Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing
Abstract Background Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly deter...
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doaj-26298e848a574fd4a5e807e26d63acbd2021-10-10T11:06:09ZengBMCBMC Medical Genomics1755-87942021-10-0114111110.1186/s12920-021-01091-xNoninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencingChao Chen0Min Chen1Yaping Zhu2Lu Jiang3Jia Li4Yaoshen Wang5Zhe Lu6Fengyu Guo7Hairong Wang8Zhiyu Peng9Yun Yang10Jun Sun11BGI Genomics, BGI-ShenzhenDepartment of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical UniversityBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenBGI Genomics, BGI-ShenzhenAbstract Background Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples. Methods The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis. Results Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call. Conclusions Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders.https://doi.org/10.1186/s12920-021-01091-xNoninvasive prenatal diagnosisDirect haplotype phasingTargeted linked-read sequencingMonogenic disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chao Chen Min Chen Yaping Zhu Lu Jiang Jia Li Yaoshen Wang Zhe Lu Fengyu Guo Hairong Wang Zhiyu Peng Yun Yang Jun Sun |
spellingShingle |
Chao Chen Min Chen Yaping Zhu Lu Jiang Jia Li Yaoshen Wang Zhe Lu Fengyu Guo Hairong Wang Zhiyu Peng Yun Yang Jun Sun Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing BMC Medical Genomics Noninvasive prenatal diagnosis Direct haplotype phasing Targeted linked-read sequencing Monogenic disease |
author_facet |
Chao Chen Min Chen Yaping Zhu Lu Jiang Jia Li Yaoshen Wang Zhe Lu Fengyu Guo Hairong Wang Zhiyu Peng Yun Yang Jun Sun |
author_sort |
Chao Chen |
title |
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
title_short |
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
title_full |
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
title_fullStr |
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
title_full_unstemmed |
Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
title_sort |
noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2021-10-01 |
description |
Abstract Background Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples. Methods The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis. Results Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call. Conclusions Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders. |
topic |
Noninvasive prenatal diagnosis Direct haplotype phasing Targeted linked-read sequencing Monogenic disease |
url |
https://doi.org/10.1186/s12920-021-01091-x |
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