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Noninvasive Prenatal Determination of Twin Zygosity by Maternal Plasma DNA Analysis.
MedLine Citation:
PMID:  23115054     Owner:  NLM     Status:  Publisher    
BACKGROUND:The current methods for distinguishing the zygosities of twins include ultrasound scanning, which is nondefinitive, and amniocentesis, which is invasive. We explored the use of massively parallel sequencing of maternal plasma DNA for the noninvasive prenatal assessment of the zygosities of twin pregnancies.METHODS:Plasma DNA was extracted from blood collected from 8 women pregnant with twins. Target enrichment and massively parallel sequencing were performed for each plasma DNA library. Apparent fractional fetal DNA concentrations were calculated for multiple genomic regions by determining the ratio of minor to major alleles among single-nucleotide polymorphism sites. Variations in the apparent fractional fetal DNA concentrations between genomic regions were used to infer whether individual fetuses in a twin pair were genotypically different and hence dizygotic.RESULTS:The extent of the variation in the apparent fractional fetal DNA concentration across chromosomes was 0.82-1.35 SDs for monozygotic twin pregnancies and 2.42-4.80 SDs for dizygotic twin pregnancies. The proportions of apparent fractional fetal DNA concentration values that deviated beyond the range expected for stochastic variation were 0.00%-1.93% for monozygotic twin pregnancies and 36.2%-78.1% for dizygotic twin pregnancies. After identifying a pair of twins as likely dizygotic, the method also allowed determination of the fractional fetal DNA concentrations contributed by the individual fetuses of a dizygotic twin pair.CONCLUSIONS:Noninvasive prenatal determination of twin zygosity by maternal plasma DNA sequencing is feasible. It is also possible to determine the relative fractional fetal DNA concentrations for each fetus for dizygotic twin pregnancies.
James Z Z Qu; Tak Y Leung; Peiyong Jiang; Gary J W Liao; Yvonne K Y Cheng; Hao Sun; Rossa W K Chiu; K C Allen Chan; Y M Dennis Lo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-31
Journal Detail:
Title:  Clinical chemistry     Volume:  -     ISSN:  1530-8561     ISO Abbreviation:  Clin. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences.
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