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Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis
PURPOSE: Emerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and inc...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042067/ https://www.ncbi.nlm.nih.gov/pubmed/31447483 http://dx.doi.org/10.1038/s41436-019-0634-7 |
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author | Wang, Huilin Dong, Zirui Zhang, Rui Chau, Matthew Hoi Kin Yang, Zhenjun Tsang, Kathy Yin Ching Wong, Hoi Kin Gui, Baoheng Meng, Zhuo Xiao, Kelin Zhu, Xiaofan Wang, Yanfang Chen, Shaoyun Leung, Tak Yeung Cheung, Sau Wai Kwok, Yvonne K. Morton, Cynthia C. Zhu, Yuanfang Choy, Kwong Wai |
author_facet | Wang, Huilin Dong, Zirui Zhang, Rui Chau, Matthew Hoi Kin Yang, Zhenjun Tsang, Kathy Yin Ching Wong, Hoi Kin Gui, Baoheng Meng, Zhuo Xiao, Kelin Zhu, Xiaofan Wang, Yanfang Chen, Shaoyun Leung, Tak Yeung Cheung, Sau Wai Kwok, Yvonne K. Morton, Cynthia C. Zhu, Yuanfang Choy, Kwong Wai |
author_sort | Wang, Huilin |
collection | PubMed |
description | PURPOSE: Emerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted. METHODS: A total of 1,023 women undergoing prenatal diagnosis were enrolled. Each sample was subjected to low-pass GS and CMA for CNV analysis in parallel. CNVs were classified according to guidelines of the American College of Medical Genetics and Genomics. RESULTS: Low-pass GS not only identified all 124 numerical disorders or pathogenic or likely pathogenic (P/LP) CNVs detected by CMA in 121 cases (11.8%, 121/1,023), but also defined 17 additional and clinically relevant P/LP CNVs in 17 cases (1.7%, 17/1,023). In addition, low-pass GS significantly reduced the technical repeat rate from 4.6% (47/1,023) for CMA to 0.5% (5/1,023) and required less DNA (50 ng) as input. CONCLUSION: In the context of prenatal diagnosis, low-pass GS identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform used. This study provides strong evidence for applying low-pass GS as an alternative prenatal diagnostic test. |
format | Online Article Text |
id | pubmed-7042067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-70420672020-03-07 Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis Wang, Huilin Dong, Zirui Zhang, Rui Chau, Matthew Hoi Kin Yang, Zhenjun Tsang, Kathy Yin Ching Wong, Hoi Kin Gui, Baoheng Meng, Zhuo Xiao, Kelin Zhu, Xiaofan Wang, Yanfang Chen, Shaoyun Leung, Tak Yeung Cheung, Sau Wai Kwok, Yvonne K. Morton, Cynthia C. Zhu, Yuanfang Choy, Kwong Wai Genet Med Article PURPOSE: Emerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted. METHODS: A total of 1,023 women undergoing prenatal diagnosis were enrolled. Each sample was subjected to low-pass GS and CMA for CNV analysis in parallel. CNVs were classified according to guidelines of the American College of Medical Genetics and Genomics. RESULTS: Low-pass GS not only identified all 124 numerical disorders or pathogenic or likely pathogenic (P/LP) CNVs detected by CMA in 121 cases (11.8%, 121/1,023), but also defined 17 additional and clinically relevant P/LP CNVs in 17 cases (1.7%, 17/1,023). In addition, low-pass GS significantly reduced the technical repeat rate from 4.6% (47/1,023) for CMA to 0.5% (5/1,023) and required less DNA (50 ng) as input. CONCLUSION: In the context of prenatal diagnosis, low-pass GS identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform used. This study provides strong evidence for applying low-pass GS as an alternative prenatal diagnostic test. 2019-08-26 2020-03 /pmc/articles/PMC7042067/ /pubmed/31447483 http://dx.doi.org/10.1038/s41436-019-0634-7 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wang, Huilin Dong, Zirui Zhang, Rui Chau, Matthew Hoi Kin Yang, Zhenjun Tsang, Kathy Yin Ching Wong, Hoi Kin Gui, Baoheng Meng, Zhuo Xiao, Kelin Zhu, Xiaofan Wang, Yanfang Chen, Shaoyun Leung, Tak Yeung Cheung, Sau Wai Kwok, Yvonne K. Morton, Cynthia C. Zhu, Yuanfang Choy, Kwong Wai Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title | Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title_full | Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title_fullStr | Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title_full_unstemmed | Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title_short | Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
title_sort | low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042067/ https://www.ncbi.nlm.nih.gov/pubmed/31447483 http://dx.doi.org/10.1038/s41436-019-0634-7 |
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