Detection of Fetal Sex, Aneuploidy and a Microdeletion from Single Placental Syncytial Nuclear Aggregates.
OBJECTIVE
A key problem in prenatal screening using extra-embryonic cells is the feasibility of extracting usable DNA from a small number of cells. Syncytial nuclear aggregates (SNAs) are multinucleated structures shed from the placenta. This study assesses the potential of SNAs as a source of fetal DNA for the detection of genetic abnormalities.


METHODS
SNAs were collected in vitro. Whole-genome amplification was used to amplify DNA from single SNAs, and DNA quality and quantity was assessed by spectrophotometry and PCR. Confocal microscopy was used to count nuclei within SNAs, determine metabolic activity and investigate DNA damage. Fetal sex and chromosomal/genetic abnormalities were investigated with array-comparative genomic hybridization (aCGH).


RESULTS
DNA was amplified from 81% of the individual SNAs. A mean of 61 ± 43 nuclei were found per SNA. DNA strand breaks were found in 76% of the SNAs. Seventy-five percent of SNAs yielded whole-genome-amplified DNA of sufficient quality for aCGH after storage and shipping. Individual SNAs from the same pregnancy reliably gave the same chromosomal profile, and fetal sex and trisomies could be detected. A microdeletion was detected in one pregnancy.


CONCLUSIONS
SNAs could provide a source of extra-embryonic DNA for the prenatal screening/diagnosis of fetal sex and chromosomal and sub-chromosomal genetic abnormalities.
School of Medical Science, Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Southport, Qld., Australia.
Olivia
O
Holland
Thomas
T
Kroneis
Amin
A
El-Heliebi
Maria
M
McDowell-Hook
Peter
P
Stone
Peter
P
Sedlmayr
Lawrence
L
Chamley
D000782:Aneuploidy; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000737:chemistry*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012732:Sex Determination Analysis
D004247:DNA