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

Chang, Liao; Yu, Huiyun; Miao, Xinyao; Zhang, Jianbo; Li, Shengbin

doi:10.1016/j.fsigen.2019.102158

Cited by 15 publications

(8 citation statements)

References 32 publications

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“…Since cffDNA is mostly DNA fragments less than 160 bp, panels consisting of shorter amplicons will inevitably yield a higher success rate compare to that including a higher proportion of long amplicons. The strong correlation between detection rate and gestational week, which was reported in previous studies, was not observed in this work [10,20]. The most probable reason is that the pregnant women enrolled in the study were not from various gestational ages but concentrated at 12 to 14 gestational weeks, and the differences in detection rates were individual differences.…”

Section: Discussioncontrasting

confidence: 64%

“…For plasma samples, a minimum depth of 50× was required for SNP allele calling. We set 2% as the threshold to distinguish paternally derived alleles from background noise in cfDNA as studied before [20]. We also formulated a rule to define an expected paternally inherited allele (ePIA) and observed paternally inherited allele (oPIA).…”

Section: Genotype Callingmentioning

confidence: 99%

“…Among these, SNP typing by high-throughput sequencing or microarray technology was the most frequently used method in NIPPT due to their short amplicon sizes. For example, Chang et al established a 5457 SNP typing system based on massively parallel sequencing (MPS) for NIPPT [20]. Qu et al selected 1795 SNPs and performed NIPPT on the basis of the Illumina HiSeq platform [21].…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive Prenatal Paternity Testing with a Combination of Well-Established SNP and STR Markers Using Massively Parallel Sequencing

Shen

et al. 2021

Genes

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Cell-free fetal DNA (cffDNA) from maternal plasma has made it possible to develop noninvasive prenatal paternity testing (NIPPT). However, most studies have focused on customized single nucleotide polymorphism (SNP) typing systems and few have used conventional short tandem repeat (STR) markers. Based on massively parallel sequencing (MPS), this study used a widely-accepted forensic multiplex assay system to evaluate the effect of noninvasive prenatal paternity testing with a combination of well-established SNP and STR markers. Using a ForenSeq DNA Signature Prep Kit, NIPPT was performed in 17 real parentage cases with monovular unborn fetuses at 7 to 24 gestational weeks. Different analytical strategies for the identification of paternally inherited allele (PIA) were developed to deal with SNPs and STRs. Combined paternity index (CPI) for 17 real trios as well as 272 unrelated trios was calculated. With the combination of SNPs and A-STRs, 82.35% (14/17), 88.24% (15/17), 94.12% (16/17), and 94.12% (16/17) of real trios could be accurately determined when the likelihood ratio (LR) threshold for paternity inclusion was set to 10,000, 1000, 100, and 10, respectively. This reveals that simultaneous surveys of SNP and STR markers included in the ForenSeq DNA Signature Prep Kit offer a promising method for NIPPT using MPS technology.

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Section: Discussioncontrasting

confidence: 64%

Section: Genotype Callingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Noninvasive Prenatal Paternity Testing with a Combination of Well-Established SNP and STR Markers Using Massively Parallel Sequencing

Shen

et al. 2021

Genes

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“…In addition, stutter products interfere the analysis of cffDNA. SNP, as a single base variation and no stutter products present during the PCR amplification, is considered more appropriate for NIPPT ( Chang et al, 2019 ; Tam et al, 2020 ). However, the biallelic nature of SNP results in limited polymorphism at a single locus.…”

Section: Introductionmentioning

confidence: 99%

Set of 15 SNP-SNP Markers for Detection of Unbalanced Degraded DNA Mixtures and Noninvasive Prenatal Paternity Testing

Zhang

Wang

et al. 2022

Front. Genet.

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Unbalanced and degraded mixtures (UDM) are very common in forensic DNA analysis. For example, DNA signals from criminal suspects are masked by a large amount of DNA from victims, or cell-free fetal DNA (cffDNA) in maternal plasma is masked by a high background of maternal DNA. Currently, detecting minor DNA in these mixtures is complex and challenging. We developed a new set of SNP-SNP microhaplotypes with short amplicons, and we successfully genotyped them using the new method of amplification-refractory mutation system PCR (ARMS-PCR) combined with SNaPshot technology based on a capillary electrophoresis (CE) platform. This panel reflects a high polymorphism in the Southwest Chinese Han population and thus has excellent potential for mixture studies. We evaluated the feasibility of this panel for UDM detection and noninvasive prenatal paternity testing (NIPPT). Fifteen SNP-SNPs detected minor DNA of homemade DNA mixtures, with a sensitivity of 0.025–0.05 ng and a specificity of 1:1,000. In addition, the panel successfully genotyped degraded DNA from single and mixed samples. Finally, 15 SNP-SNPs were applied to 26 trios. All samples displayed positive results with at least one marker to detect cffDNA. Besides, all fetal alleles in maternal plasma were confirmed by genotyping fetal genomic DNA from amniocentesis and paternal genomic DNA from peripheral blood. The results indicated that the SNP-SNP strategy based on the CE platform was useful for UDM detection and NIPPT.

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“…In recent years, the identification of fetal cell-free DNA (cfDNA) in the maternal circulation has facilitated noninvasive prenatal testing (NIPT) for investigating monogenic diseases [1], identifying aneuploidies [2], and determining paternity [3][4][5][6]. However, conventional prenatal screening options are less robust for twin pregnancies than for singletons [7], yet the miscarriage risk associated with invasive diagnosis is higher among twin pregnancies than singleton pregnancies [8].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction

Bai

Zhao

Lin

et al. 2020

Genes

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As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.

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

Cited by 15 publications

References 32 publications

Noninvasive Prenatal Paternity Testing with a Combination of Well-Established SNP and STR Markers Using Massively Parallel Sequencing

Noninvasive Prenatal Paternity Testing with a Combination of Well-Established SNP and STR Markers Using Massively Parallel Sequencing

Set of 15 SNP-SNP Markers for Detection of Unbalanced Degraded DNA Mixtures and Noninvasive Prenatal Paternity Testing

Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction

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