Applications of CytoMicroarrays

Genomic imbalances or copy number variations (CNVs) are a major cause of pregnancy losses, fetal anomalies identified during prenatal period, congenital defects in newborn, dysmorphology and developmental delay in infants, autism spectrum disorders and mental retardation. Routine karyotyping at 550 band resolution is limited to identifying aneuploidy and large structural anomalies such as chromosomal inversions, deletions and duplications larger than 5 Mb through microscopy and image analysis. Fluorescent in situ hybridization (FISH) testing can useful in detection of smaller genomic imbalances only when the clinical diagnosis is clear and narrowed down to a single condition. CytoMicroarrays can overcome these problems and can identify sub-microscopic microdeletions and duplications of >25 KB size in addition to offering differential diagnosis. Several international bodies including ACMG recommend CytoMicroarray as first tier test for congenital anomalies, developmental delay and autism disorders. The SNP backbone of the cytomicroarray facilitates identification of LOH (Loss of heterozygosity) and UPD (Uni parental disomy) along with CNVs. Limitations of CytoMicroarray include inability to detect CNVs of >25Kb, low level mosaicism of <20% and balanced translocations. The lecture presents 2yr lab experience with a set of case results to demonstrate sensitivity of Cytomicroarray in identification of genomic imbalances along with phenotypic correlation.