Array CGH is superior to other methodologies at detecting somatic mosaicism. V.R. Sutton, C. Shaw, D.A. Scott, A. Patel, S. Trilochan, A. Pursley, J. Li, P. Stankiewicz, A.C. Chinault, J.R. Lupski, A.L. Beaudet, S.W. Cheung. Molecular & Human Genetics, Baylor College of Medicine, Houston, TX.
   We have developed a targeted aCGH platform known as chromosome microarray analysis (CMA) for clinical use in our diagnostic laboratory. This platform contains bacterial artificial chromosome (BAC) clones that encompass telomeric and pericentromeric regions as well as regions of the genome involved in common microdeletion/microduplication (genomic) disorders. Therefore in a single assay, hundreds of genomic regions can be interrogated for gains or losses in copy number. We have performed CMA using the latest version of our array on 2585 samples and identified 12 cases in which the results were indicative of mosaicism. Ten had an aneuploidy, one had a ring chromosome and one had segmental aneusomy. In 11/12 cases, prior routine chromosome analysis had been normal. We therefore hypothesized that CMA may be a more sensitive method for detecting mosaicism. The presence of mosaicism in all cases was confirmed by one or more of the following methodologies: G banded chromosome analysis of stimulated T-cells or B-cells from peripheral blood or cultured skin fibroblasts; FISH analysis on stimulated T-cells or whole blood smear. Estimates of the level of mosaicism were higher for CMA compared with methodologies that use T-cells in all cases. We believe that this is due to the selection bias against aneuploid T-cells both in vivo during VDJ recombination and cellular division, and in vitro during T-cell stimulation for routine chromosome analysis and FISH. The estimates of the level of mosaicism were also higher for CMA compared with FISH of unstimulated nucleated cells from whole blood in almost all cases, likely because FISH requires that the cells are alive and aneuploid cells likely die at a faster rate than euploid cells. Thus, we assert that CMA is superior to other standard methodologies in detecting mosaicism and estimating the level of mosaicsm for both aneuploidies and other cytogenetic aberrations.