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Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study

With the development of next generation sequencing, more and more common inherited diseases have been reported. However, accurate and convenient molecular diagnosis cannot be achieved easily because of the enormous size of disease causing mutations. In this study, we introduced a new single-step met...

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Autores principales: Sun, Yan, Man, Jianfen, Wan, Yang, Pan, Gao, Du, Lique, Li, Long, Yang, Yun, Qiu, Liru, Gao, Qing, Dan, Handong, Mao, Liangwei, Cheng, Zhengyu, Fan, Chen, Yu, Jing, Lin, Mufei, Kristiansen, Karsten, Shen, Yin, Wei, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076228/
https://www.ncbi.nlm.nih.gov/pubmed/30076350
http://dx.doi.org/10.1038/s41598-018-30151-z
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author Sun, Yan
Man, Jianfen
Wan, Yang
Pan, Gao
Du, Lique
Li, Long
Yang, Yun
Qiu, Liru
Gao, Qing
Dan, Handong
Mao, Liangwei
Cheng, Zhengyu
Fan, Chen
Yu, Jing
Lin, Mufei
Kristiansen, Karsten
Shen, Yin
Wei, Xiaoming
author_facet Sun, Yan
Man, Jianfen
Wan, Yang
Pan, Gao
Du, Lique
Li, Long
Yang, Yun
Qiu, Liru
Gao, Qing
Dan, Handong
Mao, Liangwei
Cheng, Zhengyu
Fan, Chen
Yu, Jing
Lin, Mufei
Kristiansen, Karsten
Shen, Yin
Wei, Xiaoming
author_sort Sun, Yan
collection PubMed
description With the development of next generation sequencing, more and more common inherited diseases have been reported. However, accurate and convenient molecular diagnosis cannot be achieved easily because of the enormous size of disease causing mutations. In this study, we introduced a new single-step method for the genetic analysis of patients and carriers in real clinical settings. All kinds of disease causing mutations can be detected at the same time in patients with Mendelian diseases or carriers. First, we evaluated this technology using YH cell line DNA and 9 samples with known mutations. Accuracy and stability of 99.80% and 99.58% were achieved respectively. Then, a total of 303 patients were tested using our targeted NGS approaches, 50.17% of which were found to have deleterious mutations and molecular confirmation of the clinical diagnosis. We identified 219 disease causing mutations, 43.84% (96/219) of which has never been reported before. Additionally, we developed a new deleteriousness prediction method for nonsynonymous SNVs, and an automating annotation and diagnosis system for Mendelian diseases, thus greatly assisting and enhancing Mendelian diseases diagnosis and helping to make a precise diagnosis for patients with Mendelian diseases.
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spelling pubmed-60762282018-08-07 Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study Sun, Yan Man, Jianfen Wan, Yang Pan, Gao Du, Lique Li, Long Yang, Yun Qiu, Liru Gao, Qing Dan, Handong Mao, Liangwei Cheng, Zhengyu Fan, Chen Yu, Jing Lin, Mufei Kristiansen, Karsten Shen, Yin Wei, Xiaoming Sci Rep Article With the development of next generation sequencing, more and more common inherited diseases have been reported. However, accurate and convenient molecular diagnosis cannot be achieved easily because of the enormous size of disease causing mutations. In this study, we introduced a new single-step method for the genetic analysis of patients and carriers in real clinical settings. All kinds of disease causing mutations can be detected at the same time in patients with Mendelian diseases or carriers. First, we evaluated this technology using YH cell line DNA and 9 samples with known mutations. Accuracy and stability of 99.80% and 99.58% were achieved respectively. Then, a total of 303 patients were tested using our targeted NGS approaches, 50.17% of which were found to have deleterious mutations and molecular confirmation of the clinical diagnosis. We identified 219 disease causing mutations, 43.84% (96/219) of which has never been reported before. Additionally, we developed a new deleteriousness prediction method for nonsynonymous SNVs, and an automating annotation and diagnosis system for Mendelian diseases, thus greatly assisting and enhancing Mendelian diseases diagnosis and helping to make a precise diagnosis for patients with Mendelian diseases. Nature Publishing Group UK 2018-08-03 /pmc/articles/PMC6076228/ /pubmed/30076350 http://dx.doi.org/10.1038/s41598-018-30151-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sun, Yan
Man, Jianfen
Wan, Yang
Pan, Gao
Du, Lique
Li, Long
Yang, Yun
Qiu, Liru
Gao, Qing
Dan, Handong
Mao, Liangwei
Cheng, Zhengyu
Fan, Chen
Yu, Jing
Lin, Mufei
Kristiansen, Karsten
Shen, Yin
Wei, Xiaoming
Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title_full Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title_fullStr Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title_full_unstemmed Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title_short Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
title_sort targeted next-generation sequencing as a comprehensive test for mendelian diseases: a cohort diagnostic study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076228/
https://www.ncbi.nlm.nih.gov/pubmed/30076350
http://dx.doi.org/10.1038/s41598-018-30151-z
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