高通量测序技术检测自然流产绒毛样本的染色体拷贝数变异情况

Using the high-throughput sequencing to detect the chromosomal copy number variants of chorionic villi

目的探讨高通量测序(NGS)技术在检测自然流产绒毛样本的遗传学分析准确性和异常结果检出率中的应用价值。方法选取早期自然流产患者的绒毛组织作为研究对象,采用NGS方法对流产绒毛组织的染色体拷贝数变异情况进行检测。同时,我们采用比较基因组杂交芯片(a-CGH)法进行验证,以确保NGS检测结果的准确性。结果本研究共纳入256例绒毛样本,检测成功率100%。染色体异常共计145例(56.64%),染色体未见明显异常共计111例(43.36%)。染色体微缺失/微重复共34例(13.28%)。在染色体异常结果中,非整倍体128例(50%),其中三体共计94例(36.72%),主要涉及22号和16号染色体,占三体总例数的50%;单体共24例(9.37%),Turner综合征为22例(91.7%);四体共10例(3.91%)。染色体结构异常共17例(6.64%)。随机选取的5例样本同时采用a-CGH芯片检测,结果与高通量测序结果一致。结论 NGS技术是一项敏感、高效的遗传学检测手段,可有助于明确自然流产的遗传学因素,以期指导下次妊娠。

ObjectiveTo investigate the clinical application of high-throughput sequencing in detecting the accuracy of genetic analysis and the detect rate of abnormal results of chorionic villi from spontaneous abortion. MethodsChorionic villus samples were collected from early spontaneous abortion to be detected the chromosomal copy number variants （CNVs） of chorionic villi using the high-throughput sequencing. Meanwhile, we adopted array-based comparative genomic hybridization （a-CGH） to confirm the selected results of high-throughput sequencing to ensure its accuracy. ResultsA total of 256 chorionic villus samples were collected in this study. The success rate of the detection was 100%. The total of chromosomal abnormalities were 145 cases （56.64%） and the normal chromosomal samples were 111 cases （43.36%）. There were 34 cases （13.28%） of the chromosomal segment deletion or duplication. In these chromosomal abnormalities, aneuploidy was identified in 128 cases （50%）, including 94 cases （36.72%） of trisomy, 24 cases （9.37%） of monomer and 10 cases （3.91%） of tetrasome. The results of trimosy involved the 22 and the 16 chromosomal, which contributed the half number of the trimosy. Turner syndrome were detected in 22 cases （91.7%） in monomer. There were 17 cases （6.64%） involved the abnormality of the chromosomal structure. The results of the high-throughput sequencing and a-CGH of the 5 samples selected were consistent. ConclusionThe high-throughput sequencing is a susceptible and efficient technology. It may help to clarify the genetic causes of spontaneous abortion to guide the next pregnancy.