ARS | Publication request: Genome-wide array-based comparative genomic hybridization (array-CGH) analysis in Aicardi Syndrome

Submitted to: American Society of Human Genetics
Publication Type: Abstract
Publication Acceptance Date: October 23, 2007
Publication Date: October 23, 2007
Citation: Wang, X., Sutton, V.R., Eble, T., O'Neill, C., Lewis, R.A., Van Den Veyver, I.B. 2007. Genome-wide array-based comparative genomic hybridization (array-CGH) analysis in Aicardi Syndrome [abstract]. In: 57th Annual Meeting of The American Society of Human Genetics, October 23-27, 2007, San Diego, California. p. 472.

Technical Abstract: Aicardi syndrome is characterized by agenesis of the corpus callosum, chorioretinal lacunae, severe seizures (starting as infantile spasms), neuronal migration defects, mental retardation, costovertebral defects, and typical facial features. Because Aicardi syndrome is sporadic and affects only females or rarely 47, XXY males, it is thought to be caused by de novo dominant mutations in an X-linked gene, but an autosomal mutation with sex-limited effects cannot be excluded. Because genetic linkage approaches to map the gene for Aicardi syndrome cannot be used, we performed high-resolution array-CGH analysis with DNA samples of subjects with Aicardi syndrome to search for segments of copy number loss or gain that may contain the mutated gene. Genomic DNA of female subjects with Aicardi syndrome and reference female DNA were labeled differentially with Cy5 and Cy3, and co-hybridized onto human whole-genome 185k or 244k oligonucleotide DNA arrays (Agilent Technologies). After slides were scanned and feature extraction performed, results were visualized and analyzed with Alilent's CGH analytics software and displayed as log2 ratios with these settings: 1-fold cut-off, ADM-2 aberration algorithm with threshold 10.0. To date, we have tested 16 DNA samples from well-characterized females with Aicardi syndrome on the 185k array and 28 on the 244k array. We found between 7 and 21 copy number gains or losses per subject. There were a total of 146 unique copy number changes across the entire genome in the 44 studied samples. Of these, 124 were previously annotated copy number variants, 6 were also found in unrelated array-CGH hybridizations for other conditions or controls, and 16 (15 autosomal and 1X chromosomal) have not been seen before. These are currently being confirmed and studied on parental DNAs, as they may represent candidate regions for the Aicardi syndrome genes.