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Noninvasive prenatal exome sequencing diagnostic utility limited by sequencing depth and fetal fraction
Author(s) -
Filer Dayne L.,
Mieczkowski Piotr A.,
Brandt Alicia,
Gilmore Kelly L.,
Powell Bradford C.,
Berg Jonathan S.,
Wilhelmsen Kirk C.,
Vora Neeta L.
Publication year - 2022
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.6009
Subject(s) - exome sequencing , cell free fetal dna , prenatal diagnosis , exome , genotyping , dna sequencing , medicine , massive parallel sequencing , genetics , biology , fetus , computational biology , genotype , pregnancy , mutation , dna , gene
Abstract Objective Sequencing cell‐free DNA now allows detection of large chromosomal abnormalities and dominant Mendelian disorders in the prenatal period. Improving upon these methods would allow newborn screening programs to begin with prenatal genetics, ultimately improving the management of rare genetic disorders. Methods As a pilot study, we performed exome sequencing on the cell‐free DNA from three mothers with singleton pregnancies to assess the viability of broad sequencing modalities in a noninvasive prenatal setting. Results We found poor resolution of maternal and fetal genotypes due to both sampling and technical issues. Conclusion We find broad sequencing modalities inefficient for noninvasive prenatal applications. Alternatively, we suggest a more targeted path forward for noninvasive prenatal genotyping.