Microarray Analysis of Cell-Free Fetal DNA in Amniotic Fluid: a Prenatal Molecular Karyotype

Metaphase karyotype analysis of fetal cells obtained by amniocentesis or chorionic villus sampling is the current standard for prenatal cytogenetic diagnosis, particularly for the detection of trisomy 21. We previously demonstrated that large quantities of cell-free fetal DNA (cffDNA) are easily ext...

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Bibliographic Details
Published in:American journal of human genetics 2004-09, Vol.75 (3), p.485-491
Main Authors: Larrabee, Paige B., Johnson, Kirby L., Pestova, Ekaterina, Lucas, Madhuri, Wilber, Kim, LeShane, Erik S., Tantravahi, Umadevi, Cowan, Janet M., Bianchi, Diana W.
Format: Article
Language:English
Subjects:
Amniocentesis
Amniotic Fluid - metabolism
Aneuploidy
Biological and medical sciences
Cell-Free System
Chorionic Villi - metabolism
Chorionic Villi Sampling
Chromosomes, Human, Pair 21
Chromosomes, Human, X
Chromosomes, Human, Y
Cytogenetics
DNA
Female
General aspects. Genetic counseling
Genetic Techniques
Humans
Karyotyping
Male
Medical genetics
Medical sciences
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis
Pregnancy
Turner Syndrome - genetics
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Summary:Metaphase karyotype analysis of fetal cells obtained by amniocentesis or chorionic villus sampling is the current standard for prenatal cytogenetic diagnosis, particularly for the detection of trisomy 21. We previously demonstrated that large quantities of cell-free fetal DNA (cffDNA) are easily extracted from amniotic fluid (AF). In this study, we explored potential clinical applications of AF cffDNA by testing its ability to hybridize to DNA microarrays for comparative genomic hybridization (CGH) analysis. cffDNA isolated from 11 male fetuses showed significantly increased hybridization signals on SRY and decreased signals on X-chromosome markers, compared with female reference DNA. cffDNA isolated from six female fetuses showed the reverse when compared with male reference DNA. cffDNA from three fetuses with trisomy 21 had increased hybridization signals on the majority of the chromosome 21 markers, and cffDNA from a fetus with monosomy X (Turner syndrome) had decreased hybridization signals on most X-chromosome markers, compared with euploid female reference DNA. These results indicate that cffDNA extracted from AF can be analyzed using CGH microarrays to correctly identify fetal sex and aneuploidy. This technology facilitates rapid screening of samples for whole-chromosome changes and may augment standard karyotyping techniques by providing additional molecular information.
ISSN:0002-9297
1537-6605
DOI:10.1086/423288