Detection and characterizing CNVs identified by tiling resolution BAC array CGH.. Homo sapiens

In this study 405 patients with unexplained mental retardation and 89 unaffected parents were analyzed for DNA copy-number changes using a tiling-resolution genomewide microarray containing 32,447 BACs. This series contains 367 slides from 315 individuals previously not reported, plus an additional 239 slides from 179 individuals previously reported in the series GSE3191. Keywords: array CGH Overall design: A 32k tiling resolution genomic microarray consisting of 32,447 overlapping BAC clones, selected to cover the entire human genome, was used to generate genomic copy number profiles for 494 samples using methods previously described (de Vries et al. 2005). These samples were originally analyzed by this method within a diagnostic setting with the aim to identify copy number changes related to mental retardation. The samples therefore consisted of patients with unexplained mental retardation (n=405, of which 102 were run in replicate with dye-reversal) as well as unaffected parents (n=89, 38 complete trios). In all cases genomic DNA was isolated from uncultured blood leucocytes, excluding culture-induced rearrangements and aneuploidies as described by Redon et al. (2006). Hybridization was performed in a two-color experiment against a reference pool containing equal amounts of genomic DNA from 10 healthy blood donors (either mis-match or match). De novo alterations were validated by FISH and MLPA.