Application of a target array Comparative Genomic Hybridization to prenatal diagnosis

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.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.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.Speed and precision are two major requirements in prenatal chromosome analyses. Conventional G-banded karyotyping remains the gold standard in prenatal genetic diagnosis, but it is time-consuming and labor-intensive. Routinely, about 10-14 days is required to obtain the result and this may increase the patient's anxiety. To overcome these limitations, rapid fluorescent in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR), and multiplex ligation-dependent probe amplification (MLPA) have been developed and are widely used as adjuncts to conventional methods for detecting common chromosome aneuploidies such as trisomies 21, 13, 18, X and Y [1-6]. However, only a few loci may be tested at a time, so all those methods can usually be