Chromosomal Microarray Detection of Constitutional Copy Number Variation Using Saliva DNA

Chromosomal microarray (CMA) testing to detect copy number aberrations among individuals with multiple congenital anomalies and/or developmental delay is typically performed on peripheral blood DNA. However, the use of saliva DNA may be preferred for some patients, which prompted our validation study using six saliva DNA samples with a range of bacterial content (approximately 3% to 21%) and 20 paired blood and saliva specimens on the Agilent Technologies, Illumina, and Affymetrix CMA platforms. Ten of the 20 paired specimens were previously determined to carry clinically significant copy number aberrations by clinical CMA testing on blood DNA (100 kb to 2.56 Mb; five deletions, eight duplications). Notably, the quality of saliva DNA (DNA Genotek) was equivalent to blood DNA regardless of bacterial content, as was CMA quality and single-nucleotide polymorphism genotyping quality with all CMA platforms. The number of copy number variants and absence of heterozygosity regions detected by CMA were comparable between paired blood and saliva DNA and, more important, all 13 clinically significant copy number aberrations were detected in saliva DNA by all CMA platforms. These data confirm that the quality of saliva DNA is comparable to blood DNA regardless of bacterial content, including important CMA and single-nucleotide polymorphism quality metrics, and that saliva DNA is a reliable alternative for the detection of clinically significant copy number aberrations by clinical CMA testing.