Detection of chromosome abnormalities: Beyond conventional karyotyping

Pregnancy loss is a gravely unhappy and emotionally stressful event for any couple. Besides having to address what may be a couple's psychosocial embarrassment due to their loss, one of the challenges for most researchers is how to identify these pregnancy loss cases with genetic defects that are destined to miscarry from other treatable cases. It remains indisputable that chromosomal karyotyping is the gold standard for prenatal diagnosis, including pregnancy loss. However, researchers can obtain virtually the same or better diagnostic information for detecting gains and losses of genetic material across the genome using microarray analysis, also known as molecular karyotyping and/or chromosomal array analysis, including array-based comparative genomic hybridization and single nucleotide polymorphism (SNP) array. All of these different arrays create an entire genome scanning panel. Comparative genomic hybridization is able to discover and map genomic regions for chromosomal gains or losses in a single experiment without knowledge pertaining to the locations of regions of abnormalities. SNP combing across the genome (approximately 1/10 kb) with an informatics technique is used to detect gains and losses and identifies maternal cell contamination, triploidy, and uniparental disomy. In this issue, Lin et al have authored an interesting article entitled Improved assay performance of single nucleotide polymorphism array over conventional karyotyping in analyzing products of conception. We heartily applaud the publication of this article, because the diagnoses were consistent with previous reports based on traditional cell culture and karyotyping of products of conception. In Lin et al's study, approximately 64.5% (100/155) of samples were cytogenetically abnormal (including 52% single trisomy, 11% monosomy X, and 6% triploidy). SNP array not only demonstrated a higher success rate for detecting chromosomal abnormalities (98.1% vs. 85.8%), but also provided an additional ability to detect pathologic copy number variations and whole-genome uniparental disomy (UPD) compared with conventional karyotyping (G-banded karyotyping), thus contributing to a higher detection rate of abnormalities (62.6% vs. 61.3%). Furthermore, the use of SNPs also significantly improved sensitivity to mosaicism. By contrast, two cases of chromosome translocation and one case of tetraploidy were not