Research On The Application Of CNV-seq Combined With Chromosome Karyotype Analysis In Prenatal Diagnosis

ObjectiveThrough the next generation high-throughput gene sequencing(NGS)technology,to explore the application of copy number variation sequencing(CNV-seq)combined with chromosome karyotype analysis technology in prenatal diagnosis value.MethodsA retrospective analysis of 1206 pregnant women with singletons who were diagnosed prenatally in Zaozhuang Maternal and Child Health Hospital from January2016 to June 2019.Amniotic fluid puncture is performed on pregnant women with indications for prenatal diagnosis,and the second-generation high-throughput gene sequencing(NGS)technology is used to sequence fetal chromosome copy number variation(CNV-seq)in amniotic fluid cells and cytogenetics simultaneously.Karyotype analysis of chromosome G banding,the results of fetal chromosomal abnormalities detected by the two techniques were divided into two groups,the results of the two groups were compared and analyzed,and the pregnancy outcome was followed up.Result1.The success rate of CNV-seq detection of 1206 enrolled samples was 100%,and the success rate of cytogenetics-chromosome G band karyotype analysis was 99.75%(1203/1206).2.A total of 81.18%(979/1206)fetal chromosomes were detected by karyotype analysis.The abnormal positive rate of fetal chromosomes was 18.57%(224/1206).The abnormal positive rate of chromosome numbers was 11.61%(140/1206)including the abnormal positive rate of autosome 9.04%(109/1206),sex chromosome abnormality positive rate 1.82%(22/1206),chimera positive rate 0.75%(9/1206);chromosome structural abnormality positive rate 6.96%(84/1206)including chromosome microdeletions / Micro-repetitive positive rate 0.91%(11/1206),balanced translocation positive rate 1.33%(16/1206),inverted positive rate 0.33%(4/1206),chromosomepolymorphism positive rate 4.39%(53/1206).3.CNV-seq detected a total of 74.88%(903/1206)of normal fetal chromosomes,and25.12%(303/1206)of abnormal fetal chromosome abnormalities,including 11.69%(141/1206)of abnormal chromosome number including autosomal number 9.12%(110/1206),sex chromosome number abnormal positive rate 1.82%(22/1206),chimera positive rate 0.75%(9/1206);chromosome microstructure abnormality 13.43%(162/1206)including pathogenic CNVs The positive rate was 2.65%(32/1206),the positive rate of unknown pathogenic CNVs was 4.98%(60/1206);the positive rate of non-pathogenic CNVs was 5.80%(70/1206).4.Compared with the karyotype analysis results of CNV-seq,the positive rate of chromosome abnormality detected by CNV-seq,the positive rate of pathogenic CNVs,and the positive rate of unknown pathogenic CNVs were higher than the positive rate of karyotype detection,P<0.05,The difference was statistically significant;the abnormal positive rate of chromosome number and the positive rate of non-pathogenic CNVs were not different between the two groups,P>0.05,which was not statistically significant.The positive rate of chromosome balance translocation detected by chromosome karyotype analysis was higher than that detected by CNV-seq,P<0.05,the difference was statistically significant.5.The age statistics of the pregnant women in the group,with the increase of age,the incidence of fetal chromosomal abnormalities was positively correlated,and the correlation coefficient r=0.46352.6.The CNV-seq combined karyotype analysis group and one of the technical groups alone detected fetal chromosomal abnormalities.The differences were statistically significant,all P <0.05.Conclusion1.CNV-seq has the same detection rate of chromosome aneuploidy abnormality and unbalanced chromosome structure abnormality found in chromosome karyotype analysis.2.CNV-seq can detect more pathogenic and definite CNVs,but cannot detect balanced translocations and abnormal chromosome structure abnormalities.Therefore,CNV-seq cannot replace chromosome karyotype analysis.3.As the age of pregnant women increases,the detection rate of fetal chromosomal abnormalities increases,so elderly pregnant women are more suitable for CNV-seq combined with karyotype analysis for prenatal diagnosis.4.CNV-seq combined with chromosome karyotype analysis for prenatal diagnosiscan comprehensively and effectively detect fetal chromosomal abnormalities,and has high clinical application value.