通过规模试验开发和综合评估一种非侵入性产前亲子鉴定方法。

Development and comprehensive evaluation of a noninvasive prenatal paternity testing method through a scaled trial.

机构信息

College of Medicine and Forensics, Xi'an Jiaotong University, Xi'an, 710061, China.

BGI-shenzhen, Shenzhen, 518083, China.

出版信息

Forensic Sci Int Genet. 2019 Nov;43:102158. doi: 10.1016/j.fsigen.2019.102158. Epub 2019 Aug 29.

DOI:10.1016/j.fsigen.2019.102158

PMID:31479931

Abstract

PURPOSE

To eliminate the miscarriage risks caused by traditional invasive sampling methods, we develop a noninvasive prenatal paternity testing (NIPPT) method and evaluate its efficiency, reliability and sensitivity based on a scaled trial.

METHODS

We use maternal cell-free DNA and massive parallel sequencing to obtain NIPPT genotypes for parents and fetuses based on quality-controlled genome-wide single nucleotide polymorphisms (SNPs). In a preliminary testing, data from 14 pregnant women and 7 negative controls are used for setting threshold of fetal genotyping in reference to postpartum children. After that, those from 349 cases with pregnancies of 6-35 gestational weeks (GW) and 9 negative controls from non-pregnant women who have fertility experience previously are in-depth evaluated.

RESULTS

In all cases, the biological fathers have been successfully identified from unrelated with a combined paternity index (CPI) of 3.58 × 10 - 1.46 × 10 for the cases versus 1.52 × 10 - 2.30 × 10 for the controls. For negative controls, fetal SNPs originating from previous pregnancies could not be detected. Our NIPPT results completely aligned with the invasive prenatal test results using PCR-CE STR methods.

CONCLUSION

NIPPT can be applied to determine paternity accurately from 6 weeks after conception until birth and may serve as an alternative prenatal paternity test advantageous to the currently-used methods.

摘要

目的

为了消除传统有创采样方法导致的流产风险，我们开发了一种非侵入性产前亲子鉴定（NIPPT）方法，并基于一项规模试验评估其效率、可靠性和灵敏度。

方法

我们使用母体游离 DNA 和大规模平行测序，根据经过质量控制的全基因组单核苷酸多态性（SNP），获得父母和胎儿的 NIPPT 基因型。在初步测试中，我们使用 14 名孕妇和 7 名阴性对照的数据，根据产后儿童的情况，为参考确定胎儿基因分型的阈值。之后，我们对 349 例 6-35 孕周（GW）的妊娠病例和 9 名曾有生育经验的非妊娠女性的阴性对照进行了深入评估。

结果

在所有情况下，我们都成功地从无关个体中鉴定出了生物学父亲，病例的综合亲子鉴定指数（CPI）为 3.58×10 - 1.46×10 ，而对照组为 1.52×10 - 2.30×10 。对于阴性对照，以前妊娠的胎儿 SNP 无法检测到。我们的 NIPPT 结果与使用 PCR-CE STR 方法的侵入性产前检测结果完全一致。