高通量测序技术在介入性产前诊断中的应用

The application of high throughput sequencing inInterventional prenatal diagnosis

目的通过高通量测序技术(NGS)检测孕妇羊水细胞与染色体核型分析结果行对比,探讨NGS在羊水细胞产前诊断中的实际应用。方法选择2014年9月-2018年1月在新疆医科大学第一附属医院就诊的符合条件的孕妇共77例作为研究对象,年龄22~42(31±5)岁,孕龄18~27+4w。抽取孕妇羊水,提取羊水细胞DNA,制备测序文库,应用测序仪检测,所得的DNA序列与人类DNA参考数据库比对并作统计分析,并与同一样本染色体核型分析结果行对照分析。结果 77例羊水样本NGS技术检测结果例染色体数目异常,7例染色体片段缺失/重复;羊水核型结果:1例染色体结构异常,1例9号染色体臂间倒位,1例13号染色体与15号染色体罗伯逊异位。结论利用NGS检测羊水中胎儿DNA染色体数目异常,其敏感性高于染色体核型分析技术。染色体核型分析技术与高通量测序技术相结合,将在产前诊断工作中具有较好的临床实际应用价值。

Objective:To investigate the application of NGS in prenatal diagnosis of amniotic fluid by using high throughput sequencing(NGS)to detect the results of amniotic fluid cells and karyotype analysis in pregnant women. Methods:77 cases of pregnant women in the First Affiliated Hospital of Xinjiang Medical University in September 2014-2018 were selected as the subjects. The age was 22~42(31±5)and 18~27+4 weeks. The amniotic fluid was extracted from amniotic fluid,the amniotic fluid cell DNA was extracted,the sequencing library was prepared,and the DNA sequence was compared with the human DNA reference database,and the results were analyzed with the same sample chromosome karyotype analysis. Results:The number of chromosomes was abnormal in 77 amniotic fluid samples and 7 cases of chromosome fragments were missing/repeated,and the amniotic fluid karyotype results were found in 1 cases of chromosomal structure abnormalities,1 cases of inter arm inversion of chromosome 9,and 1 cases of chromosome 13 and Robertson heterotopic on chromosome 15. Conclusion:Detection of fetal DNA chromosome abnormalities in amniotic fluid by NGS is more sensitive than chromosome karyotyping. The combination of chromosome karyotyping and high-throughput sequencing technology will have better clinical application value in prenatal diagnosis.