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Detection of single clone deletions using array CGH: Identification of submicroscopic deletions in the 22q11.2 deletion syndrome as a model system
Author(s) -
Tokuyasu Taku A.,
Cotter Philip D.,
Segraves Richard,
Harris Jeffrey,
Elder Melissa E.,
Gonzales Marcos,
Pinkel Daniel,
Albertson Donna G.,
Rauen Katherine A.
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31662
Subject(s) - comparative genomic hybridization , copy number variation , fluorescence in situ hybridization , biology , genetics , chromosome , computational biology , copy number analysis , microarray , concordance , genome , gene , gene expression
Abstract Constitutional submicroscopic DNA copy number alterations have been shown to cause numerous medical genetic syndromes, and are suspected to occur in a portion of cases for which the causal events remain undiscovered. Array comparative genomic hybridization (array CGH) allows high‐throughput, high‐resolution genome scanning for DNA dosage aberrations and thus offers an attractive approach for both clinical diagnosis and discovery efforts. Here we assess this capability by applying array CGH to the analysis of copy number alterations in 44 patients with a phenotype of the 22q11.2 deletion syndrome. Twenty‐five patients had the deletion on chromosome 22 characteristic of this syndrome as determined by fluorescence in situ hybridization (FISH). The array measurements were in complete concordance with the FISH analysis, supporting their diagnostic utility. These data show that a genome‐scanning microarray has the level of sensitivity and specificity required to prospectively interrogate and identify single copy number aberrations in a clinical setting. We demonstrate that such technology is ideally suited for microdeletion syndromes such as 22q11.2. © 2007 Wiley‐Liss, Inc.