RESUMO
BACKGROUND: Although the clinical utility of array comparative genomic hybridization (aCGH) is undisputed, the implementation of this technology is a unique experience for each laboratory. OBJECTIVE: Endeavors to construct a bacterial artificial chromosome (BAC)-based CGH microarray targeting microdeletion and duplication syndromes related to mental retardation and developmental delay are described. METHOD: Covering each chromosome at the 650-band level, the array comprises 1360 BAC clones with emphasis on the subtelomeric and pericentromeric regions and enrichment of genomic hot spots containing genes associated with specific constitutional disorders. During development of the array, fluorescence in situ hybridization (FISH) and end-sequencing analysis eliminated 24% of BACs that were mismapped or cross-hybridized, underscoring the need rigorously to assess arrayed elements. Performance of the BACs was tested further with chromosome-specific add-in experiments. CONCLUSION: Of the first 500 clinical cases, 54 (11%) showed chromosome abnormalities, which were confirmed by FISH with BACs from the aberrant loci or by conventional cytogenetics. Array CGH is a powerful tool that is now being implemented in the realm of diagnostic testing.