Noninvasive prenatal diagnosis by genome-wide haplotyping of cell-free plasma DNA
| Autor: | Nathalie Brison, Eric Legius, Kris Van Den Bogaert, Huiwen Che, Darine Villela, Masoud Zamani Esteki, Maria Neofytou, Olga Tšuiko, Thierry Voet, Joris Vermeesch, Koen Devriendt, Cindy Melotte, Eftychia Dimitriadou |
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| Přispěvatelé: | RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
SELECTION DISORDERS Prenatal diagnosis Single-nucleotide polymorphism noninvasive prenatal testing 030105 genetics & heredity Biology Genome NIPD 03 medical and health sciences Genotype medicine cfDNA Genetics (clinical) MATERNAL PLASMA Genetic testing Genetics Genetics & Heredity RISK Science & Technology medicine.diagnostic_test Haplotype COST genome-wide haplotyping genomic DNA NIPS 030104 developmental biology Cell-free fetal DNA FREE FETAL DNA DISEASES Life Sciences & Biomedicine |
| Zdroj: | Genetics in Medicine, 22(5), 962-973. Nature Publishing Group |
| ISSN: | 1530-0366 1098-3600 |
| Popis: | PURPOSE: Whereas noninvasive prenatal screening for aneuploidies is widely implemented, there is an increasing need for universal approaches for noninvasive prenatal screening for monogenic diseases. Here, we present a cost-effective, generic cell-free fetal DNA (cffDNA) haplotyping approach to scan the fetal genome for the presence of inherited monogenic diseases. METHODS: Families participating in the preimplantation genetic testing for monogenic disorders (PGT-M) program were recruited for this study. Two hundred fifty thousand single-nucleotide polymorphisms (SNPs) captured from maternal plasma DNA along with genomic DNA from family members were massively parallel sequenced. Parental genotypes were phased via an available genotype from a close relative, and the fetal genome-wide haplotype and copy number were determined using cffDNA haplotyping analysis based on estimation and segmentation of fetal allele presence in the maternal plasma. RESULTS: In all families tested, mutational profiles from cffDNA haplotyping are consistent with embryo biopsy profiles. Genome-wide fetal haplotypes are on average 97% concordant with the newborn haplotypes and embryo haplotypes. CONCLUSION: We demonstrate that genome-wide targeted capture and sequencing of polymorphic SNPs from maternal plasma cell-free DNA (cfDNA) allows haplotyping and copy-number profiling of the fetal genome during pregnancy. The method enables the accurate reconstruction of the fetal haplotypes and can be easily implemented in clinical practice. ispartof: GENETICS IN MEDICINE vol:22 issue:5 pages:962-973 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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