Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies
Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was d...
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Language: | English |
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Elsevier
2017-09-01
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Series: | EBioMedicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417303328 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuan Shang Zhiyu Peng Yuhua Ye Asan Xinhua Zhang Yan Chen Baosheng Zhu Wangwei Cai Shaoke Chen Ren Cai Xiaoling Guo Chonglin Zhang Yuqiu Zhou Shuodan Huang Yanhui Liu Biyan Chen Shanhuo Yan Yajun Chen Hongmei Ding Xiaolin Yin Liusong Wu Jing He Dongai Huang Sheng He Tizhen Yan Xin Fan Yuehong Zhou Xiaofeng Wei Sumin Zhao Decheng Cai Fengyu Guo Qianqian Zhang Yun Li Xuelian Zhang Haorong Lu Huajie Huang Junfu Guo Fei Zhu Yuan Yuan Li Zhang Na Liu Zhiming Li Hui Jiang Qiang Zhang Yijia Zhang Wan Khairunnisa Wan Juhari Sarifah Hanafi Wanjun Zhou Fu Xiong Huanming Yang Jian Wang Bin Alwi Zilfalil Ming Qi Yaping Yang Ye Yin Mao Mao Xiangmin Xu |
spellingShingle |
Xuan Shang Zhiyu Peng Yuhua Ye Asan Xinhua Zhang Yan Chen Baosheng Zhu Wangwei Cai Shaoke Chen Ren Cai Xiaoling Guo Chonglin Zhang Yuqiu Zhou Shuodan Huang Yanhui Liu Biyan Chen Shanhuo Yan Yajun Chen Hongmei Ding Xiaolin Yin Liusong Wu Jing He Dongai Huang Sheng He Tizhen Yan Xin Fan Yuehong Zhou Xiaofeng Wei Sumin Zhao Decheng Cai Fengyu Guo Qianqian Zhang Yun Li Xuelian Zhang Haorong Lu Huajie Huang Junfu Guo Fei Zhu Yuan Yuan Li Zhang Na Liu Zhiming Li Hui Jiang Qiang Zhang Yijia Zhang Wan Khairunnisa Wan Juhari Sarifah Hanafi Wanjun Zhou Fu Xiong Huanming Yang Jian Wang Bin Alwi Zilfalil Ming Qi Yaping Yang Ye Yin Mao Mao Xiangmin Xu Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies EBioMedicine Hemoglobinopathy Next-generation sequencing Molecular screening Clinical genotyping |
author_facet |
Xuan Shang Zhiyu Peng Yuhua Ye Asan Xinhua Zhang Yan Chen Baosheng Zhu Wangwei Cai Shaoke Chen Ren Cai Xiaoling Guo Chonglin Zhang Yuqiu Zhou Shuodan Huang Yanhui Liu Biyan Chen Shanhuo Yan Yajun Chen Hongmei Ding Xiaolin Yin Liusong Wu Jing He Dongai Huang Sheng He Tizhen Yan Xin Fan Yuehong Zhou Xiaofeng Wei Sumin Zhao Decheng Cai Fengyu Guo Qianqian Zhang Yun Li Xuelian Zhang Haorong Lu Huajie Huang Junfu Guo Fei Zhu Yuan Yuan Li Zhang Na Liu Zhiming Li Hui Jiang Qiang Zhang Yijia Zhang Wan Khairunnisa Wan Juhari Sarifah Hanafi Wanjun Zhou Fu Xiong Huanming Yang Jian Wang Bin Alwi Zilfalil Ming Qi Yaping Yang Ye Yin Mao Mao Xiangmin Xu |
author_sort |
Xuan Shang |
title |
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies |
title_short |
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies |
title_full |
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies |
title_fullStr |
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies |
title_full_unstemmed |
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies |
title_sort |
rapid targeted next-generation sequencing platform for molecular screening and clinical genotyping in subjects with hemoglobinopathies |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2017-09-01 |
description |
Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies. |
topic |
Hemoglobinopathy Next-generation sequencing Molecular screening Clinical genotyping |
url |
http://www.sciencedirect.com/science/article/pii/S2352396417303328 |
work_keys_str_mv |
