Array-based comparative genomic hybridization for the genomewide detection of submicroscopic XXXX .

@entity1 @entity1032 @entity600 @entity4238 @entity2008
Microdeletions and microduplications, not visible by routine chromosome analysis, are a major cause of @entity1 @entity600 and @entity1032 . Novel high-resolution, whole-genome technologies can improve the diagnostic detection rate of these small @entity2008 . Array-based comparative genomic hybridization allows such a high-resolution screening by hybridizing differentially labeled test and reference DNAs to arrays consisting of thousands of genomic clones. In this study, we tested the diagnostic capacity of this technology using approximately 3,500 flourescent in situ hybridization-verified clones selected to cover the genome with an average of 1 clone per megabase (Mb). The sensitivity and specificity of the technology were tested in normal-versus-normal control experiments and through the screening of @entity1 with known microdeletion syndromes. Subsequently, a series of 20 cytogenetically normal @entity1 with @entity1032 and @entity4238 suggestive of a @entity2008 were analyzed. In this series, three microdeletions and two microduplications were identified and validated. Two of these genomic changes were identified also in one of the parents, indicating that these are large-scale genomic polymorphisms. Deletions and duplications as small as 1 Mb could be reliably detected by our approach. The percentage of false-positive results was reduced to a minimum by use of a dye-swap-replicate analysis, all but eliminating the need for laborious validation experiments and facilitating implementation in a routine diagnostic setting. This high-resolution assay will facilitate the identification of novel genes involved in @entity1 @entity1032 and/or @entity600 syndromes and will provide insight into the flexibility and plasticity of the @entity1 genome.
