Noninvasive prenatal testing of α-thalassemia and β-thalassemia through population-based parental haplotyping
Open Access
- 5 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Medicine
- Vol. 13 (1), 1-9
- https://doi.org/10.1186/s13073-021-00836-8
Abstract
Background: Noninvasive prenatal testing (NIPT) of recessive monogenic diseases depends heavily on knowing the correct parental haplotypes. However, the currently used family-based haplotyping method requires pedigrees, and molecular haplotyping is highly challenging due to its high cost, long turnaround time, and complexity. Here, we proposed a new two-step approach, population-based haplotyping-NIPT (PBH-NIPT), using α-thalassemia and β-thalassemia as prototypes.Methods: First, we deduced parental haplotypes with Beagle 4.0 with training on a large retrospective carrier screening dataset (4356 thalassemia carrier screening-positive cases). Second, we inferred fetal haplotypes using a parental haplotype-assisted hidden Markov model (HMM) and the Viterbi algorithm.Results: With this approach, we enrolled 59 couples at risk of having a fetus with thalassemia and successfully inferred 94.1% (111/118) of fetal alleles. We confirmed these alleles by invasive prenatal diagnosis, with 99.1% (110/111) accuracy (95% CI, 95.1–100%).Conclusions: These results demonstrate that PBH-NIPT is a sensitive, fast, and inexpensive strategy for NIPT of thalassemia.Keywords
Funding Information
- Major Technical Innovation Project of Hubei Province (No. 2017ACA097)
- the Special Foundation for High-level Talents of Guangdong (No. 2016TX03R171)
- the Shenzhen Municipal Government of China (No. JCYJ20170412152854656)
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