Oligonucleotide microarrays for clinical diagnosis of copy number variation

Detection of genomic copy number variation is now considered the standard of care in the evaluation of children with developmental delay, and is used for other clinical indications such as multiple congenital anomalies and autism spectrum disorders. Fluorescence in situ hybridization (FISH) was the first molecular method for detection of submicroscopic genomic copy number variation, but microarray based comparative genomic hybridization (array CGH) offers several advantages as an adjunct to traditional cytogenetic methods such as karyotype and FISH. This unit focuses on oligonucleotide arrays, but includes background information on basic differences between oligonucleotide arrays and bacterial artificial chromosome (BAC) arrays. Array sensitivity is influenced by probe coverage or density, probe location, and choice of oligo array formats (i.e., targeted versus whole genome). Array platform influences the likelihood of detecting variants of unknown significance. Clinical interpretation of such variants is discussed.