, and breaking points of aberrant chromosome in case 4 were precisely determined; the source and property of the chimeric marker chromosome in case 10 were accurately determined; a large number of submicroscopic copy number variations （CNVs） undetected by G-banding karyotype analysis were detected, including 6 potential pathological CNVs. The results of array-CGH were confirmed by FQ-PCR and FISH. Conclusion Compared with conventional cytogenetie technique, array- CGH is of comprehensive, high resolution, sensitive, rapid, accurate, less sample demand, which can serve as a useful complement for G-banding to be used in the clinical cytogenetie diagnosis.