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 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.

DOI: 10.1016/j.ebiom.2017.08.015

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@inproceedings{Shang2017RapidTN, title={Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies}, author={Xuan Shang and Zhiyu Peng and Yuhua Ye and Asan and Xinhua Zhang and Yan Chen and Bao-sheng Zhu and Wangwei Cai and Shaoke Chen and Ren Cai and Xiaoling Guo and Chonglin Zhang and Yuqiu Zhou and Shuodan Huang and Yan-Hui Liu and Biyan Chen and Shanhuo Yan and Yajun Chen and Hongmei Ding and Xiaolin Yin and Liusong Wu and Jing He and Dongai Huang and Sheng Yang He and Tizhen Yan and Xin Fan and Yuehong Zhou and Xiaofeng Wei and Sumin Zhao and Decheng Cai and Fengyu Guo and Qianqian Zhang and Yun Li and Xuelian Zhang and Haorong Lu and Huajie Huang and Junfu Guo and Fei Zhu and Yuan Yuan and Li Zhang and Na Liu and Zhiming Li and Hui Jiang and Qiang Zhang and Yijia Zhang and Wan Khairunnisa Wan Juhari and Sarifah Hanafi and Wanjun Zhou and Fu Xia Xiong and Huanming Yang and Jian Wang and Bin Alwi Zilfalil and Ming Qi and Yaping Yang and Ye Yin and Mao Mao and XiangMin Xu}, booktitle={EBioMedicine}, year={2017} }