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Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (...

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Autores principales: Zhou, Jia, Yang, Ziying, Sun, Jun, Liu, Lipei, Zhou, Xinyao, Liu, Fengxia, Xing, Ya, Cui, Shuge, Xiong, Shiyi, Liu, Xiaoyu, Yang, Yingjun, Wei, Xiuxiu, Zou, Gang, Wang, Zhonghua, Wei, Xing, Wang, Yaoshen, Zhang, Yun, Yan, Saiying, Wu, Fengyu, Zeng, Fanwei, Wang, Jian, Duan, Tao, Peng, Zhiyu, Sun, Luming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999180/
https://www.ncbi.nlm.nih.gov/pubmed/33800913
http://dx.doi.org/10.3390/genes12030376
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author Zhou, Jia
Yang, Ziying
Sun, Jun
Liu, Lipei
Zhou, Xinyao
Liu, Fengxia
Xing, Ya
Cui, Shuge
Xiong, Shiyi
Liu, Xiaoyu
Yang, Yingjun
Wei, Xiuxiu
Zou, Gang
Wang, Zhonghua
Wei, Xing
Wang, Yaoshen
Zhang, Yun
Yan, Saiying
Wu, Fengyu
Zeng, Fanwei
Wang, Jian
Duan, Tao
Peng, Zhiyu
Sun, Luming
author_facet Zhou, Jia
Yang, Ziying
Sun, Jun
Liu, Lipei
Zhou, Xinyao
Liu, Fengxia
Xing, Ya
Cui, Shuge
Xiong, Shiyi
Liu, Xiaoyu
Yang, Yingjun
Wei, Xiuxiu
Zou, Gang
Wang, Zhonghua
Wei, Xing
Wang, Yaoshen
Zhang, Yun
Yan, Saiying
Wu, Fengyu
Zeng, Fanwei
Wang, Jian
Duan, Tao
Peng, Zhiyu
Sun, Luming
author_sort Zhou, Jia
collection PubMed
description Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.
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spelling pubmed-79991802021-03-28 Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing Zhou, Jia Yang, Ziying Sun, Jun Liu, Lipei Zhou, Xinyao Liu, Fengxia Xing, Ya Cui, Shuge Xiong, Shiyi Liu, Xiaoyu Yang, Yingjun Wei, Xiuxiu Zou, Gang Wang, Zhonghua Wei, Xing Wang, Yaoshen Zhang, Yun Yan, Saiying Wu, Fengyu Zeng, Fanwei Wang, Jian Duan, Tao Peng, Zhiyu Sun, Luming Genes (Basel) Article Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies. MDPI 2021-03-06 /pmc/articles/PMC7999180/ /pubmed/33800913 http://dx.doi.org/10.3390/genes12030376 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Zhou, Jia
Yang, Ziying
Sun, Jun
Liu, Lipei
Zhou, Xinyao
Liu, Fengxia
Xing, Ya
Cui, Shuge
Xiong, Shiyi
Liu, Xiaoyu
Yang, Yingjun
Wei, Xiuxiu
Zou, Gang
Wang, Zhonghua
Wei, Xing
Wang, Yaoshen
Zhang, Yun
Yan, Saiying
Wu, Fengyu
Zeng, Fanwei
Wang, Jian
Duan, Tao
Peng, Zhiyu
Sun, Luming
Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title_full Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title_fullStr Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title_full_unstemmed Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title_short Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing
title_sort whole genome sequencing in the evaluation of fetal structural anomalies: a parallel test with chromosomal microarray plus whole exome sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999180/
https://www.ncbi.nlm.nih.gov/pubmed/33800913
http://dx.doi.org/10.3390/genes12030376
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