New technologies for the assessment of chromosomes in prenatal diagnosis

Cytogeneticists have many tools that can be used to identify chromosome abnormalities. Microscopic analysis of banded chromosomes has been used for over 40 years as the main tool for uncovering cytogenetic aberrations in prenatal testing. In this special issue of Prenatal Diagnosis, we have worked with leading authors to compile state-of-the-art information on the new cytogenetic technologies available in the clinical and diagnostic laboratories to identify alterations of the genome leading to human disease. We have called this issue ‘New cytogenetic technologies’ because each of the methods described is aimed at uncovering chromosome imbalance, either whole chromosome aneuploidies, or locus-specific gains and losses of the genome. The articles addressing aneuploidy detection showcase the use of fluorescence in situ hybridization-based microfluidics by Ho and co-workers at the National University of Singapore, the application of quantitative fluorescent-polymerase chain reaction in prenatal diagnosis by Mann and Ogilvie at Guy’s & St. Thomas’ National Health Foundation Trust, London, and multiplex ligation-dependent probe amplification in prenatal testing by Willis and Eng at Baylor College of Medicine, Houston. Beyond aneuploidy testing is a new technology using bacterial artificial chromosomes (BACs), termed BACs-on-Beads, which can detect gains or losses of whole chromosomes or chromosomal segments in a limited, targeted approach. In a collaborative study, Vialard and coauthors from several European cytogenetic laboratories describe their use of the BACs-on-Beads methodology in over 1600 prospective prenatal samples. The assay detects the common aneuploidies of chromosomes 13, 18, 21, X and Y, along with gains or losses of nine genomic regions from ten microdeletion disorders. The authors found nearly a 10% detection rate among the samples tested and among these, 7.3% represented gains or losses of the microdeletion regions tested. Finally, a review by Chiu and Lo at the Chinese University of Hong Kong delivers important insights into the use of high-throughput sequencing for the noninvasive detection of trisomy 21. The largest number of articles in this special issue is focused on the use of microarrays in prenatal testing. Brady and Vermeesch from the University Hospital in Leuven, Belgium provide a comprehensive review of the technological aspects of genomic microarrays, discussing the various array platforms and protocols used in the cytogenetics laboratory. Some of the manuscripts focus on specific applications of arrays, such as Schmid et al. on the use of array data in fetuses with congenital heart defects, and Gruchy et al., who compare the use of arrays after cultured prenatal specimens or extraction of cell-free fetal DNA. In another application, Reddy and colleagues review the literature on the clinical application of arrays after fetal death. Because many cultures fail to grow after a spontaneous abortion or stillbirth and cytogenetic analysis is not possible, arrays may be particularly suited to the study of fetal demise because the extraction of DNA for use in microarrays does not rely on the ability to culture cells. As one of the first laboratories offering prenatal testing using microarrays, Breman and colleagues from Baylor College of Medicine present their experience with over 1000 prospective prenatal array tests performed. They compare their findings to that of the published medical literature. With a variety of indications for study by microarray, they found that 4.2% of cases had an abnormality detected bymicroarray after abnormal karyotypes were excluded. This is a significant finding because many of these abnormalities would be undetectablewith routine banded chromosome analysis. To understand the ordering practices of physicians desiring microarray testing for their patients, Shaffer and co-workers from Signature Genomic Laboratories in Spokane, Washington and colleagues from Canada and Israel report on over 1400 prenatal microarrays performed for a variety of indications on two different microarray platforms. Although themajority of pregnancieswere referred for testing because of abnormal ultrasound findings, the