In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-08-09)
Kurzfassung:
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/−− SEA (4.066%), αα/−α 3.7 (2.934%), αα/−α 4.2 (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 3.7 /−α 4.2 , αα/−− THAI , −α 3.7 /−− SEA , −α 4.2 /−− SEA ). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−− SEA , 94.87% for αα/−α 3.7 , and 96.51% for αα/−α 4.2 ; 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.
Materialart:
Online-Ressource
ISSN:
2045-2322
DOI:
10.1038/s41598-022-17718-7
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2022
ZDB Id:
2615211-3
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