Korean J Obstet Gynecol.  2005 Jul;48(7):1621-1634.

Rapid prenatal diagnosis for chromosomal aneuploidy using cDNA microarray-based comparative genomic hybridization

• Yang YH
• Rha SY
• Jung YW
• Yang ES
• Lee KY
• Park CH
• Kim IK
• Hwang HS
• Park YW
• Roh JK

Abstract

OBJECTIVE
Prenatal cytogenetic diagnosis is limited to metaphase karyotype analysis of cultured cells obtained by amniocentesis or chorionic villus sampling. Moreover, genome wide analysis cannot be performed by FISH analysis using specific probe. Array comparative genomic hybridization (CGH) offers a number of advantages over conventional cytogenetic analysis and FISH. Microarray CGH can be highly comprehensive, amenable to very high resolution, sensitive and fast. The objective of this study was to determine the clinical use of cDNA microarray CGH for detection of fetal aneuploidy.
METHODS
21 amniotic fluid samples and 6 chorionic villi samples were obtained from 27 pregnant women in 9-19 gestational weeks. Genomic DNA was extracted from each sample and amplified. For cDNA microarray CGH analysis, test DNA sample and reference DNA sample were labeled with Cy3-dUTP and Cy5-dUTP, respectively. Each sample of labeled test and reference DNA was hybridized to microarray. The result was analysed with axon scanner and compared with cytogenetic analysis and FISH.
RESULTS
In 27 cases, 3 cases with trisomy 21 and 1 case with trisomy 18 had increased hybridization signals on chromosome 21 and chromosome 18. One case with 45,X had decreased signals on chromosome X. One case with 46,X,i(Xq) had decreased signal on short arm of chromosome X and increased signal on long arm. And one case with 47,XYY had two fold increased signal on Y chromosome. cDNA microarray based CGH correctly identified fetal aneuploidy in all of the 7 cases with aneuploid fetuses.
CONCLUSION
Prenatal genetic diagnosis by cDNA microarray-based CGH is an useful, innovative, rapid and accurate method. It is promising technique allowing rapid screening for whole chromosomal changes including aneuploidy, and may augment standard karyotyping techniques for prenatal genetic diagnosis by providing additional molecular information. This method may aid the discovery and description of minor genetic aberration, potentially enhancing future prenatal genetic diagnostic application.

Keyword

cDNA microarray-CGH; Prenatal diagnosis; Aneuploidy

MeSH Terms

Amniocentesis
Amniotic Fluid
Aneuploidy*
Arm
Axons
Cells, Cultured
Chorionic Villi
Chorionic Villi Sampling
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 21
Comparative Genomic Hybridization*
Cytogenetic Analysis
Cytogenetics
Diagnosis
DNA
DNA, Complementary*
Down Syndrome
Female
Fetus
Genome
Humans
Karyotype
Karyotyping
Mass Screening
Metaphase
Oligonucleotide Array Sequence Analysis
Pregnancy
Pregnant Women
Prenatal Diagnosis*
Trisomy
Y Chromosome
DNA
DNA, Complementary