Dayne L Filer1,2, Piotr A Mieczkowski1, Alicia Brandt1, Kelly L Gilmore3, Bradford C Powell1,2, Jonathan S Berg1, Kirk C Wilhelmsen1,2,4, Neeta L Vora1,3. 1. Department of Genetics, School of Medicine, UNC Chapel Hill, Chapel Hill, NC, USA. 2. Renaissance Computing Institute, Chapel Hill, NC, USA. 3. Department of Obstetrics & Gynecology, School of Medicine, UNC Chapel Hill, Chapel Hill, NC, USA. 4. Department of Neurology, School of Medicine, UNC Chapel Hill, Chapel Hill, NC, USA.
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.
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.
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