Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA

Media type: E-Article
Title: Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA
Contributor: Doan, Phuoc-Loc; Nguyen, Duy-Anh; Le, Quang Thanh; Hoang, Diem-Tuyet Thi; Nguyen, Huu Du; Nguyen, Canh Chuong; Doan, Kim Phuong Thi; Tran, Nhat Thang; Ha, Thi Minh Thi; Trinh, Thu Huong Nhat; Nguyen, Van Thong; Bui, Chi Thuong; Lai, Ngoc-Diep Thi; Duong, Thanh Hien; Mai, Hai-Ly; Huynh, Pham-Uyen Vinh; Huynh, Thu Thanh Thi; Le, Quang Vinh; Vo, Thanh Binh; Dao, Thi Hong-Thuy; Vo, Phuong Anh; Le, Duy-Khang Nguyen; Tran, Ngoc Nhu Thi; Tran, Quynh Nhu Thi; [...]
imprint: Springer Science and Business Media LLC, 2022
Published in: Scientific Reports
Language: English
DOI: 10.1038/s41598-022-17718-7
ISSN: 2045-2322
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:p>α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/−−<jats:sup>SEA</jats:sup> (4.066%), αα/−α<jats:sup>3.7</jats:sup> (2.934%), αα/−α<jats:sup>4.2</jats:sup> (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14–99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (−α<jats:sup>3.7</jats:sup>/−α<jats:sup>4.2</jats:sup>, αα/−−<jats:sup>THAI</jats:sup>, −α<jats:sup>3.7</jats:sup>/−−<jats:sup>SEA</jats:sup>, −α<jats:sup>4.2</jats:sup>/−−<jats:sup>SEA</jats:sup>). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−−<jats:sup>SEA</jats:sup>, 94.87% for αα/−α<jats:sup>3.7</jats:sup>, and 96.51% for αα/−α<jats:sup>4.2</jats:sup>; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.</jats:p>
Access State: Open Access

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