Objectives: While several studies have now conducted whole-genome surveys of structural variation in autistic individuals, we sought to achieve a significantly higher resolution analysis by employing a candidate gene strategy, primarily focused on GABA related genes. Using this approach, we have the ability to detect smaller scale structural variants that remain undetectable using standard whole genome CGH arrays.
Methods: Custom 1x244k Agilent comparative genomic hybridization (CGH) arrays were designed covering GABA related genes, as well as 28 additional autism candidate genes, including Neurexins 1-3 and Neuroligins 1-4, and SHANK3. Collectively, our probes spanned a total of 15 Mb with a density of approximately 1 probe every 150 nucleotides. 250 autism cases and 250 control individuals are currently being evaluated by aCGH. All experimental and control samples were hybridized vs. a single reference sample. Putative CNVs detected via aCGH will subsequently be validated using either standard PCR followed by gel electrophoresis or real-time quantitative PCR, depending upon the predicted size of the event.
Results: Preliminary results indicate putative CNVs in two autism candidates.
Conclusions: Pending validation of CNV events and additional analyses.