SNP单体型分析在单基因遗传病PGD中的应用

Clinical application of SNP haplotype analysis in the preimplantation genetic diagnosis(PGD) of monogenic diseases

目的探讨单核苷酸多态性(SNP)单体型分析在单基因遗传病植入前遗传学诊断(PGD)中的临床应用价值。方法活检囊胚滋养层细胞全基因组扩增产物,应用SNP单体型分析方法进行诊断,并用Sanger测序进行验证。结果共205枚胚胎同时完成了SNP单体型分析和Sanger测序验证,155枚胚胎(75.61%)诊断结果一致,18枚胚胎(8.78%)诊断结果不一致。Sanger测序失败有30枚胚胎(14.63%),单体型分析有2枚胚胎(0.98%)失败,后者诊断失败率明显低于前者(P<0.05)。41个移植周期共45枚胚胎移植,临床妊娠率为70.73%(29/41),种植率为71.11%(32/45)。胎儿中孕期羊水产前诊断结果与胚胎单体型分析诊断结果一致。结论 SNP单体型分析准确性好,与Sanger测序相比,其失败率较低,能够有效用于临床单基因病PGD。

Objective To investigate the clinical application value of single nucleotide polymorphism(SNP)haplotype analysis in the preimplantation genetic diagnosis(PGD)of monogenic diseases.Methods The whole genome amplification products of biopsied trophectoderm cells were analyzed by SNP haplotype analysis and verified by Sanger sequencing.Results A total of 205 embryos were performed SNP haplotype analysis and Sanger sequencing.Among them,Sanger sequencing failed in 14.63%(30/205)of embryos,and SNP haplotype analysis failed in 0.98%(2/205)of embryos.The failure rate of the latter was significantly lower than that of the former(P<0.05).There were consistent results in 155(75.61%)embryos,and inconsistent results in 18(8.78%)embryos.Fortyfive embryos in 41 cycles were performed embryo transplantation.The clinical pregnancy rate was 70.73%(29/41)and the implantation rate was 71.11%(32/45).The results of prenatal diagnosis of amniotic fluid during the second trimester of pregnancy were completely consistent with those of SNP haplotype analysis.Conclusion SNP haplotype analysis is accurate,and its failure rate is lower than that of Sanger sequencing.It can be effectively used in the PGD of clinical monogenic diseases.