Development of array based comparative genomic hybridization (CGH) as a diagnostic tool for cryptic chromosome aberrations in congenital disorders

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The human genome sequencing project had been conducted successfully, with 99% of the genome sequenced with 99.99% accuracy. In the post-sequence era, detection of disease-related genomic alterations is directly connected with identification of genes associated with multiple congenital anomalies with mental retardation (MCA/MR), autism, and other unknown genomic disorders. However, we had none of tools for exploring cryptic chromosome aberrations at 100kb-level. In order to overcome the situation, we have constructed high-resolution CGH-arrays as follows, (1) Whole Genome Array (WGA)-4500, which contains 4523 BACs throughout the whole genome, (2) Cancer Array-800, which harbors 800 BACs for different cancer-related genes, (3) 1p36-contig array, which covers about 20Mb spanning 1p36 region with 212 BACs, (4) Chromosome X-tiling array, which contains 1001 BACs throughout chromosome X except pseudo-autosomal region, and (5) Genome Disorder (GD)-array, which is employed as the diagnostic tool for known genomic disorders. Using those in-house BAC arrays, we explored cryptic chromosome aberrations in a large number of patients with MCA/MR, and detected de novo submicroscopic aberrations related to the pathogenesis of unknown MCA/MR in some of those patients.