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- Title
Noninvasive prenatal testing of α-thalassemia and β-thalassemia through population-based parental haplotyping.
- Authors
Chen, Chao; Li, Ru; Sun, Jun; Zhu, Yaping; Jiang, Lu; Li, Jian; Fu, Fang; Wan, Junhui; Guo, Fengyu; An, Xiaoying; Wang, Yaoshen; Fan, Linlin; Sun, Yan; Guo, Xiaosen; Zhao, Sumin; Wang, Wanyang; Zeng, Fanwei; Yang, Yun; Ni, Peixiang; Ding, Yi
- 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.
- Subjects
PRENATAL diagnosis; HIDDEN Markov models; VITERBI decoding; INVASIVE diagnosis; HAPLOTYPES; TURNAROUND time; HOMOZYGOSITY
- Publication
Genome Medicine, 2021, Vol 13, Issue 1, p1
- ISSN
1756-994X
- Publication type
Article
- DOI
10.1186/s13073-021-00836-8