应用微阵列比较基因组杂交技术精确诊断不平衡染色体畸变

Application of array-based comparative genomic hybridization in precise diagnosis of unbalanced chromosome aberration

目的探讨微阵列比较基因组杂交技术（array-based comparative genomic hybridization，array—CGH）在诊断不平衡染色体畸变中的应用价值。方法选取4例常规G显带染色体核型分析未能确诊的不平衡染色体畸变病例，按照标准的Affymetrix SNP 6．0微阵列的操作手册进行杂交、洗涤及全基因组扫描，并通过相应的计算机软件分析结果。结果通过array-CGH技术分析，明确了所有4例染色体不平衡畸变的诊断并且进行精确定位，其中对2例患者镜下染色体出现无法确定来源的额外条带进行了自身直接重复的确诊；对2例患者G显带无法识别的缺失合并重复的衍生染色体进行了精确诊断。结论array-CGH技术在DNA水平上对染色体不平衡畸变的诊断具有独特的高分辨率、高敏感性和高特异性，并且能够精确定位，对染色体疾病作出基因型-表型关系的诊断具有重大的应用价值。

Objective To evaluate the method of array-based comparative genomic hybridization （array-CGH） in identifying unbalanced chromosome aberrations. Methods Four cases that could not be diagnosed by conventional cytogenetic technique were selected to undergo array-CGH analysis. DNA samples were extracted and hybridized with the Affymetrix SNP 6.0 arrays using Human Mapping SNP6.0 assay kit following the manufacturer＇s standard protocol. The data were analyzed by two professional software packages, GCOS and Genotyping Console. Results By using array-CGH technique, all the four cases were diagnosed precisely through identifying two duplications and two complex derivative chromosomes. Conclusion Array-CGH is an effective method for whole-genome identification of unbalanced chromosomal aberrations with high sensitivity and specificity. It has a great value to investigate the correlations between genotype and phenotype in clinical service, especially in prenatal diagnosis.