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Volume 12
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10.3390/genes12010026
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Article

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

by
Zhaochen Bai
1,2,†,
Hu Zhao
1,2,†,
Shaobin Lin
3,
Linhuan Huang
3,
Zhiming He
3,
Huan Wang
4,* and
Xueling Ou
1,2,*
1
Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
2
Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-sen University, Guangzhou 510080, China
3
Fetal Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
4
Department of Gynecology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
*
Authors to whom correspondence should be addressed.
†
Both authors contributed equally to this work.
Genes 2021, 12(1), 26; https://doi.org/10.3390/genes12010026
Submission received: 21 November 2020 / Revised: 23 December 2020 / Accepted: 24 December 2020 / Published: 27 December 2020
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

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.
Keywords: microhaplotype; non-invasive prenatal testing; twins; paternity; zygosity; fetal fraction microhaplotype; non-invasive prenatal testing; twins; paternity; zygosity; fetal fraction

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MDPI and ACS Style

Bai, Z.; Zhao, H.; Lin, S.; Huang, L.; He, Z.; Wang, H.; Ou, X. Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction. Genes 2021, 12, 26. https://doi.org/10.3390/genes12010026

AMA Style

Bai Z, Zhao H, Lin S, Huang L, He Z, Wang H, Ou X. Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction. Genes. 2021; 12(1):26. https://doi.org/10.3390/genes12010026

Chicago/Turabian Style

Bai, Zhaochen, Hu Zhao, Shaobin Lin, Linhuan Huang, Zhiming He, Huan Wang, and Xueling Ou. 2021. "Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction" Genes 12, no. 1: 26. https://doi.org/10.3390/genes12010026

APA Style

Bai, Z., Zhao, H., Lin, S., Huang, L., He, Z., Wang, H., & Ou, X. (2021). Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction. Genes, 12(1), 26. https://doi.org/10.3390/genes12010026

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