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Authors: Vong, Joaquim S L and Jiang, Peiyong and Cheng, Suk-Hang and Lee, Wing-Shan and Tsang, Jason C H and Leung, Tak-Yeung and Chan, K C Allen and Chiu, Rossa W K and Lo, Y M Dennis

Cell-free DNA (cfDNA) fragments in maternal plasma contain DNA damage and may negatively impact the sensitivity of noninvasive prenatal testing (NIPT). However, some of these DNA damages are potentially reparable. We aimed to recover these damaged cfDNA molecules using PreCR DNA Repair Mix.cfDNA was extracted from twenty maternal plasma samples and was repaired and sequenced by the Illumina platform. Size profiles and fetal DNA fraction changes of repaired samples were characterized. Targeted sequencing of Chromosome Y sequences was used to enrich fetal cfDNA molecules following repair. Single molecule real-time (SMRT) sequencing platform was employed to characterize long (>250 bp) cfDNA molecules. NIPT of five trisomy 21 samples was performed.Size profiles of repaired libraries were altered, with significantly increased long (>250 bp) cfDNA molecules. Single nucleotide polymorphism (SNP)-based analyses showed both fetal- and maternal-derived cfDNA molecules were enriched by the repair. Fetal DNA fractions in maternal plasma showed a small but consistent (4.8%) increase, which were contributed by a higher increment of long fetal cfDNA molecules. Z-score values were improved in NIPT of all trisomy 21 samples.Plasma DNA repair recovers and enriches long cfDNA molecules of both fetal and maternal origins in maternal plasma.This article is protected by copyright. All rights reserved.

Journal: Prenatal diagnosis
DOI: 10.1002/pd.5406
Year: 2018

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