Application of a target array comparative genomic hybridization to prenatal diagnosis.
BACKGROUND
While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies.


METHODS
We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping.


RESULTS
In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis.


CONCLUSIONS
We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically-uncertain genomic regions.
Park
Ji Hyeon
JH
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea.
Woo
Jung Hoon
JH
Shim
Sung Han
SH
Yang
Song-Ju
SJ
Choi
Young Min
YM
Yang
Kap-Seok
KS
Cha
Dong Hyun
DH
D000782:Aneuploidy; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*