Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies

Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies. Shang, X., Peng, Z., Ye, Y., Asan, Zhang, X., Chen, Y., Zhu, B., Cai, W., Chen, S., Cai, R., Guo, X., Zhang, C., Zhou, Y., Huang, S., Liu, Y., Chen, B., Yan, S., Chen, Y., Ding, H., Yin, X., Wu, L., He, J., Huang, D., He, S., Yan, T., Fan, X., Zhou, Y., Wei, X., Zhao, S., Cai, D., Guo, F., Zhang, Q., Li, Y., Zhang, X., Lu, H., Huang, H., Guo, J., Zhu, F., Yuan, Y., Zhang, L., Liu, N., Li, Z., Jiang, H., Zhang, Q., Zhang, Y., Juhari, W. K. W., Hanafi, S., Zhou, W., Xiong, F., Yang, H., Huanming Yang, Wang, J., Bin Alwi Zilfalil, Qi, M., Ming Qi, Ming Qi, Yang, Y., Yin, Y., Mao, M., & Xu, X. EBioMedicine, 23:150–159, September, 2017. MAG ID: 2747512806
doi abstract bibtex

Abstract 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.

@article{shang_rapid_2017,
	title = {Rapid {Targeted} {Next}-{Generation} {Sequencing} {Platform} for {Molecular} {Screening} and {Clinical} {Genotyping} in {Subjects} with {Hemoglobinopathies}},
	volume = {23},
	doi = {10.1016/j.ebiom.2017.08.015},
	abstract = {Abstract  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.},
	journal = {EBioMedicine},
	author = {Shang, Xuan and Peng, Zhiyu and Ye, Yuhua and {Asan} and Zhang, Xinhua and Chen, Yan and Zhu, Baosheng and Cai, Wangwei and Chen, Shaoke and Cai, Ren and Guo, Xiaoling and Zhang, Chonglin and Zhou, Yuqiu and Huang, Shuodan and Liu, Yanhui and Chen, Biyan and Yan, Shanhuo and Chen, Yajun and Ding, Hongmei and Yin, Xiaolin and Wu, Liusong and He, Jing and Huang, Dongai and He, Sheng and Yan, Tizhen and Fan, Xin and Zhou, Yuehong and Wei, Xiaofeng and Zhao, Sumin and Cai, Decheng and Guo, Fengyu and Zhang, Qianqian and Li, Yun and Zhang, Xuelian and Lu, Haorong and Huang, Huajie and Guo, Junfu and Zhu, Fei and Yuan, Yuan and Zhang, Li and Liu, Na and Li, Zhiming and Jiang, Hui and Zhang, Qiang and Zhang, Yijia and Juhari, Wan Khairunnisa Wan and Hanafi, Sarifah and Zhou, Wanjun and Xiong, Fu and Yang, Huanming and {Huanming Yang} and Wang, Jian and {Bin Alwi Zilfalil} and Qi, Ming and {Ming Qi} and {Ming Qi} and Yang, Yaping and Yin, Ye and Mao, Mao and Xu, Xiangmin},
	month = sep,
	year = {2017},
	doi = {10.1016/j.ebiom.2017.08.015},
	pmcid = {5605365},
	note = {MAG ID: 2747512806},
	pages = {150--159},
}

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