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doaj-ddb85bcb4ac24f0987fd7226623d7a622020-11-25T01:32:02ZengElsevierEBioMedicine2352-39642017-09-0123C15015910.1016/j.ebiom.2017.08.015Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with HemoglobinopathiesXuan Shang0Zhiyu Peng1Yuhua Ye2Asan3Xinhua Zhang4Yan Chen5Baosheng Zhu6Wangwei Cai7Shaoke Chen8Ren Cai9Xiaoling Guo10Chonglin Zhang11Yuqiu Zhou12Shuodan Huang13Yanhui Liu14Biyan Chen15Shanhuo Yan16Yajun Chen17Hongmei Ding18Xiaolin Yin19Liusong Wu20Jing He21Dongai Huang22Sheng He23Tizhen Yan24Xin Fan25Yuehong Zhou26Xiaofeng Wei27Sumin Zhao28Decheng Cai29Fengyu Guo30Qianqian Zhang31Yun Li32Xuelian Zhang33Haorong Lu34Huajie Huang35Junfu Guo36Fei Zhu37Yuan Yuan38Li Zhang39Na Liu40Zhiming Li41Hui Jiang42Qiang Zhang43Yijia Zhang44Wan Khairunnisa Wan Juhari45Sarifah Hanafi46Wanjun Zhou47Fu Xiong48Huanming Yang49Jian Wang50Bin Alwi Zilfalil51Ming Qi52Yaping Yang53Ye Yin54Mao Mao55Xiangmin Xu56Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaTianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, ChinaDepartment of Hematology, 303rd Hospital of the People's Liberation Army, Nanning, Guangxi, ChinaThe Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, ChinaGenetic Diagnosis Center, First People's Hospital of Yunnan Province, Medical School of Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, ChinaDepartment of Genetic and Metabolic Laboratory, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, ChinaDepartment of Medical Genetics, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, ChinaMaternity and Child Health Care Hospital of Foshan City, Foshan, Guangdong, ChinaGuilin Women and Children health care hospital, Guilin, Guangxi, ChinaDepartment of Clinical Laboratory, Zhuhai Municipal Maternal and Child Healthcare Hospital, Zhuhai Institute of Medical Genetics, Zhuhai, Guangdong, ChinaMaternal and Child Health Hospital in Meizhou, Meizhou, Guangdong, ChinaDepartment of Prenatal Diagnosis Center, Dong Guan Maternal and Child Health Hospital, Dongguan, Guangdong, ChinaBaise Women and Children Care Hospital, Baise, Guangxi, ChinaGenetic Laboratory, Qinzhou Maternaland Child Health Hospital, Qingzhou, Guangxi, ChinaWomen and Children's Health Hospital of Shaoguan, Shaoguan, Guangdong, ChinaDepartment of Gynecology and Obstetrics, The People's Hospital of Yunfu City, Yunfu, Guangdong, ChinaDepartment of Hematology, 303rd Hospital of the People's Liberation Army, Nanning, Guangxi, ChinaThe Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, ChinaGenetic Diagnosis Center, First People's Hospital of Yunnan Province, Medical School of Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, ChinaDepartment of Genetic and Metabolic Laboratory, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, ChinaDepartment of Medical Genetics, Liuzhou Municipal Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, ChinaDepartment of Genetic and Metabolic Laboratory, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, ChinaPingguo Women and Children Care Hospital, Baise, Guangxi, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaTianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaTianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI Clinical Laboratories-Shenzhen, BGI-Shenzhen, Shenzhen, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI Clinical Laboratories-Shenzhen, BGI-Shenzhen, Shenzhen, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaTianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaTianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI Clinical Laboratories-Shenzhen, BGI-Shenzhen, Shenzhen, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Paediatric, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaDepartment of Paediatric, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaDepartment of Paediatric, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaSchool of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, USABGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaBGI-Shenzhen, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, ChinaDepartment of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaHemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.http://www.sciencedirect.com/science/article/pii/S2352396417303328HemoglobinopathyNext-generation sequencingMolecular screeningClinical genotyping |