Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0186771
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dc.titleMeasurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms
dc.contributor.authorBarrett A.N.
dc.contributor.authorXiong L.
dc.contributor.authorTan T.Z.
dc.contributor.authorAdvani H.V.
dc.contributor.authorHua R.
dc.contributor.authorLaureano-Asibal C.
dc.contributor.authorSoong R.
dc.contributor.authorBiswas A.
dc.contributor.authorNagarajan N.
dc.contributor.authorChoolani M.
dc.date.accessioned2020-03-19T08:58:43Z
dc.date.available2020-03-19T08:58:43Z
dc.date.issued2017
dc.identifier.citationBarrett A.N., Xiong L., Tan T.Z., Advani H.V., Hua R., Laureano-Asibal C., Soong R., Biswas A., Nagarajan N., Choolani M. (2017). Measurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms. PLoS ONE 12 (10) : e0186771. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0186771
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165772
dc.description.abstractObjective: Cell-free DNA from maternal plasma can be used for non-invasive prenatal testing for aneuploidies and single gene disorders, and also has applications as a biomarker for monitoring high-risk pregnancies, such as those at risk of pre-eclampsia. On average, the fractional cell-free fetal DNA concentration in plasma is approximately 15%, but can vary from less than 4% to greater than 30%. Although quantification of cell-free fetal DNA is straightforward in the case of a male fetus, there is no universal fetal marker; in a female fetus measurement is more challenging. We have developed a panel of multiplexed insertion/deletion polymorphisms that can measure fetal fraction in all pregnancies in a simple, targeted sequencing reaction. Methods: A multiplex panel of primers was designed for 35 indels plus a ZFX/ZFY amplicon. cfDNA was extracted from plasma from 157 pregnant women, and maternal genomic DNA was extracted for 20 of these samples for panel validation. Sixty-one samples from pregnancies with a male fetus were subjected to whole genome sequencing on the Ion Proton sequencing platform, and fetal fraction derived from Y chromosome counts was compared to fetal fraction measured using the indel panel. A total of 157 cell-free DNA samples were sequenced using the indel panel, and informativity was assessed, along with the proportion of fetal DNA. Results: Using gDNA we optimised the indel panel, removing amplicons giving rise to PCR bias. Good correlation was found between fetal fraction using indels and using whole genome sequencing of the Y chromosome (Spearmans r = 0.69). A median of 12 indels were informative per sample. The indel panel was informative in 157/157 cases (mean fetal fraction 14.4% (±0.58%)). Conclusions: Using our targeted next generation sequencing panel we can readily assess the fetal DNA percentage in male and female pregnancies. © 2017 Barrett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectcell free fetal DNA
dc.subjectDNA
dc.subjectgenomic DNA
dc.subjectunclassified drug
dc.subjectcell free nucleic acid
dc.subjectDNA
dc.subjectamplicon
dc.subjectArticle
dc.subjectDNA determination
dc.subjectDNA extraction
dc.subjectfemale
dc.subjectfetus
dc.subjectgenetic polymorphism
dc.subjecthuman
dc.subjectindel mutation
dc.subjectmale
dc.subjectmaternal plasma
dc.subjectpolymerase chain reaction
dc.subjectwhole genome sequencing
dc.subjectY chromosome
dc.subjectblood
dc.subjectmetabolism
dc.subjectpregnancy
dc.subjectCell-Free Nucleic Acids
dc.subjectChromosomes, Human, Y
dc.subjectDNA
dc.subjectFemale
dc.subjectFetus
dc.subjectHumans
dc.subjectINDEL Mutation
dc.subjectPregnancy
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF OBSTETRICS & GYNAECOLOGY
dc.contributor.departmentDEPT OF PATHOLOGY
dc.description.doi10.1371/journal.pone.0186771
dc.description.sourcetitlePLoS ONE
dc.description.volume12
dc.description.issue10
dc.description.pagee0186771
dc.published.statePublished
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